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  • Frontiers Media SA  (49)
  • 1
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    Image_4.tif
    Frontiers Media SA ; 2024
    In:  Frontiers in Molecular Neuroscience Vol. 17 ( 2024-4-5)
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    In: Frontiers in Molecular Neuroscience, Frontiers Media SA, Vol. 17 ( 2024-4-5)
    Abstract: Social memory is the ability to discriminate between familiar and unknown conspecifics. It is an important component of social cognition and is therefore essential for the establishment of social relationships. Although the neural circuit mechanisms underlying social memory encoding have been well investigated, little focus has been placed on the regulatory mechanisms of social memory processing. The dopaminergic system, originating from the midbrain ventral tegmental area (VTA), is a key modulator of cognitive function. This study aimed to illustrate its role in modulating social memory and explore the possible molecular mechanisms. Here, we show that the activation of VTA dopamine (DA) neurons is required for the formation, but not the retrieval, of social memory. Inhibition of VTA DA neurons before social interaction, but not 24 h after social interaction, significantly impaired social discrimination the following day. In addition, we showed that the activation of VTA DA neurons was regulated by the serine/threonine protein kinase liver kinase B1 (Lkb1). Deletion of Lkb1 in VTA DA neurons reduced the frequency of burst firing of dopaminergic neurons. Furthermore, Lkb1 plays an important role in regulating social behaviors. Both genetic and virus-mediated deletions of Lkb1 in the VTA of adult mice impaired social memory and subsequently attenuated social familiarization. Altogether, our results provide direct evidence linking social memory formation to the activation of VTA DA neurons in mice and illustrate the crucial role of Lkb1 in regulating VTA DA neuron function.
    Type of Medium: Online Resource
    ISSN: 1662-5099
    URL: Article
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    DOI: 10.3389/fnmol.2024.1289476
    DOI: 10.3389/fnmol.2024.1289476.s001
    DOI: 10.3389/fnmol.2024.1289476.s002
    DOI: 10.3389/fnmol.2024.1289476.s003
    DOI: 10.3389/fnmol.2024.1289476.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
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  • 2
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    DataSheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-10-24)
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    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-10-24)
    Abstract: Systemic inflammation and water composition are important factors affecting cancer prognosis. This study aimed to explore the association between the neutrophil-to-lymphocyte ratio (NLR) and intracellular water/total body water (ICW/TBW) ratio and overall survival (OS) in colorectal cancer (CRC). Methods This multicenter, prospective cohort included 628 patients with CRC between June 2012 and December 2019. The association between the covariates and OS was assessed using a Cox proportional hazards model and restricted cubic spline models. Concordance index (C-index), which integrated discriminant improvement (IDI) index and continuous net reclassification index, (cNRI) was used to compare the predictive ability of the markers. Results The optimal cutoff values for the NLR and ICW/TBW ratio were 2.42 and 0.61, respectively. The NLR was negatively associated with OS, while the ICW/TBW ratio was positively correlated with OS. NLR ≥2.42 and ICW/TBW ratio & lt;0.61 were both independent poor prognostic factors (hazard ratio [HR]: 2.04, 95% confidence interval [CI] : 1.44–2.88 and HR: 1.45, 95% CI: 1.04–2.02, respectively). Subsequently, we combined the two factors to construct an inflammation-water score (IWS). Patients with IWS (2, ≥1) had worse OS (HR: 2.86 and 95% CI: 1.77–4.63; HR: 1.74 and 95% CI 1.17–2.57, respectively) than those without one. Compared to its component factors, IWS score showed better predictive ability for C-index, IDI index, and cNRI. Conclusion A high NLR and a low ICW/TBW ratio were independent risk factors for poor prognosis in patients with CRC. The combination of the two factors can provide a better prognostic prediction effect.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.896160
    DOI: 10.3389/fonc.2022.896160.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 3
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    Table_1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Nutrition Vol. 9 ( 2022-5-10)
    Details
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 9 ( 2022-5-10)
    Abstract: Non-small cell lung cancer (NSCLC) is among the most prevalent malignancies worldwide. Previous studies have shown that the status of inflammation, nutrition and immune are closely related to overall survival (OS) of patients with NSCLC, but little is known about their interactive and combined roles. Hence, we chose glucose to lymphocyte ratio (GLR) and modified Glasgow Prognosis Score (mGPS) as prognostic factors and assessed the prognostic values of them for patients with NSCLC. Methods Baseline clinicopathologic and laboratory characteristics of 862 patients with NSCLC were obtained from a multicenter prospective cohort. The Cox proportional hazard regression models were used to determine prognostic values of the clinical factors. A nomogram was also constructed integrating the clinical factors with clinical significance or independent prognostic values. Concordance index (C-index) was utilized to evaluate the prediction accuracy of the TNM stage and the nomogram. Results Multivariate analyses demonstrated that GLR [Hazard ratio (HR) = 1.029, 95% confidence interval (CI) = 1.004–1.056, P = 0.023] and mGPS (score of 1: HR = 1.404, 95% CI = 1.143–1.726, P = 0.001; score of 2: HR = 1.515, 95% CI = 1.159–1.980, P = 0.002) were independent prognostic factors for patients with NSCLC. The C-indexes of the TNM stage and the nomogram were 0.642 (95% CI = 0.620–0.663) and 0.694 (95% CI = 0.671–0.717), respectively. Conclusion GLR and mGPS were independent prognostic factors for patients with NSCLC. Moreover, our constructed nomogram might be superior in predicting prognosis of patients with NSCLC compared with the TNM stage.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    URL: Article
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    DOI: 10.3389/fnut.2022.871301
    DOI: 10.3389/fnut.2022.871301.s001
    DOI: 10.3389/fnut.2022.871301.s002
    DOI: 10.3389/fnut.2022.871301.s003
    DOI: 10.3389/fnut.2022.871301.s004
    DOI: 10.3389/fnut.2022.871301.s005
    DOI: 10.3389/fnut.2022.871301.s006
    DOI: 10.3389/fnut.2022.871301.s007
    DOI: 10.3389/fnut.2022.871301.s008
    DOI: 10.3389/fnut.2022.871301.s009
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 4
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Nutrition Vol. 8 ( 2021-8-4)
    Details
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 8 ( 2021-8-4)
    Abstract: Background: Fat-free mass (FFM) depletion can be masked by a stable body weight or weight gain in the presence of a normal or high body mass index (BMI). This study investigated the prognostic value of low fat-free mass index (FFMI) in cancer patients with normal or high BMI. Methods: This multicenter retrospective cohort study included 1,602 cancer patients with normal/high BMI. The association of FFMI with patients' overall survival (OS) was analyzed by the Kaplan-Meier method and a Cox model. Results: In this analysis, there were 974 (60.8%) females and 628 (39.2%) males. Low FFMI was associated with worse OS when compared with those patients with normal FFMI. After multivariate adjustment, low FFMI was demonstrated to be an independent unfavorable prognostic factor (HR: 1.69; 95% CI: 1.28, 2.23; P & lt; 0.001) in cancer patients with normal/high BMI. For specific tumor type, low FFMI was found to be associated with worse prognosis in patients with lung cancer, breast cancer and upper gastrointestinal cancer. In subgroup analysis, the association of low FFMI with worse survival was significantly modified by weight loss ( P for interaction = 0.012), and those patients with concurrent low FFMI and weight loss showed the worst prognosis (HR: 3.53; 95% CI: 2.04, 6.11; P & lt; 0.001). Conclusion: Low FFMI was associated with worse prognosis in cancer patients with normal/high BMI. This study highlights the usefulness of FFMI for prognostic estimation in these patients.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    URL: Article
    URL: Article
    DOI: 10.3389/fnut.2021.714051
    DOI: 10.3389/fnut.2021.714051.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 5
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    Table_4.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-9-10)
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    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-9-10)
    Abstract: Recently, albumin–globulin ratio (AGR), a serological indicator that reflects nutritional status and systemic inflammatory, has been reported to be associated with the prognosis of various cancers. However, there is currently no research report on its relationship with cancer cachexia. Objectives This study aimed to explore the prognostic value of AGR in patients with cancer cachexia through a multicenter retrospective analysis. Methods We recruited 2,364 patients with cancer cachexia and randomly divided the patients into training and validation cohorts at a ratio of 7:3. The optimal stratification method was used to determine the optimal cutoff value of AGR. The survival curve was evaluated by the Kaplan–Meier method. Cox regression proportional-hazards model was used to determine independent prognostic factors in patients with cancer cachexia. The time-dependent receiver operating characteristic curve was used to compare the prognostic performance of different malnutrition evaluation tools. Results The optimal cutoff value of AGR is 1.24 in patients with cancer cachexia. Increasing AGR was associated with survival in a dose–response manner with a forward L-shape. Compared with the high AGR group, the low AGR group had a shorter overall survival; and there was consistency in training and validation cohorts. In the stratified analysis of TNM stage, AGR has good prognostic distinguishing ability for advanced patients. Multivariate survival analysis determined that low AGR was an independent risk factor affecting all-cause mortality in patients with cancer cachexia. In addition, compared with other malnutrition evaluation tools, AGR could effectively stratify the prognosis of patients with cancer cachexia. Conclusion AGR was an independent prognostic factor affecting patients with cancer cachexia, especially in advanced patients. Compared with other malnutrition evaluation tools, AGR can effectively stratify the prognosis of patients with cancer cachexia.
    Type of Medium: Online Resource
    ISSN: 2234-943X
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    DOI: 10.3389/fonc.2021.707705
    DOI: 10.3389/fonc.2021.707705.s001
    DOI: 10.3389/fonc.2021.707705.s002
    DOI: 10.3389/fonc.2021.707705.s003
    DOI: 10.3389/fonc.2021.707705.s004
    DOI: 10.3389/fonc.2021.707705.s005
    DOI: 10.3389/fonc.2021.707705.s006
    DOI: 10.3389/fonc.2021.707705.s007
    DOI: 10.3389/fonc.2021.707705.s008
    DOI: 10.3389/fonc.2021.707705.s009
    DOI: 10.3389/fonc.2021.707705.s010
    DOI: 10.3389/fonc.2021.707705.s011
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 6
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    Table_4.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Nutrition Vol. 8 ( 2022-2-7)
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    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 8 ( 2022-2-7)
    Abstract: Systemic inflammation and malnutrition are correlated with cancer sarcopenia and have deleterious effects on oncological outcomes. However, the combined effect of inflammation and malnutrition in patients with cancer sarcopenia remains unclear. Methods We prospectively collected information on 1,204 patients diagnosed with cancer sarcopenia. the mean (SD) age was 64.5 (11.4%) years, and 705 (58.60%) of the patients were male. The patients were categorized into the high advanced lung cancer inflammation index (ALI) group (≥18.39) and the low ALI group ( & lt;18.39) according to the optimal survival cut-off curve. We selected the optimal inflammation marker using the C-index, decision curve analysis (DCA), and a prognostic receiver operating characteristic curve. Univariate and multivariate survival analyses were performed to determine the prognostic value of the optimal inflammation indicator. We also analyzed the association between inflammation and malnutrition in patients with cancer. Results The C-index, DCA, and prognostic area under the curve of ALI in patients with cancer sarcopenia were higher or better than those of neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). The prognosis for patients in the low ALI group was worse than that of patients in the high ALI group [HR (95%CI) = 1.584 (1.280–1.959), P & lt; 0.001]. When the ALI was divided into quartiles, we observed that decreased ALI scores strongly correlated with decreased overall survival (OS). Patients with both a low ALI and severe malnutrition (vs. patients with high ALI and well-nourished) had a 2.262-fold death risk ( P & lt; 0.001). Subgroup analysis showed a significant interactive association between the ALI and death risk in terms of TNM stage ( P for interaction = 0.030). Conclusions The inflammation indicator of the ALI was better than those of the NLR, PNI, SII, and PLR in patients with cancer sarcopenia. Inflammation combined with severe malnutrition has a nearly 3-fold death risk in patients with cancer sarcopenia, suggesting that reducing systemic inflammation, strengthening nutritional intervention, and improving skeletal muscle mass are necessary.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    URL: Article
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    DOI: 10.3389/fnut.2021.811288
    DOI: 10.3389/fnut.2021.811288.s001
    DOI: 10.3389/fnut.2021.811288.s002
    DOI: 10.3389/fnut.2021.811288.s003
    DOI: 10.3389/fnut.2021.811288.s004
    DOI: 10.3389/fnut.2021.811288.s005
    DOI: 10.3389/fnut.2021.811288.s006
    DOI: 10.3389/fnut.2021.811288.s007
    DOI: 10.3389/fnut.2021.811288.s008
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 7
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    DataSheet1.ZIP
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-7-22)
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    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-7-22)
    Abstract: Histone H3 lysine 4 (H3K4) methyltransferase 2D (KMT2D) plays an important role in cell development in early life. However, the function of KMT2D in adult cells such as cardiomyocytes or neurons has not been reported. In this study, cardiomyocyte-specific KMT2D knockout (KMT2D-cKO) and control (KMT2D-Ctl) mice were exposed to sham or myocardial ischemia (MI) surgery. Depletion of KMT2D aggravated the ischemic area, led to the increased mortality (26.5% in KMT2D-cKO vs 12.5% in KMT2D-Ctl) of the mice, and weakened the left ventricular systolic function. RNA-seq analysis in cardiac tissues identified genes whose expression was changed by MI and KMT2D deletion. Combined with the genome-wide association study (GWAS) analysis, cardiac disease-associated genes Rasd1 , Thsd7a , Ednra , and Tns1 were identified. The expression of the Rasd1 was significantly decreased by MI or the loss of KMT2D in vivo . Meanwhile, ChIP assays demonstrated that either MI or loss of KMT2D attenuated monomethylated H3K4 (H3K4me1) enrichment on the enhancer of Rasd1 . By generating a KMT2D knockout (H9C2-KO) H9C2 monoclone, we verified that the expression of Rasd1 was controlled by KMT2D, and the expression of Rasd1 was decreased by serum starvation but not low-(O 2 ) treatment in H9C2 cells. KMT2D has a protective effect on ischemic myocardium by regulating cardiac disease-associated genes including Rasd1 . KMT2D is required for the H3K4me1 deposition on the enhancer of Rasd1 . Our data for the first time suggest that KMT2D-mediated Rasd1 expression may play an important protective effect on adult cells during nutritional deficiency caused by ischemic injury.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    URL: Article
    DOI: 10.3389/fcell.2022.946484
    DOI: 10.3389/fcell.2022.946484.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 8
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    DataSheet_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-3-30)
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    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-3-30)
    Abstract: Colorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC. Methods The clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage. Results Multivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P & lt;0.001]. The CALLY index showed the highest prognostic value (C-index = 0.666, 95% CI = 0.638-0.694, P & lt;0.001), followed by mGPS, NLR, SII, and PLR. The nomogram demonstrated higher prognostic value (C-index = 0.784, 95% CI = 0.762-0.807, P & lt;0.001) than the TNM stage. Conclusion The CALLY index was independently associated with OS in patients with CRC and showed higher prognostic value than classical CRC prognostic factors. The nomogram could provide more accurate prognostic prediction than TNM stage.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2023.1131496
    DOI: 10.3389/fimmu.2023.1131496.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 9
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    Beneficial Effect of Edoxaban on Preventing Atrial Fibrillation and Coagulation by Reducing Inflammation via HBG1/HBD Biomarkers
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-6-3)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-6-3)
    Abstract: Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. The effectiveness and mechanism of edoxaban in preventing stroke after atrial fibrillation remain unclear. Methods: The expressions of HBG1 and HBD in red blood cells were tested in AF. Sixty C57B/6J mice were randomly divided into the following groups: the control (CON) group, atrial fibrillation (AF) group, AF + edoxaban group, and AF + rivaroxaban group. H & amp;E staining assay and reticular fiber staining were performed. Myocardial fibrosis was evaluated by the Masson staining assay, Sirius red staining assay, and immunohistochemical assay for the expressions of α-SMA and COL1A1. ELISA and RT-PCR assay were performed for the detection of inflammatory parameters (TNF-α, IL-1β, IL-6, and IL-10). Blood lipids were detected by using the Beckman automatic biochemical analyzer. Furthermore, four items of coagulation were detected, and molecular docking among HBG1, HBD, and MASP1 (Xa) was performed by PyMOL 2.1 software. The BP neural network model, cubic spline interpolation, and support vector machine model were constructed to predict prothrombin time based on HBG1 and HBD expressions. COIP assay was performed to construct the interaction between HBG1 and HBD. The functional enrichment analysis was performed by DAVID and Metascape tools. Results : The expressions of HBG1 and HBD in red blood cells of the patients with atrial fibrillation were decreased. The results showed a lower level of hemoglobin in red blood cells with HBG1-siRNA and HBG1-siRNA. Compared with the AF group, the collagen fiber percentage in the AF + edoxaban group was decreased ( p & lt; 0.05). After using edoxaban, the expressions of TNF-α, IL-1β, IL-6, and IL-10 were significantly decreased ( p & lt; 0.05). The LDL-C, TC, and TG levels were downregulated in the AF + edoxaban group. The PT and APTT levels in the AF + edoxaban group were more increasing than in the AF mice ( p & lt; 0.05). Compared with the AF group, the expressions of HBG1 and HBD were downregulated in the AF + edoxaban group ( p & lt; 0.05). HBG1 protein matched well with HBD and MASP1(Xa) protein surfaces. There exists a significant interaction between HBG1, HBD, and PT via the BP neural network and support vector machine. Enrichment analysis showed that HBG1 and HBD were mainly enriched in blood coagulation. Conclusion: Edoxaban could prevent atrial fibrillation and coagulation by reducing inflammation, lipids, and fibrosis via HBG1/HBD biomarkers effectively, and the effect was superior to that of rivaroxaban.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.904317
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 10
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-3-17)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-3-17)
    Abstract: Multimorbidity has an effect on life expectancy, while its effect on healthy life years is unclear. This study aims to investigate the associations between healthy life years lost due to multimorbidity and living risk. Methods The participants of The China Health and Retirement Longitudinal Study (CHARLS) were assessed at four visits between 2011 (baseline) and 2018. At baseline, 13,949 individuals were administered surveys. A combined score based on seven health-related factors was calculated, and the participants were classified into 3 groups based on living risk. We used the adjusted Cox regression methods to examine the associations between living risk groups and multimorbidity. We estimated the healthy life years lost due to multimorbidity using the Sullivan method. Results A total of 9,091 adults aged 45 years or older (mean age of 59.55 ± 9.50 years with one disease, 52.60% women) were analyzed in the CHARLS. The probability of no multimorbidity over 7 years decreased from 0.9947 to 0.9697 in the low-risk group, whereas the probability of multimorbidity in low living risk was lower than that of high living risk, ranging from HR 1.253 (95% CI.992–1.581; P = 0.058) to 1.431 (1.05–1.949; P = 0.023) in sex, and ranging from HR 1.340 (95% CI 1.106–1.623; P = 0.003) to 2.002 (1.058–3.787; P = 0.033) in area. At 45 years, the healthy life years lost in men was & lt;0.27 years compared to women in the low-risk group. Hypertension increased the risk of multimorbidity with an HR of 1.5 (95% CI 1.21–1.91; P & lt; 0.001) in men. In urban areas, participants with diabetes had 3.2 times (95% CI 1.75–5.94, P & lt; 0.001) higher risk of multimorbidity than participants without diabetes. Conclusions These findings indicate that a low-risk lifestyle could decrease the loss of healthy life years under multimorbidity. The probability of multimorbidity in women and in urban areas was high. Hypertension was correlated with the hazard risk of multimorbidity.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.831544
    DOI: 10.3389/fmed.2022.831544.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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