cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.15049140.v1
title: Estimation of polymorphisms in the drug-metabolizing enzyme, cytochrome <i>P450 2C19</i> gene in six major ethnicities of Pakistan

description: Interindividual differences in cytochrome P450 (<i>CYP)</i> 2C19 activity may result in variations in the therapeutic response to drugs metabolized by this enzyme. Differences at gene level may translate into protein level with consequent impairment of the enzyme activity. As a result patients with such genetic differences might experience undesirable effects or no effect at all. The aim of the present study was to find out the prevalence of allelic and genotype frequencies of low activity variants of CYP2C19 genes in healthy individuals from six distinct ethnicities of Pakistan. Blood sample was taken from healthy volunteers following informed consent. Isolation of the DNA was followed by the PCR amplification and restriction fragment length polymorphism. Selected samples were sequenced by Sanger sequencing. The frequency of major alleles was 84.93% for <i>CYP2C19*2</i> and 91.85% for CYP2C19*3, while minor allele was present at 15.06% for <i>CYP2C19*2</i> and 8.14% for CYP2C19*3. For <i>CYP2C19*2</i>, the frequency of *1*1 genotype was 75.80%, *1*2 was 18.27%, and *2*2 was 5.92% whereas for <i>CYP2C19*3</i>, The frequency of *1*1 genotype was 84.19%, *1*3 was 15.30%, and *3*3 was 0.49% in the Pakistani population. A substantial variation in genotype and allelic frequencies was observed in various ethnicities. Our study demonstrates that a significant Pakistani population has at least one minor allele, which indicates a large number of patients potentially being affected by these variations. Especially, a significant genotype frequency of PM suggests implication for the treatment response and severity/frequency of adverse effects in patients receiving drugs metabolized by CYP2C19.
DOI: 10.6084/m9.figshare.13661505
title: Peripheral immune tolerance by prolactin-induced protein originated from human invariant natural killer T cells

description: invariant natural killer T (iNKT) cells have been reported to regulate a diverse set of immunological responses. iNKT cell dysfunction in cytokine secretion is linked to the development of autoimmunity, an immune response against its own tissue. Interestingly, CD4<sup>+</sup> iNKT cells preferentially secrete regulatory cytokines. Here we investigated what kind of secreting factors of it are involved in dendritic cell (DC) maturation to regulate immune responses. We found one of them, prolactin induced protein (PIP), from the supernatants of cultured CD4<sup>+</sup> iNKT cells. It was validated using RT-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis. Subsequent analysis upon PIP treatment was performed using fluorescence-activated cell sorting (FACS) analysis. We identified PIP as one of strong candidates for inducing DC maturation, to similar level to lipopolysaccharide, an already known candidate molecule. Recombinant PIP recapitulated natural function, and induction of DC differentiation by both recombinant and purified PIP was blocked by anti-Toll-like receptor (TLR)2 antibody (Ab), but not by anti-TLR4/5 or anti-receptor Ab for advanced glycation end product Ab. Interestingly, PIP induced the differentiation of naïve T cells into CD4<sup>+</sup> CD25<sup>+</sup> Foxp3<sup>+</sup> regulatory T cells and reduced the number of helper T (Th)1 and Th17 cells produced by Pam3CysSerLys4. Take in together, these results suggest that PIP is an important factor that mediates immunoregulation by iNKT cells through TLR2-mediated signaling.
DOI: 10.6084/m9.figshare.13661505.v1
title: Peripheral immune tolerance by prolactin-induced protein originated from human invariant natural killer T cells

description: invariant natural killer T (iNKT) cells have been reported to regulate a diverse set of immunological responses. iNKT cell dysfunction in cytokine secretion is linked to the development of autoimmunity, an immune response against its own tissue. Interestingly, CD4<sup>+</sup> iNKT cells preferentially secrete regulatory cytokines. Here we investigated what kind of secreting factors of it are involved in dendritic cell (DC) maturation to regulate immune responses. We found one of them, prolactin induced protein (PIP), from the supernatants of cultured CD4<sup>+</sup> iNKT cells. It was validated using RT-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis. Subsequent analysis upon PIP treatment was performed using fluorescence-activated cell sorting (FACS) analysis. We identified PIP as one of strong candidates for inducing DC maturation, to similar level to lipopolysaccharide, an already known candidate molecule. Recombinant PIP recapitulated natural function, and induction of DC differentiation by both recombinant and purified PIP was blocked by anti-Toll-like receptor (TLR)2 antibody (Ab), but not by anti-TLR4/5 or anti-receptor Ab for advanced glycation end product Ab. Interestingly, PIP induced the differentiation of naïve T cells into CD4<sup>+</sup> CD25<sup>+</sup> Foxp3<sup>+</sup> regulatory T cells and reduced the number of helper T (Th)1 and Th17 cells produced by Pam3CysSerLys4. Take in together, these results suggest that PIP is an important factor that mediates immunoregulation by iNKT cells through TLR2-mediated signaling.
DOI: 10.6084/m9.figshare.16826369
title: Identification of a prognostic chemoresistance-related gene signature associated with immune microenvironment in breast cancer

description: Breast cancer is the most common form of cancer among women globally, and chemoresistance is a major challenge to disease treatment that is associated with a poor prognosis. This study was formulated to identify a reliable prognostic biosignature capable of predicting the survival of patients with chemoresistant breast cancer (CRBC) and evaluating the associated tumor immune microenvironment. Through a series of protein-protein interaction and weighted correlation network analyses, genes that were significantly associated with breast cancer chemoresistance were identified. Moreover, univariate Cox regression and lasso-penalized Cox regression analyses were employed to generate a prognostic model, and the prognostic utility of this model was then assessed using time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curves. Finally, The CIBERSORT and ESTIMATE algorithms were additionally leveraged to assess relationships between the tumor immune microenvironment and patient prognostic signatures. Overall, a multigenic prognostic biosignature capable of predicting CRBC patient risk was successfully developed based on bioinformatics analysis and in vitro experiments. This biosignature was able to stratify CRBC patients into high- and low-risk subgroups. ROC curves also revealed that this biosignature achieved high diagnostic efficiency, and multivariate regression analyses indicated that this risk signature was an independent risk factor linked to CRBC patient outcomes. In addition, this signature was associated with the infiltration of the tumor microenvironment by multiple immune cell types. In conclusion, the chemoresistance-associated prognostic gene signature developed herein was able to effectively evaluate the prognosis of CRBC patients and to reflect the overall composition of the tumor immune microenvironment.
DOI: 10.6084/m9.figshare.16826369.v2
title: Identification of a prognostic chemoresistance-related gene signature associated with immune microenvironment in breast cancer

description: Breast cancer is the most common form of cancer among women globally, and chemoresistance is a major challenge to disease treatment that is associated with a poor prognosis. This study was formulated to identify a reliable prognostic biosignature capable of predicting the survival of patients with chemoresistant breast cancer (CRBC) and evaluating the associated tumor immune microenvironment. Through a series of protein-protein interaction and weighted correlation network analyses, genes that were significantly associated with breast cancer chemoresistance were identified. Moreover, univariate Cox regression and lasso-penalized Cox regression analyses were employed to generate a prognostic model, and the prognostic utility of this model was then assessed using time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curves. Finally, The CIBERSORT and ESTIMATE algorithms were additionally leveraged to assess relationships between the tumor immune microenvironment and patient prognostic signatures. Overall, a multigenic prognostic biosignature capable of predicting CRBC patient risk was successfully developed based on bioinformatics analysis and in vitro experiments. This biosignature was able to stratify CRBC patients into high- and low-risk subgroups. ROC curves also revealed that this biosignature achieved high diagnostic efficiency, and multivariate regression analyses indicated that this risk signature was an independent risk factor linked to CRBC patient outcomes. In addition, this signature was associated with the infiltration of the tumor microenvironment by multiple immune cell types. In conclusion, the chemoresistance-associated prognostic gene signature developed herein was able to effectively evaluate the prognosis of CRBC patients and to reflect the overall composition of the tumor immune microenvironment.
DOI: 10.6084/m9.figshare.17708078
title: Long non-coding RNA TTN-AS1/microRNA-199a-3p/runt-related transcription factor 1 gene axis regulates the progression of oral squamous cell carcinoma

description: Oral squamous cell carcinoma (OSCC) has a high degree of malignancy, which affects the quality of life and prognosis of patients with OSCC. Our study aimed to reveal the function of long non-coding RNA TTN-AS1/microRNA-199a-3p (miR-199a-3p)/runt-related transcription factor 1 (RUNX1) axis in OSCC progression, thereby providing a novel OSCC effective strategy. Real-time quantitative polymerase chain reaction and western blotting were performed to detect the expression of TTN-AS1, miR-199a-3p, and RUNX1 in OSCC. Several cell functional experiments, including Cell Counting Kit-8, flow cytometry, and cell adhesion assays, were used to assess cell proliferation, apoptosis, adhesion, and migration. A luciferase assay was performed to confirm the interaction between TTN-AS1, miR-199a-3p, and RUNX1. Our results revealed that TTN-AS1 and RUNX1 were upregulated in OSCC tissues and cells, whereas miR-199a-3p expression was downregulated. Knockdown of TTN-AS1 or RUNX1 suppressed cell proliferation, adhesion, and migration but induced apoptosis. Additionally, miR-199a-3p inhibitor partly relieved the effects of silencing TTN-AS1 and RUNX1 in OSCC cells due to their targeting relationship. In conclusion, TTN-AS1 and RUNX1 could promote OSCC progression and miR-199a-3p partly relieved the effects of TTN-AS1 and RUNX1.
DOI: 10.6084/m9.figshare.17708078.v1
title: Long non-coding RNA TTN-AS1/microRNA-199a-3p/runt-related transcription factor 1 gene axis regulates the progression of oral squamous cell carcinoma

description: Oral squamous cell carcinoma (OSCC) has a high degree of malignancy, which affects the quality of life and prognosis of patients with OSCC. Our study aimed to reveal the function of long non-coding RNA TTN-AS1/microRNA-199a-3p (miR-199a-3p)/runt-related transcription factor 1 (RUNX1) axis in OSCC progression, thereby providing a novel OSCC effective strategy. Real-time quantitative polymerase chain reaction and western blotting were performed to detect the expression of TTN-AS1, miR-199a-3p, and RUNX1 in OSCC. Several cell functional experiments, including Cell Counting Kit-8, flow cytometry, and cell adhesion assays, were used to assess cell proliferation, apoptosis, adhesion, and migration. A luciferase assay was performed to confirm the interaction between TTN-AS1, miR-199a-3p, and RUNX1. Our results revealed that TTN-AS1 and RUNX1 were upregulated in OSCC tissues and cells, whereas miR-199a-3p expression was downregulated. Knockdown of TTN-AS1 or RUNX1 suppressed cell proliferation, adhesion, and migration but induced apoptosis. Additionally, miR-199a-3p inhibitor partly relieved the effects of silencing TTN-AS1 and RUNX1 in OSCC cells due to their targeting relationship. In conclusion, TTN-AS1 and RUNX1 could promote OSCC progression and miR-199a-3p partly relieved the effects of TTN-AS1 and RUNX1.
DOI: 10.6084/m9.figshare.16826369.v1
title: Identification of a prognostic chemoresistance-related gene signature associated with immune microenvironment in breast cancer

description: Breast cancer is the most common form of cancer among women globally, and chemoresistance is a major challenge to disease treatment that is associated with a poor prognosis. This study was formulated to identify a reliable prognostic biosignature capable of predicting the survival of patients with chemoresistant breast cancer (CRBC) and evaluating the associated tumor immune microenvironment. Through a series of protein-protein interaction and weighted correlation network analyses, genes that were significantly associated with breast cancer chemoresistance were identified. Moreover, univariate Cox regression and lasso-penalized Cox regression analyses were employed to generate a prognostic model, and the prognostic utility of this model was then assessed using time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curves. Finally, The CIBERSORT and ESTIMATE algorithms were additionally leveraged to assess relationships between the tumor immune microenvironment and patient prognostic signatures. Overall, a multigenic prognostic biosignature capable of predicting CRBC patient risk was successfully developed based on bioinformatics analysis and in vitro experiments. This biosignature was able to stratify CRBC patients into high- and low-risk subgroups. ROC curves also revealed that this biosignature achieved high diagnostic efficiency, and multivariate regression analyses indicated that this risk signature was an independent risk factor linked to CRBC patient outcomes. In addition, this signature was associated with the infiltration of the tumor microenvironment by multiple immune cell types. In conclusion, the chemoresistance-associated prognostic gene signature developed herein was able to effectively evaluate the prognosis of CRBC patients and to reflect the overall composition of the tumor immune microenvironment.
DOI: 10.6084/m9.figshare.16587092
title: Evaluation of tumor microenvironmental immune regulation and prognostic in lung adenocarcinoma from the perspective of purinergic receptor P2Y13

description: Tumor-infiltrating immune cells (TICs) can serve as an important indicator to evaluate the prognosis and therapeutic response in lung adenocarcinoma (LUAD). The identification of mutated genes that can affect the abundance of TICs and prognosis has practical implications. In the presented study, tumor microenvironment (TME) scoring was performed by the ESTIMATE scoring system on 598 RNA transcripts selected from the TCGA database to determine the proportions of immune cells and stromal cells. The infiltration difference of TICs in LUAD samples was obtained by CIBERSORT. The ‘immuneeconv’ R software package, which integrates six latest algorithms, including TIMER, xCell, MCP-counter, CIBERSORT, EPIC and quanTIseq were used to verify the correlation between purinergic receptor P2Y13 (<i>P2RY13</i>) and immune cells. Based on RNA sequencing analysis of the Lewis lung cancer-bearing model in C57BL/6 mice and immunohistochemistry (IHC) of human LUAD tissues, the expression of <i>P2RY13</i> and associated pathways were verified. It was shown that differentially expressed genes (DEGs) obtained by interactive analysis based on Immunescore and Stromalscore were significantly enriched in immune-related pathways. The expression of <i>P2RY13</i> was significantly associated with prognosis and clinicopathological characteristics of LUAD patients. More importantly, this gene played an important role in maintaining the immune dominant environment and changing the regulation of TICs. <i>P2RY13</i> expression was positively correlated with the infiltration of dendritic cells (DCs) in various of tumor tissues as validated by the PanglaoDB scRNA-seq database. Therefore, <i>P2RY13</i> is expected to be a potential biomarker for predicting TME and the prognosis of LUAD after verification.
DOI: 10.6084/m9.figshare.16587092.v2
title: Evaluation of tumor microenvironmental immune regulation and prognostic in lung adenocarcinoma from the perspective of purinergic receptor P2Y13

description: Tumor-infiltrating immune cells (TICs) can serve as an important indicator to evaluate the prognosis and therapeutic response in lung adenocarcinoma (LUAD). The identification of mutated genes that can affect the abundance of TICs and prognosis has practical implications. In the presented study, tumor microenvironment (TME) scoring was performed by the ESTIMATE scoring system on 598 RNA transcripts selected from the TCGA database to determine the proportions of immune cells and stromal cells. The infiltration difference of TICs in LUAD samples was obtained by CIBERSORT. The ‘immuneeconv’ R software package, which integrates six latest algorithms, including TIMER, xCell, MCP-counter, CIBERSORT, EPIC and quanTIseq were used to verify the correlation between purinergic receptor P2Y13 (<i>P2RY13</i>) and immune cells. Based on RNA sequencing analysis of the Lewis lung cancer-bearing model in C57BL/6 mice and immunohistochemistry (IHC) of human LUAD tissues, the expression of <i>P2RY13</i> and associated pathways were verified. It was shown that differentially expressed genes (DEGs) obtained by interactive analysis based on Immunescore and Stromalscore were significantly enriched in immune-related pathways. The expression of <i>P2RY13</i> was significantly associated with prognosis and clinicopathological characteristics of LUAD patients. More importantly, this gene played an important role in maintaining the immune dominant environment and changing the regulation of TICs. <i>P2RY13</i> expression was positively correlated with the infiltration of dendritic cells (DCs) in various of tumor tissues as validated by the PanglaoDB scRNA-seq database. Therefore, <i>P2RY13</i> is expected to be a potential biomarker for predicting TME and the prognosis of LUAD after verification.
DOI: 10.6084/m9.figshare.16587092.v1
title: Evaluation of tumor microenvironmental immune regulation and prognostic in lung adenocarcinoma from the perspective of purinergic receptor P2Y13

description: Tumor-infiltrating immune cells (TICs) can serve as an important indicator to evaluate the prognosis and therapeutic response in lung adenocarcinoma (LUAD). The identification of mutated genes that can affect the abundance of TICs and prognosis has practical implications. In the presented study, tumor microenvironment (TME) scoring was performed by the ESTIMATE scoring system on 598 RNA transcripts selected from the TCGA database to determine the proportions of immune cells and stromal cells. The infiltration difference of TICs in LUAD samples was obtained by CIBERSORT. The ‘immuneeconv’ R software package, which integrates six latest algorithms, including TIMER, xCell, MCP-counter, CIBERSORT, EPIC and quanTIseq were used to verify the correlation between purinergic receptor P2Y13 (<i>P2RY13</i>) and immune cells. Based on RNA sequencing analysis of the Lewis lung cancer-bearing model in C57BL/6 mice and immunohistochemistry (IHC) of human LUAD tissues, the expression of <i>P2RY13</i> and associated pathways were verified. It was shown that differentially expressed genes (DEGs) obtained by interactive analysis based on Immunescore and Stromalscore were significantly enriched in immune-related pathways. The expression of <i>P2RY13</i> was significantly associated with prognosis and clinicopathological characteristics of LUAD patients. More importantly, this gene played an important role in maintaining the immune dominant environment and changing the regulation of TICs. <i>P2RY13</i> expression was positively correlated with the infiltration of dendritic cells (DCs) in various of tumor tissues as validated by the PanglaoDB scRNA-seq database. Therefore, <i>P2RY13</i> is expected to be a potential biomarker for predicting TME and the prognosis of LUAD after verification.
DOI: 10.6084/m9.figshare.14577492
title: Ivabradine protects rats against myocardial infarction through reinforcing autophagy via inhibiting PI3K/AKT/mTOR/p70S6K pathway

description: Ivabradine (Iva), a heart rate reducing agent that specifically inhibits the pacemaker <i>I(f)</i> ionic current, has been demonstrated to be cardioprotective in many cardiovascular diseases. Autophagy is an evolutionarily conserved metabolic process that regulates cardiac homeostasis. This study is aimed to explore whether autophagy is functionally involved in the cardioprotective effect of Iva in a rat model of myocardial infarction (MI). We observed that Iva treatment (po, 10 mg/kg/day) showed significant recovery on the hemodynamics parameters in MI rats, including left ventricular systolic pressure, left ventricular end diastolic pressure, and maximal ascending/descending rate of left ventricular pressure. Also, Iva treatment dramatically decreased infarct size, inhibited myocardial apoptosis, and reduced the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in MI rats. Moreover, Iva treatment enhanced autophagy and inhibited PI3K/AKT/mTOR/p70S6K pathway in MI rats. Simultaneously, we observed that autophagy enhancer rapamycin (ip, 10 mg/kg/day) showed similar cardioprotective effects with Iva. Furthermore, we observed that addition of autophagy inhibitor 3-methyladenine (ip, 10 mg/kg/day) counteracted the therapeutic effect of Iva, addressing that Iva attenuated post-MI cardiac injury by enhancing autophagy. In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.
DOI: 10.6084/m9.figshare.14577492.v1
title: Ivabradine protects rats against myocardial infarction through reinforcing autophagy via inhibiting PI3K/AKT/mTOR/p70S6K pathway

description: Ivabradine (Iva), a heart rate reducing agent that specifically inhibits the pacemaker <i>I(f)</i> ionic current, has been demonstrated to be cardioprotective in many cardiovascular diseases. Autophagy is an evolutionarily conserved metabolic process that regulates cardiac homeostasis. This study is aimed to explore whether autophagy is functionally involved in the cardioprotective effect of Iva in a rat model of myocardial infarction (MI). We observed that Iva treatment (po, 10 mg/kg/day) showed significant recovery on the hemodynamics parameters in MI rats, including left ventricular systolic pressure, left ventricular end diastolic pressure, and maximal ascending/descending rate of left ventricular pressure. Also, Iva treatment dramatically decreased infarct size, inhibited myocardial apoptosis, and reduced the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in MI rats. Moreover, Iva treatment enhanced autophagy and inhibited PI3K/AKT/mTOR/p70S6K pathway in MI rats. Simultaneously, we observed that autophagy enhancer rapamycin (ip, 10 mg/kg/day) showed similar cardioprotective effects with Iva. Furthermore, we observed that addition of autophagy inhibitor 3-methyladenine (ip, 10 mg/kg/day) counteracted the therapeutic effect of Iva, addressing that Iva attenuated post-MI cardiac injury by enhancing autophagy. In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.