cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.25272115
title: Effects of autoimmune abnormalities on fertility and placental morphology in mice

description: Autoimmune diseases (AIDs) alter the placental immune environment leading to fetal loss. This study investigated the effects of AIDs on pregnancy and the placenta in AID-prone MRL/MpJ-<i>Fas<sup>lpr/lpr</sup></i> mice and wild-type MRL/MpJ, which were mated with male MRL/MpJ and MRL/MpJ-<i>Fas<sup>lpr/lpr</sup></i> at five months and defined as moLpr and moMpJ, respectively. AID indices (spleen weight and serum autoantibody levels) and fertility status (number and size of fetuses, morphology, and comprehensive gene expression of placentas) were evaluated on gestational day 15.5. Both strains showed equivalent fertility, but moLpr showed lighter placentas and fetuses than moMpJ, and decreased fertility with AID severity. moLpr placentas had a higher number of T cells, higher expression of genes associated with T helper 2 and T follicular helper functions, and altered expression of genes (<i>Krt15, Slc7a3</i>, <i>Sprr2a3</i>) that significantly regulate pregnancy or immunity. The gene expression of T cell migration-associated chemokines (<i>Ccl5</i>, <i>Cxcl9</i>) was significantly increased in moLpr placentas, and CCL5 and CXCL9 were detected in moLpr placentas, particularly in T cells and placenta-component cells, respectively. Thus, AID altered placental morphofunction and fertility in mice; however, fertility was maintained at the examined time points. This study enhances our understanding of placental alterations and gestational risk due to AIDs.
DOI: 10.6084/m9.figshare.25272115.v1
title: Effects of autoimmune abnormalities on fertility and placental morphology in mice

description: Autoimmune diseases (AIDs) alter the placental immune environment leading to fetal loss. This study investigated the effects of AIDs on pregnancy and the placenta in AID-prone MRL/MpJ-<i>Fas<sup>lpr/lpr</sup></i> mice and wild-type MRL/MpJ, which were mated with male MRL/MpJ and MRL/MpJ-<i>Fas<sup>lpr/lpr</sup></i> at five months and defined as moLpr and moMpJ, respectively. AID indices (spleen weight and serum autoantibody levels) and fertility status (number and size of fetuses, morphology, and comprehensive gene expression of placentas) were evaluated on gestational day 15.5. Both strains showed equivalent fertility, but moLpr showed lighter placentas and fetuses than moMpJ, and decreased fertility with AID severity. moLpr placentas had a higher number of T cells, higher expression of genes associated with T helper 2 and T follicular helper functions, and altered expression of genes (<i>Krt15, Slc7a3</i>, <i>Sprr2a3</i>) that significantly regulate pregnancy or immunity. The gene expression of T cell migration-associated chemokines (<i>Ccl5</i>, <i>Cxcl9</i>) was significantly increased in moLpr placentas, and CCL5 and CXCL9 were detected in moLpr placentas, particularly in T cells and placenta-component cells, respectively. Thus, AID altered placental morphofunction and fertility in mice; however, fertility was maintained at the examined time points. This study enhances our understanding of placental alterations and gestational risk due to AIDs.
DOI: 10.6084/m9.figshare.25295147
title: Identification of new hub- ferroptosis-related genes in Lupus Nephritis

description: <b>Background</b>: Lupus Nephritis (LN) is the primary causation of kidney injury in systemic lupus erythematosus (SLE). Ferroptosis is a programmed cell death. Therefore, understanding the crosstalk between LN and ferroptosis is still a significant challenge. <b>Methods</b>: We obtained the expression profile of LN kidney biopsy samples from the Gene Expression Omnibus database and utilised the R-project software to identify differentially expressed genes (DEGs). Then, we conducted a functional correlation analysis. Ferroptosis-related genes (FRGs) and differentially expressed genes (DEGs) crossover to select FRGs with LN. Afterwards, we used CIBERSORT to assess the infiltration of immune cells in both LN tissues and healthy control samples. Finally, we performed immunohistochemistry on LN human renal tissue. <b>Results</b>: 10619 DEGs screened from the LN biopsy tissue were identified. 22 hub-ferroptosis-related genes with LN (FRGs-LN) were screened out. The CIBERSORT findings revealed that there were significant statistical differences in immune cells between healthy control samples and LN tissues. Immunohistochemistry further demonstrated a significant difference in HRAS, TFRC, ATM, and SRC expression in renal tissue between normal and control groups. <b>Conclusion</b>: We developed a signature that allowed us to identify 22 new biomarkers associated with FRGs-LN. These findings suggest new insights into the pathology and therapeutic potential of LN ferroptosis inhibitors and iron chelators.
DOI: 10.6084/m9.figshare.25295147.v1
title: Identification of new hub- ferroptosis-related genes in Lupus Nephritis

description: <b>Background</b>: Lupus Nephritis (LN) is the primary causation of kidney injury in systemic lupus erythematosus (SLE). Ferroptosis is a programmed cell death. Therefore, understanding the crosstalk between LN and ferroptosis is still a significant challenge. <b>Methods</b>: We obtained the expression profile of LN kidney biopsy samples from the Gene Expression Omnibus database and utilised the R-project software to identify differentially expressed genes (DEGs). Then, we conducted a functional correlation analysis. Ferroptosis-related genes (FRGs) and differentially expressed genes (DEGs) crossover to select FRGs with LN. Afterwards, we used CIBERSORT to assess the infiltration of immune cells in both LN tissues and healthy control samples. Finally, we performed immunohistochemistry on LN human renal tissue. <b>Results</b>: 10619 DEGs screened from the LN biopsy tissue were identified. 22 hub-ferroptosis-related genes with LN (FRGs-LN) were screened out. The CIBERSORT findings revealed that there were significant statistical differences in immune cells between healthy control samples and LN tissues. Immunohistochemistry further demonstrated a significant difference in HRAS, TFRC, ATM, and SRC expression in renal tissue between normal and control groups. <b>Conclusion</b>: We developed a signature that allowed us to identify 22 new biomarkers associated with FRGs-LN. These findings suggest new insights into the pathology and therapeutic potential of LN ferroptosis inhibitors and iron chelators.
DOI: 10.6084/m9.figshare.25195456
title: Bioinformatics and systems-biology approach to identify common pathogenic mechanisms for COVID-19 and systemic lupus erythematosus

description: The Coronavirus disease 2019 (COVID-19) pandemic has brought a heavy burden to the world, interestingly, it shares many clinical symptoms with systemic lupus erythematosus (SLE). It is unclear whether there is a similar pathological process between COVID-9 and SLE. In addition, we don’t know how to treat SLE patients with COVID-19. In this study, we analyse the potential similar pathogenesis between SLE and COVID-19 and explore their possible drug regimens using bioinformatics and systems biology approaches. The common differentially expressed genes (DEGs) were extracted from the COVID-19 datasets and the SLE datasets for functional enrichment, pathway analysis and candidate drug analysis. Based on the two transcriptome datasets between COVID-19 and SLE, 325 common DEGs were selected. Hub genes were identified by protein-protein interaction (PPI) analysis. few found a variety of similar functional changes between COVID-19 and SLE, which may be related to the pathogenesis of COVID-19. Besides, we explored the related regulatory networks. Then, through drug target matching, we found many candidate drugs for patients with COVID-19 only or COVID-19 combined with SLE. COVID-19 and SLE patients share many common hub genes, related pathways and regulatory networks. Based on these common targets, we found many potential drugs that could be used in treating patient with COVID-19 or COVID-19 combined with SLE.
DOI: 10.6084/m9.figshare.27297067.v1
title: Genome-wide identification of cell type-specific susceptibility genes for Juvenile dermatomyositis through the analysis of N<sup>6</sup>-methyladenosine-associated SNPs

description: Genome-wide association studies (GWASs) have pinpointed genetic loci associated with juvenile dermatomyositis (JDM). Functional genes within the GWAS loci may be cell type-specific, but their identity remains largely unknown. N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) plays a pivotal role in regulating various cellular processes and is linked to autoimmune diseases. This study aimed to underscore the potential functional genes within the GWAS loci through the analysis of m<sup>6</sup>A-associated SNPs (m<sup>6</sup>A-SNPs), specifically within relevant cell types. JDM-associated m<sup>6</sup>A-SNPs were identified from the GWAS summary dataset. The correlation between m<sup>6</sup>A-SNPs and gene expression was assessed through bulk tissue and single-cell eQTL analyses. To further investigate the relationship between gene expression and JDM, Mendelian randomization analysis was employed. Additionally, differential expression analyses were conducted on bulk tissues, as well as single-cell transcriptomic data comprising 6 JDM patients and 11 juvenile controls (99,396 cells). Seven m<sup>6</sup>A-SNPs associated with JDM were identified. Bulk tissue analysis revealed differential expression of <i>HLA-DPA1</i>, <i>HLA-DPB1</i>, <i>MICB</i>, <i>HLA-A</i>, <i>HLA-F</i>, <i>HLA-DQB2</i>, <i>HLA-DRB5</i>, <i>TAP2</i>, <i>PSMB9</i>, <i>MICA</i>, <i>AIF1</i>, and <i>DDX39B</i> influenced by m<sup>6</sup>A-SNPs, all showing associations with JDM in both differential expression and Mendelian randomization analyses. In single-cell analysis, the six m<sup>6</sup>A-SNPs within the HLA locus acted as cell-type-specific eQTLs, correlating with the expression of <i>HLA-A</i>, <i>HLA-B</i>, <i>HLA-C</i>, <i>HLA-DPB1</i>, <i>HLA-DQA1</i>, <i>HLA-DQB1</i> and <i>HLA-DRB1</i> in myeloid, T or B cells. Notably, these genes displayed abnormal expression in T, B, and myeloid cells of JDM patients. The present study identified m<sup>6</sup>A-SNPs within JDM susceptibility genes, shedding light on the intricate interplay between m<sup>6</sup>A-SNPs, gene expression, and JDM.
DOI: 10.6084/m9.figshare.26936098
title: LncRNA NONHSAT042241 inhibits rheumatoid synovial proliferation, inflammation and aggression via inactivating WNT/β-catenin signaling pathway

description: This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms. RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent <i>in situ</i> hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/β-catenin signaling pathway. Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (<i>p</i> &lt; 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (<i>p</i> &lt; 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of β-catenin (<i>p</i> &lt; 0.05), p-GSK-3β (<i>p</i> &lt; 0.05), Cyclin D1 (<i>p</i> &lt; 0.05), PCNA (<i>p</i> &lt; 0.05), and thus reduced the cell proliferation. NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/β-catenin signaling.
DOI: 10.6084/m9.figshare.27297067
title: Genome-wide identification of cell type-specific susceptibility genes for Juvenile dermatomyositis through the analysis of N<sup>6</sup>-methyladenosine-associated SNPs

description: Genome-wide association studies (GWASs) have pinpointed genetic loci associated with juvenile dermatomyositis (JDM). Functional genes within the GWAS loci may be cell type-specific, but their identity remains largely unknown. N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) plays a pivotal role in regulating various cellular processes and is linked to autoimmune diseases. This study aimed to underscore the potential functional genes within the GWAS loci through the analysis of m<sup>6</sup>A-associated SNPs (m<sup>6</sup>A-SNPs), specifically within relevant cell types. JDM-associated m<sup>6</sup>A-SNPs were identified from the GWAS summary dataset. The correlation between m<sup>6</sup>A-SNPs and gene expression was assessed through bulk tissue and single-cell eQTL analyses. To further investigate the relationship between gene expression and JDM, Mendelian randomization analysis was employed. Additionally, differential expression analyses were conducted on bulk tissues, as well as single-cell transcriptomic data comprising 6 JDM patients and 11 juvenile controls (99,396 cells). Seven m<sup>6</sup>A-SNPs associated with JDM were identified. Bulk tissue analysis revealed differential expression of <i>HLA-DPA1</i>, <i>HLA-DPB1</i>, <i>MICB</i>, <i>HLA-A</i>, <i>HLA-F</i>, <i>HLA-DQB2</i>, <i>HLA-DRB5</i>, <i>TAP2</i>, <i>PSMB9</i>, <i>MICA</i>, <i>AIF1</i>, and <i>DDX39B</i> influenced by m<sup>6</sup>A-SNPs, all showing associations with JDM in both differential expression and Mendelian randomization analyses. In single-cell analysis, the six m<sup>6</sup>A-SNPs within the HLA locus acted as cell-type-specific eQTLs, correlating with the expression of <i>HLA-A</i>, <i>HLA-B</i>, <i>HLA-C</i>, <i>HLA-DPB1</i>, <i>HLA-DQA1</i>, <i>HLA-DQB1</i> and <i>HLA-DRB1</i> in myeloid, T or B cells. Notably, these genes displayed abnormal expression in T, B, and myeloid cells of JDM patients. The present study identified m<sup>6</sup>A-SNPs within JDM susceptibility genes, shedding light on the intricate interplay between m<sup>6</sup>A-SNPs, gene expression, and JDM.
DOI: 10.6084/m9.figshare.25497743
title: Novel peripheral blood mononuclear cell mRNA signature for IFN-beta therapy responsiveness prediction in multiple sclerosis

description: Interferon-beta (IFN-β) is one of the classical drugs for immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS) patients, but the drug responsiveness of different patients varies. Currently, there is no valid model to predict IFN-β responsiveness. This research attempted to develop an IFN-β responsiveness prediction model based on mRNA expression in RRMS patient peripheral blood mononuclear cells. Peripheral blood mononuclear cell mRNA expression datasets including 50 RRMS patients receiving IFN-β treatment were obtained from GEO. Among the datasets, 24 cases from GSE24427 were included in a training set, and 18 and 9 cases from GSE19285 and GSE33464, respectively, were adopted as two independent test sets. In the training set, blood samples were collected immediately before first, second, month 1, 12, and 24 IFN-β injection, and the mRNA expression data at four time points, namely, two days, one month, one year and two years after the onset of IFN-β treatment, were compared with pre-treatment data to identify IFN-stimulated genes (ISGs). The ISGs at the one-month time point were used to construct the drug responsiveness prediction model. Next, the drug responsiveness model was verified in the two independent test sets to examine the performance of the model in predicting drug responsiveness. Finally, we used CIBERSORTx to estimate the content of cell subtypes in samples and evaluated whether differences in the proportions of cell subtypes were related to differences in IFN-β responsiveness. Among the four time points, one month was the time point when the training set GSE24427 and test set GSE33464 had the highest number of ISGs. Functional analysis showed that these one-month ISGs were enriched in biological functions such as the innate immune response, type-I interferon signalling pathway, and other IFN-β-associated functions. Based on these ISGs, we obtained a four-factor prediction model for IFN-β responsiveness including MX1, MX2, XAF1, and LAMP3. In addition, the model demonstrated favourable predictive performance within the training set and two external test sets. A higher proportion of activated NK cells and lower naive CD4/total CD4 ratio might indicate better drug responsiveness. This research developed a polygene-based biomarker model that could predict RRMS patient IFN-β responsiveness in the early treatment period. This model could probably help doctors screen out patients who would not benefit from IFN-β treatment early and determine whether a current treatment plan should be continued.
DOI: 10.6084/m9.figshare.25497743.v1
title: Novel peripheral blood mononuclear cell mRNA signature for IFN-beta therapy responsiveness prediction in multiple sclerosis

description: Interferon-beta (IFN-β) is one of the classical drugs for immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS) patients, but the drug responsiveness of different patients varies. Currently, there is no valid model to predict IFN-β responsiveness. This research attempted to develop an IFN-β responsiveness prediction model based on mRNA expression in RRMS patient peripheral blood mononuclear cells. Peripheral blood mononuclear cell mRNA expression datasets including 50 RRMS patients receiving IFN-β treatment were obtained from GEO. Among the datasets, 24 cases from GSE24427 were included in a training set, and 18 and 9 cases from GSE19285 and GSE33464, respectively, were adopted as two independent test sets. In the training set, blood samples were collected immediately before first, second, month 1, 12, and 24 IFN-β injection, and the mRNA expression data at four time points, namely, two days, one month, one year and two years after the onset of IFN-β treatment, were compared with pre-treatment data to identify IFN-stimulated genes (ISGs). The ISGs at the one-month time point were used to construct the drug responsiveness prediction model. Next, the drug responsiveness model was verified in the two independent test sets to examine the performance of the model in predicting drug responsiveness. Finally, we used CIBERSORTx to estimate the content of cell subtypes in samples and evaluated whether differences in the proportions of cell subtypes were related to differences in IFN-β responsiveness. Among the four time points, one month was the time point when the training set GSE24427 and test set GSE33464 had the highest number of ISGs. Functional analysis showed that these one-month ISGs were enriched in biological functions such as the innate immune response, type-I interferon signalling pathway, and other IFN-β-associated functions. Based on these ISGs, we obtained a four-factor prediction model for IFN-β responsiveness including MX1, MX2, XAF1, and LAMP3. In addition, the model demonstrated favourable predictive performance within the training set and two external test sets. A higher proportion of activated NK cells and lower naive CD4/total CD4 ratio might indicate better drug responsiveness. This research developed a polygene-based biomarker model that could predict RRMS patient IFN-β responsiveness in the early treatment period. This model could probably help doctors screen out patients who would not benefit from IFN-β treatment early and determine whether a current treatment plan should be continued.
DOI: 10.6084/m9.figshare.26936098.v1
title: LncRNA NONHSAT042241 inhibits rheumatoid synovial proliferation, inflammation and aggression via inactivating WNT/β-catenin signaling pathway

description: This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms. RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent <i>in situ</i> hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/β-catenin signaling pathway. Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (<i>p</i> &lt; 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (<i>p</i> &lt; 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of β-catenin (<i>p</i> &lt; 0.05), p-GSK-3β (<i>p</i> &lt; 0.05), Cyclin D1 (<i>p</i> &lt; 0.05), PCNA (<i>p</i> &lt; 0.05), and thus reduced the cell proliferation. NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/β-catenin signaling.
DOI: 10.6084/m9.figshare.27211994
title: TMEM164 promotes ferroptosis by selectively mediating ATG5-dependent autophagosome formation to inhibit the progression of LUAD

description: The study focuses on lung adenocarcinoma (LUAD), a predominant type of lung cancer. Despite advancements in diagnostics and molecular therapies, treatment remains challenging due to its low five-year survival rate. This study aims to investigate the role of the transmembrane protein TMEM164 in ferroptosis and anti-tumor immunity in LUAD, and to evaluate its potential as a therapeutic target. Through cellular experiments (such as QPCR, WB, CCK-8, EdU, Transwell, flow cytometry, CO-IP) and animal model experiments (including HE staining and IHC analysis), the relationship between TMEM164 expression and LUAD progression was explored, with particular attention to its mechanisms in ferroptosis and autophagy. The results show that TMEM164 expression is downregulated in LUAD and is associated with poor prognosis. Increasing TMEM164 expression significantly inhibits cell proliferation, migration, and invasion, while promoting an autophagy process dependent on ATG5 for autophagosome formation, thus facilitating ferroptosis. In mouse models, high TMEM164 expression combined with anti-PD-1 antibodies demonstrated synergistic anti-tumor effects. These findings highlight the critical role of TMEM164 in LUAD, suggesting that modulating TMEM164 expression could open new avenues for LUAD treatment.