cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.30636800.v1
title: Blood and adipose tissue DNA methylation in adults born preterm with a very low birth weight – a sibling comparison study

description: Preterm birth and very low birth weight (VLBW; &lt;1500 g) increase risks for poor health outcomes, potentially mediated by epigenetic modifications such as DNA methylation (DNAm). We hypothesized that DNAm differs between VLBW adults and their siblings in blood and adipose tissue. We studied 75 adults born preterm with VLBW and 73 same-sex sibling controls from the Adults Born Preterm Sibling Study. DNAm at cytosine–guanine dinucleotide (CpG) sites in blood and adipose tissue was assessed using Illumina EPIC 850K at a mean age of 29 years. Biological pathways were investigated with QIAGEN ingenuity pathway analysis (IPA). No differences were observed in blood DNAm. In adipose tissue, 458 CpG sites were differentially methylated (FDR <i>p</i> &lt; 0.05) between VLBW and siblings. Top sites were annotated to genes related to lipid metabolism (cg00264176 (<i>FADS2)</i>, 0.077 (0.007), FDR <i>p</i> = 3.24 × 10<sup>−14</sup>) and neural development (cg08277679 (<i>KIF26A)</i>, 0.053 (0.005), FDR <i>p</i> = 8.22 × 10<sup>−12</sup>). IPA identified enrichment for 81 pathways (FDR <i>p</i> &lt; 0.05). Our results suggest tissue-specific DNAm differences in VLBW adults compared to their siblings. The changes cluster in pathways related to lipid metabolism, neurodevelopment, and cardiometabolic regulation, suggesting lasting tissue-specific epigenetic modifications in VLBW adults. This study looked at how being born very early and very small (birth weight less than 1500 g) might affect long-term health through changes in genetic material DNA. We focused on a process called DNA methylation (DNAm). DNAm affects how actively genes work. We compared 75 adults born very small and premature to 73 of their siblings. We analyzed DNAm in blood and fat tissue when participants were 29 years old. No differences were found in blood samples. However, in fat tissue, we found 458 spots on the genetic material DNA that were activated differently in VLBW adults compared to their siblings. These changes were linked to genes involved in fat processing, heart health, and brain development. The findings suggest that being born early and very small cause lasting changes in how genes work in fat tissue. This could explain why adults who are born very small have higher risks for heart and metabolic diseases. These insights may help guide future treatments to improve health outcomes for people born premature or small.
DOI: 10.6084/m9.figshare.30939159
title: Mitochondrial DNA copy number reduction via <i>in vitro TFAM</i> knockout remodels the nuclear epigenome and transcriptome

description: Mitochondrial DNA copy number (mtDNA-CN) is associated with several age-related chronic diseases and is a predictor of all-cause mortality. Here, we examine site-specific differential nuclear DNA (nDNA) methylation and differential gene expression resulting from in vitro reduction of mtDNA-CN to uncover shared genes and biological pathways mediating the effect of mtDNA-CN on disease. Epigenome and transcriptome profiles were generated for three independent human embryonic kidney (HEK293T) cell lines harboring a mitochondrial transcription factor A (TFAM) knockout generated via CRISPR-Cas9, and matched control lines. We identified 2924 differentially methylated sites, 67 differentially methylated regions, and 102 differentially expressed genes associated with mtDNA-CN. Integrated analysis uncovered 24 Gene-CpG pairs. GABA<sub>A</sub> receptor genes and related pathways, the neuroactive ligand signaling pathway, ABCD1/2 gene activity, and cell signaling processes were overrepresented, providing insight into the underlying biological mechanisms facilitating these associations. We also report evidence implicating chromatin state regulatory mechanisms as modulators of mtDNA-CN effect on gene expression. We demonstrate that mitochondrial DNA variation signals to the nuclear DNA epigenome and transcriptome and may lead to nuclear remodeling relevant to development, aging, and complex disease. The amount of mitochondrial DNA, called mitochondrial DNA copy number (mtDNA-CN), has been linked with risk for various health conditions and diseases. To better understand this relationship, we studied the association between mtDNA-CN reduction and other DNA changes within the cell, specifically those in the cell nucleus. Using a cell model, we compared changes in cells with lower mtDNA-CN to normal cells. We noticed several patterns of changes that point to different genomic regions, communication processes, and signaling pathways within the cells that may be involved in the association of mtDNA-CN with disease development. Our findings help explain how the mitochondria interact with the nucleus in the context of complex disease.
DOI: 10.6084/m9.figshare.30939159.v1
title: Mitochondrial DNA copy number reduction via <i>in vitro TFAM</i> knockout remodels the nuclear epigenome and transcriptome

description: Mitochondrial DNA copy number (mtDNA-CN) is associated with several age-related chronic diseases and is a predictor of all-cause mortality. Here, we examine site-specific differential nuclear DNA (nDNA) methylation and differential gene expression resulting from in vitro reduction of mtDNA-CN to uncover shared genes and biological pathways mediating the effect of mtDNA-CN on disease. Epigenome and transcriptome profiles were generated for three independent human embryonic kidney (HEK293T) cell lines harboring a mitochondrial transcription factor A (TFAM) knockout generated via CRISPR-Cas9, and matched control lines. We identified 2924 differentially methylated sites, 67 differentially methylated regions, and 102 differentially expressed genes associated with mtDNA-CN. Integrated analysis uncovered 24 Gene-CpG pairs. GABA<sub>A</sub> receptor genes and related pathways, the neuroactive ligand signaling pathway, ABCD1/2 gene activity, and cell signaling processes were overrepresented, providing insight into the underlying biological mechanisms facilitating these associations. We also report evidence implicating chromatin state regulatory mechanisms as modulators of mtDNA-CN effect on gene expression. We demonstrate that mitochondrial DNA variation signals to the nuclear DNA epigenome and transcriptome and may lead to nuclear remodeling relevant to development, aging, and complex disease. The amount of mitochondrial DNA, called mitochondrial DNA copy number (mtDNA-CN), has been linked with risk for various health conditions and diseases. To better understand this relationship, we studied the association between mtDNA-CN reduction and other DNA changes within the cell, specifically those in the cell nucleus. Using a cell model, we compared changes in cells with lower mtDNA-CN to normal cells. We noticed several patterns of changes that point to different genomic regions, communication processes, and signaling pathways within the cells that may be involved in the association of mtDNA-CN with disease development. Our findings help explain how the mitochondria interact with the nucleus in the context of complex disease.
DOI: 10.6084/m9.figshare.31016697
title: Methylation changes of gallbladder DNA during the formation of gallstones

description: To investigate the genome-wide methylation changes in gallbladder tissues during gallstone formation, as well as alterations in key signaling pathways and associated gene expression. A combined methylation and transcriptomic analysis was performed on gallbladder tissues from gallstone model mice and normal control mice using reduced representation bisulfite sequencing (RRBS) and RNA high-throughput sequencing. Key candidate genes were validated using qRT-PCR, Western blotting, and immunohistochemistry. Cross-species validation was conducted using human gallbladder transcriptomic data from GEO datasets. Integrated RRBS and RNA-seq analysis revealed that abnormal DNA methylation may contribute to gallstone formation by dysregulating gene expression in pathways associated with gallbladder dysfunction. A total of 97 differentially methylated and expressed genes exhibiting significant inverse correlations between methylation and expression levels were identified. The top six genes with the strongest correlations were experimentally validated. Analysis of human gallstone samples identified partial overlapping differentially expressed genes with the mouse model. This study demonstrates the potential roles of DNA methylation and gene expression changes in gallbladder tissue during the formation of gallstones. These findings provide a new perspective for further understanding the causes of gallstones and searching for possible clinical therapies.
DOI: 10.6084/m9.figshare.31016697.v1
title: Methylation changes of gallbladder DNA during the formation of gallstones

description: To investigate the genome-wide methylation changes in gallbladder tissues during gallstone formation, as well as alterations in key signaling pathways and associated gene expression. A combined methylation and transcriptomic analysis was performed on gallbladder tissues from gallstone model mice and normal control mice using reduced representation bisulfite sequencing (RRBS) and RNA high-throughput sequencing. Key candidate genes were validated using qRT-PCR, Western blotting, and immunohistochemistry. Cross-species validation was conducted using human gallbladder transcriptomic data from GEO datasets. Integrated RRBS and RNA-seq analysis revealed that abnormal DNA methylation may contribute to gallstone formation by dysregulating gene expression in pathways associated with gallbladder dysfunction. A total of 97 differentially methylated and expressed genes exhibiting significant inverse correlations between methylation and expression levels were identified. The top six genes with the strongest correlations were experimentally validated. Analysis of human gallstone samples identified partial overlapping differentially expressed genes with the mouse model. This study demonstrates the potential roles of DNA methylation and gene expression changes in gallbladder tissue during the formation of gallstones. These findings provide a new perspective for further understanding the causes of gallstones and searching for possible clinical therapies.
DOI: 10.6084/m9.figshare.31036044
title: Genome-wide methylation patterns associated with chronic stress

description: Chronic social defeat stress (CSDS) is a validated animal model for depression that produces sustained behavioral and transcriptional changes in the brain, notably the nucleus accumbens (nAcc). We used genome-wide analysis of cytosine methylation patterns in mouse nAcc following CSDS to identify candidate epigenetic mechanisms. CSDS produced extensive differential methylation, increasing CG hypermethylation compared to control conditions; non-CG methylation showed the opposite trend. Highly differentially methylated (DM) regions included several genes implicated in behavioral effects of CSDS, including estrogen receptor alpha (Esr1). Analysis of DM sites within gene bodies revealed ß-catenin as a hub gene of a network including the ß-catenin-related WNT/frizzled signaling pathway. Analysis of DM sites upstream of transcription start sites revealed a gene network with the Tcf4 transcription factor as a hub. Genes DM within the gene body were enriched for synaptic function and primarily expressed in D1+ and D2+ medium spiny neurons, which, like the WNT/ß-catenin pathway, are estrogen sensitive and implicated in the behavioral effects of CSDS. We found significant overlap between DM genes associated with CSDS and those associated with major depressive disorder in genome-wide association studies, suggesting that effects on DNA methylation are implicated in the molecular pathways that link chronic stress to depression. Depression is a serious health problem affecting millions of people worldwide. One of the major risk factors for depression is long-term stress. To better understand how stress affects the brain and its links to depression, we studied mice exposed to chronic social defeat stress – a model which mimics features of depression in humans. The research focused on an area of the brain called the nucleus accumbens, which is well known to regulate motivational and emotional responses. DNA methylation is a modification to DNA that can turn genes “on” or “off” without altering the genetic code itself. In this study, we obtained data on methylation across the entire mouse genome at the resolution of single bases of DNA. It was found that stress caused widespread methylation changes throughout the genome. Some of the genes that contained the highest levels of methylation changes are known to be involved in stress and depression. Importantly, many of these genes overlapped with ones associated with depression in human studies. We identified networks of genes affected by stress, one centered on the gene which produces a protein called β-catenin, another on the transcription factor Tcf4. These genes are involved in communication between brain cells. Our results suggest that stress-induced methylation changes in the brain could be one of the ways that chronic stress increases the risk for depression. Further understanding of the mechanisms involved may eventually lead to new approaches for the prevention or treatment of depression.
DOI: 10.6084/m9.figshare.31036044.v1
title: Genome-wide methylation patterns associated with chronic stress

description: Chronic social defeat stress (CSDS) is a validated animal model for depression that produces sustained behavioral and transcriptional changes in the brain, notably the nucleus accumbens (nAcc). We used genome-wide analysis of cytosine methylation patterns in mouse nAcc following CSDS to identify candidate epigenetic mechanisms. CSDS produced extensive differential methylation, increasing CG hypermethylation compared to control conditions; non-CG methylation showed the opposite trend. Highly differentially methylated (DM) regions included several genes implicated in behavioral effects of CSDS, including estrogen receptor alpha (Esr1). Analysis of DM sites within gene bodies revealed ß-catenin as a hub gene of a network including the ß-catenin-related WNT/frizzled signaling pathway. Analysis of DM sites upstream of transcription start sites revealed a gene network with the Tcf4 transcription factor as a hub. Genes DM within the gene body were enriched for synaptic function and primarily expressed in D1+ and D2+ medium spiny neurons, which, like the WNT/ß-catenin pathway, are estrogen sensitive and implicated in the behavioral effects of CSDS. We found significant overlap between DM genes associated with CSDS and those associated with major depressive disorder in genome-wide association studies, suggesting that effects on DNA methylation are implicated in the molecular pathways that link chronic stress to depression. Depression is a serious health problem affecting millions of people worldwide. One of the major risk factors for depression is long-term stress. To better understand how stress affects the brain and its links to depression, we studied mice exposed to chronic social defeat stress – a model which mimics features of depression in humans. The research focused on an area of the brain called the nucleus accumbens, which is well known to regulate motivational and emotional responses. DNA methylation is a modification to DNA that can turn genes “on” or “off” without altering the genetic code itself. In this study, we obtained data on methylation across the entire mouse genome at the resolution of single bases of DNA. It was found that stress caused widespread methylation changes throughout the genome. Some of the genes that contained the highest levels of methylation changes are known to be involved in stress and depression. Importantly, many of these genes overlapped with ones associated with depression in human studies. We identified networks of genes affected by stress, one centered on the gene which produces a protein called β-catenin, another on the transcription factor Tcf4. These genes are involved in communication between brain cells. Our results suggest that stress-induced methylation changes in the brain could be one of the ways that chronic stress increases the risk for depression. Further understanding of the mechanisms involved may eventually lead to new approaches for the prevention or treatment of depression.
DOI: 10.6084/m9.figshare.31036044.v2
title: Genome-wide methylation patterns associated with chronic stress

description: Chronic social defeat stress (CSDS) is a validated animal model for depression that produces sustained behavioral and transcriptional changes in the brain, notably the nucleus accumbens (nAcc). We used genome-wide analysis of cytosine methylation patterns in mouse nAcc following CSDS to identify candidate epigenetic mechanisms. CSDS produced extensive differential methylation, increasing CG hypermethylation compared to control conditions; non-CG methylation showed the opposite trend. Highly differentially methylated (DM) regions included several genes implicated in behavioral effects of CSDS, including estrogen receptor alpha (Esr1). Analysis of DM sites within gene bodies revealed ß-catenin as a hub gene of a network including the ß-catenin-related WNT/frizzled signaling pathway. Analysis of DM sites upstream of transcription start sites revealed a gene network with the Tcf4 transcription factor as a hub. Genes DM within the gene body were enriched for synaptic function and primarily expressed in D1+ and D2+ medium spiny neurons, which, like the WNT/ß-catenin pathway, are estrogen sensitive and implicated in the behavioral effects of CSDS. We found significant overlap between DM genes associated with CSDS and those associated with major depressive disorder in genome-wide association studies, suggesting that effects on DNA methylation are implicated in the molecular pathways that link chronic stress to depression. Depression is a serious health problem affecting millions of people worldwide. One of the major risk factors for depression is long-term stress. To better understand how stress affects the brain and its links to depression, we studied mice exposed to chronic social defeat stress – a model which mimics features of depression in humans. The research focused on an area of the brain called the nucleus accumbens, which is well known to regulate motivational and emotional responses. DNA methylation is a modification to DNA that can turn genes “on” or “off” without altering the genetic code itself. In this study, we obtained data on methylation across the entire mouse genome at the resolution of single bases of DNA. It was found that stress caused widespread methylation changes throughout the genome. Some of the genes that contained the highest levels of methylation changes are known to be involved in stress and depression. Importantly, many of these genes overlapped with ones associated with depression in human studies. We identified networks of genes affected by stress, one centered on the gene which produces a protein called β-catenin, another on the transcription factor Tcf4. These genes are involved in communication between brain cells. Our results suggest that stress-induced methylation changes in the brain could be one of the ways that chronic stress increases the risk for depression. Further understanding of the mechanisms involved may eventually lead to new approaches for the prevention or treatment of depression.
DOI: 10.5281/zenodo.18327183
title: test data upload
DOI: 10.5281/zenodo.18327184
title: test data upload
DOI: 10.6084/m9.figshare.30561989
title: A 96-week efficacy and safety of BIC/FTC/TAF in ART-naïve HIV-1 infected patients in China

description:  To evaluate 96-week virologic, immunologic, resistance and metabolic outcomes of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) in antiretroviral therapy (ART)-naïve people living with HIV (PLWH). Retrospective cohort of ART-naïve PLWH initiating BIC/FTC/TAF between January 2020 and December 2022. Primary outcome was HIV-1 RNA &lt;50 copies/mL at week 96. Secondary outcomes included drug resistance and changes in CD4<sup>+</sup> T cell count, CD4<sup>+</sup>/CD8<sup>+</sup>, body weight, lipid profile, liver and renal function by week 96. We enrolled 228 patients; median age 32 years, 92.1% male, homosexual intercourse 57.0%. Virologic suppression did not differ by baseline HIV-1 RNA levels, CD4<sup>+</sup> T cell counts, or opportunistic infection (OI), and immune reconstitution was similarly consistent across subgroups. One patient developed V179E mutation. Median body mass index increased from 21.7 (20.0-23.7) to 23.1 (21.2-25.1) by week 48 and then stabilized. Lipid levels increased early and remained stable, liver function remained stable after week 48, and renal function showed a slight decline before stabilizing by week 48. BIC/FTC/TAF demonstrated strong efficacy in patients with high baseline HIV-1 RNA and OIs, with no patient developing drug-related resistance mutations and minimal impact on metabolism, liver and renal function, supporting its use in broader populations as a first-line regimen.
DOI: 10.6084/m9.figshare.31113099
title: A patent review of galectin-1 and galectin-3 inhibitors and their potential therapeutic applications (2022-present): an update

description: Galectin-1 (Gal-1) & Galectin-3 (Gal-3) are carbohydrate-binding proteins implicated in diverse pathological processes. These galectins have emerged as key therapeutic targets, with significant presence in drug discovery pipelines and clinical investigations. Their unique glycan-binding properties and immunomodulatory effects have prompted the development of inhibitors to modulate their function. This review presents a comprehensive summary of 19 small-molecule patents targeting Gal-1 and Gal-3, published from January 2022 to June 2025. A systematic search of Reaxys and WIPO databases yielded patents spanning modified monosaccharides & disaccharides, non-carbohydrate chemotypes and metal-coordinated complexes. The patent landscape is dominated by β-D-galactopyranose and thiodigalactoside scaffolds, with limited innovation and unresolved issues in selectivity, drug-likeness, and efficacy, highlighted by GB0139’s Phase II failure. Moreover, only a few patents provide structural evidence and strong in vitro/in vivo data, limiting confidence in their therapeutic outcome. By contrast, some diversification has emerged, including spirocyclic sugars, ruthenium-conjugates and non-carbohydrate ligands such as heterocycles and repurposed drugs. These highlight underexploited avenues with promise. Yet, robust biochemical data and structural proof of binding remain scarce. To move the field forward, future patents must diversify chemotypes, substantiate binding modes with crystallography or NMR, and demonstrate translation in relevant disease models.