cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28071074.v1
title: Causal associations of metabolic dysfunction-associated steatotic liver disease with gestational hypertension and preeclampsia: a two-sample Mendelian randomization study

description: Hypertensive disorders of pregnancy (HDPs), which include gestational hypertension (GH) and preeclampsia (PE), are the primary causes of maternal morbidity and mortality worldwide. Recent studies have found a correlation between metabolic dysfunction-associated steatotic liver disease (MASLD) and HDPs, but the causality of this association remains to be identified. Therefore, this study aims to evaluate the causal relationship between MASLD and HDPs through Mendelian randomization (MR) analysis. The summary statistics from genome-wide association studies were employed to conduct a two-sample MR analysis. Five complementary MR methods, including inverse variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode were performed to assess the causality of MASLD on GH and PE. Furthermore, we conducted various sensitivity analyses to ensure the stability and reliability of the results. Genetically predicted MASLD significantly increased the risk of GH (IVW: OR = 1.138, 95% CI: 1.062–1.220, <i>p</i> &lt; 0.001), while there was little evidence of a causal relationship between MASLD and PE (IVW: OR = 0.980, 95% CI: 0.910–1.056, <i>p</i> = 0.594). The sensitivity analyses indicated no presence of heterogeneity and horizontal pleiotropy. This MR study provided evidence supporting the causal effect of MASLD on GH. Our findings underscore the significance of providing more intensive prenatal care and early intervention for pregnant women with MASLD to prevent potential adverse obstetric outcomes.
DOI: 10.6084/m9.figshare.28320597
title: Placental ischemia during pregnancy induces hypertension, cerebral inflammation, and oxidative stress in dams postpartum

description: Preeclampsia (PE) is characterized as de novo hypertension (HTN) with end-organ damage, especially in the brain. PE is hypothesized to be caused by placental ischemia. PE affects ~5–8% of USA pregnancies and increases the risk for HTN and cerebrovascular diseases (CVD) later in life. We hypothesize that blood pressure (BP), cerebral oxidative stress, and cerebral inflammation will increase in postpartum (PP) placental ischemic dams. Placental ischemia was induced in pregnant Sprague Dawley dams, utilizing reduced uterine perfusion pressure (RUPP) surgery. At 6 weeks PP (~3 human years), BP was measured via carotid catheterization, and cerebral oxidative stress and inflammation were assessed via ELISAs, biochemical assays, and Western blots. BP, cerebral pro-inflammatory cytokines (TNF-α and IL-6), and GFAP (a marker of astrocyte activity) were increased in PP RUPP dams. Cerebral hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) was also increased in PP RUPP dams, and had a strong correlation with PP RUPP BP, proinflammatory cytokines (TNF- α and IL-6), and GFAP astrocyte activation. PP RUPP dams have increased BP, cerebral oxidative stress, and cerebral inflammation at 6 weeks postpartum. These changes in cerebral inflammation and oxidative stress may contribute to the pathology and development of HTN and CVDs in postpartum dams. <b>1. What is New?</b>
• Rat dams that experienced placental ischemia during pregnancy have high blood pressure, cerebral inflammation, and cerebral oxidative stress after giving birth. <b>2. What is Relevant?</b>
• Our observations in postpartum rat dams mirror the outcomes observed in postpartum women who have experienced preeclampsia and thus make this study clinically relevant. • The findings from this study occurred early in the postpartum period (~3–5 human years) and implied that examining women, especially those that had PE during pregnancy, after the routine 6 weeks postpartum checkup and before 10 years postpartum is warranted. <b>3. Clinical/Pathophysiological Implications?</b>
• Elucidating the mechanisms that contribute to the pathology and pathogenesis of HTN in postpartum women will help physicians provide better healthcare, along with suggestions of potential therapeutic targets to improve women’s overall health throughout life.
DOI: 10.6084/m9.figshare.28320597.v1
title: Placental ischemia during pregnancy induces hypertension, cerebral inflammation, and oxidative stress in dams postpartum

description: Preeclampsia (PE) is characterized as de novo hypertension (HTN) with end-organ damage, especially in the brain. PE is hypothesized to be caused by placental ischemia. PE affects ~5–8% of USA pregnancies and increases the risk for HTN and cerebrovascular diseases (CVD) later in life. We hypothesize that blood pressure (BP), cerebral oxidative stress, and cerebral inflammation will increase in postpartum (PP) placental ischemic dams. Placental ischemia was induced in pregnant Sprague Dawley dams, utilizing reduced uterine perfusion pressure (RUPP) surgery. At 6 weeks PP (~3 human years), BP was measured via carotid catheterization, and cerebral oxidative stress and inflammation were assessed via ELISAs, biochemical assays, and Western blots. BP, cerebral pro-inflammatory cytokines (TNF-α and IL-6), and GFAP (a marker of astrocyte activity) were increased in PP RUPP dams. Cerebral hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) was also increased in PP RUPP dams, and had a strong correlation with PP RUPP BP, proinflammatory cytokines (TNF- α and IL-6), and GFAP astrocyte activation. PP RUPP dams have increased BP, cerebral oxidative stress, and cerebral inflammation at 6 weeks postpartum. These changes in cerebral inflammation and oxidative stress may contribute to the pathology and development of HTN and CVDs in postpartum dams. <b>1. What is New?</b>
• Rat dams that experienced placental ischemia during pregnancy have high blood pressure, cerebral inflammation, and cerebral oxidative stress after giving birth. <b>2. What is Relevant?</b>
• Our observations in postpartum rat dams mirror the outcomes observed in postpartum women who have experienced preeclampsia and thus make this study clinically relevant. • The findings from this study occurred early in the postpartum period (~3–5 human years) and implied that examining women, especially those that had PE during pregnancy, after the routine 6 weeks postpartum checkup and before 10 years postpartum is warranted. <b>3. Clinical/Pathophysiological Implications?</b>
• Elucidating the mechanisms that contribute to the pathology and pathogenesis of HTN in postpartum women will help physicians provide better healthcare, along with suggestions of potential therapeutic targets to improve women’s overall health throughout life.
DOI: 10.6084/m9.figshare.28646377
title: Integrated bioinformatics analysis identifies neutrophils and villous cytotrophoblasts infiltration characterized by BLC6 upregulation as associated with the co-occurrence of gestational diabetes mellitus and pre-eclampsia

description: Gestational diabetes mellitus (GDM) patients are one of the important high-risk groups for the development of pre-eclampsia (PE). The pathogenesis of PE in GDM patients is not fully understood. This study aims to identify hub genes and pathways associated with the co-occurrence of GDM and PE. The matrix files of GDM and PE datasets were downloaded from GEO to identify differentially expressed genes (DEGs). The common DEGs were predicted for functional analysis through GO and KEGG analysis. A protein-protein interaction (PPI) network was constructed to determine the common hub genes for GDM and PE. Diagnostic hub genes were obtained through regression modeling and ROC analysis, and validated in publicly available datasets. The differences in immune infiltration between GDM and PE were analyzed. The expression and role of common hub genes in the co-occurrence of GDM and PE were explored through analysis of single-cell sequencing data. A total of 104 DEGs were identified between GDM and PE. These common DEGs were found to be involved in mucosal immune response and the JAK-STAT signaling pathway. A total of 27 common hub genes were identified for both GDM and PE. BCL6, DNAH9, and SCG2 were identified as potential diagnostic biomarkers for PE. BCL6 showed high expression in neutrophils and villous cytotrophoblasts (VCTs) in both PE and GDM. This study identified BCL6, DNAH9, and SCG2 as common hub genes in GDM and PE. BCL6 is expected to be a new target for the diagnosis and treatment of GDM concurrent with PE.
DOI: 10.6084/m9.figshare.28646377.v1
title: Integrated bioinformatics analysis identifies neutrophils and villous cytotrophoblasts infiltration characterized by BLC6 upregulation as associated with the co-occurrence of gestational diabetes mellitus and pre-eclampsia

description: Gestational diabetes mellitus (GDM) patients are one of the important high-risk groups for the development of pre-eclampsia (PE). The pathogenesis of PE in GDM patients is not fully understood. This study aims to identify hub genes and pathways associated with the co-occurrence of GDM and PE. The matrix files of GDM and PE datasets were downloaded from GEO to identify differentially expressed genes (DEGs). The common DEGs were predicted for functional analysis through GO and KEGG analysis. A protein-protein interaction (PPI) network was constructed to determine the common hub genes for GDM and PE. Diagnostic hub genes were obtained through regression modeling and ROC analysis, and validated in publicly available datasets. The differences in immune infiltration between GDM and PE were analyzed. The expression and role of common hub genes in the co-occurrence of GDM and PE were explored through analysis of single-cell sequencing data. A total of 104 DEGs were identified between GDM and PE. These common DEGs were found to be involved in mucosal immune response and the JAK-STAT signaling pathway. A total of 27 common hub genes were identified for both GDM and PE. BCL6, DNAH9, and SCG2 were identified as potential diagnostic biomarkers for PE. BCL6 showed high expression in neutrophils and villous cytotrophoblasts (VCTs) in both PE and GDM. This study identified BCL6, DNAH9, and SCG2 as common hub genes in GDM and PE. BCL6 is expected to be a new target for the diagnosis and treatment of GDM concurrent with PE.
DOI: 10.6084/m9.figshare.28569154
title: Biological effects of high-LET irradiation on the circulatory system

description: High-linear energy transfer (LET) radiation is generally thought to be more biologically effective in various tissues than low-LET radiation, but whether this also applies to the circulatory system remains unclear. We therefore reviewed biological studies about the effects of high-LET radiation on the circulatory system. We identified 76 relevant papers (24 in vitro, 2 ex vivo, 51 in vivo, one overlapping). In vitro studies used human, bovine, porcine or chick vascular endothelial cells or cardiomyocytes, while ex vivo studies used porcine hearts. In vivo studies used mice, rats, rabbits, dogs or pigs. The types of high-LET radiation used were neutrons, α particles, heavy ions and negative pions. Most studies used a single dose, although some investigated fractionation effects. Twenty-one studies estimated the relative biological effectiveness (RBE) that ranged from 0.1 to 130, depending on radiation quality and endpoint. A meta-analysis of 6 in vitro and 8 in vivo studies (selected based on the feasibility of estimating the RBE and its uncertainty) suggested an RBE of 6.69 (95% confidence intervals (CI): 2.51, 10.88) for in vitro studies and 1.14 (95% CI: 0.91, 1.37) for in vivo studies. The meta-analysis of these 14 studies yielded an RBE of 2.88 (95% CI: 1.52, 4.25). This suggests that high-LET radiation is only slightly more effective than low-LET radiation, although substantial inter-study heterogeneity complicates interpretation. Therapeutic effects have also been reported in disease models. Further research is needed to better understand the effects on the cardiovascular system and to improve radiation protection.
DOI: 10.6084/m9.figshare.28569154.v1
title: Biological effects of high-LET irradiation on the circulatory system

description: High-linear energy transfer (LET) radiation is generally thought to be more biologically effective in various tissues than low-LET radiation, but whether this also applies to the circulatory system remains unclear. We therefore reviewed biological studies about the effects of high-LET radiation on the circulatory system. We identified 76 relevant papers (24 in vitro, 2 ex vivo, 51 in vivo, one overlapping). In vitro studies used human, bovine, porcine or chick vascular endothelial cells or cardiomyocytes, while ex vivo studies used porcine hearts. In vivo studies used mice, rats, rabbits, dogs or pigs. The types of high-LET radiation used were neutrons, α particles, heavy ions and negative pions. Most studies used a single dose, although some investigated fractionation effects. Twenty-one studies estimated the relative biological effectiveness (RBE) that ranged from 0.1 to 130, depending on radiation quality and endpoint. A meta-analysis of 6 in vitro and 8 in vivo studies (selected based on the feasibility of estimating the RBE and its uncertainty) suggested an RBE of 6.69 (95% confidence intervals (CI): 2.51, 10.88) for in vitro studies and 1.14 (95% CI: 0.91, 1.37) for in vivo studies. The meta-analysis of these 14 studies yielded an RBE of 2.88 (95% CI: 1.52, 4.25). This suggests that high-LET radiation is only slightly more effective than low-LET radiation, although substantial inter-study heterogeneity complicates interpretation. Therapeutic effects have also been reported in disease models. Further research is needed to better understand the effects on the cardiovascular system and to improve radiation protection.
DOI: 10.6084/m9.figshare.28569154.v2
title: Biological effects of high-LET irradiation on the circulatory system

description: High-linear energy transfer (LET) radiation is generally thought to be more biologically effective in various tissues than low-LET radiation, but whether this also applies to the circulatory system remains unclear. We therefore reviewed biological studies about the effects of high-LET radiation on the circulatory system. We identified 76 relevant papers (24 in vitro, 2 ex vivo, 51 in vivo, one overlapping). In vitro studies used human, bovine, porcine or chick vascular endothelial cells or cardiomyocytes, while ex vivo studies used porcine hearts. In vivo studies used mice, rats, rabbits, dogs or pigs. The types of high-LET radiation used were neutrons, α particles, heavy ions and negative pions. Most studies used a single dose, although some investigated fractionation effects. Twenty-one studies estimated the relative biological effectiveness (RBE) that ranged from 0.1 to 130, depending on radiation quality and endpoint. A meta-analysis of 6 in vitro and 8 in vivo studies (selected based on the feasibility of estimating the RBE and its uncertainty) suggested an RBE of 6.69 (95% confidence intervals (CI): 2.51, 10.88) for in vitro studies and 1.14 (95% CI: 0.91, 1.37) for in vivo studies. The meta-analysis of these 14 studies yielded an RBE of 2.88 (95% CI: 1.52, 4.25). This suggests that high-LET radiation is only slightly more effective than low-LET radiation, although substantial inter-study heterogeneity complicates interpretation. Therapeutic effects have also been reported in disease models. Further research is needed to better understand the effects on the cardiovascular system and to improve radiation protection.
DOI: 10.6084/m9.figshare.28640536
title: Dosimetric impacts on height development after radiotherapy for intracranial non-germinomatous germ cell tumors

description: Intracranial non-germinomatous germ cell tumors (NGGCTs) are rare pediatric central nervous system (CNS) tumors. Growth impairment induced by radiation treatment was rarely evaluated. We aimed to evaluate the impacts of radiotherapy on height development as well as the dosimetric constraints, providing potential insights for hormonal replacement treatment. A total of 128 pediatric patients diagnosed with NGGCTs were retrospectively studied. Sex, age at irradiation, physical doses and biologically effective dose (BED), height and endocrine status were obtained for analysis. The cumulative change in height was assessed using age-matched normalized height (ANH). Cumulative physical doses and BEDs for the whole brain and pituitary were derived via dose-volume histograms (DVHs) and BED-volume histograms (BEDVHs). For pediatric patients ≤ 11.5 years, linear correlations between ANH and cumulative physical doses as well as BEDs to the whole brain and pituitary were identified. More specifically, dosimetric constraints to the pituitary were 36 Gy for physical dose (AUC = 0.70 [95% CI, 0.54–0.86], <i>p</i> &lt; .05) and 63 Gy<sub>2</sub> BED (AUC = 0.69 [95% CI, 0.53–0.86], <i>p</i> &lt; .05). Impaired hormone secretion with respect to growth hormone (GH) and thyroid-stimulating hormone (TSH) was observed following cranial irradiation (both <i>p</i> &lt; .001), particularly for those with tumors at the suprasellar region (GH: <i>p</i> &lt; .01, TSH: <i>p</i> &lt; .001). Unlikely to patients &gt; 11.5 years, the height development for patients with tumors in the suprasellar region was significantly more affected than those in the other locations (<i>p</i> &lt; .01) among patients ≤11.5 years. Our study revealed the impacts of cumulative doses and tumor locations for radiation-associated growth impairment. Reduced levels of GH and TSH were observed in patients ≤ 11.5 years particularly with tumors in the suprasellar region.
DOI: 10.6084/m9.figshare.28640536.v1
title: Dosimetric impacts on height development after radiotherapy for intracranial non-germinomatous germ cell tumors

description: Intracranial non-germinomatous germ cell tumors (NGGCTs) are rare pediatric central nervous system (CNS) tumors. Growth impairment induced by radiation treatment was rarely evaluated. We aimed to evaluate the impacts of radiotherapy on height development as well as the dosimetric constraints, providing potential insights for hormonal replacement treatment. A total of 128 pediatric patients diagnosed with NGGCTs were retrospectively studied. Sex, age at irradiation, physical doses and biologically effective dose (BED), height and endocrine status were obtained for analysis. The cumulative change in height was assessed using age-matched normalized height (ANH). Cumulative physical doses and BEDs for the whole brain and pituitary were derived via dose-volume histograms (DVHs) and BED-volume histograms (BEDVHs). For pediatric patients ≤ 11.5 years, linear correlations between ANH and cumulative physical doses as well as BEDs to the whole brain and pituitary were identified. More specifically, dosimetric constraints to the pituitary were 36 Gy for physical dose (AUC = 0.70 [95% CI, 0.54–0.86], <i>p</i> &lt; .05) and 63 Gy<sub>2</sub> BED (AUC = 0.69 [95% CI, 0.53–0.86], <i>p</i> &lt; .05). Impaired hormone secretion with respect to growth hormone (GH) and thyroid-stimulating hormone (TSH) was observed following cranial irradiation (both <i>p</i> &lt; .001), particularly for those with tumors at the suprasellar region (GH: <i>p</i> &lt; .01, TSH: <i>p</i> &lt; .001). Unlikely to patients &gt; 11.5 years, the height development for patients with tumors in the suprasellar region was significantly more affected than those in the other locations (<i>p</i> &lt; .01) among patients ≤11.5 years. Our study revealed the impacts of cumulative doses and tumor locations for radiation-associated growth impairment. Reduced levels of GH and TSH were observed in patients ≤ 11.5 years particularly with tumors in the suprasellar region.
DOI: 10.6084/m9.figshare.28525551
title: Prohibitin2 knockdown decreases glioma malignant phenotypes and radio-resistance by inhibiting mitophagy

description: Prohibitin2 (PHB2), located in inner mitochondrial membrane (IMM), is an important receptor to induce mitophagy. PHB2 was identified as a cancer-promoting factor in most cancers. However, the function of PHB2 in glioma cells remains unclear. This study delved into the impact of PHB2 knockdown on the phenotype, radiosensitivity and mitophagy of glioma cells. PHB2 expression and its clinical relevance in glioma were investigated by western blot, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and TCGA databases. The malignant phenotypes of glioma cells were analyzed in vitro using cell proliferation, cell cycle, wound healing and transwell assay. The radiosensitivity of glioma cells was detected by colony forming assay. The potential mechanism by which PHB2 regulated mitophagy was investigated by coimmunoprecipitation assay. The expression of PHB2 was significantly upregulated in glioma cells and closely correlated with the malignant degree of glioma. The knockdown of PHB2 inhibited the proliferation, migration and invasion activities of glioma cells. Furthermore, PHB2 knockdown enhanced the radiosensitivity of normoxic and hypoxic glioma cells and suppressed the ionizing radiation-induced mitophagy in glioma cells. Cyanide 3-chlorophenylhydrazone (CCCP), a mitophagy agonist, could reverse the phenotypes and radiosensitivity changes elicited by PHB2 knockdown. Additionally, PHB2 regulated the expression of PGAM5 and PINK1 by directly binding to PARL. Our findings revealed that PHB2 knockdown decreased glioma malignant phenotypes and radio-resistance by inhibiting mitophagy <i>via</i> PARL–PGAM5–PINK1–Parkin pathway. PHB2 is a promising candidate target for the development of new therapeutic strategy to enhance the efficacy of radiotherapy for glioma.
DOI: 10.6084/m9.figshare.28525551.v1
title: Prohibitin2 knockdown decreases glioma malignant phenotypes and radio-resistance by inhibiting mitophagy

description: Prohibitin2 (PHB2), located in inner mitochondrial membrane (IMM), is an important receptor to induce mitophagy. PHB2 was identified as a cancer-promoting factor in most cancers. However, the function of PHB2 in glioma cells remains unclear. This study delved into the impact of PHB2 knockdown on the phenotype, radiosensitivity and mitophagy of glioma cells. PHB2 expression and its clinical relevance in glioma were investigated by western blot, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and TCGA databases. The malignant phenotypes of glioma cells were analyzed in vitro using cell proliferation, cell cycle, wound healing and transwell assay. The radiosensitivity of glioma cells was detected by colony forming assay. The potential mechanism by which PHB2 regulated mitophagy was investigated by coimmunoprecipitation assay. The expression of PHB2 was significantly upregulated in glioma cells and closely correlated with the malignant degree of glioma. The knockdown of PHB2 inhibited the proliferation, migration and invasion activities of glioma cells. Furthermore, PHB2 knockdown enhanced the radiosensitivity of normoxic and hypoxic glioma cells and suppressed the ionizing radiation-induced mitophagy in glioma cells. Cyanide 3-chlorophenylhydrazone (CCCP), a mitophagy agonist, could reverse the phenotypes and radiosensitivity changes elicited by PHB2 knockdown. Additionally, PHB2 regulated the expression of PGAM5 and PINK1 by directly binding to PARL. Our findings revealed that PHB2 knockdown decreased glioma malignant phenotypes and radio-resistance by inhibiting mitophagy <i>via</i> PARL–PGAM5–PINK1–Parkin pathway. PHB2 is a promising candidate target for the development of new therapeutic strategy to enhance the efficacy of radiotherapy for glioma.