cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.30819457
title: Leveraging plasma concentrations to optimize extracorporeal treatment in acute diquat poisoning: a multi-center retrospective cohort study

description: Diquat poisoning is common in Asia and the optimal enhanced elimination strategy is unknown. This study aimed to evaluate the clinical value of plasma diquat concentrations in guiding personalized extracorporeal treatment regimens for patients with acute diquat poisoning. This multi-center retrospective cohort study included 163 patients with acute diquat poisoning admitted between February 2022 and July 2023. Patients were divided into three groups based on plasma diquat concentrations measured upon presentation to the emergency department: low (&lt;100 μg/L), medium (100–1,000 μg/L), and high (≥1,000 μg/L). The evaluated extracorporeal treatment regimens included hemoperfusion alone and a combination of hemoperfusion with continuous veno-venous hemodiafiltration. Kaplan-Meier survival curves were used to estimate cumulative survival probabilities, with survival probabilities compared using log-rank tests. All 66 patients survived in the low concentration group, regardless of the extracorporeal treatment used. In the medium and high concentration groups, five patients who refused extracorporeal treatment died, whereas 92 patients who received extracorporeal treatment had a case fatality rate of 48.9%. In the high concentration group, patients receiving hemoperfusion combined with continuous veno-venous hemodiafiltration had a case fatality rate of 76.7% and better survival probabilities, compared to hemoperfusion-only patients, which had no survivors. Additionally, among those treated with a combination of hemoperfusion and continuous veno-venous hemodiafiltration, the time interval from the end of hemoperfusion session to the initiation of continuous veno-venous hemodiafiltration was, on average, shorter for survivors than deaths (3.7 h versus 4.7 h). This retrospective observational study of diquat poisoned patients highlights the potential for personalized extracorporeal treatment regimens using an initial plasma diquat concentration. Future randomized trials are warranted to evaluate the optimal use of extracorporeal treatments. Obtaining plasma diquat concentrations may be of great value for guiding extracorporeal treatment regimens to improve prognosis in patients with acute diquat poisoning.
DOI: 10.6084/m9.figshare.30819457.v1
title: Leveraging plasma concentrations to optimize extracorporeal treatment in acute diquat poisoning: a multi-center retrospective cohort study

description: Diquat poisoning is common in Asia and the optimal enhanced elimination strategy is unknown. This study aimed to evaluate the clinical value of plasma diquat concentrations in guiding personalized extracorporeal treatment regimens for patients with acute diquat poisoning. This multi-center retrospective cohort study included 163 patients with acute diquat poisoning admitted between February 2022 and July 2023. Patients were divided into three groups based on plasma diquat concentrations measured upon presentation to the emergency department: low (&lt;100 μg/L), medium (100–1,000 μg/L), and high (≥1,000 μg/L). The evaluated extracorporeal treatment regimens included hemoperfusion alone and a combination of hemoperfusion with continuous veno-venous hemodiafiltration. Kaplan-Meier survival curves were used to estimate cumulative survival probabilities, with survival probabilities compared using log-rank tests. All 66 patients survived in the low concentration group, regardless of the extracorporeal treatment used. In the medium and high concentration groups, five patients who refused extracorporeal treatment died, whereas 92 patients who received extracorporeal treatment had a case fatality rate of 48.9%. In the high concentration group, patients receiving hemoperfusion combined with continuous veno-venous hemodiafiltration had a case fatality rate of 76.7% and better survival probabilities, compared to hemoperfusion-only patients, which had no survivors. Additionally, among those treated with a combination of hemoperfusion and continuous veno-venous hemodiafiltration, the time interval from the end of hemoperfusion session to the initiation of continuous veno-venous hemodiafiltration was, on average, shorter for survivors than deaths (3.7 h versus 4.7 h). This retrospective observational study of diquat poisoned patients highlights the potential for personalized extracorporeal treatment regimens using an initial plasma diquat concentration. Future randomized trials are warranted to evaluate the optimal use of extracorporeal treatments. Obtaining plasma diquat concentrations may be of great value for guiding extracorporeal treatment regimens to improve prognosis in patients with acute diquat poisoning.
DOI: 10.15468/dl.9ym5gt
title: Occurrence Download

description: A dataset listing the 3422 species recorded in GBIF matching the query:
{
 "and" : [
 "DatasetKey is Fungi (S)",
 {
 "or" : [
 "Geometry POLYGON((37.39187 68.83404,41.39187 68.83404,41.39187 72.83404,37.39187 72.83404,37.39187 68.83404))",
 "Geometry POLYGON((47.50795 70.53045,38.51406 74.15521,13.63099 71.97504,-32.23781 63.56923,-18.31265 38.54294,-2.742 35.19015,20.61395 36.64509,36.18459 38.07302,48.16201 51.19799,55.94732 63.36253,47.50795 70.53045))"
 ]
 },
 "HasCoordinate is true",
 "HasGeospatialIssue is false",
 "OccurrenceStatus is Present"
 ]
}

 The dataset's 3422 records were derived from 1 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0037275-251120083545085/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.6084/m9.figshare.30244801
title: FASN regulates CSE-induced apoptosis, oxidative stress and mitochondrial damage in type 2 alveolar epithelial cells by regulating NRF2 expression and nuclear translocation

description: Smoking is a major etiological factor in numerous chronic lung diseases. However, the precise underlying mechanisms remain incompletely elucidated. In this study, we investigated the effects of cigarette smoke extract (CSE) on mitochondrial oxidative phosphorylation (OXPHOS), mitochondrial structure, and the antioxidant regulator Nuclear factor erythroid 2-related factor 2 (NRF2) in a rat lung epithelial-T-antigen negative cell line (RLE-6TN), focusing on the associated molecular pathways. CSE exposure significantly reduced cell viability, induced oxidative-antioxidant imbalance, and disrupted OXPHOS complex subunit expression and mitochondrial ultrastructure. Furthermore, an increased BCL2-Associated X (BAX) / B-cell lymphoma/leukemia 2 (BCL2) ratio activated the intrinsic apoptosis pathway. NRF2 knockdown exacerbated CSE-induced mitochondrial damage and apoptosis. Co-immunoprecipitation (co-IP) analysis revealed a direct interaction between NRF2 and Fatty Acid Synthase (FASN). CSE treatment significantly reduced NRF2-FASN binding. Notably, FASN knockout amplified oxidative stress, exacerbated damage to OXPHOS and mitochondrial structure, and diminished NRF2 expression and nuclear translocation. Collectively, our findings demonstrate that CSE exposure impairs NRF2 expression and nuclear translocation by disrupting FASN expression and its interaction with FASN. This impairment leads to mitochondrial OXPHOS dysfunction, structural damage, and ultimately apoptosis. Our findings identify FASN as a potential therapeutic target for mitigating smoking-associated lung injury.
DOI: 10.6084/m9.figshare.30244801.v1
title: FASN regulates CSE-induced apoptosis, oxidative stress and mitochondrial damage in type 2 alveolar epithelial cells by regulating NRF2 expression and nuclear translocation

description: Smoking is a major etiological factor in numerous chronic lung diseases. However, the precise underlying mechanisms remain incompletely elucidated. In this study, we investigated the effects of cigarette smoke extract (CSE) on mitochondrial oxidative phosphorylation (OXPHOS), mitochondrial structure, and the antioxidant regulator Nuclear factor erythroid 2-related factor 2 (NRF2) in a rat lung epithelial-T-antigen negative cell line (RLE-6TN), focusing on the associated molecular pathways. CSE exposure significantly reduced cell viability, induced oxidative-antioxidant imbalance, and disrupted OXPHOS complex subunit expression and mitochondrial ultrastructure. Furthermore, an increased BCL2-Associated X (BAX) / B-cell lymphoma/leukemia 2 (BCL2) ratio activated the intrinsic apoptosis pathway. NRF2 knockdown exacerbated CSE-induced mitochondrial damage and apoptosis. Co-immunoprecipitation (co-IP) analysis revealed a direct interaction between NRF2 and Fatty Acid Synthase (FASN). CSE treatment significantly reduced NRF2-FASN binding. Notably, FASN knockout amplified oxidative stress, exacerbated damage to OXPHOS and mitochondrial structure, and diminished NRF2 expression and nuclear translocation. Collectively, our findings demonstrate that CSE exposure impairs NRF2 expression and nuclear translocation by disrupting FASN expression and its interaction with FASN. This impairment leads to mitochondrial OXPHOS dysfunction, structural damage, and ultimately apoptosis. Our findings identify FASN as a potential therapeutic target for mitigating smoking-associated lung injury.
DOI: 10.6084/m9.figshare.30755207
title: Multi-omics revealed GOT1/ALDH3A1 pathway attenuated head and neck squamous cell carcinoma and increased cisplatin sensitivity through ROS induced by mitochondrial dysfunction

description: Current treatment options for head and neck squamous cell carcinoma (HNSCC) are limited. Aspartate aminotransaminase (GOT1) plays an important role in cancer development but its role in HNSCC remains unknown. We combined proteomics and metabolomics to identify high GOT1expression in human cancer tissues. The effects of GOT1 knockdown on cancer cell proliferation were confirmed using CCK8, wound healing assays, colony formation assays, and EdU assays. The anti-apoptotic ability of cancer cells was evaluated using TUNEL assay and flow cytometry. GOT1 knockdown caused mitochondrial dysfunction and was characterized by reduced mitochondrial membrane potential and altered expression of mitochondrial electron transport chain complexes and key transcription factors, as measured by JC-1 and qRT-PCR. Given that mitochondria are the primary source of reactive oxygen species (ROS), we assessed cellular ROS and mitochondrial superoxide levels by flow cytometry and found a significant increase. GOT1 knockdown increased the sensitivity of cells to cisplatin and decreased the volume of tumors in vivo. In summary, GOT1 knockdown inhibited proliferation and promoted apoptosis via ROS overproduction from mitochondrial dysfunction, thereby increasing cisplatin sensitivity. RNA-seq further identified aldehyde dehydrogenase 3A1 (ALDH3A1) as potentially downstream target of GOT1. These findings suggest that GOT1 knockdown may improve clinical outcomes in HNSCC.
DOI: 10.6084/m9.figshare.30755207.v1
title: Multi-omics revealed GOT1/ALDH3A1 pathway attenuated head and neck squamous cell carcinoma and increased cisplatin sensitivity through ROS induced by mitochondrial dysfunction

description: Current treatment options for head and neck squamous cell carcinoma (HNSCC) are limited. Aspartate aminotransaminase (GOT1) plays an important role in cancer development but its role in HNSCC remains unknown. We combined proteomics and metabolomics to identify high GOT1expression in human cancer tissues. The effects of GOT1 knockdown on cancer cell proliferation were confirmed using CCK8, wound healing assays, colony formation assays, and EdU assays. The anti-apoptotic ability of cancer cells was evaluated using TUNEL assay and flow cytometry. GOT1 knockdown caused mitochondrial dysfunction and was characterized by reduced mitochondrial membrane potential and altered expression of mitochondrial electron transport chain complexes and key transcription factors, as measured by JC-1 and qRT-PCR. Given that mitochondria are the primary source of reactive oxygen species (ROS), we assessed cellular ROS and mitochondrial superoxide levels by flow cytometry and found a significant increase. GOT1 knockdown increased the sensitivity of cells to cisplatin and decreased the volume of tumors in vivo. In summary, GOT1 knockdown inhibited proliferation and promoted apoptosis via ROS overproduction from mitochondrial dysfunction, thereby increasing cisplatin sensitivity. RNA-seq further identified aldehyde dehydrogenase 3A1 (ALDH3A1) as potentially downstream target of GOT1. These findings suggest that GOT1 knockdown may improve clinical outcomes in HNSCC.
DOI: 10.6084/m9.figshare.29663011
title: Sodium–glucose cotransporter 2 inhibitors ameliorate glutathione cysteine ligase modifier-mediated oxidative stress and subsequent ferroptosis in proximal tubules of diabetic kidney disease

description: Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease. The precise molecular mechanism of ferroptosis, an iron-dependent and non-apoptotic form of regulated cell death, remains poorly understood in DKD, as does the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on ferroptosis-mediated DKD. This study used bulk RNA sequencing, in vitro and in vivo models, and human kidney samples to explore the molecular mechanisms involved in oxidative stress and ferroptosis in the proximal tubule (PT) of DKD. High glucose (HG) induced features of ferroptosis in HK-2 cells. Transcriptome analysis of primary PT cells from diabetic patients indicated that glutathione cysteine ligase modifier (GCLM) subunit is involved in ferroptosis. Immunohistochemical staining revealed that db/db mice and diabetic patients had lower glutathione peroxidase 4 and GCLM expression in the PT. Suppression of GCLM enhanced ferroptosis, whereas GCLM overexpression mitigated HG-induced ferroptosis in HK-2 cells. Antioxidants reduced oxidative stress and ferroptosis in both in vitro and in vivo models of DKD. Furthermore, SGLT2i attenuated PT ferroptosis in these models and improved DKD by increasing GCLM expression. SGLT2i reduced ferroptosis in PT by boosting GCLM expression, thereby slowing DKD progression, revealing that GCLM has the potential against DKD.
DOI: 10.6084/m9.figshare.29663011.v1
title: Sodium–glucose cotransporter 2 inhibitors ameliorate glutathione cysteine ligase modifier-mediated oxidative stress and subsequent ferroptosis in proximal tubules of diabetic kidney disease

description: Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease. The precise molecular mechanism of ferroptosis, an iron-dependent and non-apoptotic form of regulated cell death, remains poorly understood in DKD, as does the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on ferroptosis-mediated DKD. This study used bulk RNA sequencing, in vitro and in vivo models, and human kidney samples to explore the molecular mechanisms involved in oxidative stress and ferroptosis in the proximal tubule (PT) of DKD. High glucose (HG) induced features of ferroptosis in HK-2 cells. Transcriptome analysis of primary PT cells from diabetic patients indicated that glutathione cysteine ligase modifier (GCLM) subunit is involved in ferroptosis. Immunohistochemical staining revealed that db/db mice and diabetic patients had lower glutathione peroxidase 4 and GCLM expression in the PT. Suppression of GCLM enhanced ferroptosis, whereas GCLM overexpression mitigated HG-induced ferroptosis in HK-2 cells. Antioxidants reduced oxidative stress and ferroptosis in both in vitro and in vivo models of DKD. Furthermore, SGLT2i attenuated PT ferroptosis in these models and improved DKD by increasing GCLM expression. SGLT2i reduced ferroptosis in PT by boosting GCLM expression, thereby slowing DKD progression, revealing that GCLM has the potential against DKD.
DOI: 10.6084/m9.figshare.29653479
title: Alpha-linolenic acid protects against heatstroke-induced acute lung injury by inhibiting ferroptosis through Nrf2 activation

description: Heatstroke (HS)-induced acute lung injury (ALI) has high morbidity and mortality with no specific therapies. Ferroptosis, a form of programmed cell death driven by lipid peroxidation due to reduced Glutathione Peroxidase 4 (GPX4) activity, is closely linked to HS-induced ALI. This study investigated the effect of alpha-linolenic acid (ALA), a plant-derived ω-3 fatty acid, on ferroptosis in a mouse model of HS-induced ALI. Histopathology analysis found that ALA can attenuate lung injury and improve the 7-day survival rate in mice with HS-induced ALI. In addition, ALA significantly reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing the level of antioxidant glutathione (GSH). Further analysis showed that ALA upregulated the levels of SLC7A11 and GPX4 by promoting the nuclear translocation of Nrf2. This led to increased GSH synthesis but reduced ROS accumulation, which in turn suppressed ferroptosis and protected the mice against HS-induced ALI. Additionally, the protective effect of ALA was found to be diminished in <i>Nrf2</i>-deficient mice. In summary, ALA inhibits ferroptosis in macrophages by activating the Nrf2/SLC7A11/GPX4 pathway and attenuates HS-induced ALI.
DOI: 10.6084/m9.figshare.29653479.v1
title: Alpha-linolenic acid protects against heatstroke-induced acute lung injury by inhibiting ferroptosis through Nrf2 activation

description: Heatstroke (HS)-induced acute lung injury (ALI) has high morbidity and mortality with no specific therapies. Ferroptosis, a form of programmed cell death driven by lipid peroxidation due to reduced Glutathione Peroxidase 4 (GPX4) activity, is closely linked to HS-induced ALI. This study investigated the effect of alpha-linolenic acid (ALA), a plant-derived ω-3 fatty acid, on ferroptosis in a mouse model of HS-induced ALI. Histopathology analysis found that ALA can attenuate lung injury and improve the 7-day survival rate in mice with HS-induced ALI. In addition, ALA significantly reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing the level of antioxidant glutathione (GSH). Further analysis showed that ALA upregulated the levels of SLC7A11 and GPX4 by promoting the nuclear translocation of Nrf2. This led to increased GSH synthesis but reduced ROS accumulation, which in turn suppressed ferroptosis and protected the mice against HS-induced ALI. Additionally, the protective effect of ALA was found to be diminished in <i>Nrf2</i>-deficient mice. In summary, ALA inhibits ferroptosis in macrophages by activating the Nrf2/SLC7A11/GPX4 pathway and attenuates HS-induced ALI.
DOI: 10.6084/m9.figshare.29586647
title: ACSF2-PGK1 interaction promotes ferroptosis in renal tubular epithelial cells of diabetic nephropathy by regulating Keap1/Nrf2 signaling

description: Recent studies have highlighted the strong association between kidney disease and ferroptosis. However, the role of ferroptosis in diabetic nephropathy (DN) remains unclear. This study aimed to determine the role of ACSF2 in renal tubule injury in DN and its underlying mechanisms. We established diabetic kidney disease models both in vivo, using db/db mice, and in vitro, using high glucose induced HK-2 cells. A significant upregulation of ACSF2 was observed in the renal tubules of patients with DN and db/db mice. ACSF2 expression correlated with renal tubule injury and renal function, indicating its potential as an independent biomarker in patients with DN. Silencing ACSF2 alleviated high glucose-induced renal tubular epithelial cell injury by reducing oxidative stress-induced ferroptosis in vivo and in vitro. Mechanistically, liquid chromatography-tandem mass spectrometry and co-immunoprecipitation demonstrated that ACSF2 specifically binds to PGK1. ACSF2 affected Keap1 dimerization by regulating PGK1 phosphorylation at serine 203, which subsequently affects the levels of NRF2. Moreover, PGK1 stabilizes ACSF2 via deubiquitination, establishing a positive feedback loop. The results provide evidence that the interaction between ACSF2 and PGK1 promotes DN progression by regulating oxidative stress-induced ferroptosis. ACSF2 participates in crosstalk between oxidative stress and ferroptosis. This could be a potential therapeutic target for DN.
DOI: 10.6084/m9.figshare.29586647.v1
title: ACSF2-PGK1 interaction promotes ferroptosis in renal tubular epithelial cells of diabetic nephropathy by regulating Keap1/Nrf2 signaling

description: Recent studies have highlighted the strong association between kidney disease and ferroptosis. However, the role of ferroptosis in diabetic nephropathy (DN) remains unclear. This study aimed to determine the role of ACSF2 in renal tubule injury in DN and its underlying mechanisms. We established diabetic kidney disease models both in vivo, using db/db mice, and in vitro, using high glucose induced HK-2 cells. A significant upregulation of ACSF2 was observed in the renal tubules of patients with DN and db/db mice. ACSF2 expression correlated with renal tubule injury and renal function, indicating its potential as an independent biomarker in patients with DN. Silencing ACSF2 alleviated high glucose-induced renal tubular epithelial cell injury by reducing oxidative stress-induced ferroptosis in vivo and in vitro. Mechanistically, liquid chromatography-tandem mass spectrometry and co-immunoprecipitation demonstrated that ACSF2 specifically binds to PGK1. ACSF2 affected Keap1 dimerization by regulating PGK1 phosphorylation at serine 203, which subsequently affects the levels of NRF2. Moreover, PGK1 stabilizes ACSF2 via deubiquitination, establishing a positive feedback loop. The results provide evidence that the interaction between ACSF2 and PGK1 promotes DN progression by regulating oxidative stress-induced ferroptosis. ACSF2 participates in crosstalk between oxidative stress and ferroptosis. This could be a potential therapeutic target for DN.
DOI: 10.6084/m9.figshare.30293191
title: Expression, localization and regulation of NADPH oxidases in pancreatic beta cells

description: Reactive oxygen species (ROS) are short-lived and act in a site-specific manner, underscoring the importance of identifying the subcellular localization of their sources. ROS-generating NADPH oxidases (NOX) regulate pancreatic beta cell (dys)function. However, their subcellular localization and cytokine-mediated regulation in these cells remain largely unknown. We characterized the expression, subcellular localization and time-dependent cytokine-induced regulation of NOX isoforms in beta cells. Isoforms were studied via RT-qPCR, immunoblotting and immunofluorescence in rat islets and beta cell lines. Beta cells express DUOX1 and DUOX2 proteins and <i>Duoxa2</i> transcripts; lacking <i>Duoxa1</i> expression. In INS-1E cells, NOX1 and DUOX1 localize in the endoplasmic reticulum (ER); DUOX2 in insulin vesicles; and NOX2 and NOX4 in vesicles, ER and plasma membrane. In INS-1E, cytokines increased expression of <i>Nox1</i> and <i>Duox1</i> at 4-8 h (returning to baseline at 16 h) and <i>Nox2</i> and <i>p47phox</i> at 8 h (persisting until 24 h). <i>Duox(a)2</i>, <i>p67phox</i> and <i>p40phox</i> were downregulated and DUOX1 upregulated at 16-24 h. The absence of <i>Duoxa1</i> in beta cells might lead to DUOX1 mismatching, impairing its trafficking and activity. NOXs in beta cells are diverse in subcellular localization and cytokine-induced regulation, suggesting their isoform-specific involvement in beta cell function, stress and apoptosis.