Pub Date : 2023-09-28DOI: 10.32604/biocell.2023.029644
Daniella M Adams, Kalie F Beckers, Juliet P Flanagan, Viviane C L Gomes, Chin-Chi Liu, Jenny L Sones
Background: Women with obesity have higher risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension, aberrant fetoplacental development, and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 mice have higher visceral white adipose tissue (WAT) and circulating leptin. We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface.
Methods: To test this hypothesis, BPH/5 mice were fed ad libitum (lib) and pair-fed (PF) to C57 ad lib controls beginning at embryonic day (e) 0.5. Hypoxia-related genes, hypoxia inducible factor (Hif) 1α, stem cell factor (Scf), heme oxygenase-1 (Ho-1), leptin (Lep), and leptin receptor (LepR) were assessed in e7.5 implantation sites.
Results: BPH/5 ad lib had 1.5 to 2-fold increase in Hif1α, Scf, and Ho-1 mRNA and a greater than 3-fold increase in leptin mRNA vs. C57 that was attenuated with PF. Exogenous leptin promoted Hif1α and Ho-1 mRNA expression in e7.5 decidua in vitro. While hypoxic conditions in vitro did not change decidual leptin mRNA. Furthermore, BPH/5 PF mice demonstrated improved fetal and placental outcomes later in gestation, with greater placental vascular area by e18.5 and attenuation of FGR.
Conclusion: In conclusion, pair-feeding BPH/5 mice beginning at conception may improve placental vasculature formation via decreased leptin and hypoxia-associated markers in this model. Future investigations are needed to better determine the effect of hypoxia and leptin on pregnancy outcomes in obese pregnant women.
{"title":"Reversal of maternal obesity attenuates hypoxia and improves placental development in the preeclamptic-like BPH/5 mouse model.","authors":"Daniella M Adams, Kalie F Beckers, Juliet P Flanagan, Viviane C L Gomes, Chin-Chi Liu, Jenny L Sones","doi":"10.32604/biocell.2023.029644","DOIUrl":"10.32604/biocell.2023.029644","url":null,"abstract":"<p><strong>Background: </strong>Women with obesity have higher risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension, aberrant fetoplacental development, and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 mice have higher visceral white adipose tissue (WAT) and circulating leptin. We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface.</p><p><strong>Methods: </strong>To test this hypothesis, BPH/5 mice were fed <i>ad libitum</i> (lib) and pair-fed (PF) to C57 ad lib controls beginning at embryonic day (e) 0.5. Hypoxia-related genes, hypoxia inducible factor (Hif) 1α, stem cell factor (Scf), heme oxygenase-1 (Ho-1), leptin (Lep), and leptin receptor (LepR) were assessed in e7.5 implantation sites.</p><p><strong>Results: </strong>BPH/5 ad lib had 1.5 to 2-fold increase in <i>Hif1α</i>, <i>Scf</i>, and <i>Ho-1</i> mRNA and a greater than 3-fold increase in leptin mRNA <i>vs</i>. C57 that was attenuated with PF. Exogenous leptin promoted Hif1α and Ho-1 mRNA expression in e7.5 decidua <i>in vitro</i>. While hypoxic conditions <i>in vitro</i> did not change decidual leptin mRNA. Furthermore, BPH/5 PF mice demonstrated improved fetal and placental outcomes later in gestation, with greater placental vascular area by e18.5 and attenuation of FGR.</p><p><strong>Conclusion: </strong>In conclusion, pair-feeding BPH/5 mice beginning at conception may improve placental vasculature formation via decreased leptin and hypoxia-associated markers in this model. Future investigations are needed to better determine the effect of hypoxia and leptin on pregnancy outcomes in obese pregnant women.</p>","PeriodicalId":55384,"journal":{"name":"Biocell","volume":"47 9","pages":"2051-2058"},"PeriodicalIF":1.2,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria-Luisa Veisaga, Mariam Ahumada, Stacy Soriano, Leonardo Acuna, Wei Zhang, Ivy Leung, Robert Barnum, Manuel A Barbieri
Backgorund: Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells. This study evaluates the effect of A. montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1 (IGF-1) stimulation.
Methods: MTT assay was performed to determine the proliferation of cancer cells. Propidium iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of apoptosis. Protein expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with A. montana leaves hexane extract.
Results: A. montana leaves hexane (sub-fraction V) blocked the constitutive stimulation of the PI3K/mTOR signaling pathways. This inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNNEL) staining, activation of caspase-3, and cleavage of PPAR. It also limited the expression of various downstream genes that regulate proliferation, survival, metastasis, and angiogenesis (i.e., cyclin D1, survivin, COX-2, and VEGF). It increased the expression of p53 and p21. Interestingly, we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 stimulation.
Conclusion: Our study indicates that A. montana leaves (sub-fraction V) extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.
{"title":"Anti-proliferative effect of <i>Annona</i> extracts on breast cancer cells.","authors":"Maria-Luisa Veisaga, Mariam Ahumada, Stacy Soriano, Leonardo Acuna, Wei Zhang, Ivy Leung, Robert Barnum, Manuel A Barbieri","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Backgorund: </strong>Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells. This study evaluates the effect of A. montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1 (IGF-1) stimulation.</p><p><strong>Methods: </strong>MTT assay was performed to determine the proliferation of cancer cells. Propidium iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of apoptosis. Protein expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with A. <i>montana</i> leaves hexane extract.</p><p><strong>Results: </strong>A. <i>montana</i> leaves hexane (sub-fraction V) blocked the constitutive stimulation of the PI3K/mTOR signaling pathways. This inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNNEL) staining, activation of caspase-3, and cleavage of PPAR. It also limited the expression of various downstream genes that regulate proliferation, survival, metastasis, and angiogenesis (i.e., cyclin D1, survivin, COX-2, and VEGF). It increased the expression of p53 and p21. Interestingly, we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 stimulation.</p><p><strong>Conclusion: </strong>Our study indicates that A. <i>montana</i> leaves (sub-fraction V) extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.</p>","PeriodicalId":55384,"journal":{"name":"Biocell","volume":"47 8","pages":"1835-1852"},"PeriodicalIF":0.8,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538365/pdf/nihms-1927735.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41152106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-21DOI: 10.32604/biocell.2023.028014
James L Rosenberg, William Woolley, Ihsan Elnunu, Julia Kamml, David S Kammer, Claire Acevedo
Age and diabetes have long been known to induce an oxidative reaction between glucose and collagen, leading to the accumulation of advanced glycation end-products (AGEs) cross-links in collagenous tissues. More recently, AGEs content has been related to loss of bone quality, independent of bone mass, and increased fracture risk with aging and diabetes. Loss of bone quality is mostly attributed to changes in material properties, structural organization, or cellular remodeling. Though all these factors play a role in bone fragility disease, some common recurring patterns can be found between diabetic and age-related bone fragility. The main pattern we will discuss in this viewpoint is the increase of fibrillar collagen stiffness and loss of collagen-induced plasticity with AGE accumulation. This study focused on recent related experimental studies and discusses the correlation between fluorescent AGEs content at the molecular and fibrillar scales, collagen deformation mechanisms at the nanoscale, and resistance to bone fracture at the macroscale.
{"title":"Effect of non-enzymatic glycation on collagen nanoscale mechanisms in diabetic and age-related bone fragility.","authors":"James L Rosenberg, William Woolley, Ihsan Elnunu, Julia Kamml, David S Kammer, Claire Acevedo","doi":"10.32604/biocell.2023.028014","DOIUrl":"https://doi.org/10.32604/biocell.2023.028014","url":null,"abstract":"<p><p>Age and diabetes have long been known to induce an oxidative reaction between glucose and collagen, leading to the accumulation of advanced glycation end-products (AGEs) cross-links in collagenous tissues. More recently, AGEs content has been related to loss of bone quality, independent of bone mass, and increased fracture risk with aging and diabetes. Loss of bone quality is mostly attributed to changes in material properties, structural organization, or cellular remodeling. Though all these factors play a role in bone fragility disease, some common recurring patterns can be found between diabetic and age-related bone fragility. The main pattern we will discuss in this viewpoint is the increase of fibrillar collagen stiffness and loss of collagen-induced plasticity with AGE accumulation. This study focused on recent related experimental studies and discusses the correlation between fluorescent AGEs content at the molecular and fibrillar scales, collagen deformation mechanisms at the nanoscale, and resistance to bone fracture at the macroscale.</p>","PeriodicalId":55384,"journal":{"name":"Biocell","volume":"47 7","pages":"1651-1659"},"PeriodicalIF":1.2,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10293963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.32604/biocell.2023.025203
Xiaoxu Zhang, Lin Zhang, Lin Du, Huiyan Sun, Xia Zhao, Yang Sun, Wen Wang, Lisheng Wang
: Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine and clinical therapy due to their capabilities of proliferation, differentiation, and immune regulation. However, during in vitro expansion, MSCs are prone to aging, which largely limits their application. Prostaglandin E-2 (PGE-2) is a key effector secreted by MSCs to exert immunomodulatory effects. By screening the compound library for PGE-2 secretion, the antioxidant trolox was veri fi ed as a stimulator of MSCs to secrete PGE-2. The effect of antioxidant trolox on biological characteristics of MSCS, including aging, proliferation, and gene expression, was examined. The results demonstrated that trolox can resist aging, promote proliferation, and enhance PGE-2 secretion of MSCs without affecting their surface marker expression. Furthermore, trolox treatment up-regulates miR-17-92 clusters in MSCs and may contribute to its anti-aging effects. Thus, trolox addition might be bene fi cial for MSCs expansion and their application.
{"title":"The antioxidant trolox inhibits aging and enhances prostaglandin E-2 secretion in mesenchymal stem cells","authors":"Xiaoxu Zhang, Lin Zhang, Lin Du, Huiyan Sun, Xia Zhao, Yang Sun, Wen Wang, Lisheng Wang","doi":"10.32604/biocell.2023.025203","DOIUrl":"https://doi.org/10.32604/biocell.2023.025203","url":null,"abstract":": Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine and clinical therapy due to their capabilities of proliferation, differentiation, and immune regulation. However, during in vitro expansion, MSCs are prone to aging, which largely limits their application. Prostaglandin E-2 (PGE-2) is a key effector secreted by MSCs to exert immunomodulatory effects. By screening the compound library for PGE-2 secretion, the antioxidant trolox was veri fi ed as a stimulator of MSCs to secrete PGE-2. The effect of antioxidant trolox on biological characteristics of MSCS, including aging, proliferation, and gene expression, was examined. The results demonstrated that trolox can resist aging, promote proliferation, and enhance PGE-2 secretion of MSCs without affecting their surface marker expression. Furthermore, trolox treatment up-regulates miR-17-92 clusters in MSCs and may contribute to its anti-aging effects. Thus, trolox addition might be bene fi cial for MSCs expansion and their application.","PeriodicalId":55384,"journal":{"name":"Biocell","volume":"72 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90402015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.32604/biocell.2023.030541
ELYN AMIELA SALLEH, YEONG YEH LEE, ANDEE DZULKARNAEN ZAKARIA, NUR ASYILLA CHE JALIL, MARAHAINI MUSA
Colorectal cancer (CRC) is a major global health concern. Accumulation of cancer-associated fibroblasts (CAFs) in CRC is associated with poor prognosis and disease recurrence. CAFs are the main cellular component of the tumor microenvironment. CAF-tumor cell interplay, which is facilitated by various secretomes, drives colorectal carcinogenesis. The complexity of CAF populations contributes to the heterogeneity of CRC and influences patient survival and treatment response. Due to their significant roles in colorectal carcinogenesis, different clinical applications utilizing or targeting CAFs have been suggested. Circulating CAFs (cCAFs) which can be detected in blood samples, have been proposed to help in determining patient prognosis and enables the detection of cancer through liquid biopsy. Liquid biopsy is gaining traction as it is non-invasive, allows frequent and easy sampling, and shows concordance to tissue biopsy analysis. In addition, CAF-targeted therapy is currently being studied extensively to be used as one of the treatment avenues for CRC. Various mechanisms of CAF-targeted therapy have been reported, including blocking the signaling pathways involving CAFs and cancer cells, thus abolishing the CAF-tumor cell crosstalk and subsequently hindering tumorigenesis. These translational applications of cCAFs and utilization of CAFs as key targets for CRC therapy, although still in the early phases of development, will potentially improve CRC patient management in the future.
{"title":"Cancer-associated fibroblasts of colorectal cancer: Translational prospects in liquid biopsy and targeted therapy","authors":"ELYN AMIELA SALLEH, YEONG YEH LEE, ANDEE DZULKARNAEN ZAKARIA, NUR ASYILLA CHE JALIL, MARAHAINI MUSA","doi":"10.32604/biocell.2023.030541","DOIUrl":"https://doi.org/10.32604/biocell.2023.030541","url":null,"abstract":"Colorectal cancer (CRC) is a major global health concern. Accumulation of cancer-associated fibroblasts (CAFs) in CRC is associated with poor prognosis and disease recurrence. CAFs are the main cellular component of the tumor microenvironment. CAF-tumor cell interplay, which is facilitated by various secretomes, drives colorectal carcinogenesis. The complexity of CAF populations contributes to the heterogeneity of CRC and influences patient survival and treatment response. Due to their significant roles in colorectal carcinogenesis, different clinical applications utilizing or targeting CAFs have been suggested. Circulating CAFs (cCAFs) which can be detected in blood samples, have been proposed to help in determining patient prognosis and enables the detection of cancer through liquid biopsy. Liquid biopsy is gaining traction as it is non-invasive, allows frequent and easy sampling, and shows concordance to tissue biopsy analysis. In addition, CAF-targeted therapy is currently being studied extensively to be used as one of the treatment avenues for CRC. Various mechanisms of CAF-targeted therapy have been reported, including blocking the signaling pathways involving CAFs and cancer cells, thus abolishing the CAF-tumor cell crosstalk and subsequently hindering tumorigenesis. These translational applications of cCAFs and utilization of CAFs as key targets for CRC therapy, although still in the early phases of development, will potentially improve CRC patient management in the future.","PeriodicalId":55384,"journal":{"name":"Biocell","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135506333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.32604/biocell.2023.028331
Qiao-mei Zhou, Jian Liu, L. Xin, Yanyan Fang, L. Wan, D. Huang, J. Wen
{"title":"Exploration of the oxidative-inflammatory potential targets of Coicis Semen in osteoarthritis: Data mining and systematic pharmacology","authors":"Qiao-mei Zhou, Jian Liu, L. Xin, Yanyan Fang, L. Wan, D. Huang, J. Wen","doi":"10.32604/biocell.2023.028331","DOIUrl":"https://doi.org/10.32604/biocell.2023.028331","url":null,"abstract":"","PeriodicalId":55384,"journal":{"name":"Biocell","volume":"191 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86823146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The development and prognosis of breast cancer are intricately linked to psychological stress. In addition, depression is the most common psychological comorbidity among breast cancer survivors, and reportedly, Fang-Xia-Dihuang decoction (FXDH) can effectively manage depression in such patients. However, its pharmacological and molecular mechanisms remain obscure. Methods: Public databases were used for obtaining active components and related targets. Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways. Molecule docking was used to understand the interactions between main compounds and hub targets. In addition, an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology. Results: 174 active components of FXDH and 163 intersection targets of FXDH, breast cancer, and depression were identified. Quercetin, methyl ferulate, luteolin, ferulaldehyde, wogonin, and diincarvilone were identified as the principal active components of FXDH. Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK2/STAT3) signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression. In addition, in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression. FXDH treatment downregulated the expression of epinephrine, PI3K, AKT, STAT3, and JAK2 compared with the control treatment (p < 0.05). Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), AKT, and STAT3. Conclusion: This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress. The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways. This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.
{"title":"Fang-Xia-Dihuang decoction inhibits breast cancer progression induced by psychological stress via down-regulation of PI3K/AKT and JAK2/STAT3 pathways: An in vivo and a network pharmacology assessment","authors":"LINGYAN LV, JING ZHAO, XUAN WANG, LIUYAN XU, YINGYI FAN, CHUNHUI WANG, HONGQIAO FAN, XIAOHUA PEI","doi":"10.32604/biocell.2023.030742","DOIUrl":"https://doi.org/10.32604/biocell.2023.030742","url":null,"abstract":"<b>Background:</b> The development and prognosis of breast cancer are intricately linked to psychological stress. In addition, depression is the most common psychological comorbidity among breast cancer survivors, and reportedly, Fang-Xia-Dihuang decoction (FXDH) can effectively manage depression in such patients. However, its pharmacological and molecular mechanisms remain obscure. <b>Methods:</b> Public databases were used for obtaining active components and related targets. Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways. Molecule docking was used to understand the interactions between main compounds and hub targets. In addition, an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology. <b>Results:</b> 174 active components of FXDH and 163 intersection targets of FXDH, breast cancer, and depression were identified. Quercetin, methyl ferulate, luteolin, ferulaldehyde, wogonin, and diincarvilone were identified as the principal active components of FXDH. Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK2/STAT3) signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression. In addition, <i>in vivo</i> experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression. FXDH treatment downregulated the expression of epinephrine, PI3K, AKT, STAT3, and JAK2 compared with the control treatment (<i>p</i> < 0.05). Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), AKT, and STAT3. <b>Conclusion:</b> This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress. The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways. This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.","PeriodicalId":55384,"journal":{"name":"Biocell","volume":"88 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135753664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.32604/biocell.2023.029277
CHUNYANG XU, CAIYUN YANG, JINSONG ZHANG, XIAOHUA PAN, JUN WANG, LEI JIANG, HONGWEI YE, BO CHEN
Background: The lung is one of the primary target organs of hydrogen sulfide (H2S), as exposure to H2S can cause acute lung injury (ALI) and pulmonary edema. Dexamethasone (Dex) exerts a protective effect on ALI caused by exposure to toxic gases and is commonly used in the clinic; however, the underlying mechanisms remain elusive, and the dose is unclear. Methods:In vivo experiments: divided C57BL6 mice into 6 groups at random, 12 in each group. The mice were exposed to H2S for 3 h and 5 or 50 mg/kg Dex pretreated before exposure, sacrificed 12 h later. The morphological changes of HE staining and the ultrastructural changes of lungs under transmission electron microscopy were evaluated. The wet/dry ratio of lung tissue was measured. Bronchial alveolar lavage fluid (BALF) protein content and lung permeability index were detected. The expression of AQP5 protein was measured by immunohistochemistry and Western Blot (WB). In vitro experiments: divided human lung adenocarcinoma cell line A549 into 4 groups. 1 μmol/L dexamethasone was added to pre-incubation. The WB analyzed the protein of p-ERK1/2, p-JNK, and p-p38 in MAPK pathway after 1 h of NaHS exposure; six hours after NaHS exposure, the AQP5 protein was measured by WB. Results: Dex treatment could significantly attenuate the H2S-induced destruction to the alveolar wall, increase the wet-to-dry weight ratio and decrease pulmonary permeability index, with high-dose dexamethasone seemingly functioning better. Additionally, our previous studies showed that aquaporin 5 (AQP 5), a critical protein that regulates water flux, decreased both in a mouse and cell model following the exposure to H2S. This study indicates that tThe decrease in AQP 5 can be alleviated by Dex treatment. Additionally, the mitogen activated protein kinase (MAPK) pathway may be involved in the protective effects of Dex in ALI caused by exposure to H2S since H2S-induced MAPK activation could be inhibited by Dex. Conclusion: The present results indicate that AQP 5 may be considered a therapeutic target for Dex in H2S or other hazardous gases-induced ALI.
{"title":"The therapeutic mechanism of dexamethasone in lung injury induced by hydrogen sulfide","authors":"CHUNYANG XU, CAIYUN YANG, JINSONG ZHANG, XIAOHUA PAN, JUN WANG, LEI JIANG, HONGWEI YE, BO CHEN","doi":"10.32604/biocell.2023.029277","DOIUrl":"https://doi.org/10.32604/biocell.2023.029277","url":null,"abstract":"<b>Background:</b> The lung is one of the primary target organs of hydrogen sulfide (H<sub>2</sub>S), as exposure to H<sub>2</sub>S can cause acute lung injury (ALI) and pulmonary edema. Dexamethasone (Dex) exerts a protective effect on ALI caused by exposure to toxic gases and is commonly used in the clinic; however, the underlying mechanisms remain elusive, and the dose is unclear. <b>Methods:</b> <i>In vivo</i> experiments: divided C57BL6 mice into 6 groups at random, 12 in each group. The mice were exposed to H<sub>2</sub>S for 3 h and 5 or 50 mg/kg Dex pretreated before exposure, sacrificed 12 h later. The morphological changes of HE staining and the ultrastructural changes of lungs under transmission electron microscopy were evaluated. The wet/dry ratio of lung tissue was measured. Bronchial alveolar lavage fluid (BALF) protein content and lung permeability index were detected. The expression of AQP5 protein was measured by immunohistochemistry and Western Blot (WB). <i>In vitro</i> experiments: divided human lung adenocarcinoma cell line A549 into 4 groups. 1 μmol/L dexamethasone was added to pre-incubation. The WB analyzed the protein of p-ERK1/2, p-JNK, and p-p38 in MAPK pathway after 1 h of NaHS exposure; six hours after NaHS exposure, the AQP5 protein was measured by WB. <b>Results:</b> Dex treatment could significantly attenuate the H<sub>2</sub>S-induced destruction to the alveolar wall, increase the wet-to-dry weight ratio and decrease pulmonary permeability index, with high-dose dexamethasone seemingly functioning better. Additionally, our previous studies showed that aquaporin 5 (AQP 5), a critical protein that regulates water flux, decreased both in a mouse and cell model following the exposure to H<sub>2</sub>S. This study indicates that tThe decrease in AQP 5 can be alleviated by Dex treatment. Additionally, the mitogen activated protein kinase (MAPK) pathway may be involved in the protective effects of Dex in ALI caused by exposure to H<sub>2</sub>S since H<sub>2</sub>S-induced MAPK activation could be inhibited by Dex. <b>Conclusion:</b> The present results indicate that AQP 5 may be considered a therapeutic target for Dex in H<sub>2</sub>S or other hazardous gases-induced ALI.","PeriodicalId":55384,"journal":{"name":"Biocell","volume":"281 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135755121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.32604/biocell.2023.029986
GAOZHONG LI, FUXIN LI, NING WEI, QING JIA
Background: This study was aimed at identifying natural killer (NK) cell-related genes to design a risk prognosis model for the accurate evaluation of gastric cancer (GC) prognosis. Methods: We obtained NK cell-related genes from various databases, followed by Cox regression analysis and molecular typing to identify prognostic genes. Various immune algorithms and enrichment analyses were used to investigate the mutations, immune status, and pathway variations among different genotypes. The key prognostic genes were assessed using the least absolute shrinkage and selection operator (Lasso) regression analysis and univariate Cox regression analysis. Thereafter, the risk score (RS) prognosis model was constructed based on the selected important prognostic genes. A Receiver Operating Characteristics (ROC) curve was plotted for analyzing the robustness of the model. Subsequently, the decision and calibration curves were used for assessing the reliability and prediction accuracy of the proposed model. The ‘pRRophetic’ R software package was utilized for predicting the half-maximal inhibitory concentration (IC50) of immunotherapy and chemotherapy drugs. Results: We screened 21 prognostic genes and three molecular subtypes and found that the C1 subtype had the worst prognosis. Further, the pathways promoting tumor proliferation, such as epithelial-mesenchymal transition were significantly up-regulated. The results also showed that the macrophages in the M2 stage were significantly infiltrated in the C1 subtype, and there was significant overexpression in the C1 subtype, accompanied by a severe inflammatory reaction. The C1 was highly sensitive to drugs like 5-fluorouracil and paclitaxel. The ROC, calibration curve, and decision curve showed that the risk model was robust and strongly reliable. Conclusion: Overall, our proposed NK cell-related RS model can be used as a more accurate prediction index for GC patients, providing a valuable contribution to personalized medicine.
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