Han Zhang, Lulu Han, Lijun Qiu, Bo Zhao, Yang Gao, Z. Chu, Xiaoxin Dai
PFOA, a newly emerging persistent organic pollutant, is widely present in various environmental media. Previous reports have proved that PFOA exposure can accumulate in the ovary and lead to reproductive toxicity in pregnant mice. However, the potential mechanism of PFOA exposure on fertility remains unclear. In this study, we explore how PFOA compromises fertility in the zebrafish. The data show that PFOA (100 mg/L for 15 days) exposure significantly impaired fertilization and hatching capability. Based on tissue sections, we found that PFOA exposure led to ovarian damage and a decrease in the percentage of mature oocytes. Moreover, through in vitro incubation, we determined that PFOA inhibits oocyte development. We also sequenced the transcriptome of the ovary of female zebrafish and a total of 284 overlapping DEGs were obtained. Functional enrichment analysis showed that 284 overlapping DEGs function mainly in complement and coagulation cascades signaling pathways. In addition, we identified genes that may be associated with immunity, such as LOC108191474 and ZGC:173837. We found that exposure to PFOA can cause an inflammatory response that can lead to ovarian damage and delayed oocyte development.
{"title":"Perfluorooctanoic Acid (PFOA) Exposure Compromises Fertility by Affecting Ovarian and Oocyte Development","authors":"Han Zhang, Lulu Han, Lijun Qiu, Bo Zhao, Yang Gao, Z. Chu, Xiaoxin Dai","doi":"10.3390/ijms25010136","DOIUrl":"https://doi.org/10.3390/ijms25010136","url":null,"abstract":"PFOA, a newly emerging persistent organic pollutant, is widely present in various environmental media. Previous reports have proved that PFOA exposure can accumulate in the ovary and lead to reproductive toxicity in pregnant mice. However, the potential mechanism of PFOA exposure on fertility remains unclear. In this study, we explore how PFOA compromises fertility in the zebrafish. The data show that PFOA (100 mg/L for 15 days) exposure significantly impaired fertilization and hatching capability. Based on tissue sections, we found that PFOA exposure led to ovarian damage and a decrease in the percentage of mature oocytes. Moreover, through in vitro incubation, we determined that PFOA inhibits oocyte development. We also sequenced the transcriptome of the ovary of female zebrafish and a total of 284 overlapping DEGs were obtained. Functional enrichment analysis showed that 284 overlapping DEGs function mainly in complement and coagulation cascades signaling pathways. In addition, we identified genes that may be associated with immunity, such as LOC108191474 and ZGC:173837. We found that exposure to PFOA can cause an inflammatory response that can lead to ovarian damage and delayed oocyte development.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"30 22","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138948169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The development of healthy peri-implant soft tissues is critical to achieving the esthetic and biological success of implant restorations throughout all stages of healing and tissue maturation, starting with provisionalization. The purpose of this study was to investigate the effects of eight different implant provisional materials on human gingival fibroblasts at various stages of cell settlement by examining initial cell attachment, growth, and function. Eight different specimens—bis-acrylic 1 and 2, flowable and bulk–fill composites, self-curing acrylic 1 and 2, milled acrylic, and titanium (Ti) alloy as a control—were fabricated in rectangular plates (n = 3). The condition of human gingival fibroblasts was divided into two groups: those in direct contact with test materials (contact experiment) and those in close proximity to test materials (proximity experiment). The proximity experiment was further divided into three phases: pre-settlement, early settlement, and late settlement. A cell culture insert containing each test plate was placed into a well where the cells were pre-cultured. The number of attached cells, cell proliferation, resistance to detachment, and collagen production were evaluated. In the contact experiment, bis-acrylics and composites showed detrimental effects on cells. The number of cells attached to milled acrylic and self-curing acrylic was relatively high, being approximately 70% and 20–30%, respectively, of that on Ti alloy. There was a significant difference between self-curing acrylic 1 and 2, even with the same curing modality. The cell retention ability also varied considerably among the materials. Although the detrimental effects were mitigated in the proximity experiment compared to the contact experiment, adverse effects on cell growth and collagen production remained significant during all phases of cell settlement for bis-acrylics and flowable composite. Specifically, the early settlement phase was not sufficient to significantly mitigate the material cytotoxicity. The flowable composite was consistently more cytotoxic than the bulk–fill composite. The harmful effects of the provisional materials on gingival fibroblasts vary considerably depending on the curing modality and compositions. Pre-settlement of cells mitigated the harmful effects, implying the susceptibility to material toxicity varies depending on the progress of wound healing and tissue condition. However, cell pre-settlement was not sufficient to fully restore the fibroblastic function to the normal level. Particularly, the adverse effects of bis-acrylics and flowable composite remained significant. Milled and self-curing acrylic exhibited excellent and acceptable biocompatibility, respectively, compared to other materials.
{"title":"Disparity in the Influence of Implant Provisional Materials on Human Gingival Fibroblasts with Different Phases of Cell Settlement: An In Vitro Study","authors":"Takanori Matsuura, Stella Stavrou, Keiji Komatsu, James Cheng, Alisa Pham, Stephany Ferreira, Tomomi Baba, Ting-Ling Chang, Denny Chao, Takahiro Ogawa","doi":"10.3390/ijms25010123","DOIUrl":"https://doi.org/10.3390/ijms25010123","url":null,"abstract":"The development of healthy peri-implant soft tissues is critical to achieving the esthetic and biological success of implant restorations throughout all stages of healing and tissue maturation, starting with provisionalization. The purpose of this study was to investigate the effects of eight different implant provisional materials on human gingival fibroblasts at various stages of cell settlement by examining initial cell attachment, growth, and function. Eight different specimens—bis-acrylic 1 and 2, flowable and bulk–fill composites, self-curing acrylic 1 and 2, milled acrylic, and titanium (Ti) alloy as a control—were fabricated in rectangular plates (n = 3). The condition of human gingival fibroblasts was divided into two groups: those in direct contact with test materials (contact experiment) and those in close proximity to test materials (proximity experiment). The proximity experiment was further divided into three phases: pre-settlement, early settlement, and late settlement. A cell culture insert containing each test plate was placed into a well where the cells were pre-cultured. The number of attached cells, cell proliferation, resistance to detachment, and collagen production were evaluated. In the contact experiment, bis-acrylics and composites showed detrimental effects on cells. The number of cells attached to milled acrylic and self-curing acrylic was relatively high, being approximately 70% and 20–30%, respectively, of that on Ti alloy. There was a significant difference between self-curing acrylic 1 and 2, even with the same curing modality. The cell retention ability also varied considerably among the materials. Although the detrimental effects were mitigated in the proximity experiment compared to the contact experiment, adverse effects on cell growth and collagen production remained significant during all phases of cell settlement for bis-acrylics and flowable composite. Specifically, the early settlement phase was not sufficient to significantly mitigate the material cytotoxicity. The flowable composite was consistently more cytotoxic than the bulk–fill composite. The harmful effects of the provisional materials on gingival fibroblasts vary considerably depending on the curing modality and compositions. Pre-settlement of cells mitigated the harmful effects, implying the susceptibility to material toxicity varies depending on the progress of wound healing and tissue condition. However, cell pre-settlement was not sufficient to fully restore the fibroblastic function to the normal level. Particularly, the adverse effects of bis-acrylics and flowable composite remained significant. Milled and self-curing acrylic exhibited excellent and acceptable biocompatibility, respectively, compared to other materials.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"13 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138948525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiwon Jang, Su Rim Kim, Jo Eun Lee, Seoyeon Lee, Hyeong Jig Son, W. Choe, Kyung-Sik Yoon, Sung Soo Kim, E. Yeo, I. Kang
Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.
酮体（KBs），如乙酰乙酸和β-羟基丁酸，是葡萄糖缺乏时的重要替代能源。在肝脏中生成的酮体在肝外组织中代谢为乙酰-CoA，进入三羧酸循环和电子传递链产生 ATP。葡萄糖代谢减少和线粒体功能障碍与脑缺血和神经变性过程中神经元死亡和脑损伤增加有关。KBs和生酮饮食（KD）通过代谢和信号功能协调各种细胞过程，显示出神经保护作用。它们能增强线粒体功能，减轻氧化应激和细胞凋亡，调节组蛋白和非组蛋白的表观遗传和翻译后修饰。此外，KBs 和 KD 还有助于减少神经炎症，调节自噬、神经传递系统和肠道微生物组。本综述旨在探讨 KBs 和 KD 对脑缺血和神经退行性疾病（包括阿尔茨海默病和帕金森病）中脑损伤的神经保护作用的分子机制。
{"title":"Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases","authors":"Jiwon Jang, Su Rim Kim, Jo Eun Lee, Seoyeon Lee, Hyeong Jig Son, W. Choe, Kyung-Sik Yoon, Sung Soo Kim, E. Yeo, I. Kang","doi":"10.3390/ijms25010124","DOIUrl":"https://doi.org/10.3390/ijms25010124","url":null,"abstract":"Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"14 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138952276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Subramanian Muthamil, Pandiyan Muthuramalingam, Hyun-Yong Kim, Hyun-Jun Jang, Ji-Hyo Lyu, Ung Cheol Shin, Younghoon Go, Seong-Hoon Park, Hee Gu Lee, Hyunsuk Shin, Jun Hong Park
Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.
{"title":"Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach","authors":"Subramanian Muthamil, Pandiyan Muthuramalingam, Hyun-Yong Kim, Hyun-Jun Jang, Ji-Hyo Lyu, Ung Cheol Shin, Younghoon Go, Seong-Hoon Park, Hee Gu Lee, Hyunsuk Shin, Jun Hong Park","doi":"10.3390/ijms25010156","DOIUrl":"https://doi.org/10.3390/ijms25010156","url":null,"abstract":"Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"48 20","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138952613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emerson Carlos de Almeida, Victor Diego Faria, Felipe Dalmazzo Cirinêu, Maria G. A. Santiago, Beatriz Miotto, J. Vieira, C. Braga, Jiri Adamec, A. A. H. Fernandes, M. Buzalaf, P. Padilha
Results obtained from rat studies indicate that, even at low concentrations, mercurial species cause harmful effects on the kidneys, by inducing the nephrotic oxidative stress response. In the present work, Hg-associated proteins were identified as possible mercury-exposure biomarkers in rat kidneys exposed to low mercury chloride concentrations for 30 days (Hg-30) and 60 days (Hg-60), using metalloproteomic strategies. The renal proteomic profile was fractioned by two-dimensional electrophoresis and the mercury determinations in kidney samples, protein pellets and protein spots were performed using graphite furnace atomic absorption spectrometry. The characterization of Hg-associated protein spots and the analysis of differentially expressed proteins were performed by liquid chromatography, coupled with tandem mass spectrometry. Eleven Hg-associated protein spots with a concentration range of 79 ± 1 to 750 ± 9 mg kg−1 in the Hg-60 group were identified. The characterization and expression analyses allowed the identification of 53 proteins that were expressed only in the Hg-60 group, 13 “upregulated” proteins (p > 0.95) and 47 “downregulated” proteins (p < 0.05). Actin isoforms and hemoglobin subunits were identified in protein spots of the Hg-60 group, with mercury concentrations in the range of 138 to 750 mg kg−1, which qualifies these proteins as potential mercury-exposure biomarkers.
{"title":"Metalloproteomic Investigation of Hg-Binding Proteins in Renal Tissue of Rats Exposed to Mercury Chloride","authors":"Emerson Carlos de Almeida, Victor Diego Faria, Felipe Dalmazzo Cirinêu, Maria G. A. Santiago, Beatriz Miotto, J. Vieira, C. Braga, Jiri Adamec, A. A. H. Fernandes, M. Buzalaf, P. Padilha","doi":"10.3390/ijms25010164","DOIUrl":"https://doi.org/10.3390/ijms25010164","url":null,"abstract":"Results obtained from rat studies indicate that, even at low concentrations, mercurial species cause harmful effects on the kidneys, by inducing the nephrotic oxidative stress response. In the present work, Hg-associated proteins were identified as possible mercury-exposure biomarkers in rat kidneys exposed to low mercury chloride concentrations for 30 days (Hg-30) and 60 days (Hg-60), using metalloproteomic strategies. The renal proteomic profile was fractioned by two-dimensional electrophoresis and the mercury determinations in kidney samples, protein pellets and protein spots were performed using graphite furnace atomic absorption spectrometry. The characterization of Hg-associated protein spots and the analysis of differentially expressed proteins were performed by liquid chromatography, coupled with tandem mass spectrometry. Eleven Hg-associated protein spots with a concentration range of 79 ± 1 to 750 ± 9 mg kg−1 in the Hg-60 group were identified. The characterization and expression analyses allowed the identification of 53 proteins that were expressed only in the Hg-60 group, 13 “upregulated” proteins (p > 0.95) and 47 “downregulated” proteins (p < 0.05). Actin isoforms and hemoglobin subunits were identified in protein spots of the Hg-60 group, with mercury concentrations in the range of 138 to 750 mg kg−1, which qualifies these proteins as potential mercury-exposure biomarkers.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"64 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138953145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingyang Du, Zhuxiang Jiang, Chaogang Wang, Chenchen Wei, Qingyuan Li, Rihao Cong, Wei Wang, Guofan Zhang, Li Li
As the world’s largest farmed marine animal, oysters have enormous economic and ecological value. However, mass summer mortality caused by high temperature poses a significant threat to the oyster industry. To investigate the molecular mechanisms underlying heat adaptation and improve the heat tolerance ability in the oyster, we conducted genome-wide association analysis (GWAS) analysis on the F2 generation derived from the hybridization of relatively heat-tolerant Crassostrea angulata ♀ and heat-sensitive Crassostrea gigas ♂, which are the dominant cultured species in southern and northern China, respectively. Acute heat stress experiment (semi-lethal temperature 42 °C) demonstrated that the F2 population showed differentiation in heat tolerance, leading to extremely differentiated individuals (approximately 20% of individuals die within the first four days with 10% survival after 14 days). Genome resequencing and GWAS of the two divergent groups had identified 18 significant SNPs associated with heat tolerance, with 26 candidate genes located near these SNPs. Eleven candidate genes that may associate with the thermal resistance were identified, which were classified into five categories: temperature sensor (Trpm2), transcriptional factor (Gata3), protein ubiquitination (Ube2h, Usp50, Uchl3), heat shock subfamily (Dnajc17, Dnaja1), and transporters (Slc16a9, Slc16a14, Slc16a9, Slc16a2). The expressional differentiation of the above genes between C. gigas and C. angulata under sublethal temperature (37 °C) further supports their crucial role in coping with high temperature. Our results will contribute to understanding the molecular mechanisms underlying heat tolerance, and provide genetic markers for heat-resistance breeding in the oyster industry.
{"title":"Genome-Wide Association Analysis of Heat Tolerance in F2 Progeny from the Hybridization between Two Congeneric Oyster Species","authors":"Mingyang Du, Zhuxiang Jiang, Chaogang Wang, Chenchen Wei, Qingyuan Li, Rihao Cong, Wei Wang, Guofan Zhang, Li Li","doi":"10.3390/ijms25010125","DOIUrl":"https://doi.org/10.3390/ijms25010125","url":null,"abstract":"As the world’s largest farmed marine animal, oysters have enormous economic and ecological value. However, mass summer mortality caused by high temperature poses a significant threat to the oyster industry. To investigate the molecular mechanisms underlying heat adaptation and improve the heat tolerance ability in the oyster, we conducted genome-wide association analysis (GWAS) analysis on the F2 generation derived from the hybridization of relatively heat-tolerant Crassostrea angulata ♀ and heat-sensitive Crassostrea gigas ♂, which are the dominant cultured species in southern and northern China, respectively. Acute heat stress experiment (semi-lethal temperature 42 °C) demonstrated that the F2 population showed differentiation in heat tolerance, leading to extremely differentiated individuals (approximately 20% of individuals die within the first four days with 10% survival after 14 days). Genome resequencing and GWAS of the two divergent groups had identified 18 significant SNPs associated with heat tolerance, with 26 candidate genes located near these SNPs. Eleven candidate genes that may associate with the thermal resistance were identified, which were classified into five categories: temperature sensor (Trpm2), transcriptional factor (Gata3), protein ubiquitination (Ube2h, Usp50, Uchl3), heat shock subfamily (Dnajc17, Dnaja1), and transporters (Slc16a9, Slc16a14, Slc16a9, Slc16a2). The expressional differentiation of the above genes between C. gigas and C. angulata under sublethal temperature (37 °C) further supports their crucial role in coping with high temperature. Our results will contribute to understanding the molecular mechanisms underlying heat tolerance, and provide genetic markers for heat-resistance breeding in the oyster industry.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"29 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138948237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure–volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure–volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.
{"title":"PD-L1 and AKT Overexpressing Adipose-Derived Mesenchymal Stem Cells Enhance Myocardial Protection by Upregulating CD25+ T Cells in Acute Myocardial Infarction Rat Model","authors":"Yu-Kai Lin, Lien-Cheng Hsiao, Mei-Yao Wu, Yun-Fang Chen, Yen‐Nien Lin, Chia-Ming Chang, Wei-Hsin Chung, Ke-Wei Chen, Chiung‐Ray Lu, Wei-Yu Chen, Shih-Sheng Chang, Woei-Cheang Shyu, An‐Sheng Lee, Chu-Huang Chen, Long-Bin Jeng, Kuan-Cheng Chang","doi":"10.3390/ijms25010134","DOIUrl":"https://doi.org/10.3390/ijms25010134","url":null,"abstract":"This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure–volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure–volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"59 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138951068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Chalkidi, M. Melissari, Ana Henriques, Athanasia Stavropoulou, George Kollias, V. Koliaraki
Cancer-associated fibroblasts (CAFs) comprise a group of heterogeneous subpopulations with distinct identities indicative of their diverse origins, activation patterns, and pro-tumorigenic functions. CAFs originate mainly from resident fibroblasts, which are activated upon different stimuli, including growth factors and inflammatory mediators, but the extent to which they also maintain some of their homeostatic properties, at least at the earlier stages of carcinogenesis, is not clear. In response to cytokines, such as interleukin 1 (IL-1) and tumor necrosis factor (TNF), as well as microbial products, CAFs acquire an immunoregulatory phenotype, but its specificity and pathophysiological significance in individual CAF subsets is yet to be determined. In this study, we analyzed the properties of Col6a1-positive fibroblasts in colitis-associated cancer. We found that Col6a1+ cells partly maintain their homeostatic features during adenoma development, while their activation is characterized by the acquisition of a distinct proangiogenic signature associated with their initial perivascular location. In vitro and in vivo experiments showed that Col6a1+ cells respond to innate immune stimuli and exert pro-tumorigenic functions. However, Col6a1+-specific inhibition of TNF receptor 1 (TNFR1) or IL-1 receptor (IL-1R) signaling does not significantly affect tumorigenesis, suggesting that activation of other subsets acts in a compensatory way or that multiple immune stimuli are necessary to drive the proinflammatory activation of this subset. In conclusion, our results show that adenoma-associated CAF subsets can partly maintain the properties of homeostatic fibroblasts while they become activated to support tumor growth through distinct and compensatory mechanisms.
{"title":"Activation and Functions of Col6a1+ Fibroblasts in Colitis-Associated Cancer","authors":"N. Chalkidi, M. Melissari, Ana Henriques, Athanasia Stavropoulou, George Kollias, V. Koliaraki","doi":"10.3390/ijms25010148","DOIUrl":"https://doi.org/10.3390/ijms25010148","url":null,"abstract":"Cancer-associated fibroblasts (CAFs) comprise a group of heterogeneous subpopulations with distinct identities indicative of their diverse origins, activation patterns, and pro-tumorigenic functions. CAFs originate mainly from resident fibroblasts, which are activated upon different stimuli, including growth factors and inflammatory mediators, but the extent to which they also maintain some of their homeostatic properties, at least at the earlier stages of carcinogenesis, is not clear. In response to cytokines, such as interleukin 1 (IL-1) and tumor necrosis factor (TNF), as well as microbial products, CAFs acquire an immunoregulatory phenotype, but its specificity and pathophysiological significance in individual CAF subsets is yet to be determined. In this study, we analyzed the properties of Col6a1-positive fibroblasts in colitis-associated cancer. We found that Col6a1+ cells partly maintain their homeostatic features during adenoma development, while their activation is characterized by the acquisition of a distinct proangiogenic signature associated with their initial perivascular location. In vitro and in vivo experiments showed that Col6a1+ cells respond to innate immune stimuli and exert pro-tumorigenic functions. However, Col6a1+-specific inhibition of TNF receptor 1 (TNFR1) or IL-1 receptor (IL-1R) signaling does not significantly affect tumorigenesis, suggesting that activation of other subsets acts in a compensatory way or that multiple immune stimuli are necessary to drive the proinflammatory activation of this subset. In conclusion, our results show that adenoma-associated CAF subsets can partly maintain the properties of homeostatic fibroblasts while they become activated to support tumor growth through distinct and compensatory mechanisms.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"56 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138951930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad M. El-Diasty, Javier Rodríguez, Luis Pérez, Sonia Eiras, Angel L. Fernández
There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1β (IL-1β); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 β, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid.
{"title":"Accumulation of Inflammatory Mediators in the Normal Pericardial Fluid","authors":"Mohammad M. El-Diasty, Javier Rodríguez, Luis Pérez, Sonia Eiras, Angel L. Fernández","doi":"10.3390/ijms25010157","DOIUrl":"https://doi.org/10.3390/ijms25010157","url":null,"abstract":"There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1β (IL-1β); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 β, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"11 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138952313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kinesin family member17 (KIF17), a homologous dimer of the kinesin-2 protein family, has important microtubule-dependent and -independent roles in spermiogenesis. Little is known about KIF17 in the mollusk, Phascolosoma esculenta, a newly developed mariculture species in China. Here, we cloned the open reading frame of Pe-kif17 and its related gene, Pe-act, and performed bioinformatics analysis on both. Pe-KIF17 and Pe-ACT are structurally conserved, indicating that they may be functionally conserved. The expression pattern of kif17/act mRNA performed during spermiogenesis revealed their expression in diverse tissues, with the highest expression level in the coelomic fluid of P. esculenta. The expressions of Pe-kif17 and Pe-act mRNA were relatively high during the breeding season (July–September), suggesting that Pe-KIF17/ACT may be involved in spermatogenesis, particularly during spermiogenesis. Further analysis of Pe-kif17 mRNA via fluorescence in situ hybridization revealed the continuous expression of this mRNA during spermiogenesis, suggesting potential functions in this process. Immunofluorescence showed that Pe-KIF17 co-localized with α-tubulin and migrated from the perinuclear cytoplasm to one side of the spermatid, forming the sperm tail. Pe-KIF17 and Pe-ACT also colocalized. KIF17 may participate in spermiogenesis of P. esculenta, particularly in nuclear reshaping and tail formation by interacting with microtubule structures similar to the manchette. Moreover, Pe-KIF17 with Pe-ACT is also involved in nuclear reshaping and tail formation in the absence of microtubules. This study provides evidence for the role of KIF17 during spermiogenesis and provides theoretical data for studies of the reproductive biology of P. esculenta. These findings are important for spermatogenesis in mollusks.
{"title":"Expression Dynamics Indicate Potential Roles of KIF17 for Nuclear Reshaping and Tail Formation during Spermiogenesis in Phascolosoma esculenta","authors":"Yue Pan, Jingqian Wang, Xinming Gao, Chen Du, Congcong Hou, Daojun Tang, Junquan Zhu","doi":"10.3390/ijms25010128","DOIUrl":"https://doi.org/10.3390/ijms25010128","url":null,"abstract":"Kinesin family member17 (KIF17), a homologous dimer of the kinesin-2 protein family, has important microtubule-dependent and -independent roles in spermiogenesis. Little is known about KIF17 in the mollusk, Phascolosoma esculenta, a newly developed mariculture species in China. Here, we cloned the open reading frame of Pe-kif17 and its related gene, Pe-act, and performed bioinformatics analysis on both. Pe-KIF17 and Pe-ACT are structurally conserved, indicating that they may be functionally conserved. The expression pattern of kif17/act mRNA performed during spermiogenesis revealed their expression in diverse tissues, with the highest expression level in the coelomic fluid of P. esculenta. The expressions of Pe-kif17 and Pe-act mRNA were relatively high during the breeding season (July–September), suggesting that Pe-KIF17/ACT may be involved in spermatogenesis, particularly during spermiogenesis. Further analysis of Pe-kif17 mRNA via fluorescence in situ hybridization revealed the continuous expression of this mRNA during spermiogenesis, suggesting potential functions in this process. Immunofluorescence showed that Pe-KIF17 co-localized with α-tubulin and migrated from the perinuclear cytoplasm to one side of the spermatid, forming the sperm tail. Pe-KIF17 and Pe-ACT also colocalized. KIF17 may participate in spermiogenesis of P. esculenta, particularly in nuclear reshaping and tail formation by interacting with microtubule structures similar to the manchette. Moreover, Pe-KIF17 with Pe-ACT is also involved in nuclear reshaping and tail formation in the absence of microtubules. This study provides evidence for the role of KIF17 during spermiogenesis and provides theoretical data for studies of the reproductive biology of P. esculenta. These findings are important for spermatogenesis in mollusks.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"38 22","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138952495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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