Pub Date : 2024-10-01eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1479864
Pooja Rai, Andreas Bergmann
Protein aggregation is a common pathological occurrence in neurodegenerative diseases. This often leads to neuroinflammation, which exacerbates the aggregation and progression of diseases like Parkinson's and Alzheimer's. Here, we focus on immune responses and neurotoxicity in a Parkinson's disease model in Drosophila. Mutations in the SNCA gene that encodes the alpha (α)-Synuclein protein have been linked to familial Parkinson's disease, disrupting autophagy regulation in neuronal cells and promoting the formation of Lewy bodies, a hallmark of Parkinson's pathology. This results in the loss of dopaminergic neurons, manifesting as movement disorders. α-Synuclein aggregation triggers innate immune responses by activating microglial cells, leading to phagocytic activity and the expression of neuroprotective antimicrobial peptides (AMPs). However, sustained AMP expression or chronic inflammation resulting from inadequate microglial phagocytosis can induce neuronal toxicity and apoptosis, leading to severe dopaminergic neuron loss. This review underscores the mechanistic connection between immune response pathways and α-Synuclein-mediated neurodegeneration using Drosophila models. Furthermore, we extensively explore factors influencing neuroinflammation and key immune signaling pathways implicated in neurodegenerative diseases, particularly Parkinson's disease. Given the limited success of traditional treatments, recent research has focused on therapies targeting inflammatory signaling pathways. Some of these approaches have shown promising results in animal models and clinical trials. We provide an overview of current therapeutic strategies showing potential in treating neurodegenerative diseases, offering new avenues for future research and treatment development.
{"title":"Unraveling the intricate link between cell death and neuroinflammation using <i>Drosophila</i> as a model.","authors":"Pooja Rai, Andreas Bergmann","doi":"10.3389/fcell.2024.1479864","DOIUrl":"https://doi.org/10.3389/fcell.2024.1479864","url":null,"abstract":"<p><p>Protein aggregation is a common pathological occurrence in neurodegenerative diseases. This often leads to neuroinflammation, which exacerbates the aggregation and progression of diseases like Parkinson's and Alzheimer's. Here, we focus on immune responses and neurotoxicity in a Parkinson's disease model in <i>Drosophila</i>. Mutations in the SNCA gene that encodes the alpha (α)-Synuclein protein have been linked to familial Parkinson's disease, disrupting autophagy regulation in neuronal cells and promoting the formation of Lewy bodies, a hallmark of Parkinson's pathology. This results in the loss of dopaminergic neurons, manifesting as movement disorders. α-Synuclein aggregation triggers innate immune responses by activating microglial cells, leading to phagocytic activity and the expression of neuroprotective antimicrobial peptides (AMPs). However, sustained AMP expression or chronic inflammation resulting from inadequate microglial phagocytosis can induce neuronal toxicity and apoptosis, leading to severe dopaminergic neuron loss. This review underscores the mechanistic connection between immune response pathways and α-Synuclein-mediated neurodegeneration using <i>Drosophila</i> models. Furthermore, we extensively explore factors influencing neuroinflammation and key immune signaling pathways implicated in neurodegenerative diseases, particularly Parkinson's disease. Given the limited success of traditional treatments, recent research has focused on therapies targeting inflammatory signaling pathways. Some of these approaches have shown promising results in animal models and clinical trials. We provide an overview of current therapeutic strategies showing potential in treating neurodegenerative diseases, offering new avenues for future research and treatment development.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1479864"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-09-30eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1480695
Vijay Pratap Singh, Pushpendra Singh
The mechanism that synchronizes the timing of parturition remains a mystery. Each mammalian species has a specific duration of gestation that is determined by integrated interactions among the mother, placenta, and fetus. Senescence is primarily driven by DNA damage and is one of the critical factors influencing both parturition and lifespan. In this study, we investigated senescence as a physiological process during pregnancy and observed a gradual physiological increase in senescence in the maternal decidua and placental cells with gestation. This increase in senescence was associated with a gradual physiological increase in DNA damage during gestation. An analysis of the AnAge dataset revealed a positive correlation between the gestation period and maximum lifespan across 740 mammalian species. This finding supports the hypothesis that the rates of DNA damage and senescence may impact both the gestation period and lifespan. We suggest that the relationship between gestation period and lifespan in mammals is mediated by species-specific rates of DNA damage and senescence, necessitating further explorations into their causal roles.
使分娩时间同步的机制仍然是一个谜。每种哺乳动物都有特定的妊娠期,这是由母体、胎盘和胎儿之间的综合相互作用决定的。衰老主要由 DNA 损伤驱动,是影响分娩和寿命的关键因素之一。在这项研究中,我们将衰老作为孕期的一个生理过程进行了研究,并观察到母体蜕膜和胎盘细胞的衰老随着妊娠而逐渐增加。衰老的增加与妊娠期 DNA 损伤的逐渐增加有关。对 AnAge 数据集的分析表明,在 740 种哺乳动物中,妊娠期与最长寿命呈正相关。这一发现支持了 DNA 损伤率和衰老率可能同时影响妊娠期和寿命的假设。我们认为哺乳动物的妊娠期和寿命之间的关系是由特定物种的DNA损伤率和衰老率介导的,因此有必要进一步探索它们的因果作用。
{"title":"Linking DNA damage and senescence to gestation period and lifespan in placental mammals.","authors":"Vijay Pratap Singh, Pushpendra Singh","doi":"10.3389/fcell.2024.1480695","DOIUrl":"https://doi.org/10.3389/fcell.2024.1480695","url":null,"abstract":"<p><p>The mechanism that synchronizes the timing of parturition remains a mystery. Each mammalian species has a specific duration of gestation that is determined by integrated interactions among the mother, placenta, and fetus. Senescence is primarily driven by DNA damage and is one of the critical factors influencing both parturition and lifespan. In this study, we investigated senescence as a physiological process during pregnancy and observed a gradual physiological increase in senescence in the maternal decidua and placental cells with gestation. This increase in senescence was associated with a gradual physiological increase in DNA damage during gestation. An analysis of the AnAge dataset revealed a positive correlation between the gestation period and maximum lifespan across 740 mammalian species. This finding supports the hypothesis that the rates of DNA damage and senescence may impact both the gestation period and lifespan. We suggest that the relationship between gestation period and lifespan in mammals is mediated by species-specific rates of DNA damage and senescence, necessitating further explorations into their causal roles.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1480695"},"PeriodicalIF":4.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-09-30eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1461132
Irene Iavarone, Daniela Mele, Francesca Caprio, Giada Andreoli, Maria Giovanna Vastarella, Pasquale de Franciscis, Carlo Ronsini
Background: Ovulatory dysfunction is more common in women with obesity. Body fat distribution is also crucial because anovulatory women have a greater waist circumference and more abdominal fat than ovulatory women of similar BMI. The primary aim of the present study is to determine whether there is a relationship between BMI and reproductive characteristics, including hormonal values, antral follicle count (AFC), endometrial assessment at transvaginal ultrasound evaluation (TVUS) during controlled ovarian stimulation (COS), and oocyte retrieval after Ovum Pick-Up (OPU).
Methods: Data from a cohort of 183 patients were analyzed and divided into three groups based on weight status: normal weight, overweight, and obesity. Evaluated reproductive characteristics included: age, basal values of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-beta-estradiol (E2), thyroid stimulating hormone (TSH), anti-müllerian hormone (AMH), antral-follicle-count (AFC), duration of COS, E2, and progesterone at the last monitoring, TVUS endometrial thickness at the last monitoring before OPU, FOI after OPU. Additionally, the number of meiosis II oocytes retrieved (MII), the total dose of FSH administered, the ratio between MII and total FSH administered, and OSI were registered.
Results: AMH levels were significantly lower in obese patients compared to normal weight and overweight women (1.05 IQR 1.20, 1.58 IQR 2.16, 1.32 IQR 1.38, respectively, p-value = 0.032). When looking at the MII/FSH ratio, the normal weight group showed a median value of 3.3 with an IQR of 4.0, the overweight group showed a median value of 2.3 with an IQR of 1.9, and the obese group had a median value of 2.6 with an IQR of 2.8. Those data were statistically significant (p-value = 0.049).
Conclusion: These results emphasize the importance of considering weight status in fertility assessment and treatment planning.
{"title":"Obesity may impair response to ovarian stimulation. A retrospective observational study on oocyte quality.","authors":"Irene Iavarone, Daniela Mele, Francesca Caprio, Giada Andreoli, Maria Giovanna Vastarella, Pasquale de Franciscis, Carlo Ronsini","doi":"10.3389/fcell.2024.1461132","DOIUrl":"https://doi.org/10.3389/fcell.2024.1461132","url":null,"abstract":"<p><strong>Background: </strong>Ovulatory dysfunction is more common in women with obesity. Body fat distribution is also crucial because anovulatory women have a greater waist circumference and more abdominal fat than ovulatory women of similar BMI. The primary aim of the present study is to determine whether there is a relationship between BMI and reproductive characteristics, including hormonal values, antral follicle count (AFC), endometrial assessment at transvaginal ultrasound evaluation (TVUS) during controlled ovarian stimulation (COS), and oocyte retrieval after Ovum Pick-Up (OPU).</p><p><strong>Methods: </strong>Data from a cohort of 183 patients were analyzed and divided into three groups based on weight status: normal weight, overweight, and obesity. Evaluated reproductive characteristics included: age, basal values of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-beta-estradiol (E2), thyroid stimulating hormone (TSH), anti-müllerian hormone (AMH), antral-follicle-count (AFC), duration of COS, E2, and progesterone at the last monitoring, TVUS endometrial thickness at the last monitoring before OPU, FOI after OPU. Additionally, the number of meiosis II oocytes retrieved (MII), the total dose of FSH administered, the ratio between MII and total FSH administered, and OSI were registered.</p><p><strong>Results: </strong>AMH levels were significantly lower in obese patients compared to normal weight and overweight women (1.05 IQR 1.20, 1.58 IQR 2.16, 1.32 IQR 1.38, respectively, <i>p</i>-value = 0.032). When looking at the MII/FSH ratio, the normal weight group showed a median value of 3.3 with an IQR of 4.0, the overweight group showed a median value of 2.3 with an IQR of 1.9, and the obese group had a median value of 2.6 with an IQR of 2.8. Those data were statistically significant (<i>p</i>-value = 0.049).</p><p><strong>Conclusion: </strong>These results emphasize the importance of considering weight status in fertility assessment and treatment planning.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1461132"},"PeriodicalIF":4.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-09-30eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1449015
Anna Trengove, Lilith M Caballero Aguilar, Claudia Di Bella, Carmine Onofrillo, Serena Duchi, Andrea J O'Connor
Articular cartilage injuries in the knee can lead to post-traumatic osteoarthritis if untreated, causing debilitating problems later in life. Standard surgical treatments fail to ensure long lasting repair of damaged cartilage, often resulting in fibrotic tissue. While there is a vast amount of research into cartilage regeneration, integrating engineered implants with cartilage remains a challenge. As cartilage is a load bearing tissue, it is imperative to evaluate tissue repair strategies and their ability to integrate under mechanical loading. This work established a dynamically loaded ex vivo model of cartilage repair using human cartilage explants. The model was used to assess the efficacy of a stem cell therapy delivered in a bioadhesive hydrogel comprised of photocrosslinkable gelatin methacryloyl (GelMA) and microbial transglutaminase to repair the model defect. Extensive neocartilage production and integration were observed via histology and immunohistochemistry after 28 days chondrogenic culture. Analysis of culture media allowed monitoring of glycosaminoglycan and type II collagen production over time. A mechanical assessment of integration via a push out test showed a 15-fold increase in push out strength over the culture duration. The model was successful in exhibiting robust chondrogenesis with transglutaminase or without, and under both culture conditions. The work also highlights several limitations of ex vivo models and challenges of working with bioreactors that must be overcome to increase their utility. This ex vivo model has the potential to delay the need for costly pre-clinical studies and provide a more nuanced assessment of cartilage repair strategies than is possible in vivo.
膝关节软骨损伤如不及时治疗,可能会导致创伤后骨关节炎,给患者日后的生活带来严重影响。标准的手术治疗无法确保对受损软骨进行长期持久的修复,往往会导致纤维组织的形成。虽然对软骨再生进行了大量研究,但将工程植入物与软骨结合仍是一项挑战。软骨是一种承重组织,因此必须评估组织修复策略及其在机械负荷下的整合能力。这项研究利用人体软骨外植体建立了动态加载的软骨修复体外模型。该模型用于评估干细胞疗法在由光交联甲基丙烯酰明胶(GelMA)和微生物转谷氨酰胺酶组成的生物粘性水凝胶中的疗效,以修复模型缺损。经过 28 天的软骨培养后,通过组织学和免疫组化观察到了广泛的新软骨生成和整合。通过对培养基的分析,可以监测糖胺聚糖和 II 型胶原蛋白随时间推移的生成情况。通过推出试验对整合进行的力学评估显示,在培养期间,推出强度增加了 15 倍。无论是否使用转谷氨酰胺酶,在两种培养条件下,该模型都能成功地表现出稳健的软骨生成。这项工作还强调了体内外模型的一些局限性以及使用生物反应器工作所面临的挑战,要提高这些模型的实用性,就必须克服这些挑战。这种体外模型有可能推迟昂贵的临床前研究,并对软骨修复策略进行比体内更细致的评估。
{"title":"A dynamically loaded <i>ex vivo</i> model to study neocartilage and integration in human cartilage repair.","authors":"Anna Trengove, Lilith M Caballero Aguilar, Claudia Di Bella, Carmine Onofrillo, Serena Duchi, Andrea J O'Connor","doi":"10.3389/fcell.2024.1449015","DOIUrl":"https://doi.org/10.3389/fcell.2024.1449015","url":null,"abstract":"<p><p>Articular cartilage injuries in the knee can lead to post-traumatic osteoarthritis if untreated, causing debilitating problems later in life. Standard surgical treatments fail to ensure long lasting repair of damaged cartilage, often resulting in fibrotic tissue. While there is a vast amount of research into cartilage regeneration, integrating engineered implants with cartilage remains a challenge. As cartilage is a load bearing tissue, it is imperative to evaluate tissue repair strategies and their ability to integrate under mechanical loading. This work established a dynamically loaded <i>ex vivo</i> model of cartilage repair using human cartilage explants. The model was used to assess the efficacy of a stem cell therapy delivered in a bioadhesive hydrogel comprised of photocrosslinkable gelatin methacryloyl (GelMA) and microbial transglutaminase to repair the model defect. Extensive neocartilage production and integration were observed via histology and immunohistochemistry after 28 days chondrogenic culture. Analysis of culture media allowed monitoring of glycosaminoglycan and type II collagen production over time. A mechanical assessment of integration via a push out test showed a 15-fold increase in push out strength over the culture duration. The model was successful in exhibiting robust chondrogenesis with transglutaminase or without, and under both culture conditions. The work also highlights several limitations of <i>ex vivo</i> models and challenges of working with bioreactors that must be overcome to increase their utility. This <i>ex vivo</i> model has the potential to delay the need for costly pre-clinical studies and provide a more nuanced assessment of cartilage repair strategies than is possible <i>in vivo</i>.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1449015"},"PeriodicalIF":4.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-09-30eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1471216
Laura K Hillert-Richter, Corinna König, Nikita V Ivanisenko, Dirk Reinhold, Inna N Lavrik
Death receptor (DR) networks are controlled by the assembly of the Death-Inducing Signaling Complex (DISC) and complex II. The family of small molecules FLIPins (FLIP interactors) were developed to target the caspase-8/c-FLIPL heterodimer. FLIPin compounds were shown to promote apoptosis and caspase-8 activation at the DISC upon stimulation with death ligands (DLs) such as CD95L and TRAIL. To further investigate the role of FLIPin compounds in the DL-mediated cell death response, we analyzed their effects in combination with DLs and SMAC mimetics treatment. FLIPins were found to enhance cell viability loss and cell death induced by DL and SMAC mimetics in acute myeloid leukemia (AML), colon and pancreatic cancer cells. FLIPins enhanced both DL/BV6-induced apoptosis and DL/BV6/zVAD-fmk-induced necroptosis via an increase in complex II formation. Our results indicate that targeting the caspase-8/c-FLIPL heterodimer plays a prominent role in enhancing cell death induced by co-stimulation of DL/SMAC mimetics and opens new therapeutic strategies for targeting DR networks.
{"title":"Targeting caspase-8/c-FLIP<sub>L</sub> heterodimer in complex II promotes DL-mediated cell death.","authors":"Laura K Hillert-Richter, Corinna König, Nikita V Ivanisenko, Dirk Reinhold, Inna N Lavrik","doi":"10.3389/fcell.2024.1471216","DOIUrl":"https://doi.org/10.3389/fcell.2024.1471216","url":null,"abstract":"<p><p>Death receptor (DR) networks are controlled by the assembly of the Death-Inducing Signaling Complex (DISC) and complex II. The family of small molecules FLIPins (FLIP interactors) were developed to target the caspase-8/c-FLIP<sub>L</sub> heterodimer. FLIPin compounds were shown to promote apoptosis and caspase-8 activation at the DISC upon stimulation with death ligands (DLs) such as CD95L and TRAIL. To further investigate the role of FLIPin compounds in the DL-mediated cell death response, we analyzed their effects in combination with DLs and SMAC mimetics treatment. FLIPins were found to enhance cell viability loss and cell death induced by DL and SMAC mimetics in acute myeloid leukemia (AML), colon and pancreatic cancer cells. FLIPins enhanced both DL/BV6-induced apoptosis and DL/BV6/zVAD-fmk-induced necroptosis via an increase in complex II formation. Our results indicate that targeting the caspase-8/c-FLIP<sub>L</sub> heterodimer plays a prominent role in enhancing cell death induced by co-stimulation of DL/SMAC mimetics and opens new therapeutic strategies for targeting DR networks.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1471216"},"PeriodicalIF":4.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer has become an important public health problem worldwide, and there is currently a lack of effective treatment and prevention strategies. Natural plant active ingredients have been proven to be a safe and highly promising method for preventing and treating cancer. It has been found that diallyl trisulfide have anticancer effects in multiple types of cancer via inhibiting cancer proliferation, enhancing chemotherapy sensitivity, inducing apoptosis/autophagy, suppressing invasion/migration, regulating microenvironment. With the deepening of research on new strategies for cancer prevention and treatment, the role of diallyl trisulfides in cancers occurrence, prognosis, and drug resistance is also receiving increasing attention. In order to better understand the relationship between diallyl trisulfides and various cancer, as well as the role and mechanism of diallyl trisulfides in cancer prevention and treatment, we briefly summarized the role and function of diallyl trisulfide in cancers.
{"title":"The potential of diallyl trisulfide for cancer prevention and treatment, with mechanism insights.","authors":"Ling Lu, Zihan Gao, Jiajia Song, Longtao Jin, Zhaofeng Liang","doi":"10.3389/fcell.2024.1450836","DOIUrl":"https://doi.org/10.3389/fcell.2024.1450836","url":null,"abstract":"<p><p>Cancer has become an important public health problem worldwide, and there is currently a lack of effective treatment and prevention strategies. Natural plant active ingredients have been proven to be a safe and highly promising method for preventing and treating cancer. It has been found that diallyl trisulfide have anticancer effects in multiple types of cancer via inhibiting cancer proliferation, enhancing chemotherapy sensitivity, inducing apoptosis/autophagy, suppressing invasion/migration, regulating microenvironment. With the deepening of research on new strategies for cancer prevention and treatment, the role of diallyl trisulfides in cancers occurrence, prognosis, and drug resistance is also receiving increasing attention. In order to better understand the relationship between diallyl trisulfides and various cancer, as well as the role and mechanism of diallyl trisulfides in cancer prevention and treatment, we briefly summarized the role and function of diallyl trisulfide in cancers.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1450836"},"PeriodicalIF":4.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-09-27eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1492867
Ming-Chuan Hsu
{"title":"Editorial: Breakthroughs in tumor stem cell research.","authors":"Ming-Chuan Hsu","doi":"10.3389/fcell.2024.1492867","DOIUrl":"https://doi.org/10.3389/fcell.2024.1492867","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1492867"},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-09-27eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1493626
F Pagliari, S Di Franco, L Tirinato
{"title":"Editorial: Lipid alterations in cancer development, resistance and recurrence.","authors":"F Pagliari, S Di Franco, L Tirinato","doi":"10.3389/fcell.2024.1493626","DOIUrl":"https://doi.org/10.3389/fcell.2024.1493626","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1493626"},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-09-27eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1451274
Travis H Stracker
The transcription factor p53 (encoded by TP53) plays diverse roles in human development and disease. While best known for its role in tumor suppression, p53 signaling also influences mammalian development by triggering cell fate decisions in response to a wide variety of stresses. After over 4 decades of study, a new pathway that triggers p53 activation in response to mitotic delays was recently identified. Termed the mitotic surveillance or mitotic stopwatch pathway, the USP28 and 53BP1 proteins activate p53 in response to delayed mitotic progression to control cell fate and promote genomic stability. In this Minireview, I discuss its identification, potential roles in neurodevelopmental disorders and cancer, as well as explore outstanding questions about its function, regulation and potential use as a biomarker for anti-mitotic therapies.
{"title":"Regulation of p53 by the mitotic surveillance/stopwatch pathway: implications in neurodevelopment and cancer.","authors":"Travis H Stracker","doi":"10.3389/fcell.2024.1451274","DOIUrl":"https://doi.org/10.3389/fcell.2024.1451274","url":null,"abstract":"<p><p>The transcription factor p53 (encoded by <i>TP53</i>) plays diverse roles in human development and disease. While best known for its role in tumor suppression, p53 signaling also influences mammalian development by triggering cell fate decisions in response to a wide variety of stresses. After over 4 decades of study, a new pathway that triggers p53 activation in response to mitotic delays was recently identified. Termed the mitotic surveillance or mitotic stopwatch pathway, the USP28 and 53BP1 proteins activate p53 in response to delayed mitotic progression to control cell fate and promote genomic stability. In this Minireview, I discuss its identification, potential roles in neurodevelopmental disorders and cancer, as well as explore outstanding questions about its function, regulation and potential use as a biomarker for anti-mitotic therapies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1451274"},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-09-27eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1483345
John H Henson, Gabriela Reyes, Nina T Lo, Karina Herrera, Quenelle W McKim, Hannah Y Herzon, Maritriny Galvez-Ceron, Alexandra E Hershey, Rachael S Kim, Charles B Shuster
Our knowledge of the assembly and dynamics of the cytokinetic contractile ring (CR) in animal cells remains incomplete. We have previously used super-resolution light microscopy and platinum replica electron microscopy to elucidate the ultrastructural organization of the CR in first division sea urchin embryos. To date, our studies indicate that the CR initiates as an equatorial band of clusters containing myosin II, actin, septin and anillin, which then congress over time into patches which coalesce into a linear array characteristic of mature CRs. In the present study, we applied super-resolution interferometric photoactivated localization microscopy to confirm the existence of septin filament-like structures in the developing CR, demonstrate the close associations between septin2, anillin, and myosin II in the CR, as well as to show that septin2 appears consistently submembranous, whereas anillin is more widely distributed in the early CR. We also provide evidence that the major actin cross-linking protein α-actinin only associates with the linearized, late-stage CR and not with the early CR clusters, providing further support to the idea that α-actinin associates with actomyosin structures under tension and can serve as a counterbalance. In addition, we show that inhibition of actomyosin contraction does not stop the assembly of the early CR clusters but does arrest the progression of these structures to the aligned arrays required for functional cytokinesis. Taken together our results reinforce and extend our model for a cluster to patch to linear structural progression of the CR in sea urchin embryos and highlight the evolutionary relationships with cytokinesis in fission yeast.
{"title":"Cytokinetic contractile ring structural progression in an early embryo: positioning of scaffolding proteins, recruitment of α-actinin, and effects of myosin II inhibition.","authors":"John H Henson, Gabriela Reyes, Nina T Lo, Karina Herrera, Quenelle W McKim, Hannah Y Herzon, Maritriny Galvez-Ceron, Alexandra E Hershey, Rachael S Kim, Charles B Shuster","doi":"10.3389/fcell.2024.1483345","DOIUrl":"https://doi.org/10.3389/fcell.2024.1483345","url":null,"abstract":"<p><p>Our knowledge of the assembly and dynamics of the cytokinetic contractile ring (CR) in animal cells remains incomplete. We have previously used super-resolution light microscopy and platinum replica electron microscopy to elucidate the ultrastructural organization of the CR in first division sea urchin embryos. To date, our studies indicate that the CR initiates as an equatorial band of clusters containing myosin II, actin, septin and anillin, which then congress over time into patches which coalesce into a linear array characteristic of mature CRs. In the present study, we applied super-resolution interferometric photoactivated localization microscopy to confirm the existence of septin filament-like structures in the developing CR, demonstrate the close associations between septin2, anillin, and myosin II in the CR, as well as to show that septin2 appears consistently submembranous, whereas anillin is more widely distributed in the early CR. We also provide evidence that the major actin cross-linking protein α-actinin only associates with the linearized, late-stage CR and not with the early CR clusters, providing further support to the idea that α-actinin associates with actomyosin structures under tension and can serve as a counterbalance. In addition, we show that inhibition of actomyosin contraction does not stop the assembly of the early CR clusters but does arrest the progression of these structures to the aligned arrays required for functional cytokinesis. Taken together our results reinforce and extend our model for a cluster to patch to linear structural progression of the CR in sea urchin embryos and highlight the evolutionary relationships with cytokinesis in fission yeast.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1483345"},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}