首页 > 最新文献

Cells最新文献

英文 中文
Omega-3 Fatty Acids and Neuroinflammation in Depression: Targeting Damage-Associated Molecular Patterns and Neural Biomarkers. 欧米茄-3 脂肪酸与抑郁症的神经炎症:针对损伤相关分子模式和神经生物标志物。
IF 8.3 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-29 DOI: 10.3390/cells13211791
Ikbal Andrian Malau, Jane Pei-Chen Chang, Yi-Wen Lin, Cheng-Chen Chang, Wei-Che Chiu, Kuan-Pin Su

Major Depressive Disorder (MDD) is a prevalent mental health condition with a complex pathophysiology involving neuroinflammation, neurodegeneration, and disruptions in neuronal and glial cell function. Microglia, the innate immune cells of the central nervous system, release inflammatory cytokines in response to pathological changes associated with MDD. Damage-associated molecular patterns (DAMPs) act as alarms, triggering microglial activation and subsequent inflammatory cytokine release. This review examines the cellular mechanisms underlying MDD pathophysiology, focusing on the lipid-mediated modulation of neuroinflammation. We explore the intricate roles of microglia and astrocytes in propagating inflammatory cascades and discuss how these processes affect neuronal integrity at the cellular level. Central to our analysis are three key molecules: High Mobility Group Box 1 (HMGB1) and S100 Calcium Binding Protein β (S100β) as alarmins, and Neuron-Specific Enolase (NSE) as an indicator of neuronal stress. We present evidence from in vitro and ex vivo studies demonstrating how these molecules reflect and contribute to the neuroinflammatory milieu characteristic of MDD. The review then explores the potential of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) as neuroinflammation modulators, examining their effects on microglial activation, cytokine production, and neuronal resilience in cellular models of depression. We critically analyze experimental data on how ω-3 PUFA supplementation influences the expression and release of HMGB1, S100β, and NSE in neuronal and glial cultures. By integrating findings from lipidomic and cellular neurobiology, this review aims to elucidate the mechanisms by which ω-3 PUFAs may exert their antidepressant effects through modulation of neuroinflammatory markers. These insights contribute to our understanding of lipid-mediated neuroprotection in MDD and may inform the development of targeted, lipid-based therapies for both depression and neurodegenerative disorders.

重度抑郁症(MDD)是一种常见的精神疾病,其病理生理学十分复杂,涉及神经炎症、神经变性以及神经元和神经胶质细胞功能紊乱。中枢神经系统的先天性免疫细胞小胶质细胞会释放炎性细胞因子,以应对与 MDD 相关的病理变化。损伤相关分子模式(DAMPs)就像警报器一样,会触发小胶质细胞的活化并随之释放炎性细胞因子。本综述探讨了 MDD 病理生理学的细胞机制,重点是脂质介导的神经炎症调节。我们探讨了小胶质细胞和星形胶质细胞在传播炎症级联中的复杂作用,并讨论了这些过程如何在细胞水平上影响神经元的完整性。我们分析的核心是三个关键分子:高迁移率基团框 1(HMGB1)和 S100 钙结合蛋白 β(S100β)是警报蛋白,而神经元特异性烯醇化酶(NSE)则是神经元应激的指标。我们介绍了体外和体内研究的证据,证明这些分子是如何反映并促成 MDD 特征性神经炎症环境的。综述随后探讨了欧米伽-3 多不饱和脂肪酸(ω-3 PUFAs)作为神经炎症调节剂的潜力,研究了它们在抑郁症细胞模型中对小胶质细胞活化、细胞因子产生和神经元恢复力的影响。我们认真分析了补充ω-3 PUFA如何影响神经元和神经胶质细胞培养物中HMGB1、S100β和NSE的表达和释放的实验数据。本综述综合了脂质组学和细胞神经生物学的研究结果,旨在阐明ω-3 PUFAs通过调节神经炎症标记物发挥抗抑郁作用的机制。这些见解有助于我们理解脂质介导的多发性抑郁症神经保护作用,并为开发治疗抑郁症和神经退行性疾病的基于脂质的靶向疗法提供参考。
{"title":"Omega-3 Fatty Acids and Neuroinflammation in Depression: Targeting Damage-Associated Molecular Patterns and Neural Biomarkers.","authors":"Ikbal Andrian Malau, Jane Pei-Chen Chang, Yi-Wen Lin, Cheng-Chen Chang, Wei-Che Chiu, Kuan-Pin Su","doi":"10.3390/cells13211791","DOIUrl":"10.3390/cells13211791","url":null,"abstract":"<p><p>Major Depressive Disorder (MDD) is a prevalent mental health condition with a complex pathophysiology involving neuroinflammation, neurodegeneration, and disruptions in neuronal and glial cell function. Microglia, the innate immune cells of the central nervous system, release inflammatory cytokines in response to pathological changes associated with MDD. Damage-associated molecular patterns (DAMPs) act as alarms, triggering microglial activation and subsequent inflammatory cytokine release. This review examines the cellular mechanisms underlying MDD pathophysiology, focusing on the lipid-mediated modulation of neuroinflammation. We explore the intricate roles of microglia and astrocytes in propagating inflammatory cascades and discuss how these processes affect neuronal integrity at the cellular level. Central to our analysis are three key molecules: High Mobility Group Box 1 (HMGB1) and S100 Calcium Binding Protein β (S100β) as alarmins, and Neuron-Specific Enolase (NSE) as an indicator of neuronal stress. We present evidence from in vitro and ex vivo studies demonstrating how these molecules reflect and contribute to the neuroinflammatory milieu characteristic of MDD. The review then explores the potential of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) as neuroinflammation modulators, examining their effects on microglial activation, cytokine production, and neuronal resilience in cellular models of depression. We critically analyze experimental data on how ω-3 PUFA supplementation influences the expression and release of HMGB1, S100β, and NSE in neuronal and glial cultures. By integrating findings from lipidomic and cellular neurobiology, this review aims to elucidate the mechanisms by which ω-3 PUFAs may exert their antidepressant effects through modulation of neuroinflammatory markers. These insights contribute to our understanding of lipid-mediated neuroprotection in MDD and may inform the development of targeted, lipid-based therapies for both depression and neurodegenerative disorders.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603253","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}
引用次数: 0
Low Iron Diet Improves Clinical Arthritis in the Mouse Model of Collagen-Induced Arthritis. 低铁饮食可改善胶原蛋白诱发关节炎小鼠模型的临床关节炎症状
IF 8.3 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-29 DOI: 10.3390/cells13211792
Godehard A Scholz, Sisi Xie, Tasneem Arsiwala, Daniel Guggisberg, Monique Vogel, Martin Bachmann, Burkhard Möller
<p><p><b>Background:</b> In response to inflammation, the absorption of nutritional iron is restricted. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). <b>Methods:</b> Six- to eight-week-old male DBA/1 mice were fed either a normal (51 mg/kg) or a low iron diet (5 mg/kg) starting four weeks before the first immunization. From day 4 after the second collagen booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. Concentrations of mouse anti-bovine and anti-mouse collagen type 2 IgG antibodies were measured by ELISA; blood cell counts were performed and mediators of inflammation, tissue matrix degradation, oxygenation and oxidative stress were measured in the mouse sera of both diet groups at the end of the experiment by bead-based multiplex assay. Fe<sup>2+</sup>, Fe<sup>3+</sup>, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) were quantified in whole paw tissue by ELISA. Quantitative PCR was performed in the tissues for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to compare cross-sectional data. Nonlinear regression models were used for longitudinal data of the arthritis scores. <b>Results:</b> Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (<i>p</i> < 0.001). The immune response against bovine and mouse type 2 collagen did not differ between the two diet groups. Mice fed a low iron diet exhibited significantly lower serum levels of tissue inhibitor of metalloproteinase-1 (TIMP-1), a central regulator of inflammation and tissue matrix degradation (<i>p</i> < 0.05). In addition, a low iron diet led to a significant reduction in red blood cell indices, indicating restricted iron uptake and latent iron deficiency, but had no effect on hemoglobin concentrations or red blood cell counts. There were no differences between the dietary groups in Fe<sup>2+</sup> or Fe<sup>3+</sup> content in the paws. Based on calculation of the GSH/GSSG ratio and high MDA levels, high oxidative stress and lipid peroxidation were likewise detected in the paws of both diet groups of mice. Consequently, no differences associated with gene expression of key regulators of iron metabolism and ferroptosis could be detected between the paws of both diet groups. <b>Conclusions:</b> Restricted dietary iron intake alleviates immune-mediated inflammation in CIA without causing anemia. This finding suggests a promising option for dietary treatment of arthritis in inflammation. The underlying mechanism causing reduced arthritis may be linked to the complex regulatory network of TIMP-1 and appears to be indepe
背景:在炎症反应中,营养铁的吸收受到限制。由于铁的存在和吸收在慢性炎症中的病理生理意义尚不清楚,我们在胶原诱导的关节炎(CIA)小鼠模型中测试了低铁饮食对关节炎临床病程的影响。研究方法从第一次免疫前四周开始,给六到八周大的雄性 DBA/1 小鼠喂食正常饮食(51 毫克/千克)或低铁饮食(5 毫克/千克)。从第 25 天注射第二次胶原蛋白加强剂后的第 4 天起,使用标准临床关节炎评分法定期监测关节炎的发展情况,直至实验结束(第 34 天)。实验结束时,用酶联免疫吸附法测定小鼠抗牛和抗小鼠 2 型胶原蛋白 IgG 抗体的浓度;进行血细胞计数,并用珠式多重检测法测定两种饮食组小鼠血清中的炎症、组织基质降解、氧和氧化应激介质。通过酶联免疫吸附试验(ELISA)对整个爪组织中的Fe2+、Fe3+、氧化型和还原型谷胱甘肽(GSH和GSSG)以及丙二醛(MDA)进行量化。对组织中的谷胱甘肽过氧化物酶 4 及其他铁代谢和铁变态反应的关键调节基因进行了定量 PCR 检测。我们使用非参数检验来比较横截面数据。非线性回归模型用于关节炎评分的纵向数据。结果显示与喂食正常铁质食物的小鼠相比,喂食低铁食物的小鼠关节炎病程明显较轻(p < 0.001)。两组小鼠对牛和小鼠 2 型胶原蛋白的免疫反应没有差异。喂食低铁饮食的小鼠血清中金属蛋白酶组织抑制剂-1(TIMP-1)的水平明显较低(p < 0.05),TIMP-1是炎症和组织基质降解的核心调节因子。此外,低铁饮食导致红细胞指数显著下降,表明铁吸收受限和潜在缺铁,但对血红蛋白浓度或红细胞计数没有影响。不同饮食组爪子中的 Fe2+ 或 Fe3+ 含量没有差异。根据 GSH/GSSG 比率和高 MDA 水平的计算结果,两组饮食的小鼠爪子中同样检测到了高氧化应激和脂质过氧化反应。因此,两个饮食组的小鼠爪子在铁代谢和铁变态反应关键调节因子的基因表达方面没有发现差异。结论限制饮食中铁的摄入量可减轻 CIA 免疫介导的炎症,但不会导致贫血。这一发现为炎症性关节炎的饮食治疗提供了一种很有前景的选择。导致关节炎减轻的根本机制可能与 TIMP-1 的复杂调控网络有关,而且似乎与滑膜组织中的局部铁水平、氧化应激和铁变态反应无关。
{"title":"Low Iron Diet Improves Clinical Arthritis in the Mouse Model of Collagen-Induced Arthritis.","authors":"Godehard A Scholz, Sisi Xie, Tasneem Arsiwala, Daniel Guggisberg, Monique Vogel, Martin Bachmann, Burkhard Möller","doi":"10.3390/cells13211792","DOIUrl":"10.3390/cells13211792","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; In response to inflammation, the absorption of nutritional iron is restricted. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). &lt;b&gt;Methods:&lt;/b&gt; Six- to eight-week-old male DBA/1 mice were fed either a normal (51 mg/kg) or a low iron diet (5 mg/kg) starting four weeks before the first immunization. From day 4 after the second collagen booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. Concentrations of mouse anti-bovine and anti-mouse collagen type 2 IgG antibodies were measured by ELISA; blood cell counts were performed and mediators of inflammation, tissue matrix degradation, oxygenation and oxidative stress were measured in the mouse sera of both diet groups at the end of the experiment by bead-based multiplex assay. Fe&lt;sup&gt;2+&lt;/sup&gt;, Fe&lt;sup&gt;3+&lt;/sup&gt;, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) were quantified in whole paw tissue by ELISA. Quantitative PCR was performed in the tissues for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to compare cross-sectional data. Nonlinear regression models were used for longitudinal data of the arthritis scores. &lt;b&gt;Results:&lt;/b&gt; Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). The immune response against bovine and mouse type 2 collagen did not differ between the two diet groups. Mice fed a low iron diet exhibited significantly lower serum levels of tissue inhibitor of metalloproteinase-1 (TIMP-1), a central regulator of inflammation and tissue matrix degradation (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). In addition, a low iron diet led to a significant reduction in red blood cell indices, indicating restricted iron uptake and latent iron deficiency, but had no effect on hemoglobin concentrations or red blood cell counts. There were no differences between the dietary groups in Fe&lt;sup&gt;2+&lt;/sup&gt; or Fe&lt;sup&gt;3+&lt;/sup&gt; content in the paws. Based on calculation of the GSH/GSSG ratio and high MDA levels, high oxidative stress and lipid peroxidation were likewise detected in the paws of both diet groups of mice. Consequently, no differences associated with gene expression of key regulators of iron metabolism and ferroptosis could be detected between the paws of both diet groups. &lt;b&gt;Conclusions:&lt;/b&gt; Restricted dietary iron intake alleviates immune-mediated inflammation in CIA without causing anemia. This finding suggests a promising option for dietary treatment of arthritis in inflammation. The underlying mechanism causing reduced arthritis may be linked to the complex regulatory network of TIMP-1 and appears to be indepe","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603186","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}
引用次数: 0
Molecular and Cellular Effects of Microplastics and Nanoplastics: Focus on Inflammation and Senescence. 微塑料和纳米塑料的分子和细胞效应:关注炎症和衰老。
IF 8.3 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-29 DOI: 10.3390/cells13211788
Faiza Mahmud, Drishty B Sarker, Jonathan A Jocelyn, Qing-Xiang Amy Sang

Microplastics and nanoplastics (MNPs) are ubiquitous environmental contaminants. Their prevalence, persistence, and increasing industrial production have led to questions about their long-term impact on human and animal health. This narrative review describes the effects of MNPs on oxidative stress, inflammation, and aging. Exposure to MNPs leads to increased production of reactive oxygen species (ROS) across multiple experimental models, including cell lines, organoids, and animal systems. ROS can cause damage to cellular macromolecules such as DNA, proteins, and lipids. Direct interaction between MNPs and immune cells or an indirect result of oxidative stress-mediated cellular damage may lead to increased production of pro-inflammatory cytokines throughout different MNP-exposure conditions. This inflammatory response is a common feature in the pathogenesis of neurodegenerative, cardiovascular, and other age-related diseases. MNPs also act as cell senescence inducers by promoting mitochondrial dysfunction, impairing autophagy, and activating DNA damage responses, exacerbating cellular aging altogether. Increased senescence of reproductive cells and transfer of MNPs/induced damages from parents to offspring in animals further corroborates the transgenerational health risks of the tiny particles. This review aims to provoke a deeper investigation into the notorious effects these pervasive particles may have on human well-being and longevity.

微塑料和纳米塑料(MNPs)是无处不在的环境污染物。它们的普遍性、持久性和不断增加的工业生产使人们对其对人类和动物健康的长期影响产生了疑问。本综述介绍了 MNPs 对氧化应激、炎症和衰老的影响。暴露于 MNPs 会导致多种实验模型中活性氧(ROS)的产生增加,包括细胞系、有机体和动物系统。ROS 可对 DNA、蛋白质和脂质等细胞大分子造成损伤。在不同的 MNP 暴露条件下,MNP 与免疫细胞之间的直接相互作用或氧化应激介导的细胞损伤的间接结果可能会导致促炎细胞因子的产生增加。这种炎症反应是神经退行性疾病、心血管疾病和其他老年相关疾病发病机制中的一个共同特征。MNP 还可通过促进线粒体功能障碍、损害自噬和激活 DNA 损伤反应来诱导细胞衰老,从而全面加剧细胞衰老。生殖细胞衰老的加剧以及 MNPs/诱导的损伤从父母转移到动物的后代,进一步证实了微小颗粒的跨代健康风险。本综述旨在促使人们更深入地研究这些无处不在的微粒可能对人类福祉和寿命产生的恶名昭彰的影响。
{"title":"Molecular and Cellular Effects of Microplastics and Nanoplastics: Focus on Inflammation and Senescence.","authors":"Faiza Mahmud, Drishty B Sarker, Jonathan A Jocelyn, Qing-Xiang Amy Sang","doi":"10.3390/cells13211788","DOIUrl":"10.3390/cells13211788","url":null,"abstract":"<p><p>Microplastics and nanoplastics (MNPs) are ubiquitous environmental contaminants. Their prevalence, persistence, and increasing industrial production have led to questions about their long-term impact on human and animal health. This narrative review describes the effects of MNPs on oxidative stress, inflammation, and aging. Exposure to MNPs leads to increased production of reactive oxygen species (ROS) across multiple experimental models, including cell lines, organoids, and animal systems. ROS can cause damage to cellular macromolecules such as DNA, proteins, and lipids. Direct interaction between MNPs and immune cells or an indirect result of oxidative stress-mediated cellular damage may lead to increased production of pro-inflammatory cytokines throughout different MNP-exposure conditions. This inflammatory response is a common feature in the pathogenesis of neurodegenerative, cardiovascular, and other age-related diseases. MNPs also act as cell senescence inducers by promoting mitochondrial dysfunction, impairing autophagy, and activating DNA damage responses, exacerbating cellular aging altogether. Increased senescence of reproductive cells and transfer of MNPs/induced damages from parents to offspring in animals further corroborates the transgenerational health risks of the tiny particles. This review aims to provoke a deeper investigation into the notorious effects these pervasive particles may have on human well-being and longevity.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603213","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}
引用次数: 0
Therapeutic Potential of Stearoyl-CoA Desaturase1 (SCD1) in Modulating the Effects of Fatty Acids on Osteoporosis. 硬脂酰-CoA 不饱和酶 1 (SCD1) 在调节脂肪酸对骨质疏松症影响方面的治疗潜力
IF 8.3 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-28 DOI: 10.3390/cells13211781
Young-Jin Seo, Jin-Ho Park, June-Ho Byun

Osteoporosis is a common skeletal disease, primarily associated with aging, that results from decreased bone density and bone volume. This reduction significantly increases the risk of fractures in osteoporosis patients compared to individuals with normal bone density. Additionally, the bone regeneration process in these patients is slow, making complete healing difficult. Along with the decline in bone volume and density, osteoporosis is characterized by an increase in marrow adipose tissue (MAT), which is fat within the bone. In this altered bone microenvironment, osteoblasts are influenced by various factors secreted by adipocytes. Notably, saturated fatty acids promote osteoclast activity, inhibit osteoblast differentiation, and induce apoptosis, further reducing osteoblast formation. In contrast, monounsaturated fatty acids inhibit osteoclast formation and mitigate the apoptosis caused by saturated fatty acids. Leveraging these properties, we aimed to investigate the effects of overexpressing stearoyl-CoA desaturase 1 (SCD1), an enzyme that converts saturated fatty acids into monounsaturated fatty acids, on osteogenic differentiation and bone regeneration in both in vivo and in vitro models. Through this novel approach, we seek to develop a stem cell-based therapeutic strategy that harnesses SCD1 to improve bone regeneration in the adipocyte-rich osteoporotic environment.

骨质疏松症是一种常见的骨骼疾病,主要与衰老有关,是骨密度和骨量降低的结果。与骨密度正常的人相比,骨密度的降低大大增加了骨质疏松症患者骨折的风险。此外,这些患者的骨再生过程缓慢,很难完全愈合。随着骨量和骨密度的下降,骨质疏松症的特点是骨髓脂肪组织(MAT)的增加,即骨内脂肪的增加。在这种改变了的骨微环境中,成骨细胞受到脂肪细胞分泌的各种因素的影响。值得注意的是,饱和脂肪酸会促进破骨细胞的活性、抑制成骨细胞分化并诱导细胞凋亡,从而进一步减少成骨细胞的形成。相反,单不饱和脂肪酸可抑制破骨细胞的形成,并减轻饱和脂肪酸引起的细胞凋亡。利用这些特性,我们旨在研究在体内和体外模型中过表达硬脂酰-CoA 去饱和酶 1(SCD1)(一种将饱和脂肪酸转化为单不饱和脂肪酸的酶)对成骨分化和骨再生的影响。通过这种新方法,我们试图开发一种基于干细胞的治疗策略,利用SCD1改善富含脂肪细胞的骨质疏松症环境中的骨再生。
{"title":"Therapeutic Potential of Stearoyl-CoA Desaturase1 (SCD1) in Modulating the Effects of Fatty Acids on Osteoporosis.","authors":"Young-Jin Seo, Jin-Ho Park, June-Ho Byun","doi":"10.3390/cells13211781","DOIUrl":"10.3390/cells13211781","url":null,"abstract":"<p><p>Osteoporosis is a common skeletal disease, primarily associated with aging, that results from decreased bone density and bone volume. This reduction significantly increases the risk of fractures in osteoporosis patients compared to individuals with normal bone density. Additionally, the bone regeneration process in these patients is slow, making complete healing difficult. Along with the decline in bone volume and density, osteoporosis is characterized by an increase in marrow adipose tissue (MAT), which is fat within the bone. In this altered bone microenvironment, osteoblasts are influenced by various factors secreted by adipocytes. Notably, saturated fatty acids promote osteoclast activity, inhibit osteoblast differentiation, and induce apoptosis, further reducing osteoblast formation. In contrast, monounsaturated fatty acids inhibit osteoclast formation and mitigate the apoptosis caused by saturated fatty acids. Leveraging these properties, we aimed to investigate the effects of overexpressing stearoyl-CoA desaturase 1 (SCD1), an enzyme that converts saturated fatty acids into monounsaturated fatty acids, on osteogenic differentiation and bone regeneration in both in vivo and in vitro models. Through this novel approach, we seek to develop a stem cell-based therapeutic strategy that harnesses SCD1 to improve bone regeneration in the adipocyte-rich osteoporotic environment.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603453","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}
引用次数: 0
Eosinophil-Basophil/Lymphocyte (EB/LR) and Eosinophil-Basophil-Platelet/Lymphocyte (EBP/LR) Ratios Could Serve as Useful Additional Markers for Assessing the Severity of Wasp Allergic Reactions. 嗜酸性粒细胞-嗜碱性粒细胞/淋巴细胞(EB/LR)和嗜酸性粒细胞-嗜碱性粒细胞-血小板/淋巴细胞(EBP/LR)比率可作为评估黄蜂过敏反应严重程度的有用附加标记。
IF 8.3 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-28 DOI: 10.3390/cells13211786
Weronika Urbańska, Łukasz Szymański, Aneta Lewicka, Martyna Ciepielak, Karolina Kostrzeńska-Sęk, Andrzej Chciałowski, Sławomir Lewicki

Wasp venom allergy can trigger severe allergic reactions, and predicting these acute responses remains challenging. This study evaluates the utility of immune system indexes, particularly the eosinophil-basophil/lymphocyte (EB/LR) and eosinophil-basophil-platelet/lymphocyte (EBP/LR) ratios, in assessing the severity of allergic reactions in patients with wasp venom allergy. A total of 61 patients with confirmed wasp venom allergy were categorized according to the Mueller scale, which classifies the severity of allergic reactions. Blood samples were analyzed for total and specific IgE levels alongside a range of hematological and biochemical parameters. This study found significant differences in the EB/LR and EBP/LR indexes between patients with mild (Mueller I-II) and severe (Mueller III-IV) allergic reactions, with higher values indicating more severe responses. However, no significant differences were observed in other immune indexes, such as the platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, and systemic inflammatory response index, as well as in additional blood parameters. These findings suggest that the EB/LR and EBP/LR ratios may serve as useful markers for predicting the severity of allergic reactions in patients with wasp venom allergy. This is the first study to establish such a link, although further research with larger cohorts is necessary to confirm these results and their potential application in clinical settings.

黄蜂毒液过敏可引发严重的过敏反应,而预测这些急性反应仍具有挑战性。本研究评估了免疫系统指标,尤其是嗜酸性粒细胞-嗜碱性粒细胞/淋巴细胞(EB/LR)和嗜酸性粒细胞-嗜碱性粒细胞-血小板/淋巴细胞(EBP/LR)比率在评估黄蜂毒过敏患者过敏反应严重程度方面的实用性。共有 61 名确诊为黄蜂毒液过敏的患者根据穆勒评分法进行了分类,该评分法对过敏反应的严重程度进行了分类。对血液样本进行了总 IgE 和特异性 IgE 水平分析,同时还分析了一系列血液学和生化参数。研究发现,轻度(穆勒 I-II)和重度(穆勒 III-IV)过敏反应患者的 EB/LR 和 EBP/LR 指数存在明显差异,数值越高表示反应越严重。然而,在其他免疫指标(如血小板与淋巴细胞比值、中性粒细胞与淋巴细胞比值、全身免疫炎症指数、全身炎症反应指数)以及其他血液参数方面没有观察到明显差异。这些研究结果表明,EB/LR 和 EBP/LR 比率可作为预测黄蜂毒液过敏患者过敏反应严重程度的有用指标。这是第一项建立这种联系的研究,尽管有必要对更大的群体进行进一步研究,以确认这些结果及其在临床环境中的潜在应用。
{"title":"Eosinophil-Basophil/Lymphocyte (EB/LR) and Eosinophil-Basophil-Platelet/Lymphocyte (EBP/LR) Ratios Could Serve as Useful Additional Markers for Assessing the Severity of Wasp Allergic Reactions.","authors":"Weronika Urbańska, Łukasz Szymański, Aneta Lewicka, Martyna Ciepielak, Karolina Kostrzeńska-Sęk, Andrzej Chciałowski, Sławomir Lewicki","doi":"10.3390/cells13211786","DOIUrl":"10.3390/cells13211786","url":null,"abstract":"<p><p>Wasp venom allergy can trigger severe allergic reactions, and predicting these acute responses remains challenging. This study evaluates the utility of immune system indexes, particularly the eosinophil-basophil/lymphocyte (EB/LR) and eosinophil-basophil-platelet/lymphocyte (EBP/LR) ratios, in assessing the severity of allergic reactions in patients with wasp venom allergy. A total of 61 patients with confirmed wasp venom allergy were categorized according to the Mueller scale, which classifies the severity of allergic reactions. Blood samples were analyzed for total and specific IgE levels alongside a range of hematological and biochemical parameters. This study found significant differences in the EB/LR and EBP/LR indexes between patients with mild (Mueller I-II) and severe (Mueller III-IV) allergic reactions, with higher values indicating more severe responses. However, no significant differences were observed in other immune indexes, such as the platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, and systemic inflammatory response index, as well as in additional blood parameters. These findings suggest that the EB/LR and EBP/LR ratios may serve as useful markers for predicting the severity of allergic reactions in patients with wasp venom allergy. This is the first study to establish such a link, although further research with larger cohorts is necessary to confirm these results and their potential application in clinical settings.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603102","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}
引用次数: 0
Islet Transplantation: Current Limitations and Challenges for Successful Outcomes. 胰岛移植:目前的局限性和成功的挑战。
IF 8.3 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-28 DOI: 10.3390/cells13211783
Allan Langlois, Michel Pinget, Laurence Kessler, Karim Bouzakri

Islet transplantation is a promising approach for treating patients with unstable T1DM. However, it is confronted with numerous obstacles throughout the various stages of the transplantation procedure. Significant progress has been made over the last 25 years in understanding the mechanisms behind the loss of functional islet mass and in developing protective strategies. Nevertheless, at present, two to three pancreases are still needed to treat a single patient, which limits the maximal number of patients who can benefit from islet transplantation. Thus, this publication provides an overview of recent scientific findings on the various issues affecting islet transplantation. Specifically, we will focus on the understanding of the mechanisms involved and the strategies developed to alleviate these problems from the isolation stage to the post-transplantation phase. Finally, we hope that this review will highlight new avenues of action, enabling us to propose pancreatic islet transplantation to a maximum number of patients with T1DM.

胰岛移植是治疗不稳定型 T1DM 患者的一种很有前景的方法。然而,在移植过程的各个阶段,它都面临着重重障碍。在过去的 25 年中,人们在了解功能性胰岛丧失的机制和开发保护策略方面取得了重大进展。然而,目前治疗一名患者仍需要两到三个胰腺,这限制了最多可从胰岛移植中获益的患者人数。因此,本刊物概述了影响胰岛移植的各种问题的最新科学发现。具体来说,我们将重点关注对相关机制的理解,以及为缓解从分离阶段到移植后阶段的这些问题而制定的策略。最后,我们希望这篇综述能突出新的行动途径,使我们能为尽可能多的 T1DM 患者提出胰岛移植建议。
{"title":"Islet Transplantation: Current Limitations and Challenges for Successful Outcomes.","authors":"Allan Langlois, Michel Pinget, Laurence Kessler, Karim Bouzakri","doi":"10.3390/cells13211783","DOIUrl":"10.3390/cells13211783","url":null,"abstract":"<p><p>Islet transplantation is a promising approach for treating patients with unstable T1DM. However, it is confronted with numerous obstacles throughout the various stages of the transplantation procedure. Significant progress has been made over the last 25 years in understanding the mechanisms behind the loss of functional islet mass and in developing protective strategies. Nevertheless, at present, two to three pancreases are still needed to treat a single patient, which limits the maximal number of patients who can benefit from islet transplantation. Thus, this publication provides an overview of recent scientific findings on the various issues affecting islet transplantation. Specifically, we will focus on the understanding of the mechanisms involved and the strategies developed to alleviate these problems from the isolation stage to the post-transplantation phase. Finally, we hope that this review will highlight new avenues of action, enabling us to propose pancreatic islet transplantation to a maximum number of patients with T1DM.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603155","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}
引用次数: 0
The TMEM63B Channel Facilitates Intestinal Motility and Enhances Proliferation of Intestinal Stem Cells. TMEM63B 通道促进肠道运动并增强肠道干细胞的增殖。
IF 8.3 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-28 DOI: 10.3390/cells13211784
Jing-Jing Tu, Yan-Yu Zang, Yun Stone Shi, Xiao-Yu Teng

The intestines are in a constant state of motion and self-renewal. The mechanical breakdown of food facilitates intestinal movement and aids digestion. It is believed that mechanical stimulation, triggered by changes in osmotic pressure within the intestines, plays a crucial role in regulating gastrointestinal motility. While TRPs and PIEZO1/2 have been identified as mechanosensitive ion channels involved in this process, there still exist numerous unidentified channels with similar properties. In this study, we demonstrate that the TMEM63B expressed in intestinal stem cells contributes to the regulation of intestinal motility and digestion. The deletion of TMEM63B in intestinal stem cells not only decelerates intestinal motility and impairs digestion but also attenuates the proliferation of intestinal stem cells and exacerbates DSS-induced colitis in mice. Collectively, our findings unveil the pivotal role of TMEM63B in governing optimal digestive function and modulating intestinal motility.

肠道处于不断运动和自我更新的状态。食物的机械分解有利于肠道运动并帮助消化。人们认为,肠道内渗透压变化引发的机械刺激在调节肠胃蠕动方面起着至关重要的作用。虽然 TRPs 和 PIEZO1/2 已被确定为参与这一过程的机械敏感性离子通道,但仍有许多具有类似特性的未确定通道存在。在这项研究中,我们证明了在肠干细胞中表达的 TMEM63B 有助于调节肠道运动和消化。在肠干细胞中缺失 TMEM63B 不仅会减慢肠道蠕动和损害消化功能,而且会减弱肠干细胞的增殖并加剧 DSS 诱导的小鼠结肠炎。总之,我们的研究结果揭示了TMEM63B在调控最佳消化功能和调节肠道运动中的关键作用。
{"title":"The TMEM63B Channel Facilitates Intestinal Motility and Enhances Proliferation of Intestinal Stem Cells.","authors":"Jing-Jing Tu, Yan-Yu Zang, Yun Stone Shi, Xiao-Yu Teng","doi":"10.3390/cells13211784","DOIUrl":"10.3390/cells13211784","url":null,"abstract":"<p><p>The intestines are in a constant state of motion and self-renewal. The mechanical breakdown of food facilitates intestinal movement and aids digestion. It is believed that mechanical stimulation, triggered by changes in osmotic pressure within the intestines, plays a crucial role in regulating gastrointestinal motility. While TRPs and PIEZO1/2 have been identified as mechanosensitive ion channels involved in this process, there still exist numerous unidentified channels with similar properties. In this study, we demonstrate that the TMEM63B expressed in intestinal stem cells contributes to the regulation of intestinal motility and digestion. The deletion of TMEM63B in intestinal stem cells not only decelerates intestinal motility and impairs digestion but also attenuates the proliferation of intestinal stem cells and exacerbates DSS-induced colitis in mice. Collectively, our findings unveil the pivotal role of TMEM63B in governing optimal digestive function and modulating intestinal motility.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603447","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}
引用次数: 0
Adipose Tissue Macrophages of the Human Fetus. 人类胎儿的脂肪组织巨噬细胞
IF 8.3 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-28 DOI: 10.3390/cells13211787
Ádám Radványi, Katalin Gyurina, Emese Rácz, Ilona Kovács, Gábor Méhes, Tamás Röszer

Prenatal adipose tissue development affects body composition and growth trajectory in early infancy, therefore it is a key determinant of adiposity in childhood. Childhood overweight and obesity increase the probability of being obese as an adult. After birth and in adulthood, adipose tissue macrophages (ATMs) are relevant constituents of the fat depots, and they are necessary for physiological adipose tissue development and fat metabolism. In obesity, however, ATMs may induce chronic inflammation leading to insulin resistance, pancreatic beta cell damage and self-immunity. Despite being relevant regulators of adipose tissue development and functioning, it is unknown whether ATMs are present in the fetal adipose tissue, therefore it is elusive whether they may affect the prenatal establishment of fat depots. Here we studied the distribution of ATMs in the human fetus between gestational weeks 17 and 38 and labeled ATMs in the early postnatal life. We found that CD45+/CD14+/CD68+ ATMs infiltrated the fetal adipose tissue from the 17th week of gestation and remained persistent throughout the second and third trimesters. ATMs were phagocytic in the neonate and expressed interleukin-6, along with other pro-inflammatory gene products. These findings show that ATMs colonize the adipose tissue early in gestation, raising the possibility that intrauterine ATM-adipocyte communication may exist, eventually allowing ATMs to affect prenatal adipose tissue development.

产前脂肪组织的发育会影响婴儿早期的身体组成和生长轨迹,因此是决定儿童期脂肪含量的关键因素。儿童期超重和肥胖会增加成年后肥胖的概率。出生后和成年后,脂肪组织巨噬细胞(ATMs)是脂肪储库的相关组成成分,它们是脂肪组织生理发育和脂肪代谢所必需的。然而,在肥胖症中,ATMs 可能会诱发慢性炎症,导致胰岛素抵抗、胰岛β细胞损伤和自身免疫。尽管ATMs是脂肪组织发育和功能的相关调控因子,但ATMs是否存在于胎儿脂肪组织中仍是未知数,因此它们是否会影响产前脂肪储藏的建立也是未知数。在此,我们研究了人类胎儿在孕 17 周至 38 周期间的 ATMs 分布情况,并对出生后早期的 ATMs 进行了标记。我们发现,CD45+/CD14+/CD68+ ATMs 从妊娠第 17 周开始渗入胎儿脂肪组织,并在妊娠第二和第三孕期持续存在。在新生儿体内,ATMs 具有吞噬功能,并表达白细胞介素-6 及其他促炎基因产物。这些研究结果表明,ATMs 在妊娠早期就定植于脂肪组织,这就提出了一种可能性,即宫内 ATM 与脂肪细胞之间可能存在交流,最终使 ATMs 影响产前脂肪组织的发育。
{"title":"Adipose Tissue Macrophages of the Human Fetus.","authors":"Ádám Radványi, Katalin Gyurina, Emese Rácz, Ilona Kovács, Gábor Méhes, Tamás Röszer","doi":"10.3390/cells13211787","DOIUrl":"10.3390/cells13211787","url":null,"abstract":"<p><p>Prenatal adipose tissue development affects body composition and growth trajectory in early infancy, therefore it is a key determinant of adiposity in childhood. Childhood overweight and obesity increase the probability of being obese as an adult. After birth and in adulthood, adipose tissue macrophages (ATMs) are relevant constituents of the fat depots, and they are necessary for physiological adipose tissue development and fat metabolism. In obesity, however, ATMs may induce chronic inflammation leading to insulin resistance, pancreatic beta cell damage and self-immunity. Despite being relevant regulators of adipose tissue development and functioning, it is unknown whether ATMs are present in the fetal adipose tissue, therefore it is elusive whether they may affect the prenatal establishment of fat depots. Here we studied the distribution of ATMs in the human fetus between gestational weeks 17 and 38 and labeled ATMs in the early postnatal life. We found that CD45<sup>+</sup>/CD14<sup>+</sup>/CD68<sup>+</sup> ATMs infiltrated the fetal adipose tissue from the 17th week of gestation and remained persistent throughout the second and third trimesters. ATMs were phagocytic in the neonate and expressed interleukin-6, along with other pro-inflammatory gene products. These findings show that ATMs colonize the adipose tissue early in gestation, raising the possibility that intrauterine ATM-adipocyte communication may exist, eventually allowing ATMs to affect prenatal adipose tissue development.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603014","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}
引用次数: 0
Prognostic Indicators for Precision Treatment of Non-Small Cell Lung Carcinoma. 非小细胞肺癌精准治疗的预后指标
IF 8.3 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-28 DOI: 10.3390/cells13211785
Damayanti Das Ghosh, Hannah McDonald, Rajeswari Dutta, Keerthana Krishnan, Jaya Thilakan, Manash K Paul, Neha Arya, Mahadev Rao, Vivek M Rangnekar

Non-small cell lung cancer (NSCLC) has established predictive biomarkers that enable decisions on treatment regimens for many patients. However, resistance to therapy is widespread. It is therefore essential to have a panel of molecular biomarkers that may help overcome therapy resistance and prevent adverse effects of treatment. We performed in silico analysis of NSCLC prognostic indicators, separately for adenocarcinomas and squamous carcinomas, by using The Cancer Genome Atlas (TCGA) and non-TCGA data sources in cBioPortal as well as UALCAN. This review describes lung cancer biology, elaborating on the key genetic alterations and specific genes responsible for resistance to conventional treatments. Importantly, we examined the mechanisms associated with resistance to immune checkpoint inhibitors. Our analysis indicated that a robust prognostic biomarker was lacking for NSCLC, especially for squamous cell carcinomas. In this work, our screening uncovered previously unidentified prognostic gene expression indicators, namely, MYO1E, FAM83 homologs, and DKK1 for adenocarcinoma, and FGA and TRIB1 for squamous cell carcinoma. It was further observed that overexpression of these genes was associated with poor prognosis. Additionally, FAM83 homolog and TRIB1 unexpectedly harbored copy number amplifications. In conclusion, this study elucidated novel prognostic indicators for NSCLC that may serve as targets to overcome therapy resistance toward improved patient outcomes.

非小细胞肺癌(NSCLC)已建立了预测性生物标志物,可帮助许多患者决定治疗方案。然而,耐药性非常普遍。因此,建立一个有助于克服耐药性和预防治疗不良反应的分子生物标记物小组至关重要。我们利用 cBioPortal 中的癌症基因组图谱(TCGA)和非 TCGA 数据源以及 UALCAN,分别对腺癌和鳞癌的 NSCLC 预后指标进行了硅分析。这篇综述描述了肺癌生物学,详细阐述了导致传统治疗耐药性的关键基因改变和特定基因。重要的是,我们研究了与免疫检查点抑制剂耐药性相关的机制。我们的分析表明,NSCLC,尤其是鳞状细胞癌缺乏强有力的预后生物标志物。在这项工作中,我们的筛选发现了以前未被发现的预后基因表达指标,即腺癌的MYO1E、FAM83同源物和DKK1,以及鳞癌的FGA和TRIB1。进一步观察发现,这些基因的过表达与预后不良有关。此外,FAM83同源基因和TRIB1意外地存在拷贝数扩增。总之,本研究阐明了NSCLC的新型预后指标,这些指标可作为克服耐药性、改善患者预后的靶点。
{"title":"Prognostic Indicators for Precision Treatment of Non-Small Cell Lung Carcinoma.","authors":"Damayanti Das Ghosh, Hannah McDonald, Rajeswari Dutta, Keerthana Krishnan, Jaya Thilakan, Manash K Paul, Neha Arya, Mahadev Rao, Vivek M Rangnekar","doi":"10.3390/cells13211785","DOIUrl":"10.3390/cells13211785","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) has established predictive biomarkers that enable decisions on treatment regimens for many patients. However, resistance to therapy is widespread. It is therefore essential to have a panel of molecular biomarkers that may help overcome therapy resistance and prevent adverse effects of treatment. We performed in silico analysis of NSCLC prognostic indicators, separately for adenocarcinomas and squamous carcinomas, by using The Cancer Genome Atlas (TCGA) and non-TCGA data sources in cBioPortal as well as UALCAN. This review describes lung cancer biology, elaborating on the key genetic alterations and specific genes responsible for resistance to conventional treatments. Importantly, we examined the mechanisms associated with resistance to immune checkpoint inhibitors. Our analysis indicated that a robust prognostic biomarker was lacking for NSCLC, especially for squamous cell carcinomas. In this work, our screening uncovered previously unidentified prognostic gene expression indicators, namely, <i>MYO1E</i>, <i>FAM83</i> homologs, and <i>DKK1</i> for adenocarcinoma, and <i>FGA</i> and <i>TRIB1</i> for squamous cell carcinoma. It was further observed that overexpression of these genes was associated with poor prognosis. Additionally, <i>FAM83</i> homolog and <i>TRIB1</i> unexpectedly harbored copy number amplifications. In conclusion, this study elucidated novel prognostic indicators for NSCLC that may serve as targets to overcome therapy resistance toward improved patient outcomes.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603412","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}
引用次数: 0
Improving the Genome Editing Efficiency of CRISPR/Cas9 in Melon and Watermelon. 提高 CRISPR/Cas9 在甜瓜和西瓜中的基因组编辑效率。
IF 8.3 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-28 DOI: 10.3390/cells13211782
Zhuanrong Wang, Lili Wan, Jian Ren, Na Zhang, Hongxia Zeng, Jiaqi Wei, Mi Tang

CRISPR/Cas9 is a powerful genome editing tool for trait improvement in various crops; however, enhancing mutation efficiency using CRISPR/Cas9 in watermelon and melon remains challenging. We designed four CRISPR systems with different sgRNA expression cassettes to target the phytoene desaturase (PDS) gene in melon. The constructed vectors were delivered to host plants using Agrobacterium-mediated transformation. Phenotypic and genotypic analyses of the edited melon seedlings revealed that the CRISPR systems with tRNA and Csy4 spacers driven by the Pol II-type promoter significantly improved mutation efficiency, reaching 25.20% and 42.82%, respectively. Notably, 78.95% of the mutations generated by the Csy4 system involved large-fragment deletions (LDs) between the two target sites. In watermelon, the Csy4 system achieved a PDS editing efficiency of 41.48%, with 71.43% of the edited seedlings showing LD between the two target sites. Sequencing analysis indicated that the edited melon seedlings exhibited heterozygous, three-allele mutation and chimeric events; the edited watermelon seedlings included 2/14 homozygous mutations. Compared to the commonly used Pol III promoter, using the Pol II promoter to drive sgRNA expression cassettes containing Csy4 showed the best improvement in CRISPR/Cas9 editing efficiency in melon; this system was also effective in watermelon.

CRISPR/Cas9是一种强大的基因组编辑工具,可用于改良各种作物的性状;然而,利用CRISPR/Cas9提高西瓜和甜瓜的突变效率仍具有挑战性。我们设计了四种带有不同 sgRNA 表达盒的 CRISPR 系统,以甜瓜中的植物烯去饱和酶(PDS)基因为靶标。利用农杆菌介导的转化技术将构建的载体传递给宿主植物。对编辑后甜瓜幼苗的表型和基因型分析表明,由Pol II型启动子驱动的带有tRNA和Csy4间隔的CRISPR系统显著提高了突变效率,分别达到25.20%和42.82%。值得注意的是,Csy4 系统产生的突变中有 78.95% 涉及两个目标位点之间的大片段缺失(LD)。在西瓜中,Csy4 系统的 PDS 编辑效率为 41.48%,71.43% 的编辑苗在两个目标位点之间出现 LD。测序分析表明,编辑后的甜瓜幼苗表现出杂合、三等位基因突变和嵌合事件;编辑后的西瓜幼苗包括 2/14 个同源突变。与常用的Pol III启动子相比,使用Pol II启动子驱动含有Csy4的sgRNA表达盒对甜瓜的CRISPR/Cas9编辑效率提高最快;该系统对西瓜也有效。
{"title":"Improving the Genome Editing Efficiency of CRISPR/Cas9 in Melon and Watermelon.","authors":"Zhuanrong Wang, Lili Wan, Jian Ren, Na Zhang, Hongxia Zeng, Jiaqi Wei, Mi Tang","doi":"10.3390/cells13211782","DOIUrl":"10.3390/cells13211782","url":null,"abstract":"<p><p>CRISPR/Cas9 is a powerful genome editing tool for trait improvement in various crops; however, enhancing mutation efficiency using CRISPR/Cas9 in watermelon and melon remains challenging. We designed four CRISPR systems with different sgRNA expression cassettes to target the phytoene desaturase (<i>PDS</i>) gene in melon. The constructed vectors were delivered to host plants using <i>Agrobacterium</i>-mediated transformation. Phenotypic and genotypic analyses of the edited melon seedlings revealed that the CRISPR systems with tRNA and Csy4 spacers driven by the Pol II-type promoter significantly improved mutation efficiency, reaching 25.20% and 42.82%, respectively. Notably, 78.95% of the mutations generated by the Csy4 system involved large-fragment deletions (LDs) between the two target sites. In watermelon, the Csy4 system achieved a <i>PDS</i> editing efficiency of 41.48%, with 71.43% of the edited seedlings showing LD between the two target sites. Sequencing analysis indicated that the edited melon seedlings exhibited heterozygous, three-allele mutation and chimeric events; the edited watermelon seedlings included 2/14 homozygous mutations. Compared to the commonly used Pol III promoter, using the Pol II promoter to drive sgRNA expression cassettes containing Csy4 showed the best improvement in CRISPR/Cas9 editing efficiency in melon; this system was also effective in watermelon.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603130","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}
引用次数: 0
期刊
Cells
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1