Eva Tvrdá, Michal Ďuračka, Marek Halenár, Juraj Pivko, Eduard Kolesár, Ľubica Chrastinová, Ľubomír Ondruška, Rastislav Jurčík, Adriana Kolesárová
Background: Apricot kernels containing amygdalin (AMG) as the major cyanogenic glycoside are potentially useful as a complementary therapy for the management of several ailments including cancer. Nevertheless, little is known regarding the toxic and therapeutic doses of AMG, particularly in terms of male reproduction. Hence, this study evaluates selected qualitative characteristics of rabbit testicular tissue following in vivo administration of AMG or apricot kernels for 28 days.
Methods: The rabbits were randomly divided into five groups (Control, P1, P2, P3, P4). The Control received no AMG/apricot kernels while the experimental groups P1 and P2 received a daily intramuscular injection of amygdalin at a dose of 0.6 and 3.0 mg/kg of body weight (b.w.) for 28 days, respectively. P3 and P4 received a daily dose of 60 and 300 mg/kg b.w. of crushed apricot kernels mixed with feed for 28 days, respectively. Changes to the testicular structure were quantified morphometrically, while tissue lysates were subjected to the evaluation of reactive oxygen species (ROS) production, total antioxidant capacity, activities of antioxidant enzymes, and glutathione concentration. The extent of damage to the proteins and lipids was quantified as well. Levels of selected cytokines were determined by the enzyme-linked immunosorbent assay while a luminometric approach was used to assess the activity of caspases.
Results: Rabbits treated with 3.0 mg/kg b.w. AMG presented a significantly increased protein oxidation (p = 0.0118) accompanied by a depletion of superoxide dismutase (p = 0.0464), catalase (p = 0.0317), and glutathione peroxidase (p = 0.0002). Significantly increased levels of interleukin-1 beta (p = 0.0012), tumor necrosis factors alpha (p = 0.0159), caspase-3/7 (p = 0.0014), and caspase-9 (p = 0.0243) were also recorded in the experimental group P2 when compared to the Control. No effects were observed in the rabbits treated with apricot kernels at the oxidative, inflammatory, and histopathological levels.
Conclusions: Apricot kernels did not induce toxicity in the testicular tissues of male rabbits, unlike pure AMG, which had a negative effect on male reproductive structures carried out through oxidative, inflammatory, and pro-apoptotic mechanisms.
{"title":"The Effects of Apricot Kernels and Pure Amygdalin on the Structural, Oxidative, and Inflammatory Characteristics of Rabbit Testicular Tissue.","authors":"Eva Tvrdá, Michal Ďuračka, Marek Halenár, Juraj Pivko, Eduard Kolesár, Ľubica Chrastinová, Ľubomír Ondruška, Rastislav Jurčík, Adriana Kolesárová","doi":"10.31083/j.fbl2906235","DOIUrl":"https://doi.org/10.31083/j.fbl2906235","url":null,"abstract":"<p><strong>Background: </strong>Apricot kernels containing amygdalin (AMG) as the major cyanogenic glycoside are potentially useful as a complementary therapy for the management of several ailments including cancer. Nevertheless, little is known regarding the toxic and therapeutic doses of AMG, particularly in terms of male reproduction. Hence, this study evaluates selected qualitative characteristics of rabbit testicular tissue following <i>in vivo</i> administration of AMG or apricot kernels for 28 days.</p><p><strong>Methods: </strong>The rabbits were randomly divided into five groups (Control, P1, P2, P3, P4). The Control received no AMG/apricot kernels while the experimental groups P1 and P2 received a daily intramuscular injection of amygdalin at a dose of 0.6 and 3.0 mg/kg of body weight (b.w.) for 28 days, respectively. P3 and P4 received a daily dose of 60 and 300 mg/kg b.w. of crushed apricot kernels mixed with feed for 28 days, respectively. Changes to the testicular structure were quantified morphometrically, while tissue lysates were subjected to the evaluation of reactive oxygen species (ROS) production, total antioxidant capacity, activities of antioxidant enzymes, and glutathione concentration. The extent of damage to the proteins and lipids was quantified as well. Levels of selected cytokines were determined by the enzyme-linked immunosorbent assay while a luminometric approach was used to assess the activity of caspases.</p><p><strong>Results: </strong>Rabbits treated with 3.0 mg/kg b.w. AMG presented a significantly increased protein oxidation (<i>p</i> = 0.0118) accompanied by a depletion of superoxide dismutase (<i>p</i> = 0.0464), catalase (<i>p</i> = 0.0317), and glutathione peroxidase (<i>p</i> = 0.0002). Significantly increased levels of interleukin-1 beta (<i>p</i> = 0.0012), tumor necrosis factors alpha (<i>p</i> = 0.0159), caspase-3/7 (<i>p</i> = 0.0014), and caspase-9 (<i>p</i> = 0.0243) were also recorded in the experimental group P2 when compared to the Control. No effects were observed in the rabbits treated with apricot kernels at the oxidative, inflammatory, and histopathological levels.</p><p><strong>Conclusions: </strong>Apricot kernels did not induce toxicity in the testicular tissues of male rabbits, unlike pure AMG, which had a negative effect on male reproductive structures carried out through oxidative, inflammatory, and pro-apoptotic mechanisms.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hugo Aguilar-Díaz, Rosa Estela Quiroz-Castañeda, Daniela Ríos-Jasso, Raquel Cossío-Bayúgar, Estefan Miranda-Miranda
Background: Hormone receptors exert their function through binding with their ligands, which results in cellular signaling activation mediated by genomic or non-genomic mechanisms. The intrinsic molecular communication of tick Rhipicephalus microplus and its host Bos taurus comprises an endocrine regulation involving hormones. In the present study, we performed a molecular and in silico analysis of a Membrane Associated Progesterone Receptor in R. microplus (RmMAPRC).
Methods: The RmMAPRC protein sequence was analyzed with bioinformatics tools, and its structure was characterized by three-dimensional (3D) modeling and molecular docking. A semi-quantitative reverse transcription and polymerase chain reaction (sqRT-PCR) assessed the RmMAPRC gene presence and relative expression in tick organs and embryonic cells.
Results: RmMAPRC relative expression in salivary glands, ovaries, and embryonic cells showed overexpression of 3%, 13%, and 24%, respectively. Bioinformatic analysis revealed that RmMAPRC corresponded to a Progesterone Receptor Membrane Component 1 (RmPGRMC1) of ~23.7 kDa, with an N-terminal transmembrane domain and a C-terminal Cytochrome b5-like heme/steroid binding domain. The docking results suggest that RmPGRMC1 could bind to progesterone (P4), some progestins, and P4 antagonists. The phylogenetic reconstruction showed that Rhipicephalus spp. MAPRC receptors were clustered in a clade that includes R. appendiculatus, R. sanguineus, and R. microplus (RmMAPRC), and mammals and helminths MAPRC receptors clustered in two separated clades away from ticks.
Conclusions: The presence of RmPGRMC1 highlights the importance of transregulation as a conserved adaptive mechanism that has succeeded for arthropod parasites, making it a target for tick control.
{"title":"A Novel Receptor Binding Progesterone, a Possible Transregulation Mechanism in the <i>Rhipicephalus microplus</i>-Host Interaction.","authors":"Hugo Aguilar-Díaz, Rosa Estela Quiroz-Castañeda, Daniela Ríos-Jasso, Raquel Cossío-Bayúgar, Estefan Miranda-Miranda","doi":"10.31083/j.fbl2906238","DOIUrl":"https://doi.org/10.31083/j.fbl2906238","url":null,"abstract":"<p><strong>Background: </strong>Hormone receptors exert their function through binding with their ligands, which results in cellular signaling activation mediated by genomic or non-genomic mechanisms. The intrinsic molecular communication of tick <i>Rhipicephalus microplus</i> and its host <i>Bos taurus</i> comprises an endocrine regulation involving hormones. In the present study, we performed a molecular and <i>in silico</i> analysis of a Membrane Associated Progesterone Receptor in <i>R. microplus</i> (RmMAPRC).</p><p><strong>Methods: </strong>The RmMAPRC protein sequence was analyzed with bioinformatics tools, and its structure was characterized by three-dimensional (3D) modeling and molecular docking. A semi-quantitative reverse transcription and polymerase chain reaction (sqRT-PCR) assessed the <i>RmMAPRC</i> gene presence and relative expression in tick organs and embryonic cells.</p><p><strong>Results: </strong><i>RmMAPRC</i> relative expression in salivary glands, ovaries, and embryonic cells showed overexpression of 3%, 13%, and 24%, respectively. Bioinformatic analysis revealed that RmMAPRC corresponded to a Progesterone Receptor Membrane Component 1 (RmPGRMC1) of ~23.7 kDa, with an N-terminal transmembrane domain and a C-terminal Cytochrome b5-like heme/steroid binding domain. The docking results suggest that RmPGRMC1 could bind to progesterone (P4), some progestins, and P4 antagonists. The phylogenetic reconstruction showed that <i>Rhipicephalus</i> spp. MAPRC receptors were clustered in a clade that includes <i>R. appendiculatus</i>, <i>R. sanguineus</i>, and <i>R. microplus</i> (RmMAPRC), and mammals and helminths MAPRC receptors clustered in two separated clades away from ticks.</p><p><strong>Conclusions: </strong>The presence of RmPGRMC1 highlights the importance of transregulation as a conserved adaptive mechanism that has succeeded for arthropod parasites, making it a target for tick control.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hua Guan, Le Wang, Zhanyi Geng, Bowen Duan, Yang Gao, Zheyong Liang, Xinglong Zheng, Tao Shi, Fengwei Guo
Background: This study aimed to elucidate the molecular mechanism through which C1q/tumor necrosis factor (TNF)-related protein 9 (CTRP9) acts in the formation and differentiation of brown adipose tissue (BAT).
Methods: Adenovirus particles encoding CTRP9 and green fluorescent protein were inoculated into the scapula of C57BL/6J mice and fed a high-fat diet for 8 weeks; the body weight, lipid droplet morphology, glucose tolerance, insulin tolerance, and protein expression levels were analyzed. In addition, CTRP9 adenovirus was transfected into brown preadipocytes, and differentiation was induced to identify the effect of CTRP9 overexpression on adipocyte differentiation.
Results: CTRP9 overexpression significantly increased the weight gain of mice. Additionally, the CTRP9 overexpression group exhibited significantly increased adipose tissue weight and glucose clearance rates and decreased insulin sensitivity and serum triglyceride levels compared to the control group. Furthermore, CTRP9 overexpression significantly upregulated the adipose triglyceride lipase (ATGL) and perilipin 1 protein expression levels in BAT. The cell experiment results confirmed that CTRP9 overexpression significantly inhibited the adipogenesis of brown adipocytes as evidenced by the downregulation of uncoupling protein 1, beta-3 adrenergic receptor, ATGL, and hormone-sensitive lipase mRNA levels and the significant suppression of uncoupling protein 1, ATGL, and perilipin 1 protein levels in brown adipocytes.
Conclusions: The finding of this study demonstrated that CTRP9 promotes lipolysis by upregulating ATGL expression in vivo and inhibits the differentiation of brown preadipocytes in vitro.
背景:本研究旨在阐明C1q/肿瘤坏死因子(TNF)相关蛋白9(CTRP9)在棕色脂肪组织(BAT)形成和分化过程中的分子机制:方法:将编码CTRP9和绿色荧光蛋白的腺病毒颗粒接种到C57BL/6J小鼠肩胛骨中,喂食高脂饮食8周,分析体重、脂滴形态、葡萄糖耐量、胰岛素耐量和蛋白表达水平。此外,还将CTRP9腺病毒转染至棕色前脂肪细胞,并诱导其分化,以确定CTRP9过表达对脂肪细胞分化的影响:结果:CTRP9过表达能显著增加小鼠的体重增加。此外,与对照组相比,CTRP9过表达组的脂肪组织重量和葡萄糖清除率明显增加,胰岛素敏感性和血清甘油三酯水平下降。此外,CTRP9 的过表达还能明显上调 BAT 中脂肪甘油三酯脂酶(ATGL)和过脂素 1 蛋白的表达水平。细胞实验结果证实,CTRP9的过表达明显抑制了棕色脂肪细胞的脂肪生成,表现为棕色脂肪细胞中解偶联蛋白1、β-3肾上腺素能受体、ATGL和激素敏感性脂肪酶mRNA水平的下调,以及解偶联蛋白1、ATGL和过脂素1蛋白水平的明显抑制:本研究结果表明,CTRP9 在体内通过上调 ATGL 的表达促进脂肪分解,在体外抑制棕色前脂肪细胞的分化。
{"title":"CTRP9 Promotes Brown Adipose Tissue Lipolysis in Mice Fed a High-Fat Diet.","authors":"Hua Guan, Le Wang, Zhanyi Geng, Bowen Duan, Yang Gao, Zheyong Liang, Xinglong Zheng, Tao Shi, Fengwei Guo","doi":"10.31083/j.fbl2906236","DOIUrl":"10.31083/j.fbl2906236","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to elucidate the molecular mechanism through which C1q/tumor necrosis factor (TNF)-related protein 9 (CTRP9) acts in the formation and differentiation of brown adipose tissue (BAT).</p><p><strong>Methods: </strong>Adenovirus particles encoding CTRP9 and green fluorescent protein were inoculated into the scapula of C57BL/6J mice and fed a high-fat diet for 8 weeks; the body weight, lipid droplet morphology, glucose tolerance, insulin tolerance, and protein expression levels were analyzed. In addition, CTRP9 adenovirus was transfected into brown preadipocytes, and differentiation was induced to identify the effect of CTRP9 overexpression on adipocyte differentiation.</p><p><strong>Results: </strong>CTRP9 overexpression significantly increased the weight gain of mice. Additionally, the CTRP9 overexpression group exhibited significantly increased adipose tissue weight and glucose clearance rates and decreased insulin sensitivity and serum triglyceride levels compared to the control group. Furthermore, CTRP9 overexpression significantly upregulated the adipose triglyceride lipase (ATGL) and perilipin 1 protein expression levels in BAT. The cell experiment results confirmed that CTRP9 overexpression significantly inhibited the adipogenesis of brown adipocytes as evidenced by the downregulation of uncoupling protein 1, beta-3 adrenergic receptor, ATGL, and hormone-sensitive lipase mRNA levels and the significant suppression of uncoupling protein 1, ATGL, and perilipin 1 protein levels in brown adipocytes.</p><p><strong>Conclusions: </strong>The finding of this study demonstrated that CTRP9 promotes lipolysis by upregulating ATGL expression <i>in vivo</i> and inhibits the differentiation of brown preadipocytes <i>in vitro</i>.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Pang, Sile Hu, Binhong Wen, Dubala Wu, Feng Song, Jun Yin, Jianghong Wu
Background: Under fasting conditions, the pathway converting gluconeogenesis precursors into muscle glycogen becomes crucial due to reduced glycogen reserves. However, there is limited research on skeletal muscle gluconeogenesis and the impact of fasting on gluconeogenic gene expression.
Methods: Sheep fetal skeletal muscle cells cultured in vitro were used to study the effects of varying lactic acid concentrations (0 to 30 mM) and 2.5 mM glucose on the expression of gluconeogenesis-related genes after 6 h of fasting. The effects on mRNA and protein expression of key genes involved in skeletal muscle gluconeogenesis were measured by quantitative real time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting at 48 h.
Results: Fasting increased the expression of key gluconeogenic genes, fructose-1,6-bisphosphatase 2 (FBP2), glucose-6-phosphatase 3 (G6PC3), pyruvate kinase M (PKM), monocarboxylate transporter1 (MCTS1), glucose transporter type 4 (GLUT4), pyruvate carboxylase (PC), and lactate dehydrogenase A (LDHA). The mRNA levels of FBP2, G6PC3, and MCTS1 significantly decreased with glucose addition. Additionally, 10 mM lactic acid significantly promoted the expression of FBP2, PC, MCTS1, LDHA, GLUT4, and PKM while inhibiting phosphoenolpyruvate carboxykinase (PEPCK) expression. At the protein level, 10 mM lactic acid significantly increased FBP2 and PKM protein expression.
Conclusions: This study shows that fasting regulates key gluconeogenic gene expression in sheep skeletal muscle cells and highlights the role of lactic acid in inducing these gene expressions.
背景:在禁食条件下,由于糖原储备减少,将糖元生成前体转化为肌糖原的途径变得至关重要。然而,有关骨骼肌糖元生成以及禁食对糖元生成基因表达的影响的研究十分有限:方法:采用体外培养的绵羊胎儿骨骼肌细胞,研究不同浓度的乳酸(0 至 30 mM)和 2.5 mM 葡萄糖对禁食 6 小时后糖元生成相关基因表达的影响。在 48 小时后,通过实时定量聚合酶链式反应 (qRT-PCR)、免疫荧光和 Western 印迹检测了对骨骼肌糖元生成关键基因 mRNA 和蛋白质表达的影响:结果:禁食增加了关键糖元生成基因果糖-1,6-二磷酸酶2(FBP2)、葡萄糖-6-磷酸酶3(G6PC3)、丙酮酸激酶M(PKM)、单羧酸盐转运体1(MCTS1)、葡萄糖转运体4型(GLUT4)、丙酮酸羧化酶(PC)和乳酸脱氢酶A(LDHA)的表达。加入葡萄糖后,FBP2、G6PC3 和 MCTS1 的 mRNA 水平明显下降。此外,10 mM 乳酸能明显促进 FBP2、PC、MCTS1、LDHA、GLUT4 和 PKM 的表达,同时抑制磷酸烯醇丙酮酸羧激酶(PEPCK)的表达。在蛋白质水平上,10 mM 乳酸能显著增加 FBP2 和 PKM 蛋白的表达:本研究表明,空腹可调节绵羊骨骼肌细胞中关键糖原基因的表达,并强调了乳酸在诱导这些基因表达中的作用。
{"title":"Expression Regulation of Gluconeogenesis Related Genes in Ovine Skeletal Muscle Cells.","authors":"Yue Pang, Sile Hu, Binhong Wen, Dubala Wu, Feng Song, Jun Yin, Jianghong Wu","doi":"10.31083/j.fbl2906237","DOIUrl":"10.31083/j.fbl2906237","url":null,"abstract":"<p><strong>Background: </strong>Under fasting conditions, the pathway converting gluconeogenesis precursors into muscle glycogen becomes crucial due to reduced glycogen reserves. However, there is limited research on skeletal muscle gluconeogenesis and the impact of fasting on gluconeogenic gene expression.</p><p><strong>Methods: </strong>Sheep fetal skeletal muscle cells cultured <i>in vitro</i> were used to study the effects of varying lactic acid concentrations (0 to 30 mM) and 2.5 mM glucose on the expression of gluconeogenesis-related genes after 6 h of fasting. The effects on mRNA and protein expression of key genes involved in skeletal muscle gluconeogenesis were measured by quantitative real time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting at 48 h.</p><p><strong>Results: </strong>Fasting increased the expression of key gluconeogenic genes, fructose-1,6-bisphosphatase 2 (<i>FBP2</i>), glucose-6-phosphatase 3 (<i>G6PC3</i>), pyruvate kinase M (<i>PKM</i>), monocarboxylate transporter1 (<i>MCTS1</i>), glucose transporter type 4 (<i>GLUT4</i>), pyruvate carboxylase (<i>PC</i>), and lactate dehydrogenase A (<i>LDHA</i>). The mRNA levels of <i>FBP2</i>, <i>G6PC3</i>, and <i>MCTS1</i> significantly decreased with glucose addition. Additionally, 10 mM lactic acid significantly promoted the expression of <i>FBP2</i>, <i>PC</i>, <i>MCTS1</i>, <i>LDHA</i>, <i>GLUT4</i>, and <i>PKM</i> while inhibiting phosphoenolpyruvate carboxykinase (<i>PEPCK</i>) expression. At the protein level, 10 mM lactic acid significantly increased FBP2 and PKM protein expression.</p><p><strong>Conclusions: </strong>This study shows that fasting regulates key gluconeogenic gene expression in sheep skeletal muscle cells and highlights the role of lactic acid in inducing these gene expressions.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allan John R Barcena, Archana Mishra, Dominic Karl M Bolinas, Benjamin M Martin, Marites P Melancon
Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration capabilities. Despite their potential, the clinical application of MSC therapies is hindered by limited cell retention and engraftment at the target sites. Electrospun scaffolds, with their high surface area-to-volume ratio and tunable physicochemical properties, can be used as platforms for MSC delivery. However, synthetic polymers often lack the bioactive cues necessary for optimal cell-scaffold interactions. Integrating electrospun scaffolds and biological polymers, such as polysaccharides, proteins, and composites, combines the mechanical integrity of synthetic materials with the bioactivity of natural polymers and represents a strategic approach to enhance cell-scaffold interactions. The molecular interactions between MSCs and blended or functionalized scaffolds have been examined in recent studies, and it has been shown that integration can enhance MSC adhesion, proliferation, and paracrine secretion through the activation of multiple signaling pathways, such as FAK/Src, MAPK, PI3K/Akt, Wnt/β-catenin, and YAP/TAZ. Preclinical studies on small animals also reveal that the integration of electrospun scaffolds and natural polymers represents a promising approach to enhancing the delivery and efficacy of MSCs in the context of regenerating bone, cartilage, muscle, cardiac, vascular, and nervous tissues. Future research should concentrate on identifying the distinct characteristics of the MSC niche, investigating the processes involved in MSC-scaffold interactions, and applying new technologies in stem cell treatment and biofabrication to enhance scaffold design. Research on large animal models and collaboration among materials scientists, engineers, and physicians are crucial to translating these advancements into clinical use.
{"title":"Integration of Electrospun Scaffolds and Biological Polymers for Enhancing the Delivery and Efficacy of Mesenchymal Stem/Stromal Cell Therapies.","authors":"Allan John R Barcena, Archana Mishra, Dominic Karl M Bolinas, Benjamin M Martin, Marites P Melancon","doi":"10.31083/j.fbl2906228","DOIUrl":"https://doi.org/10.31083/j.fbl2906228","url":null,"abstract":"<p><p>Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration capabilities. Despite their potential, the clinical application of MSC therapies is hindered by limited cell retention and engraftment at the target sites. Electrospun scaffolds, with their high surface area-to-volume ratio and tunable physicochemical properties, can be used as platforms for MSC delivery. However, synthetic polymers often lack the bioactive cues necessary for optimal cell-scaffold interactions. Integrating electrospun scaffolds and biological polymers, such as polysaccharides, proteins, and composites, combines the mechanical integrity of synthetic materials with the bioactivity of natural polymers and represents a strategic approach to enhance cell-scaffold interactions. The molecular interactions between MSCs and blended or functionalized scaffolds have been examined in recent studies, and it has been shown that integration can enhance MSC adhesion, proliferation, and paracrine secretion through the activation of multiple signaling pathways, such as FAK/Src, MAPK, PI3K/Akt, Wnt/β-catenin, and YAP/TAZ. Preclinical studies on small animals also reveal that the integration of electrospun scaffolds and natural polymers represents a promising approach to enhancing the delivery and efficacy of MSCs in the context of regenerating bone, cartilage, muscle, cardiac, vascular, and nervous tissues. Future research should concentrate on identifying the distinct characteristics of the MSC niche, investigating the processes involved in MSC-scaffold interactions, and applying new technologies in stem cell treatment and biofabrication to enhance scaffold design. Research on large animal models and collaboration among materials scientists, engineers, and physicians are crucial to translating these advancements into clinical use.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The inhibitors of mammalian target of rapapmycin (mTOR), everolimus, temsirolimus and rapamycin, have a wide range of clinical utility; however, as is inevitably the case with other chemotherapeutic agents, resistance development constrains their effectiveness. One putative mechanism of resistance is the promotion of autophagy, which is a direct consequence of the inhibition of the mTOR signaling pathway. Autophagy is primarily considered to be a cytoprotective survival mechanism, whereby cytoplasmic components are recycled to generate energy and metabolic intermediates. The autophagy induced by everolimus and temsirolimus appears to play a largely protective function, whereas a cytotoxic function appears to predominate in the case of rapamycin. In this review we provide an overview of the autophagy induced in response to mTOR inhibitors in different tumor models in an effort to determine whether autophagy targeting could be of clinical utility as adjuvant therapy in association with mTOR inhibition.
{"title":"The Cytoprotective and Cytotoxic Functions of Autophagy in Response to mTOR Inhibitors.","authors":"Ahmed M Elshazly, Aya A Elzahed, David A Gewirtz","doi":"10.31083/j.fbl2906231","DOIUrl":"10.31083/j.fbl2906231","url":null,"abstract":"<p><p>The inhibitors of mammalian target of rapapmycin (mTOR), everolimus, temsirolimus and rapamycin, have a wide range of clinical utility; however, as is inevitably the case with other chemotherapeutic agents, resistance development constrains their effectiveness. One putative mechanism of resistance is the promotion of autophagy, which is a direct consequence of the inhibition of the mTOR signaling pathway. Autophagy is primarily considered to be a cytoprotective survival mechanism, whereby cytoplasmic components are recycled to generate energy and metabolic intermediates. The autophagy induced by everolimus and temsirolimus appears to play a largely protective function, whereas a cytotoxic function appears to predominate in the case of rapamycin. In this review we provide an overview of the autophagy induced in response to mTOR inhibitors in different tumor models in an effort to determine whether autophagy targeting could be of clinical utility as adjuvant therapy in association with mTOR inhibition.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bonnie C Carney, Cynthia M Simbulan-Rosenthal, Dean S Rosenthal, Jeffrey W Shupp
<p><strong>Background: </strong>Existing animal models for testing therapeutics in the skin are limited. Mouse and rat models lack similarity to human skin in structure and wound healing mechanism. Pigs are regarded as the best model with regards to similarity to human skin; however, these studies are expensive, time-consuming, and only small numbers of biologic replicates can be obtained. In addition, local-regional effects of treating wounds that are closely adjacent to one-another with different treatments make assessment of treatment effectiveness difficult in pig models. Therefore, here, a novel nude mouse model of xenografted porcine hypertrophic scar (HTS) cells was developed. This model system was developed to test if supplying hypo-pigmented cells with exogenous alpha melanocyte stimulating hormone (α-MSH) will reverse pigment loss <i>in vivo</i>.</p><p><strong>Methods: </strong>Dyschromic HTSs were created in red Duroc pigs. Epidermal scar cells (keratinocytes and melanocytes) were derived from regions of hyper-, hypo-, or normally pigmented scar or skin and were cryopreserved. Dermal fibroblasts (DFs) were isolated separately. Excisional wounds were created on nude mice and a grafting dome was placed. DFs were seeded on day 0 and formed a dermis. On day 3, epidermal cells were seeded onto the dermis. The grafting dome was removed on day 7 and hypo-pigmented xenografts were treated with synthetic α-MSH delivered with microneedling. On day 10, the xenografts were excised and saved. Sections were stained using hematoxylin and eosin hematoxylin and eosin (H&E) to assess xenograft structure. RNA was isolated and quantitative real-time polymerase chain reaction (qRT-PCR) was performed for melanogenesis-related genes <i>TYR</i>, <i>TYRP1</i>, and <i>DCT</i>.</p><p><strong>Results: </strong>The seeding of HTSDFs formed a dermis that is similar in structure and cellularity to HTS dermis from the porcine model. When hyper-, hypo-, and normally-pigmented epidermal cells were seeded, a fully stratified epithelium was formed by day 14. H&E staining and measurement of the epidermis showed the average thickness to be 0.11 ± 0.07 µm <i>vs.</i> 0.06 ± 0.03 µm in normal pig skin. Hypo-pigmented xenografts that were treated with synthetic α-MSH showed increases in pigmentation and had increased gene expression of <i>TYR</i>, <i>TYRP1</i>, and <i>DCT</i> compared to untreated controls (TYR: 2.7 ± 1.1 <i>vs.</i> 0.3 ± 1.1; TYRP1: 2.6 ± 0.6 <i>vs.</i> 0.3 ± 0.7; DCT 0.7 ± 0.9 <i>vs.</i> 0.3 ± 1-fold change from control; n = 3).</p><p><strong>Conclusions: </strong>The developed nude mouse skin xenograft model can be used to study treatments for the skin. The cells that can be xenografted can be derived from patient samples or from pig samples and form a robust dual-skin layer containing epidermis and dermis that is responsive to treatment. Specifically, we found that hypo-pigmented regions of scar can be stimulated to make melanin by synthetic α-MSH <i>in vi
{"title":"A Nude Mouse Model of Xenografted Hypertrophic Scar Cells to Test Therapeutics in the Skin.","authors":"Bonnie C Carney, Cynthia M Simbulan-Rosenthal, Dean S Rosenthal, Jeffrey W Shupp","doi":"10.31083/j.fbl2906230","DOIUrl":"10.31083/j.fbl2906230","url":null,"abstract":"<p><strong>Background: </strong>Existing animal models for testing therapeutics in the skin are limited. Mouse and rat models lack similarity to human skin in structure and wound healing mechanism. Pigs are regarded as the best model with regards to similarity to human skin; however, these studies are expensive, time-consuming, and only small numbers of biologic replicates can be obtained. In addition, local-regional effects of treating wounds that are closely adjacent to one-another with different treatments make assessment of treatment effectiveness difficult in pig models. Therefore, here, a novel nude mouse model of xenografted porcine hypertrophic scar (HTS) cells was developed. This model system was developed to test if supplying hypo-pigmented cells with exogenous alpha melanocyte stimulating hormone (α-MSH) will reverse pigment loss <i>in vivo</i>.</p><p><strong>Methods: </strong>Dyschromic HTSs were created in red Duroc pigs. Epidermal scar cells (keratinocytes and melanocytes) were derived from regions of hyper-, hypo-, or normally pigmented scar or skin and were cryopreserved. Dermal fibroblasts (DFs) were isolated separately. Excisional wounds were created on nude mice and a grafting dome was placed. DFs were seeded on day 0 and formed a dermis. On day 3, epidermal cells were seeded onto the dermis. The grafting dome was removed on day 7 and hypo-pigmented xenografts were treated with synthetic α-MSH delivered with microneedling. On day 10, the xenografts were excised and saved. Sections were stained using hematoxylin and eosin hematoxylin and eosin (H&E) to assess xenograft structure. RNA was isolated and quantitative real-time polymerase chain reaction (qRT-PCR) was performed for melanogenesis-related genes <i>TYR</i>, <i>TYRP1</i>, and <i>DCT</i>.</p><p><strong>Results: </strong>The seeding of HTSDFs formed a dermis that is similar in structure and cellularity to HTS dermis from the porcine model. When hyper-, hypo-, and normally-pigmented epidermal cells were seeded, a fully stratified epithelium was formed by day 14. H&E staining and measurement of the epidermis showed the average thickness to be 0.11 ± 0.07 µm <i>vs.</i> 0.06 ± 0.03 µm in normal pig skin. Hypo-pigmented xenografts that were treated with synthetic α-MSH showed increases in pigmentation and had increased gene expression of <i>TYR</i>, <i>TYRP1</i>, and <i>DCT</i> compared to untreated controls (TYR: 2.7 ± 1.1 <i>vs.</i> 0.3 ± 1.1; TYRP1: 2.6 ± 0.6 <i>vs.</i> 0.3 ± 0.7; DCT 0.7 ± 0.9 <i>vs.</i> 0.3 ± 1-fold change from control; n = 3).</p><p><strong>Conclusions: </strong>The developed nude mouse skin xenograft model can be used to study treatments for the skin. The cells that can be xenografted can be derived from patient samples or from pig samples and form a robust dual-skin layer containing epidermis and dermis that is responsive to treatment. Specifically, we found that hypo-pigmented regions of scar can be stimulated to make melanin by synthetic α-MSH <i>in vi","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated by TIG1 in melanoma cells and its impact on cell growth.
Methods: The effects of TIG1 expression on cell viability and death were assessed using water-soluble tetrazolium 1 (WST-1) mitochondrial staining and lactate dehydrogenase release assays. RNA sequencing and Western blot analysis were employed to investigate the genes regulated by TIG1 in melanoma cells. Additionally, the correlation between TIG1 expression and its downstream genes was analyzed in a melanoma tissue array.
Results: TIG1 expression in melanoma cells was associated with decreased cell viability and increased cell death. RNA-sequencing (RNA-seq), quantitative reverse transcription PCR (reverse RT-QPCR), and immunoblots revealed that TIG1 expression induced the expression of Endoplasmic Reticulum (ER) stress response-related genes such as Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (HERPUD1), Binding immunoglobulin protein (BIP), and DNA damage-inducible transcript 3 (DDIT3). Furthermore, analysis of the melanoma tissue array revealed a positive correlation between TIG1 expression and the expression of HERPUD1, BIP, and DDIT3. Additionally, attenuation of the ER stress response in melanoma cells weakened the impact of TIG1 on cell growth.
Conclusions: TIG1 expression effectively hinders the growth of melanoma cells. TIG1 induces the upregulation of ER stress response-related genes, leading to an increase in caspase-3 activity and subsequent cell death. These findings suggest that the ability of retinoic acid to prevent melanoma formation may be associated with the anticancer effect of TIG1.
{"title":"Tazarotene-induced Gene 1 Induces Melanoma Cell Death by Triggering Endoplasmic Reticulum Stress Response.","authors":"Chun-Hua Wang, I-Shiang Tzeng, Lu-Kai Wang, Chang-Chieh Wu, Mao-Liang Chen, Chan-Yen Kuo, Rong-Yaun Shyu, Fu-Ming Tsai","doi":"10.31083/j.fbl2906233","DOIUrl":"10.31083/j.fbl2906233","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated by TIG1 in melanoma cells and its impact on cell growth.</p><p><strong>Methods: </strong>The effects of TIG1 expression on cell viability and death were assessed using water-soluble tetrazolium 1 (WST-1) mitochondrial staining and lactate dehydrogenase release assays. RNA sequencing and Western blot analysis were employed to investigate the genes regulated by TIG1 in melanoma cells. Additionally, the correlation between <i>TIG1</i> expression and its downstream genes was analyzed in a melanoma tissue array.</p><p><strong>Results: </strong>TIG1 expression in melanoma cells was associated with decreased cell viability and increased cell death. RNA-sequencing (RNA-seq), quantitative reverse transcription PCR (reverse RT-QPCR), and immunoblots revealed that TIG1 expression induced the expression of Endoplasmic Reticulum (ER) stress response-related genes such as Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (HERPUD1), Binding immunoglobulin protein (BIP), and DNA damage-inducible transcript 3 (DDIT3). Furthermore, analysis of the melanoma tissue array revealed a positive correlation between <i>TIG1</i> expression and the expression of <i>HERPUD1</i>, <i>BIP</i>, and <i>DDIT3</i>. Additionally, attenuation of the ER stress response in melanoma cells weakened the impact of TIG1 on cell growth.</p><p><strong>Conclusions: </strong>TIG1 expression effectively hinders the growth of melanoma cells. TIG1 induces the upregulation of ER stress response-related genes, leading to an increase in caspase-3 activity and subsequent cell death. These findings suggest that the ability of retinoic acid to prevent melanoma formation may be associated with the anticancer effect of TIG1.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irma Wati Ngadimon, Eryse Amira Seth, Mohd Farooq Shaikh
Neuroinflammation has emerged as a shared molecular mechanism in epilepsy and cognitive impairment, offering new insights into the complex interplay between immune responses and brain function. Evidence reveals involvement of High mobility group box 1 (HMGB1) in blood-brain barrier disruption and correlations with epilepsy severity and drug resistance. While anti-inflammatory treatments show promise, translating these discoveries faces challenges in elucidating mechanisms and developing reliable biomarkers. However, strategically targeting neuroinflammation and HMGB1-mediated inflammation holds therapeutic potential. This review synthesises knowledge on HMGB1 and related biomarkers in epilepsy and cognitive impairment to shape future research and treatments targeting these intricate inflammatory processes.
{"title":"Exploring the Neuroinflammatory Pathway in Epilepsy and Cognitive Impairment: Role of HMGB1 and Translational Challenges.","authors":"Irma Wati Ngadimon, Eryse Amira Seth, Mohd Farooq Shaikh","doi":"10.31083/j.fbl2906229","DOIUrl":"10.31083/j.fbl2906229","url":null,"abstract":"<p><p>Neuroinflammation has emerged as a shared molecular mechanism in epilepsy and cognitive impairment, offering new insights into the complex interplay between immune responses and brain function. Evidence reveals involvement of High mobility group box 1 (HMGB1) in blood-brain barrier disruption and correlations with epilepsy severity and drug resistance. While anti-inflammatory treatments show promise, translating these discoveries faces challenges in elucidating mechanisms and developing reliable biomarkers. However, strategically targeting neuroinflammation and HMGB1-mediated inflammation holds therapeutic potential. This review synthesises knowledge on HMGB1 and related biomarkers in epilepsy and cognitive impairment to shape future research and treatments targeting these intricate inflammatory processes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Alzheimer's disease is characterized by extracellular beta-amyloid plaques, intraneuronal tau neurofibrillary tangles and excessive neurodegeneration. The mechanisms of neuron degeneration and the potential of these neurons to form new nerve fibers for compensation remain elusive. The present study aimed to evaluate the impact of beta-amyloid and tau on new formations of nerve fibers from mouse organotypic brain slices connected to collagen-based microcontact prints.
Methods: Organotypic brain slices of postnatal day 8-10 wild-type mice were connected to established collagen-based microcontact prints loaded with polyornithine to enhance nerve fiber outgrowth. Human beta-amyloid(42) or P301S mutated aggregated tau was co-loaded to the prints. Nerve fibers were immunohistochemically stained with neurofilament antibodies. The physiological activity of outgrown neurites was tested with neurotracer MiniRuby, voltage-sensitive dye FluoVolt, and calcium-sensitive dye Rhod-4.
Results: Immunohistochemical staining revealed newly formed nerve fibers extending along the prints derived from the brain slices. While collagen-only microcontact prints stimulated nerve fiber growth, those loaded with polyornithine significantly enhanced nerve fiber outgrowth. Beta-amyloid(42) significantly increased the neurofilament-positive nerve fibers, while tau had only a weak effect. MiniRuby crystals, retrogradely transported along these newly formed nerve fibers, reached the hippocampus, while FluoVolt and Rhod-4 monitored electrical activity in newly formed nerve fibers.
Conclusions: Our data provide evidence that intact nerve fibers can form along collagen-based microcontact prints from mouse brain slices. The Alzheimer's peptide beta-amyloid(42) stimulates this growth, hinting at a neuroprotective function when physiologically active. This "brain-on-chip" model may offer a platform for screening bioactive factors or testing drug effects on nerve fiber growth.
背景:阿尔茨海默病的特征是细胞外 beta 淀粉样蛋白斑块、神经元内 tau 神经纤维缠结和过度神经变性。神经元变性的机制以及这些神经元形成新神经纤维进行补偿的潜力仍然难以捉摸。本研究旨在评估β-淀粉样蛋白和tau对连接到基于胶原蛋白的微接触印迹的小鼠器质性脑切片中新神经纤维形成的影响:方法:将出生后第8-10天野生型小鼠的器质性脑切片连接到已建立的装有聚鸟氨酸的胶原基微接触印迹上,以促进神经纤维的生长。人β-淀粉样蛋白(42)或P301S突变聚合tau被共同加载到印迹上。用神经丝抗体对神经纤维进行免疫组化染色。用神经示踪剂 MiniRuby、电压敏感染料 FluoVolt 和钙敏感染料 Rhod-4 检测外生神经元的生理活性:免疫组化染色显示,新形成的神经纤维沿着脑片上的印迹延伸。只含胶原蛋白的微接触印迹刺激了神经纤维的生长,而含有聚鸟氨酸的印迹则显著促进了神经纤维的生长。β-淀粉样蛋白(42)能显著增加神经丝蛋白阳性神经纤维的数量,而 tau 的影响较弱。沿着这些新形成的神经纤维逆向运输的迷你红宝石晶体到达了海马体,而 FluoVolt 和 Rhod-4 则监测了新形成的神经纤维的电活动:我们的数据证明,完整的神经纤维可以沿着小鼠大脑切片上基于胶原蛋白的微接触印迹形成。阿尔茨海默氏症肽β-淀粉样蛋白(42)会刺激神经纤维的生长,这表明神经纤维在生理活性下具有保护功能。这种 "芯片上的大脑 "模型可为筛选生物活性因子或测试药物对神经纤维生长的影响提供一个平台。
{"title":"Brain Slice Derived Nerve Fibers Grow along Microcontact Prints and are Stimulated by Beta-Amyloid(42).","authors":"Katharina Steiner, Christian Humpel","doi":"10.31083/j.fbl2906232","DOIUrl":"10.31083/j.fbl2906232","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease is characterized by extracellular beta-amyloid plaques, intraneuronal tau neurofibrillary tangles and excessive neurodegeneration. The mechanisms of neuron degeneration and the potential of these neurons to form new nerve fibers for compensation remain elusive. The present study aimed to evaluate the impact of beta-amyloid and tau on new formations of nerve fibers from mouse organotypic brain slices connected to collagen-based microcontact prints.</p><p><strong>Methods: </strong>Organotypic brain slices of postnatal day 8-10 wild-type mice were connected to established collagen-based microcontact prints loaded with polyornithine to enhance nerve fiber outgrowth. Human beta-amyloid(42) or P301S mutated aggregated tau was co-loaded to the prints. Nerve fibers were immunohistochemically stained with neurofilament antibodies. The physiological activity of outgrown neurites was tested with neurotracer MiniRuby, voltage-sensitive dye FluoVolt, and calcium-sensitive dye Rhod-4.</p><p><strong>Results: </strong>Immunohistochemical staining revealed newly formed nerve fibers extending along the prints derived from the brain slices. While collagen-only microcontact prints stimulated nerve fiber growth, those loaded with polyornithine significantly enhanced nerve fiber outgrowth. Beta-amyloid(42) significantly increased the neurofilament-positive nerve fibers, while tau had only a weak effect. MiniRuby crystals, retrogradely transported along these newly formed nerve fibers, reached the hippocampus, while FluoVolt and Rhod-4 monitored electrical activity in newly formed nerve fibers.</p><p><strong>Conclusions: </strong>Our data provide evidence that intact nerve fibers can form along collagen-based microcontact prints from mouse brain slices. The Alzheimer's peptide beta-amyloid(42) stimulates this growth, hinting at a neuroprotective function when physiologically active. This \"brain-on-chip\" model may offer a platform for screening bioactive factors or testing drug effects on nerve fiber growth.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}