Biomedicine & Pharmacotherapy最新文献_第4页

Photoaging protective effect of enzyme extracted pomegranate peel against oxidative damage in UVB-irradiated HaCaT cells 石榴皮酶提取物对 UVB 照射下 HaCaT 细胞氧化损伤的光老化保护作用。

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2024-11-18 DOI: 10.1016/j.biopha.2024.117679

Yeok Boo Chang , Hae Dun Kim , Sang Min Kim , Ji Hoon Lim , Moon Jea Woo , Hyung Joo Suh , Kyungae Jo

In this study, the ultraviolet B (UVB)-induced skin photoaging inhibitory activity of pomegranate peel extract with increased ellagic acid content through enzymatic hydrolysis was evaluated in HaCaT cells. Among various enzymes, Viscozyme with high tannase and β-glucosidase activities was used, and 1.0 % Viscozyme was added to hydrolyze pomegranate peel for 2 h at 40°C to establish the optimal reaction conditions for high ellagic acid content. Subsequently, when cells were treated with enzyme extracted pomegranate peels (40 μg/mL), the gene expression of matrix metalloproteinases (MMP)-2 and 13, which play key role in skin elasticity and moisture, and the protein expression of MMP13 were downregulated compared to the UVB-control group (UVB-C). In addition, the protein expression levels of tissue inhibitors, metalloproteinase-1 and 2, and collagen type I alpha 1 were upregulated, the gene expression of hyaluronic acid synthase-1, and filaggrin significantly increased, and interleukin-1β increased by photoaging was decreased. Furthermore, compared to the UVB-C, there was a significant increase in the gene expression of superoxide dismutase-1 and glutathione peroxidase, which resulted in a decrease in reactive oxygen species and malondialdehyde levels. These results were confirmed to be due to the inhibition of the mitogen-activated protein kinase pathway and downregulation of the protein expression of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase, and P38. In conclusion, pomegranate peel, from which ellagic acid was extracted using Viscozyme, showed a reactive oxygen species inhibitory effect in UVB-irradiated HaCaT cells and thus may have a significant potential as a cosmetic ingredient with anti-aging effects.

本研究通过酶水解法评估了鞣花酸含量增加的石榴皮提取物在 HaCaT 细胞中抑制紫外线 B（UVB）诱导的皮肤光老化活性。在各种酶中，使用了具有高单宁酶和β-葡萄糖苷酶活性的 Viscozyme，并加入 1.0 % Viscozyme 在 40°C 下水解石榴皮 2 小时，以确定高鞣花酸含量的最佳反应条件。随后，用酶提取的石榴皮（40 μg/mL）处理细胞，与 UVB 对照组（UVB-C）相比，对皮肤弹性和保湿起关键作用的基质金属蛋白酶（MMP）-2 和 13 的基因表达以及 MMP13 的蛋白表达均出现下调。此外，组织抑制剂、金属蛋白酶-1和2、胶原蛋白Ⅰ型α1的蛋白表达水平上调，透明质酸合成酶-1和丝胶蛋白的基因表达显著增加，光老化增加的白细胞介素-1β减少。此外，与 UVB-C 相比，超氧化物歧化酶-1 和谷胱甘肽过氧化物酶的基因表达明显增加，从而导致活性氧和丙二醛水平下降。这些结果被证实是由于抑制了丝裂原活化蛋白激酶途径，下调了磷酸化细胞外信号调节激酶、c-Jun N 端激酶和 P38 的蛋白表达。总之，使用 Viscozyme 从石榴皮中提取的鞣花酸在 UVB 照射的 HaCaT 细胞中显示出活性氧抑制作用，因此石榴皮作为一种具有抗衰老作用的化妆品成分可能具有很大的潜力。

{"title":"Photoaging protective effect of enzyme extracted pomegranate peel against oxidative damage in UVB-irradiated HaCaT cells","authors":"Yeok Boo Chang , Hae Dun Kim , Sang Min Kim , Ji Hoon Lim , Moon Jea Woo , Hyung Joo Suh , Kyungae Jo","doi":"10.1016/j.biopha.2024.117679","DOIUrl":"10.1016/j.biopha.2024.117679","url":null,"abstract":"<div><div>In this study, the ultraviolet B (UVB)-induced skin photoaging inhibitory activity of pomegranate peel extract with increased ellagic acid content through enzymatic hydrolysis was evaluated in HaCaT cells. Among various enzymes, Viscozyme with high tannase and β-glucosidase activities was used, and 1.0 % Viscozyme was added to hydrolyze pomegranate peel for 2 h at 40°C to establish the optimal reaction conditions for high ellagic acid content. Subsequently, when cells were treated with enzyme extracted pomegranate peels (40 μg/mL), the gene expression of matrix metalloproteinases (MMP)-2 and 13, which play key role in skin elasticity and moisture, and the protein expression of MMP13 were downregulated compared to the UVB-control group (UVB-C). In addition, the protein expression levels of tissue inhibitors, metalloproteinase-1 and 2, and collagen type I alpha 1 were upregulated, the gene expression of hyaluronic acid synthase-1, and filaggrin significantly increased, and interleukin-1β increased by photoaging was decreased. Furthermore, compared to the UVB-C, there was a significant increase in the gene expression of superoxide dismutase-1 and glutathione peroxidase, which resulted in a decrease in reactive oxygen species and malondialdehyde levels. These results were confirmed to be due to the inhibition of the mitogen-activated protein kinase pathway and downregulation of the protein expression of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase, and P38. In conclusion, pomegranate peel, from which ellagic acid was extracted using Viscozyme, showed a reactive oxygen species inhibitory effect in UVB-irradiated HaCaT cells and thus may have a significant potential as a cosmetic ingredient with anti-aging effects.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117679"},"PeriodicalIF":6.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cooperative tumor inhibition by CpG-oligodeoxynucleotide and cyclic dinucleotide in head and neck cancer involves T helper cytokine and macrophage phenotype reprogramming CpG-寡脱氧核苷酸和环状二核苷酸对头颈癌的协同肿瘤抑制作用涉及T辅助细胞因子和巨噬细胞表型重编程。

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2024-11-18 DOI: 10.1016/j.biopha.2024.117692

Zaida Nur Imana , Jen-Chih Tseng , Jing-Xing Yang , Yi-Ling Liu , Po-Yen Lin , Ming-Hsi Huang , Linyi Chen , Yunping Luo , Chien-Chia Wang , Guann-Yi Yu , Tsung-Hsien Chuang

Head and neck cancer ranks as the sixth most common cancer worldwide, highlighting the critical need for the development of new therapies to enhance treatment efficacy. The activation of innate immune receptors given their potent immune stimulatory properties aid in the eradication of cancer cells. In this study, we investigated the immune mechanism and anti-tumor function of a Toll-like receptor 9 (TLR9) agonist, CpG-oligodeoxynucleotide-2722 (CpG-2722), in combination with cyclic dinucleotides, which are agonists of stimulator of interferon genes (STING). Our results revealed that CpG-2722 stimulation increased the expression of Th1 pro-inflammatory cytokines. Stimulation by STING agonists exhibited lower expression of Th1 cytokines but higher expression of Th2 cytokines compared to CpG-2722. However, the combination of these two agonists significantly enhanced Th1 cytokines while reducing Th2 cytokines. Moreover, in vivo experiment showed that both CpG-2722 and 2’3’-c-di-AMP suppressed head and neck tumor growth, with their combination proving more effective than the use of these agonists alone. The combined treatment cooperatively promoted the production of Th1 cytokines and type I interferons, while suppressing Th2 cytokines in the tumors as observed in vitro. Additionally, it led to the accumulation of M1 macrophages, dendritic cells, and T cells, shaping a favorable tumor microenvironment for T cell-mediated tumor killing. The anti-tumor activity of the CpG-2722 and 2’3’-c-di-AMP combination depends on the macrophage presence but does not directly activate M1 macrophage polarization, instead working through a reprogrammed cytokine profile. Furthermore, this combination shows a cooperative anti-tumor activity with anti-PD-1 in treating head and neck tumors. Overall, these findings highlight a Th response and macrophage phenotype reprograming involved functional mechanism underlying the cooperative activity of the combination of TLR9 and STING agonists in the immunotherapy of head and neck cancer.

头颈部癌症是全球第六大常见癌症，因此亟需开发新的疗法来提高治疗效果。先天性免疫受体具有强大的免疫刺激特性，激活先天性免疫受体有助于消灭癌细胞。在这项研究中，我们研究了Toll样受体9（TLR9）激动剂CpG-寡脱氧核苷酸-2722（CpG-2722）与环状二核苷酸（干扰素基因刺激器（STING）的激动剂）结合使用的免疫机制和抗肿瘤功能。我们的研究结果表明，CpG-2722 的刺激增加了 Th1 促炎细胞因子的表达。与 CpG-2722 相比，STING 激动剂的刺激表现出较低的 Th1 细胞因子表达，但较高的 Th2 细胞因子表达。然而，这两种激动剂联合使用会显著提高 Th1 细胞因子的表达，同时降低 Th2 细胞因子的表达。此外，体内实验表明，CpG-2722 和 2'3'-c-di-AMP 都能抑制头颈部肿瘤的生长，而且它们的组合比单独使用这两种激动剂更有效。正如体外观察到的那样，联合治疗可协同促进 Th1 细胞因子和 I 型干扰素的产生，同时抑制肿瘤中的 Th2 细胞因子。此外，它还导致了 M1 巨噬细胞、树突状细胞和 T 细胞的聚集，为 T 细胞介导的肿瘤杀伤创造了有利的肿瘤微环境。CpG-2722和2'3'-c-di-AMP组合的抗肿瘤活性取决于巨噬细胞的存在，但并不直接激活M1巨噬细胞的极化，而是通过重新编程的细胞因子谱发挥作用。此外，在治疗头颈部肿瘤时，这种组合与抗-PD-1 具有协同抗肿瘤活性。总之，这些研究结果凸显了 TLR9 和 STING 激动剂组合在头颈部肿瘤免疫疗法中的协同活性背后涉及 Th 反应和巨噬细胞表型重编程的功能机制。

{"title":"Cooperative tumor inhibition by CpG-oligodeoxynucleotide and cyclic dinucleotide in head and neck cancer involves T helper cytokine and macrophage phenotype reprogramming","authors":"Zaida Nur Imana , Jen-Chih Tseng , Jing-Xing Yang , Yi-Ling Liu , Po-Yen Lin , Ming-Hsi Huang , Linyi Chen , Yunping Luo , Chien-Chia Wang , Guann-Yi Yu , Tsung-Hsien Chuang","doi":"10.1016/j.biopha.2024.117692","DOIUrl":"10.1016/j.biopha.2024.117692","url":null,"abstract":"<div><div>Head and neck cancer ranks as the sixth most common cancer worldwide, highlighting the critical need for the development of new therapies to enhance treatment efficacy. The activation of innate immune receptors given their potent immune stimulatory properties aid in the eradication of cancer cells. In this study, we investigated the immune mechanism and anti-tumor function of a Toll-like receptor 9 (TLR9) agonist, CpG-oligodeoxynucleotide-2722 (CpG-2722), in combination with cyclic dinucleotides, which are agonists of stimulator of interferon genes (STING). Our results revealed that CpG-2722 stimulation increased the expression of Th1 pro-inflammatory cytokines. Stimulation by STING agonists exhibited lower expression of Th1 cytokines but higher expression of Th2 cytokines compared to CpG-2722. However, the combination of these two agonists significantly enhanced Th1 cytokines while reducing Th2 cytokines. Moreover, <em>in vivo</em> experiment showed that both CpG-2722 and 2’3’-c-di-AMP suppressed head and neck tumor growth, with their combination proving more effective than the use of these agonists alone. The combined treatment cooperatively promoted the production of Th1 cytokines and type I interferons, while suppressing Th2 cytokines in the tumors as observed <em>in vitro</em>. Additionally, it led to the accumulation of M1 macrophages, dendritic cells, and T cells, shaping a favorable tumor microenvironment for T cell-mediated tumor killing. The anti-tumor activity of the CpG-2722 and 2’3’-c-di-AMP combination depends on the macrophage presence but does not directly activate M1 macrophage polarization, instead working through a reprogrammed cytokine profile. Furthermore, this combination shows a cooperative anti-tumor activity with anti-PD-1 in treating head and neck tumors. Overall, these findings highlight a Th response and macrophage phenotype reprograming involved functional mechanism underlying the cooperative activity of the combination of TLR9 and STING agonists in the immunotherapy of head and neck cancer.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117692"},"PeriodicalIF":6.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel chitosan-peptide system for cartilage tissue engineering with adipose-derived stromal cells 利用脂肪基质细胞进行软骨组织工程的新型壳聚糖-肽系统。

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2024-11-18 DOI: 10.1016/j.biopha.2024.117683

Agata Tymińska , Natalia Karska , Aneta Skoniecka , Małgorzata Zawrzykraj , Adrianna Banach-Kopeć , Szymon Mania , Jacek Zieliński , Karolina Kondej , Katarzyna Gurzawska-Comis , Piotr M. Skowron , Robert Tylingo , Sylwia Rodziewicz-Motowidło , Michał Pikuła

The natural healing process of cartilage injuries often fails to fully restore the tissue’s biological and mechanical functions. Cartilage grafts are costly and require surgical intervention, often associated with complications such as intraoperative infection and rejection by the recipient due to ischemia. Novel tissue engineering technologies aim to ideally fill the cartilage defect to prevent disease progression or regenerate damaged tissue. Despite many studies on designing biocompatible composites to stimulate chondrogenesis, only few focus on peptides and carriers that promote stem cell proliferation or differentiation to promote healing. Our research aimed to design a carbohydrate chitosan-based biomaterial to stimulate stem cells into the chondrogenesis pathway. Our strategy was to combine chitosan with a novel peptide (UG28) that sequence was based on the copin protein. The construct stimulated human adipose-derived stem cells (AD-SCs) cells to undergo chondrogenic differentiation. Chitosan 75/500 allows AD-SCs to grow and has no harmful effects on the cells. The combination of UG28 peptide with the chitosan composite offers promising properties for cell differentiation, indicating its potential for clinical applications in cartilage regeneration.

软骨损伤的自然愈合过程往往无法完全恢复组织的生物和机械功能。软骨移植成本高昂，而且需要手术干预，经常会出现术中感染和受体因缺血而产生排斥反应等并发症。新型组织工程技术旨在理想地填补软骨缺损，防止疾病恶化或再生受损组织。尽管有许多关于设计生物相容性复合材料以刺激软骨生成的研究，但只有少数研究关注促进干细胞增殖或分化以促进愈合的肽和载体。我们的研究旨在设计一种基于壳聚糖的碳水化合物生物材料，以刺激干细胞进入软骨生成途径。我们的策略是将壳聚糖与基于 copin 蛋白序列的新型多肽（UG28）相结合。这种构建物能刺激人类脂肪源性干细胞（AD-SCs）细胞进行软骨分化。壳聚糖 75/500 可使 AD-SCs 生长，且对细胞无害。UG28肽与壳聚糖复合材料的结合为细胞分化提供了良好的特性，显示了其在软骨再生方面的临床应用潜力。

{"title":"A novel chitosan-peptide system for cartilage tissue engineering with adipose-derived stromal cells","authors":"Agata Tymińska , Natalia Karska , Aneta Skoniecka , Małgorzata Zawrzykraj , Adrianna Banach-Kopeć , Szymon Mania , Jacek Zieliński , Karolina Kondej , Katarzyna Gurzawska-Comis , Piotr M. Skowron , Robert Tylingo , Sylwia Rodziewicz-Motowidło , Michał Pikuła","doi":"10.1016/j.biopha.2024.117683","DOIUrl":"10.1016/j.biopha.2024.117683","url":null,"abstract":"<div><div>The natural healing process of cartilage injuries often fails to fully restore the tissue’s biological and mechanical functions. Cartilage grafts are costly and require surgical intervention, often associated with complications such as intraoperative infection and rejection by the recipient due to ischemia. Novel tissue engineering technologies aim to ideally fill the cartilage defect to prevent disease progression or regenerate damaged tissue. Despite many studies on designing biocompatible composites to stimulate chondrogenesis, only few focus on peptides and carriers that promote stem cell proliferation or differentiation to promote healing. Our research aimed to design a carbohydrate chitosan-based biomaterial to stimulate stem cells into the chondrogenesis pathway. Our strategy was to combine chitosan with a novel peptide (UG28) that sequence was based on the copin protein. The construct stimulated human adipose-derived stem cells (AD-SCs) cells to undergo chondrogenic differentiation. Chitosan 75/500 allows AD-SCs to grow and has no harmful effects on the cells. The combination of UG28 peptide with the chitosan composite offers promising properties for cell differentiation, indicating its potential for clinical applications in cartilage regeneration.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117683"},"PeriodicalIF":6.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing lung cancer growth inhibition with calcium ions: Role of mid- and high-frequency electric field pulses 用钙离子增强对肺癌生长的抑制作用：中频和高频电场脉冲的作用

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2024-11-17 DOI: 10.1016/j.biopha.2024.117691

Nina Rembiałkowska , Julia Kucharczyk , Eivina Radzevičiūtė-Valčiukė , Vitalij Novickij , Margherita Tonci , Ata Dündar , Julita Kulbacka , Wojciech Szlasa

Calcium electroporation (CaEP) involves the combination of calcium ions with electroporation, which is induced by pulsed electric fields (PEFs). This study explores the application of high-frequency unipolar nanosecond pulsed electric fields (nsPEFs: 8–14 kV/cm, 200 ns, 10 kHz, 100 kHz, 1 MHz repetition frequency pulse bursts, n = 100) and their potential in inhibiting lung cancer cell growth. As a reference, standard microsecond range parametric protocols were used (100 µs x 8 pulses). Methods included cell permeability quantification through Yo-Pro-1 uptake, cell viability assays, immunofluorescence studies for apoptosis and EMT markers, analysis of cell death types depending on repetition frequency pulse bursts. We determined the susceptibility of human lung cancer to electric pulses, characterized the efficacy of CaEP, and investigated cell death types depending on repetition frequency pulse bursts. We have shown that adding calcium ions to the applied nsPEF protocol increases cytotoxicity. Additionally, the use of these electroporation parameters can modulate key cellular processes, such as the epithelial-mesenchymal transition and apoptosis, as indicated by changes in the expression of markers such as E-cadherin, N-cadherin, BCL-2, and p53. Changes in cell morphology over time were observed using holotomographic microscopy. The study provides insights into the modulation of key cellular processes, indicating that nsPEF technology could improve the outcomes of conventional cancer treatments through enhanced efficacy and potentially mitigating drug resistance mechanisms. The promising results advocate for further research to optimize nsPEF protocols for clinical application, highlighting the potential of electrical fields in advancing cancer therapy.

钙电穿孔（CaEP）涉及钙离子与电穿孔的结合，而电穿孔是由脉冲电场（PEFs）诱导的。本研究探索了高频单极纳秒脉冲电场（nsPEFs）的应用：8-14 kV/cm、200 ns、10 kHz、100 kHz、1 MHz 重复频率脉冲串，n = 100）的应用及其抑制肺癌细胞生长的潜力。作为参考，使用了标准微秒范围参数方案（100 µs x 8 脉冲）。研究方法包括通过 Yo-Pro-1 摄取量化细胞渗透性、细胞活力测定、细胞凋亡和 EMT 标记的免疫荧光研究，以及根据重复频率脉冲串分析细胞死亡类型。我们确定了人类肺癌对电脉冲的易感性，描述了 CaEP 的功效，并根据重复频率脉冲串研究了细胞死亡类型。我们发现，在应用的 nsPEF 方案中加入钙离子会增加细胞毒性。此外，这些电穿孔参数的使用可以调节关键的细胞过程，如上皮-间质转化和细胞凋亡，如 E-cadherin、N-cadherin、BCL-2 和 p53 等标志物的表达变化。使用全息显微镜观察了细胞形态随时间的变化。这项研究深入揭示了关键细胞过程的调控，表明 nsPEF 技术可以通过增强疗效和潜在的减轻耐药机制来改善传统癌症治疗的结果。这些令人鼓舞的结果推动了进一步的研究，以优化 nsPEF 方案的临床应用，凸显了电场在推进癌症治疗方面的潜力。

{"title":"Enhancing lung cancer growth inhibition with calcium ions: Role of mid- and high-frequency electric field pulses","authors":"Nina Rembiałkowska , Julia Kucharczyk , Eivina Radzevičiūtė-Valčiukė , Vitalij Novickij , Margherita Tonci , Ata Dündar , Julita Kulbacka , Wojciech Szlasa","doi":"10.1016/j.biopha.2024.117691","DOIUrl":"10.1016/j.biopha.2024.117691","url":null,"abstract":"<div><div>Calcium electroporation (CaEP) involves the combination of calcium ions with electroporation, which is induced by pulsed electric fields (PEFs). This study explores the application of high-frequency unipolar nanosecond pulsed electric fields (nsPEFs: 8–14 kV/cm, 200 ns, 10 kHz, 100 kHz, 1 MHz repetition frequency pulse bursts, n = 100) and their potential in inhibiting lung cancer cell growth. As a reference, standard microsecond range parametric protocols were used (100 µs x 8 pulses). Methods included cell permeability quantification through Yo-Pro-1 uptake, cell viability assays, immunofluorescence studies for apoptosis and EMT markers, analysis of cell death types depending on repetition frequency pulse bursts. We determined the susceptibility of human lung cancer to electric pulses, characterized the efficacy of CaEP, and investigated cell death types depending on repetition frequency pulse bursts. We have shown that adding calcium ions to the applied nsPEF protocol increases cytotoxicity. Additionally, the use of these electroporation parameters can modulate key cellular processes, such as the epithelial-mesenchymal transition and apoptosis, as indicated by changes in the expression of markers such as E-cadherin, N-cadherin, BCL-2, and p53. Changes in cell morphology over time were observed using holotomographic microscopy. The study provides insights into the modulation of key cellular processes, indicating that nsPEF technology could improve the outcomes of conventional cancer treatments through enhanced efficacy and potentially mitigating drug resistance mechanisms. The promising results advocate for further research to optimize nsPEF protocols for clinical application, highlighting the potential of electrical fields in advancing cancer therapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117691"},"PeriodicalIF":6.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis, characterisation, and anti-tumour activity of nano-immuno-conjugates for enhanced photodynamic therapy of oesophageal cancer stem cells 用于增强食道癌干细胞光动力疗法的纳米免疫共轭物的合成、表征和抗肿瘤活性。

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2024-11-16 DOI: 10.1016/j.biopha.2024.117693

Onyisi Christiana Didamson , Rahul Chandran , Heidi Abrahamse

In recent times, oesophageal cancer has been listed as the eleventh most prevalent type of cancer. It is a lethal disease attributed to a high mortality rate, tumour metastasis and poor treatment outcome. A subset of oesophageal cancer referred to as stem cells (CSCs) has been revealed to drive carcinogenesis, metastasis, and treatment failure. Therefore, it is essential to target these CSCs to improve the efficacy of treatment for oesophageal cancer. In this present study, we employed a strategy to target oesophageal CSCs with a nano-immuno-conjugate (NIC) consisting of AlPcS₄Cl, gold nanoparticle (AuNPs) and anti-CD271 antibody synthesised using a chemical reaction. The synthesised NIC was characterised using ultraviolet-visible spectroscopy, transmission electron microscope (TEM), Fourier transform infra-red (FTIR) spectroscopy, dynamic light scattering (DLS), and zeta potential (ZP). The in vitro anti-tumour action of NIC-mediated photodynamic therapy (PDT) was performed on oesophageal CSCs using cell viability/cytotoxicity assays and morphological examination via light microscopy. The characterisation analysis confirmed the successful synthesis of the NIC. The synthesised nano-immuno-conjugates showed significant cytotoxicity and reduction in cell viability in the HKESC-1 oesophageal CSCs. Fluorescence microscopy confirmed the rapid internalisation of the targeted NIC in key cellular organelles of the CSCs, resulting in enhanced effects. Interestingly, NIC exhibited cytocompatibility with non-tumour WS1 cells, thus supporting its clinical application as a safe anti-tumour agent for enhanced PDT. The study demonstrates the improved effects of NIC-mediated PDT as targeted therapeutics against oesophageal CSCs.

近来，食道癌已被列为发病率第十一位的癌症类型。食道癌是一种致命疾病，死亡率高、肿瘤转移和治疗效果差。研究发现，食管癌的一个亚群被称为干细胞（CSCs），它们是癌变、转移和治疗失败的驱动因素。因此，针对这些干细胞提高食道癌的治疗效果至关重要。在本研究中，我们采用了一种靶向食管癌 CSCs 的策略，即利用化学反应合成由 AlPcS4Cl、金纳米粒子（AuNPs）和抗 CD271 抗体组成的纳米免疫共轭物（NIC）。利用紫外可见光谱、透射电子显微镜（TEM）、傅立叶变换红外光谱（FTIR）、动态光散射（DLS）和 zeta 电位（ZP）对合成的 NIC 进行了表征。利用细胞存活率/毒性测定法和光镜形态学检查法，对食道癌细胞间充质干细胞进行了 NIC 介导的光动力疗法（PDT）体外抗肿瘤作用研究。表征分析证实成功合成了 NIC。合成的纳米免疫共轭物在 HKESC-1 食管干细胞中显示出显著的细胞毒性并降低了细胞活力。荧光显微镜证实，靶向 NIC 在 CSCs 的关键细胞器中快速内化，从而增强了作用。有趣的是，NIC 与非肿瘤 WS1 细胞表现出细胞相容性，因此支持其作为一种安全的抗肿瘤药物应用于临床，以增强 PDT 的效果。这项研究表明，NIC 介导的光导光疗作为针对食道癌细胞间充质干细胞的靶向疗法，具有更好的效果。

{"title":"Synthesis, characterisation, and anti-tumour activity of nano-immuno-conjugates for enhanced photodynamic therapy of oesophageal cancer stem cells","authors":"Onyisi Christiana Didamson , Rahul Chandran , Heidi Abrahamse","doi":"10.1016/j.biopha.2024.117693","DOIUrl":"10.1016/j.biopha.2024.117693","url":null,"abstract":"<div><div>In recent times, oesophageal cancer has been listed as the eleventh most prevalent type of cancer. It is a lethal disease attributed to a high mortality rate, tumour metastasis and poor treatment outcome. A subset of oesophageal cancer referred to as stem cells (CSCs) has been revealed to drive carcinogenesis, metastasis, and treatment failure. Therefore, it is essential to target these CSCs to improve the efficacy of treatment for oesophageal cancer. In this present study, we employed a strategy to target oesophageal CSCs with a nano-immuno-conjugate (NIC) consisting of AlPcS<sub>4</sub>Cl, gold nanoparticle (AuNPs) and anti-CD271 antibody synthesised using a chemical reaction. The synthesised NIC was characterised using ultraviolet-visible spectroscopy, transmission electron microscope (TEM), Fourier transform infra-red (FTIR) spectroscopy, dynamic light scattering (DLS), and zeta potential (ZP). The <em>in vitro</em> anti-tumour action of NIC-mediated photodynamic therapy (PDT) was performed on oesophageal CSCs using cell viability/cytotoxicity assays and morphological examination via light microscopy. The characterisation analysis confirmed the successful synthesis of the NIC. The synthesised nano-immuno-conjugates showed significant cytotoxicity and reduction in cell viability in the HKESC-1 oesophageal CSCs. Fluorescence microscopy confirmed the rapid internalisation of the targeted NIC in key cellular organelles of the CSCs, resulting in enhanced effects. Interestingly, NIC exhibited cytocompatibility with non-tumour WS1 cells, thus supporting its clinical application as a safe anti-tumour agent for enhanced PDT. The study demonstrates the improved effects of NIC-mediated PDT as targeted therapeutics against oesophageal CSCs.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117693"},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","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 possible role of hypoxia-induced exosomes on the fibroblast metabolism in idiopathic pulmonary fibrosis 缺氧诱导的外泌体对特发性肺纤维化中成纤维细胞代谢的可能作用

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2024-11-16 DOI: 10.1016/j.biopha.2024.117680

Noé Alvarado-Vasquez , Claudia Rangel-Escareño , Javier de Jesús Ramos-Abundis , Carina Becerril , María Cristina Negrete-García

Idiopathic pulmonary fibrosis (IPF) has a high incidence and prevalence among patients over 65 years old. While its exact etiology remains unknown, several risk factors have recently been identified. Hypoxia is associated with IPF due to the abnormal architecture of lung parenchyma and the accumulation of extracellular matrix produced by activated fibroblasts. Exosomes play a crucial role in intercellular communication during both physiological and pathological processes, including hypoxic diseases like IPF. Recent findings suggest that a hypoxic microenvironment influences the content of exosomes in various diseases, thereby altering cellular metabolism. Although the role of exosomes in IPF is an emerging area of research, the significance of hypoxic exosomes as inducers of metabolic reprogramming in fibroblasts is still underexplored. In this study, we analyze and discuss the relationship between hypoxia, exosomal cargo, and the metabolic reprogramming of fibroblasts in the progression of IPF.

特发性肺纤维化（IPF）在 65 岁以上的患者中发病率和流行率都很高。虽然其确切病因尚不清楚，但最近已确定了几个风险因素。由于肺实质结构异常以及活化的成纤维细胞产生的细胞外基质堆积，缺氧与 IPF 有关。外泌体在生理和病理过程（包括 IPF 等缺氧性疾病）中的细胞间通信中发挥着至关重要的作用。最近的研究结果表明，缺氧微环境会影响各种疾病中外泌体的含量，从而改变细胞的新陈代谢。虽然外泌体在 IPF 中的作用是一个新兴的研究领域，但低氧外泌体作为成纤维细胞代谢重编程诱导剂的意义仍未得到充分探索。在本研究中，我们分析并讨论了IPF进展过程中缺氧、外泌体货物和成纤维细胞代谢重编程之间的关系。

{"title":"The possible role of hypoxia-induced exosomes on the fibroblast metabolism in idiopathic pulmonary fibrosis","authors":"Noé Alvarado-Vasquez , Claudia Rangel-Escareño , Javier de Jesús Ramos-Abundis , Carina Becerril , María Cristina Negrete-García","doi":"10.1016/j.biopha.2024.117680","DOIUrl":"10.1016/j.biopha.2024.117680","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) has a high incidence and prevalence among patients over 65 years old. While its exact etiology remains unknown, several risk factors have recently been identified. Hypoxia is associated with IPF due to the abnormal architecture of lung parenchyma and the accumulation of extracellular matrix produced by activated fibroblasts. Exosomes play a crucial role in intercellular communication during both physiological and pathological processes, including hypoxic diseases like IPF. Recent findings suggest that a hypoxic microenvironment influences the content of exosomes in various diseases, thereby altering cellular metabolism. Although the role of exosomes in IPF is an emerging area of research, the significance of hypoxic exosomes as inducers of metabolic reprogramming in fibroblasts is still underexplored. In this study, we analyze and discuss the relationship between hypoxia, exosomal cargo, and the metabolic reprogramming of fibroblasts in the progression of IPF.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117680"},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Monosaccharides improve symptoms of an animal model for type III galactosemia, through the activation of the insulin pathway 通过激活胰岛素途径，单糖可改善 III 型半乳糖血症动物模型的症状。

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2024-11-16 DOI: 10.1016/j.biopha.2024.117677

Patricia Lucas-Rodríguez , Ana María Brokate-Llanos , José Manuel Hernandez-Curiel , Piedad del Socorro Murdoch , Andrés Garzón , Angel Carrión , Manuel J. Muñoz

Type III galactosemia is characterized by the inability to metabolize galactose due to deficiency of the UDP-galactose-4-epimerase (GALE) gene, which catalyzes the interconversion of UDP-Galactose and UDP-Glucose. Additionally, GALE interconverts UDP-N-Acetylgalactosamine and UDP-N-Acetylglucosamine. These four sugars are needed for glycosylation of biomolecules. GALE deletion is considered lethal, and all described patients carry hypomorphic mutations. Symptoms are diverse and can range from mild to severe, without effective treatment. We have previously generated a Caenorhabditis elegans model for type III galactosemia, which carries a hypomorphic mutation in the GALE gene homologue. In this model, we observed that the symptoms varied depending on the diet. The aim of this work is to identify which dietary metabolites might alleviate the symptoms of type III galactosemia. To identify the molecules responsible, we used a C. elegans model of type III galactosemia and a mouse model to test whether the respond to the treatment is conserved in mammals and thus could be a putative intervention in patients.

We found that high levels of monosaccharides in the diet is responsible for the beneficial effect in the C. elegans model. This intervention generates an increase of gale-1 expression through activation of the insulin pathway which may explain the reduction of the symptoms in animals carrying hypomorphic mutations. The increase of the GALE gene expression after monosaccharides treatment is also conserved in mammals and if maintained in humans, monosaccharide treatment combined with monitorization of GALE expression could be included in the management of patients with type III galactosemia.

III 型半乳糖血症的特征是由于缺乏 UDP-半乳糖-4-epimerase（GALE）基因而无法代谢半乳糖，该基因可催化 UDP-半乳糖和 UDP-葡萄糖的相互转化。此外，GALE 还能相互转化 UDP-N-乙酰半乳糖胺和 UDP-N-乙酰葡糖胺。生物大分子的糖基化需要这四种糖。GALE 基因缺失被认为是致命的，所有描述的患者都携带低形突变。症状多种多样，从轻微到严重不等，且没有有效的治疗方法。我们以前曾为 III 型半乳糖血症建立了一个 elegans Caenorhabditis 模型，该模型携带 GALE 基因同源物的低形变突变。在该模型中，我们观察到症状随饮食而变化。这项工作的目的是确定哪些饮食代谢物可减轻 III 型半乳糖血症的症状。为了确定负责的分子，我们使用了III型半乳糖血症的优雅小鼠模型和小鼠模型，以测试哺乳动物对治疗的反应是否一致，从而对患者进行干预。我们发现，饮食中的高浓度单糖对优雅小鼠模型产生了有益影响。这种干预措施通过激活胰岛素途径增加了 GALE-1 的表达，这可能是携带低形态突变的动物症状减轻的原因。单糖治疗后 GALE 基因表达的增加在哺乳动物中也得到了保留，如果在人类中得到保留，单糖治疗结合 GALE 表达的监测可被纳入 III 型半乳糖血症患者的治疗中。

{"title":"Monosaccharides improve symptoms of an animal model for type III galactosemia, through the activation of the insulin pathway","authors":"Patricia Lucas-Rodríguez , Ana María Brokate-Llanos , José Manuel Hernandez-Curiel , Piedad del Socorro Murdoch , Andrés Garzón , Angel Carrión , Manuel J. Muñoz","doi":"10.1016/j.biopha.2024.117677","DOIUrl":"10.1016/j.biopha.2024.117677","url":null,"abstract":"<div><div>Type III galactosemia is characterized by the inability to metabolize galactose due to deficiency of the UDP-galactose-4-epimerase (GALE) gene, which catalyzes the interconversion of UDP-Galactose and UDP-Glucose. Additionally, GALE interconverts UDP-N-Acetylgalactosamine and UDP-N-Acetylglucosamine. These four sugars are needed for glycosylation of biomolecules. GALE deletion is considered lethal, and all described patients carry hypomorphic mutations. Symptoms are diverse and can range from mild to severe, without effective treatment. We have previously generated a <em>Caenorhabditis elegans</em> model for type III galactosemia, which carries a hypomorphic mutation in the GALE gene homologue. In this model, we observed that the symptoms varied depending on the diet. The aim of this work is to identify which dietary metabolites might alleviate the symptoms of type III galactosemia. To identify the molecules responsible, we used a <em>C. elegans</em> model of type III galactosemia and a mouse model to test whether the respond to the treatment is conserved in mammals and thus could be a putative intervention in patients.</div><div>We found that high levels of monosaccharides in the diet is responsible for the beneficial effect in the <em>C. elegans</em> model. This intervention generates an increase of <em>gale-1</em> expression through activation of the insulin pathway which may explain the reduction of the symptoms in animals carrying hypomorphic mutations. The increase of the GALE gene expression after monosaccharides treatment is also conserved in mammals and if maintained in humans, monosaccharide treatment combined with monitorization of GALE expression could be included in the management of patients with type III galactosemia.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117677"},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of breast cancer growth with AN-329, a novel Hsp110 inhibitor, by inactivating p-STAT3/c-Myc axis 新型 Hsp110 抑制剂 AN-329 通过使 p-STAT3/c-Myc 轴失活来抑制乳腺癌的生长。

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2024-11-16 DOI: 10.1016/j.biopha.2024.117694

Junnan Li , Ruizhe Gao , Congke Zhao , Honglin Xiang , Xiangyang Le , Xinyang Zhang , Qinling Cai , Lei He , Qianbin Li , Liqing Hu , Hui Zou

Breast cancer, a leading cause of cancer-related mortality in women, is characterized by its propensity for metastasis. Heat shock protein 110 (Hsp110), a molecular chaperone encoded by the HSPH1 gene, has been implicated in cancer progression, including breast cancer, where it is upregulated and associated with worse outcomes. However, the role of Hsp110 in breast cancer pathogenesis and its potential as a therapeutic target have not been thoroughly investigated. This study utilized the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database to analyze HSPH1 gene expression in breast cancer and its correlation with tumor progression and survival. Furthermore, a comprehensive screen of the Specs database led to the identification of AN-329, a novel inhibitor that binds directly to the nucleotide-binding domain of Hsp110, neutralizing its chaperone activity and inhibiting breast cancer cell growth. AN-329 was validated in vitro for its antitumor efficacy and was found to regulate the cell cycle through the p-STAT3/c-Myc axis. This work suggests that AN-329 could be a promising lead for developing innovative therapeutic agents against breast cancer, warranting further research and potential clinical translation.

乳腺癌是女性癌症相关死亡的主要原因，其特点是容易转移。热休克蛋白 110（Hsp110）是一种由 HSPH1 基因编码的分子伴侣蛋白，已被证实与癌症进展有关，包括与乳腺癌的进展有关。然而，Hsp110 在乳腺癌发病机制中的作用及其作为治疗靶点的潜力尚未得到深入研究。本研究利用基因表达总库（GEO）和癌症基因组图谱（TCGA）数据库分析了乳腺癌中 HSPH1 基因的表达及其与肿瘤进展和生存的相关性。此外，通过对Specs数据库的全面筛选，发现了一种新型抑制剂AN-329，它能直接与Hsp110的核苷酸结合域结合，中和其伴侣活性，抑制乳腺癌细胞的生长。AN-329 的抗肿瘤功效在体外进行了验证，发现它能通过 p-STAT3/c-Myc 轴调节细胞周期。这项研究表明，AN-329 有望成为开发创新型乳腺癌治疗药物的先导，值得进一步研究，并有可能应用于临床。

{"title":"Inhibition of breast cancer growth with AN-329, a novel Hsp110 inhibitor, by inactivating p-STAT3/c-Myc axis","authors":"Junnan Li , Ruizhe Gao , Congke Zhao , Honglin Xiang , Xiangyang Le , Xinyang Zhang , Qinling Cai , Lei He , Qianbin Li , Liqing Hu , Hui Zou","doi":"10.1016/j.biopha.2024.117694","DOIUrl":"10.1016/j.biopha.2024.117694","url":null,"abstract":"<div><div>Breast cancer, a leading cause of cancer-related mortality in women, is characterized by its propensity for metastasis. Heat shock protein 110 (Hsp110), a molecular chaperone encoded by the <em>HSPH1</em> gene, has been implicated in cancer progression, including breast cancer, where it is upregulated and associated with worse outcomes. However, the role of Hsp110 in breast cancer pathogenesis and its potential as a therapeutic target have not been thoroughly investigated. This study utilized the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database to analyze <em>HSPH1</em> gene expression in breast cancer and its correlation with tumor progression and survival. Furthermore, a comprehensive screen of the Specs database led to the identification of AN-329, a novel inhibitor that binds directly to the nucleotide-binding domain of Hsp110, neutralizing its chaperone activity and inhibiting breast cancer cell growth. AN-329 was validated in vitro for its antitumor efficacy and was found to regulate the cell cycle through the p-STAT3/c-Myc axis. This work suggests that AN-329 could be a promising lead for developing innovative therapeutic agents against breast cancer, warranting further research and potential clinical translation.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117694"},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transplant of gut microbiota ameliorates metabolic and heart disorders in rats fed with a hypercaloric diet by modulating microbial metabolism and diversity 通过调节微生物的新陈代谢和多样性，移植肠道微生物群可改善以高热量饮食喂养的大鼠的代谢和心脏疾病。

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2024-11-15 DOI: 10.1016/j.biopha.2024.117667

Betsy Anaid Peña-Ocaña , Mayel Silva-Flores , Toya Shotaro , Leslie García-Gálvez , Luz Hernández-Esquivel , Diana Xochiquetzal Robledo-Cadena , Diana Barrera-Oviedo , Israel Pérez-Torres , Oswaldo Tostado-Islas , Toshinari Maeda , José S. Rodríguez-Zavala , Álvaro Marín-Hernández , Rodolfo García-Contreras , Ricardo Jasso-Chávez

Metabolic syndrome (MS) is a cluster of metabolic disorders which have a tight correlation with dysbiosis of gut microbiota (GM) that have to be treated to avoid higher risks for health. In this work, probiotics obtained from healthy cultured GM were provided to rats with metabolic syndrome (MSR) as therapy in treating MS through the correction of dysbiosis. MSR showed obesity, high blood pressure, abnormal blood chemistry parameters and high heart rate respect to control rats (CNTR). Cultivated GM from feces of MSR in media favoring anaerobic species, showed dysbiosis as judged by differences in the 16S rRNA metabarcoding analysis and by affected intermediary metabolism (methane and SCFA production, nutrients consumption and enzyme activities) compared to CNTR. The metabarcoding analysis of cultured healthy GM identified 211 species, which were further transplanted alive in MSR once a week for 9 weeks. Thereafter, in transplanted MSR the excess of Clostridium and Lactobacillus diminished, while Prevotella, Eubacterium, Faecalibacterium and methanogens, among others increased, leading to the recovery of the microbial metabolic capacity. The presence of butyric acid-producing bacteria in the transplanted GM correlated with increased levels of anti-inflammatory cytokines. Therefore, transplanted MSR recovered the normal levels of weight, blood glucose, triglycerides and cholesterol as well as the heart function. Data suggested that the great diversity of species contained in the GM transplanted restored the microbial metabolism, consuming excessive nutrients and secondary metabolites produced by MS. The use of cultivated GM as probiotics may be a safer alternative for the treatment of different diseases.

代谢综合征（MS）是一组代谢紊乱疾病，与肠道微生物群（GM）的菌群失调密切相关。在这项研究中，从健康培养的 GM 中获得的益生菌被提供给患有代谢综合征的大鼠（MSR），作为通过纠正菌群失调治疗代谢综合征的疗法。与对照组大鼠（CNTR）相比，MSR 表现出肥胖、高血压、血液化学指标异常和高心率。与 CNTR 相比，通过 16S rRNA 代谢编码分析的差异和受影响的中间代谢（甲烷和 SCFA 的产生、营养物质的消耗和酶活性）判断，从 MSR 粪便中培养的 GM 在有利于厌氧物种的培养基中显示出菌群失调。对培养的健康转基因生物进行的代谢编码分析确定了 211 个物种，将这些物种活体移植到 MSR 中，每周一次，持续 9 周。此后，在移植的 MSR 中，梭状芽孢杆菌和乳酸杆菌的数量减少，而普雷沃特氏菌、优杆菌、粪杆菌和甲烷菌等数量增加，从而恢复了微生物的代谢能力。移植的转基因中存在产丁酸的细菌与抗炎细胞因子水平的增加有关。因此，移植的 MSR 恢复了正常的体重、血糖、甘油三酯和胆固醇水平以及心脏功能。数据表明，移植的转基因所含物种的多样性恢复了微生物的新陈代谢，消耗了 MS 产生的过多营养物质和次级代谢产物。使用培育的转基因作为益生菌可能是治疗不同疾病的一种更安全的替代方法。

{"title":"Transplant of gut microbiota ameliorates metabolic and heart disorders in rats fed with a hypercaloric diet by modulating microbial metabolism and diversity","authors":"Betsy Anaid Peña-Ocaña , Mayel Silva-Flores , Toya Shotaro , Leslie García-Gálvez , Luz Hernández-Esquivel , Diana Xochiquetzal Robledo-Cadena , Diana Barrera-Oviedo , Israel Pérez-Torres , Oswaldo Tostado-Islas , Toshinari Maeda , José S. Rodríguez-Zavala , Álvaro Marín-Hernández , Rodolfo García-Contreras , Ricardo Jasso-Chávez","doi":"10.1016/j.biopha.2024.117667","DOIUrl":"10.1016/j.biopha.2024.117667","url":null,"abstract":"<div><div>Metabolic syndrome (MS) is a cluster of metabolic disorders which have a tight correlation with dysbiosis of gut microbiota (GM) that have to be treated to avoid higher risks for health. In this work, probiotics obtained from healthy cultured GM were provided to rats with metabolic syndrome (MSR) as therapy in treating MS through the correction of dysbiosis. MSR showed obesity, high blood pressure, abnormal blood chemistry parameters and high heart rate respect to control rats (CNTR). Cultivated GM from feces of MSR in media favoring anaerobic species, showed dysbiosis as judged by differences in the 16S rRNA metabarcoding analysis and by affected intermediary metabolism (methane and SCFA production, nutrients consumption and enzyme activities) compared to CNTR. The metabarcoding analysis of cultured healthy GM identified 211 species, which were further transplanted alive in MSR once a week for 9 weeks. Thereafter, in transplanted MSR the excess of <em>Clostridium</em> and <em>Lactobacillus</em> diminished, while <em>Prevotella</em>, <em>Eubacterium</em>, <em>Faecalibacterium</em> and methanogens, among others increased, leading to the recovery of the microbial metabolic capacity. The presence of butyric acid-producing bacteria in the transplanted GM correlated with increased levels of anti-inflammatory cytokines. Therefore, transplanted MSR recovered the normal levels of weight, blood glucose, triglycerides and cholesterol as well as the heart function. Data suggested that the great diversity of species contained in the GM transplanted restored the microbial metabolism, consuming excessive nutrients and secondary metabolites produced by MS. The use of cultivated GM as probiotics may be a safer alternative for the treatment of different diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117667"},"PeriodicalIF":6.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acute effects of L-DOPA/carbidopa/buspirone (Spinalon™) on rhythmic electrical activity of the lumbosacral spinal cord in cats L-DOPA/卡比多巴/丁螺环酮（Spinalon™）对猫腰骶部脊髓节律性电活动的急性影响。

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2024-11-15 DOI: 10.1016/j.biopha.2024.117687

Mayra Moreno-Castillo , Pierre A. Guertin , Elias Manjarrez

Discovered by Guertin and colleagues in 2004, Spinalon™ is a fixed-drug combination (L-DOPA, carbidopa, and buspirone) that can acutely induce temporary episodes of rhythmic locomotor-like activity in complete or near-complete spinal cord-injured (SCI) subjects. However, little is known about the mechanisms of action or the direct effects of Spinalon™ on neural elements of the central pattern generators (CPGs). Our study aims at characterizing the effects of Spinalon™ on electrical activity of the spinal cord in segmental areas known to contain key rhythmogenic elements of the CPGs (i.e., lumbosacral) for scratching and locomotion. We recorded spinal cord dorsum signals from decerebrate cats using a multielectrode array placed over the lumbosacral region. We found that a single intravenous injection of 100/25/7.5 mg/kg L-DOPA/carbidopa/buspirone (Spinalon™) specifically reduced the amplitude of electrical sinusoidal waves associated with fictive scratching and promoted the appearance of electrical sinusoidal-like waves occurring at frequencies compatible with fictive locomotion. These observations suggest a profound impact of Spinalon™ on the lumbosacral CPGs.

Spinalon™是由Guertin及其同事于2004年发现的一种固定组合药物（L-DOPA、卡比多巴和丁螺环酮），可急性诱导完全或接近完全脊髓损伤（SCI）受试者出现暂时性节律性运动样活动。然而，人们对 Spinalon™ 的作用机制或对中枢模式发生器（CPG）神经元的直接影响知之甚少。我们的研究旨在确定 Spinalon™ 对已知包含用于搔抓和运动的中央模式发生器（即腰骶部）关键节律发生元件的节段区域脊髓电活动的影响。我们使用放置在腰骶部的多电极阵列记录了去脑猫的脊髓背侧信号。我们发现，单次静脉注射 100/25/7.5 mg/kg L-DOPA/ 卡比多巴/丁螺环酮（Spinalon™）可特异性地降低与假性抓挠相关的正弦波的振幅，并促进出现与假性运动频率相匹配的正弦波。这些观察结果表明 Spinalon™ 对腰骶部 CPG 有深远的影响。

{"title":"Acute effects of L-DOPA/carbidopa/buspirone (Spinalon™) on rhythmic electrical activity of the lumbosacral spinal cord in cats","authors":"Mayra Moreno-Castillo , Pierre A. Guertin , Elias Manjarrez","doi":"10.1016/j.biopha.2024.117687","DOIUrl":"10.1016/j.biopha.2024.117687","url":null,"abstract":"<div><div>Discovered by Guertin and colleagues in 2004, Spinalon™ is a fixed-drug combination (L-DOPA, carbidopa, and buspirone) that can acutely induce temporary episodes of rhythmic locomotor-like activity in complete or near-complete spinal cord-injured (SCI) subjects. However, little is known about the mechanisms of action or the direct effects of Spinalon™ on neural elements of the central pattern generators (CPGs). Our study aims at characterizing the effects of Spinalon™ on electrical activity of the spinal cord in segmental areas known to contain key rhythmogenic elements of the CPGs (i.e., lumbosacral) for scratching and locomotion. We recorded spinal cord dorsum signals from decerebrate cats using a multielectrode array placed over the lumbosacral region. We found that a single intravenous injection of 100/25/7.5 mg/kg L-DOPA/carbidopa/buspirone (Spinalon™) specifically reduced the amplitude of electrical sinusoidal waves associated with fictive scratching and promoted the appearance of electrical sinusoidal-like waves occurring at frequencies compatible with fictive locomotion. These observations suggest a profound impact of Spinalon™ on the lumbosacral CPGs.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117687"},"PeriodicalIF":6.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0