A. Majdalawieh, Sarah M Yousef, I. Abu-Yousef, G. Nasrallah
Natural products with known safety profiles are a promising source for the discovery of new drug leads. Berberine presents an example of one such phytochemical that has been extensively studied for its anti-inflammatory and immunomodulatory properties against myriads of diseases, ranging from respiratory disorders to viral infections. A growing body of research supports the pluripotent therapeutic role berberine may play against the dreaded disease COVID-19. The exact pathophysiological features of COVID-19 are yet to be elucidated. However, compelling evidence suggests inflammation and immune dysregulations as major features of this disease. Being a potent immunomodulatory and anti-inflammatory agent, berberine may prove to be useful for the prevention and treatment of COVID-19. This review aims to revisit the pharmacological anti-inflammatory and immunomodulatory benefits of berberine on a multitude of respiratory infections, which like COVID-19, are known to adversely affect the airways and lungs. We speculate that berberine may help alleviate COVID-19 via preventing cytokine storm, restoring Th1/Th2 balance, and enhancing cell-mediated immunity. Furthermore, the role this promising phytochemical plays on other important inflammatory mediators involved in respiratory disorders will be underscored. We further highlight the role of berberine against COVID-19 by underscoring direct evidence from in silico, in vitro, and in vivo studies suggesting the inhibitory potential berberine may play against three critical SARS-CoV-2 targets, namely main protease, spike protein, and angiotensin-converting enzyme 2 receptor. Further preclinical and clinical trials are certainly required to further substantiate the efficacy and potency of berberine against COVID-19 in humans.
{"title":"Immunomodulatory and Anti-Inflammatory Effects of Berberine in Lung Tissue and its Potential Application in Prophylaxis and Treatment of COVID-19.","authors":"A. Majdalawieh, Sarah M Yousef, I. Abu-Yousef, G. Nasrallah","doi":"10.31083/j.fbl2705166","DOIUrl":"https://doi.org/10.31083/j.fbl2705166","url":null,"abstract":"Natural products with known safety profiles are a promising source for the discovery of new drug leads. Berberine presents an example of one such phytochemical that has been extensively studied for its anti-inflammatory and immunomodulatory properties against myriads of diseases, ranging from respiratory disorders to viral infections. A growing body of research supports the pluripotent therapeutic role berberine may play against the dreaded disease COVID-19. The exact pathophysiological features of COVID-19 are yet to be elucidated. However, compelling evidence suggests inflammation and immune dysregulations as major features of this disease. Being a potent immunomodulatory and anti-inflammatory agent, berberine may prove to be useful for the prevention and treatment of COVID-19. This review aims to revisit the pharmacological anti-inflammatory and immunomodulatory benefits of berberine on a multitude of respiratory infections, which like COVID-19, are known to adversely affect the airways and lungs. We speculate that berberine may help alleviate COVID-19 via preventing cytokine storm, restoring Th1/Th2 balance, and enhancing cell-mediated immunity. Furthermore, the role this promising phytochemical plays on other important inflammatory mediators involved in respiratory disorders will be underscored. We further highlight the role of berberine against COVID-19 by underscoring direct evidence from in silico, in vitro, and in vivo studies suggesting the inhibitory potential berberine may play against three critical SARS-CoV-2 targets, namely main protease, spike protein, and angiotensin-converting enzyme 2 receptor. Further preclinical and clinical trials are certainly required to further substantiate the efficacy and potency of berberine against COVID-19 in humans.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"28 12 1","pages":"166"},"PeriodicalIF":3.1,"publicationDate":"2022-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90619589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
of the mechanisms-based combi-natorial approach for the therapy of SCI, integrating regenerative, neuromodulation, and rehabilitation therapies.
结合再生、神经调节和康复治疗，以机制为基础的综合方法治疗脊髓损伤。
{"title":"Implementing Principles of Neuroontogenesis and Neuroplasticity for Spinal Cord Injury Therapy.","authors":"Igor A. Lavrov, R. Islamov","doi":"10.31083/j.fbl2705163","DOIUrl":"https://doi.org/10.31083/j.fbl2705163","url":null,"abstract":"of the mechanisms-based combi-natorial approach for the therapy of SCI, integrating regenerative, neuromodulation, and rehabilitation therapies.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"6 1","pages":"163"},"PeriodicalIF":3.1,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80482444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Zarà, Mauro Vismara, Gianluca De Dona, S. M. G. Trivigno, P. Amadio, L. Sandrini, G. Guidetti, S. Barbieri
BACKGROUND Platelet-derived extracellular vesicles (PEVs) are small vesicles released by activated platelets that are gaining growing interest in the field of vascular biology. The mode of platelet activation is a critical determinant of PEVs release, phenotype and function. However, only very limited information is available concerning the impact of the platelet purification procedure on PEVs release. METHODS Washed or isolated platelets were separated by differential centrifugations. For washed platelets, the platelet pellet was washed by resuspension in PIPES buffer and finally resuspended in HEPES buffer. Isolated platelets were obtained by directly resuspending the platelet pellet in HEPES, skipping the washing steps in PIPES buffer. PEVs release was induced in washed or isolated platelets by stimulation with different agonist and analysed by Nanoparticle Tracking Analysis. RESULTS Isolated platelets showed a higher release of PEVs upon adenosine diphosphate (ADP) stimulation compared to washed platelets, whereas PEVs released upon stimulation with strong agonists (thrombin, collagen, A23187, U46619) were similar in the two groups. This different responsiveness to ADP was also observed as a higher α-granules release and protein kinase C activation in isolated platelets compared to washed ones. Residual plasma contamination appeared to be essential for the ability of platelets to release PEVs in response to ADP. CONCLUSIONS In conclusion, our study strongly suggests that procedure adopted for platelets preparation is a critical determinant of PEVs release upon ADP stimulation.
{"title":"The Impact of Platelet Isolation Protocol on the Release of Extracellular Vesicles.","authors":"M. Zarà, Mauro Vismara, Gianluca De Dona, S. M. G. Trivigno, P. Amadio, L. Sandrini, G. Guidetti, S. Barbieri","doi":"10.31083/j.fbl2705161","DOIUrl":"https://doi.org/10.31083/j.fbl2705161","url":null,"abstract":"BACKGROUND\u0000Platelet-derived extracellular vesicles (PEVs) are small vesicles released by activated platelets that are gaining growing interest in the field of vascular biology. The mode of platelet activation is a critical determinant of PEVs release, phenotype and function. However, only very limited information is available concerning the impact of the platelet purification procedure on PEVs release.\u0000\u0000\u0000METHODS\u0000Washed or isolated platelets were separated by differential centrifugations. For washed platelets, the platelet pellet was washed by resuspension in PIPES buffer and finally resuspended in HEPES buffer. Isolated platelets were obtained by directly resuspending the platelet pellet in HEPES, skipping the washing steps in PIPES buffer. PEVs release was induced in washed or isolated platelets by stimulation with different agonist and analysed by Nanoparticle Tracking Analysis.\u0000\u0000\u0000RESULTS\u0000Isolated platelets showed a higher release of PEVs upon adenosine diphosphate (ADP) stimulation compared to washed platelets, whereas PEVs released upon stimulation with strong agonists (thrombin, collagen, A23187, U46619) were similar in the two groups. This different responsiveness to ADP was also observed as a higher α-granules release and protein kinase C activation in isolated platelets compared to washed ones. Residual plasma contamination appeared to be essential for the ability of platelets to release PEVs in response to ADP.\u0000\u0000\u0000CONCLUSIONS\u0000In conclusion, our study strongly suggests that procedure adopted for platelets preparation is a critical determinant of PEVs release upon ADP stimulation.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"44 1","pages":"161"},"PeriodicalIF":3.1,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74457688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laurynas Taura, Liucija Kamaitytė-Bukelskienė, Z. Sinkevičienė, Z. Gudžinskas
BACKGROUND Wet, intermittently flooded freshwater coastal and shallow water habitats are notable for their high biodiversity. Many of the usually semiaquatic annuals or small perennials common in such habitats are in decline due to the high sensitivity of such habitats to changes caused by anthropogenic and natural factors. The Euro-Siberian semiaquatic Elatine hydropiper rarely occurs in Lithuania and is protected there and in other Baltic and Central European countries. In 2020, we found a large population of Elatine hydropiper in southern Lithuania (Varėna district) in Lake Pabezninkai and its exposed shores. The water level of the lake has receded by about 1.5-1.6 m since 2018, exposing wide, wet, and sandy or silty shores. The aim of this study was to determine the status of the Elatine hydropiper population and to assess its potential for long-term survival. The objectives of the study were to (a) determine the size and quantitative characteristics of the population, (b) assess the seed bank in the shallows and exposed shores of the lake, (c) assess the species diversity in the communities with Elatine hydropiper, (d) evaluate the conservation value of the studied species and the lake habitat. METHODS The studies were carried out between 2020 and 2021. The number and coverage of plant patches as well as seed bank studies were carried out at three sites with different shoreline substrate. At each site, the number of patches and coverage was assessed in 50 sample plots of 100 cm2. The seed bank was examined in the top 5 cm of the substrate. A total of 90 substrate samples were analyzed. RESULTS We found that Elatine hydropiper grows on ca. 0.38 ha in the lake and on ca. 0.95 ha on the shores. On the exposed shores, the mean number of Elatine hydropiper patches per 1 m2 was 2155 ± 1241.5 and their mean cover was 23.17% of the surface. Seed bank analyses revealed that the seeds and seed shells were significantly more abundant in the bottom sediments than in the shore sand or silt. The mean number of seeds per liter of soil was 85.8 ± 210.2, and the mean number of seed shells was 217.0 ± 265.8. CONCLUSIONS The assessment of the status of the species in Lithuania according to the IUCN (International Union for Conservation of Nature) criteria has led us to conclude that it should now be classified as vulnerable [A3; B1ab(iii); C2a(ii); D2]. The key to protecting Elatine hydropiper and other co-occurring rare species with similar ecological and biological characteristics, as well as the plant communities of shallows and exposed wet banks, is to protect their habitats. The survival of the species and their habitats could be assured by recurring significant water level fluctuations in the lake, resulting in periodic emergence of patches of wet sand or silt free from perennial vegetation.
{"title":"Study on the Rare Semiaquatic Plant Elatine hydropiper (Elatinaceae) in Lithuania: Population Density, Seed Bank and Conservation Challenges.","authors":"Laurynas Taura, Liucija Kamaitytė-Bukelskienė, Z. Sinkevičienė, Z. Gudžinskas","doi":"10.31083/j.fbl2705162","DOIUrl":"https://doi.org/10.31083/j.fbl2705162","url":null,"abstract":"BACKGROUND\u0000Wet, intermittently flooded freshwater coastal and shallow water habitats are notable for their high biodiversity. Many of the usually semiaquatic annuals or small perennials common in such habitats are in decline due to the high sensitivity of such habitats to changes caused by anthropogenic and natural factors. The Euro-Siberian semiaquatic Elatine hydropiper rarely occurs in Lithuania and is protected there and in other Baltic and Central European countries. In 2020, we found a large population of Elatine hydropiper in southern Lithuania (Varėna district) in Lake Pabezninkai and its exposed shores. The water level of the lake has receded by about 1.5-1.6 m since 2018, exposing wide, wet, and sandy or silty shores. The aim of this study was to determine the status of the Elatine hydropiper population and to assess its potential for long-term survival. The objectives of the study were to (a) determine the size and quantitative characteristics of the population, (b) assess the seed bank in the shallows and exposed shores of the lake, (c) assess the species diversity in the communities with Elatine hydropiper, (d) evaluate the conservation value of the studied species and the lake habitat.\u0000\u0000\u0000METHODS\u0000The studies were carried out between 2020 and 2021. The number and coverage of plant patches as well as seed bank studies were carried out at three sites with different shoreline substrate. At each site, the number of patches and coverage was assessed in 50 sample plots of 100 cm2. The seed bank was examined in the top 5 cm of the substrate. A total of 90 substrate samples were analyzed.\u0000\u0000\u0000RESULTS\u0000We found that Elatine hydropiper grows on ca. 0.38 ha in the lake and on ca. 0.95 ha on the shores. On the exposed shores, the mean number of Elatine hydropiper patches per 1 m2 was 2155 ± 1241.5 and their mean cover was 23.17% of the surface. Seed bank analyses revealed that the seeds and seed shells were significantly more abundant in the bottom sediments than in the shore sand or silt. The mean number of seeds per liter of soil was 85.8 ± 210.2, and the mean number of seed shells was 217.0 ± 265.8.\u0000\u0000\u0000CONCLUSIONS\u0000The assessment of the status of the species in Lithuania according to the IUCN (International Union for Conservation of Nature) criteria has led us to conclude that it should now be classified as vulnerable [A3; B1ab(iii); C2a(ii); D2]. The key to protecting Elatine hydropiper and other co-occurring rare species with similar ecological and biological characteristics, as well as the plant communities of shallows and exposed wet banks, is to protect their habitats. The survival of the species and their habitats could be assured by recurring significant water level fluctuations in the lake, resulting in periodic emergence of patches of wet sand or silt free from perennial vegetation.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"60 1","pages":"162"},"PeriodicalIF":3.1,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75582340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liang Gong, Qiaojun Lou, Chenrui Yu, Yunyun Chen, Jun Hong, Wei Wu, Shengzhe Fan, Liangyu Chen, Chengliang Liu
BACKGROUND With the development of high-throughput genome sequencing and phenotype screening techniques, there is a possibility of leveraging multi-omics to speed up the breeding process. However, the heterogeneity of big data handicaps the progress and the lack of a comprehensive database supporting end-to-end association analysis impedes the efficient use of these data. METHODS In response to this problem, a scalable entity-relationship model and a database architecture are firstly proposed in this paper to manage the cross-platform data sets and explore the relationship among multi-omics, and finally accelerate our breeding efficiency. First, the targeted omics data of crops should be normalized before being stored in the database. A typical breeding data content and structure is demonstrated with the case study of rice (Oryza sativa L). Second, the structure, patterns and hierarchy of multi-omics data are described with the entity-relationship modeling technique. Third, some statistical tools used frequently in the agricultural analysis have been embedded into the database to help breeding. RESULTS As a result, a general-purpose scalable database, called GpemDB integrating genomics, phenomics, enviromics and management, is developed. It is the first database designed to manage all these four omics data together. The GpemDB involving Gpem metadata-level layer and informative-level layer provides a visualized scheme to display the content of the database and facilitates users to manage, analyze and share breeding data. CONCLUSIONS GpemDB has been successfully applied to a rice population, which demonstrates this database architecture and model are promising to serve as a powerful tool to utilize the big data for high precise and efficient research and breeding of crops.
{"title":"GpemDB: A Scalable Database Architecture with the Multi-omics Entity-relationship Model to Integrate Heterogeneous Big-data for Precise Crop Breeding.","authors":"Liang Gong, Qiaojun Lou, Chenrui Yu, Yunyun Chen, Jun Hong, Wei Wu, Shengzhe Fan, Liangyu Chen, Chengliang Liu","doi":"10.31083/j.fbl2705159","DOIUrl":"https://doi.org/10.31083/j.fbl2705159","url":null,"abstract":"BACKGROUND\u0000With the development of high-throughput genome sequencing and phenotype screening techniques, there is a possibility of leveraging multi-omics to speed up the breeding process. However, the heterogeneity of big data handicaps the progress and the lack of a comprehensive database supporting end-to-end association analysis impedes the efficient use of these data.\u0000\u0000\u0000METHODS\u0000In response to this problem, a scalable entity-relationship model and a database architecture are firstly proposed in this paper to manage the cross-platform data sets and explore the relationship among multi-omics, and finally accelerate our breeding efficiency. First, the targeted omics data of crops should be normalized before being stored in the database. A typical breeding data content and structure is demonstrated with the case study of rice (Oryza sativa L). Second, the structure, patterns and hierarchy of multi-omics data are described with the entity-relationship modeling technique. Third, some statistical tools used frequently in the agricultural analysis have been embedded into the database to help breeding.\u0000\u0000\u0000RESULTS\u0000As a result, a general-purpose scalable database, called GpemDB integrating genomics, phenomics, enviromics and management, is developed. It is the first database designed to manage all these four omics data together. The GpemDB involving Gpem metadata-level layer and informative-level layer provides a visualized scheme to display the content of the database and facilitates users to manage, analyze and share breeding data.\u0000\u0000\u0000CONCLUSIONS\u0000GpemDB has been successfully applied to a rice population, which demonstrates this database architecture and model are promising to serve as a powerful tool to utilize the big data for high precise and efficient research and breeding of crops.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"1 3 1","pages":"159"},"PeriodicalIF":3.1,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76278925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND The interactions between platelets and tumor cells are well-known to play important roles in the progression of malignant tumors. Danshensu, a main water-soluble component of Salvia miltiorrhiza, can resist platelet aggregation and exert significant anti-tumor effects on various types of tumors. However, whether Danshensu could inhibit the progression of malignant tumors by suppressing the activities of platelets had not been reported. METHODS The effects of Danshensu on the platelet activity and epithelial-mesenchymal transformation (EMT)-like invasive phenotype of SW620 colon cancer cells were assessed by stimulating with the supernatants from co-cultured platelets and SW620 cells with direct contact (SCP). The expression and secretion of proteins were determined by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin and eosin (H&E) staining was performed to analyzed the histopathology of tumor tissues and immunohistochemical staining was conducted to examine the protein expression in tumors. RESULTS Co-incubation of SW620 cells with platelets directly or SCP both generated long spindle-shaped invasive phenotype. Pretreatment of platelets with Danshensu (25 μM) inhibited the morphological changes of SW620 cells induced by SCP, which was associated with the inhibitory effects of Danshensu on platelet secretion. Danshensu diminished the secretion of a list of biological factors in SCP, including interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β and vascular endothelial growth factor (VEGF) that are all involved in tumor cell EMT and chemoresistance. Moreover, Danshensu up-regulated the expression of E-cadherin but down-regulated the levels of N-cadherin and Vimentin, resulting in the repression of SW620 cell migration. It was also shown that Danshensu enhanced the sensitivity of SW620 cells to oxaliplatin by suppressing the expression of MDR1. Furthermore, Danshensu could not only reduced the growth of subcutaneous tumors and liver metastasis that induced by SCP, but also down-regulated the expression of MDR1 in vivo. Mechanistic studies revealed that Danshensu suppressed the activation of the TGF-β/Smad signaling pathway. CONCLUSIONS Danshensu attenuated EMT-like characteristics and chemoresistance by inhibiting secretion capability of platelets and activation of the TGF-β/Smad signaling pathway, suggesting that it may be optimized to be a therapeutic agent for fighting against colon cancer.
{"title":"Danshensu Attenuated Epithelial-Mesenchymal Transformation and Chemoresistance of Colon Cancer Cells Induced by Platelets.","authors":"Yuzhu Cao, Ke-quan Lu, Yawen Xia, Yufei Wang, Aiyun Wang, Yang Zhao","doi":"10.31083/j.fbl2705160","DOIUrl":"https://doi.org/10.31083/j.fbl2705160","url":null,"abstract":"BACKGROUND\u0000The interactions between platelets and tumor cells are well-known to play important roles in the progression of malignant tumors. Danshensu, a main water-soluble component of Salvia miltiorrhiza, can resist platelet aggregation and exert significant anti-tumor effects on various types of tumors. However, whether Danshensu could inhibit the progression of malignant tumors by suppressing the activities of platelets had not been reported.\u0000\u0000\u0000METHODS\u0000The effects of Danshensu on the platelet activity and epithelial-mesenchymal transformation (EMT)-like invasive phenotype of SW620 colon cancer cells were assessed by stimulating with the supernatants from co-cultured platelets and SW620 cells with direct contact (SCP). The expression and secretion of proteins were determined by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin and eosin (H&E) staining was performed to analyzed the histopathology of tumor tissues and immunohistochemical staining was conducted to examine the protein expression in tumors.\u0000\u0000\u0000RESULTS\u0000Co-incubation of SW620 cells with platelets directly or SCP both generated long spindle-shaped invasive phenotype. Pretreatment of platelets with Danshensu (25 μM) inhibited the morphological changes of SW620 cells induced by SCP, which was associated with the inhibitory effects of Danshensu on platelet secretion. Danshensu diminished the secretion of a list of biological factors in SCP, including interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β and vascular endothelial growth factor (VEGF) that are all involved in tumor cell EMT and chemoresistance. Moreover, Danshensu up-regulated the expression of E-cadherin but down-regulated the levels of N-cadherin and Vimentin, resulting in the repression of SW620 cell migration. It was also shown that Danshensu enhanced the sensitivity of SW620 cells to oxaliplatin by suppressing the expression of MDR1. Furthermore, Danshensu could not only reduced the growth of subcutaneous tumors and liver metastasis that induced by SCP, but also down-regulated the expression of MDR1 in vivo. Mechanistic studies revealed that Danshensu suppressed the activation of the TGF-β/Smad signaling pathway.\u0000\u0000\u0000CONCLUSIONS\u0000Danshensu attenuated EMT-like characteristics and chemoresistance by inhibiting secretion capability of platelets and activation of the TGF-β/Smad signaling pathway, suggesting that it may be optimized to be a therapeutic agent for fighting against colon cancer.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"1 1","pages":"160"},"PeriodicalIF":3.1,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89579017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Schrick, T. Molnár, M. Tőkés-Füzesi, Abigél Molnár, E. Ezer
INTRODUCTION Exploration of novel and effective antiplatelet strategies for the secondary prevention of ischemic stroke is utmost. Some platelet derived microparticles (PMVs) in convalescent stroke subjects were found to be predictive for the next vascular event. Patients with high-on-treatment platelet reactivity (HTPR) had a significantly higher risk for ischemic stroke. Here, we aimed to explore associations among circulating microparticles and responsivness to antiplatelet (clopidogrel) therapy. METHODS A total of 18 patients on clopidogrel therapy due to secondary stroke prevention were rospectively recruited into this study. Twenty age-matched healthy subjects served as controls. Flow cytometric measurements of microparicles (MVs) and data analysis were performed on Beckman-Coulter FC-500 cytometer with CXP software. Besides, platelet aggregometry data were revealed. Both measurements were performed in whole blood and from the lower and upper blood fractions separated after 1-hour gravity sedimentation by the analogy with erythrocyte sedimentation rate. RESULTS The total number of circulating MVs, and particularly the platelet derived CD42+ and PAC-1+ were significantly higher in post-stroke patients (p < 0.001). The platelet aggregation in the whole blood (area under the curve, AUC) showed a significant negative correlation with the total number of MPs in the lower blood sample after 1-hour gravity sedimentation (r = -0.650, p = 0.005). Next, we analyzed associations among MPs and aggregometry data obtained from clopidogrel responders and non-responders. Both, area under the curve (AUC) and velocity in the whole blood showed opposite correlation with the total number of MVs in the lower blood sample after 1-hour gravity sedimentation. Importantly, a significant negative correlation was observed for the velocity (r = -0.801, p = 0.005), but not for the AUC in responders. Platelet derived CD42+ and PAC-1+ MVs showed positive correlations with neutrophils in the lower blood sample (p = 0.008 and p = 0.006 respectively). CONCLUSIONS Circulating MVs may allow to monitor the response to antiplatelet therapy in post-stroke patients. In addition, the link between platelet derived MVs and neutrophil granulocytes might become therapeutic targets in the future.
探索新的有效的抗血小板策略对缺血性脑卒中的二级预防至关重要。一些血小板衍生微粒(PMVs)在恢复期中风受试者中被发现可以预测下一个血管事件。治疗时血小板反应性高(HTPR)的患者发生缺血性卒中的风险明显更高。在这里，我们的目的是探讨循环微粒与抗血小板(氯吡格雷)治疗反应性之间的关系。方法回顾性研究18例因继发性脑卒中预防而接受氯吡格雷治疗的患者。20名年龄匹配的健康受试者作为对照。在Beckman-Coulter FC-500型细胞仪上使用CXP软件进行微颗粒(MVs)的流式细胞术测量和数据分析。此外，还显示了血小板聚集数据。这两种测量都是在全血中进行的，并从1小时重力沉降后通过与红细胞沉降率的类比分离的下部和上部血液馏分。结果卒中后患者外周血mv总数，尤其是血小板来源的CD42+和PAC-1+明显升高(p < 0.001)。全血血小板聚集(曲线下面积，AUC)与重力沉降1小时后下血MPs总数呈显著负相关(r = -0.650, p = 0.005)。接下来，我们分析了从氯吡格雷应答者和无应答者中获得的MPs和聚合数据之间的关联。曲线下面积(area under the curve, AUC)和全血流速与重力沉降1h后下段血样中mv总数呈相反的相关关系。重要的是，在速度上观察到显著的负相关(r = -0.801, p = 0.005)，但在应答者的AUC上没有观察到显著的负相关。血小板来源的CD42+和PAC-1+ mv与下血检中性粒细胞呈正相关(p = 0.008和p = 0.006)。结论循环MVs可监测脑卒中后患者抗血小板治疗的反应。此外，血小板衍生的mv与中性粒细胞之间的联系可能成为未来的治疗靶点。
{"title":"Circulating Microvesicles in Convalescent Ischemic Stroke Patients: A Contributor to High-On-Treatment Residual Platelet Reactivity?","authors":"D. Schrick, T. Molnár, M. Tőkés-Füzesi, Abigél Molnár, E. Ezer","doi":"10.31083/j.fbl2705158","DOIUrl":"https://doi.org/10.31083/j.fbl2705158","url":null,"abstract":"INTRODUCTION\u0000Exploration of novel and effective antiplatelet strategies for the secondary prevention of ischemic stroke is utmost. Some platelet derived microparticles (PMVs) in convalescent stroke subjects were found to be predictive for the next vascular event. Patients with high-on-treatment platelet reactivity (HTPR) had a significantly higher risk for ischemic stroke. Here, we aimed to explore associations among circulating microparticles and responsivness to antiplatelet (clopidogrel) therapy.\u0000\u0000\u0000METHODS\u0000A total of 18 patients on clopidogrel therapy due to secondary stroke prevention were rospectively recruited into this study. Twenty age-matched healthy subjects served as controls. Flow cytometric measurements of microparicles (MVs) and data analysis were performed on Beckman-Coulter FC-500 cytometer with CXP software. Besides, platelet aggregometry data were revealed. Both measurements were performed in whole blood and from the lower and upper blood fractions separated after 1-hour gravity sedimentation by the analogy with erythrocyte sedimentation rate.\u0000\u0000\u0000RESULTS\u0000The total number of circulating MVs, and particularly the platelet derived CD42+ and PAC-1+ were significantly higher in post-stroke patients (p < 0.001). The platelet aggregation in the whole blood (area under the curve, AUC) showed a significant negative correlation with the total number of MPs in the lower blood sample after 1-hour gravity sedimentation (r = -0.650, p = 0.005). Next, we analyzed associations among MPs and aggregometry data obtained from clopidogrel responders and non-responders. Both, area under the curve (AUC) and velocity in the whole blood showed opposite correlation with the total number of MVs in the lower blood sample after 1-hour gravity sedimentation. Importantly, a significant negative correlation was observed for the velocity (r = -0.801, p = 0.005), but not for the AUC in responders. Platelet derived CD42+ and PAC-1+ MVs showed positive correlations with neutrophils in the lower blood sample (p = 0.008 and p = 0.006 respectively).\u0000\u0000\u0000CONCLUSIONS\u0000Circulating MVs may allow to monitor the response to antiplatelet therapy in post-stroke patients. In addition, the link between platelet derived MVs and neutrophil granulocytes might become therapeutic targets in the future.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"1 1","pages":"158"},"PeriodicalIF":3.1,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72571090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coronavirus disease 2019 (COVID-19), which broke out at the end of 2019, is a global pandemic and seriously threatens human health. Vaccination is the most effective way to prevent and control COVID-19. At present, more than 13 COVID-19 vaccines have been urgently authorized for use, but the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has brought unprecedented challenges to the protective efficiency of these COVID-19 vaccines. In particular, the recent emergence of Delta and Omicron variants, which are rapidly spreading worldwide, may bring many challenges to the medical systems. Interestingly, previous studies have shown that the Bacillus Calmette-Guerin (BCG) vaccine used to prevent tuberculosis can induce non-specific trained immunity, protecting against infectious diseases caused by respiratory viruses. Therefore, there is a hypothesis that BCG plays an essential role in reducing the incidence, severity, hospitalization, and mortality of COVID-19 and enhancing the protection efficiency of the COVID-19 vaccine. To confirm this hypothesis, 56 clinical trials have been conducted globally to assess BCG's protective effectiveness against COVID-19 infection. Herein, this review discussed the trained immunity induced by BCG and its underlying mechanisms and summarised BCG's latest research progress in preventing COVID-19, especially the ongoing clinical trials. We hope this review will provide new strategies for fighting against COVID-19.
{"title":"The Potential Roles of BCG Vaccine in the Prevention or Treatment of COVID-19.","authors":"Jie Wang, Qian Zhang, Hongmei Wang, W. Gong","doi":"10.31083/j.fbl2705157","DOIUrl":"https://doi.org/10.31083/j.fbl2705157","url":null,"abstract":"Coronavirus disease 2019 (COVID-19), which broke out at the end of 2019, is a global pandemic and seriously threatens human health. Vaccination is the most effective way to prevent and control COVID-19. At present, more than 13 COVID-19 vaccines have been urgently authorized for use, but the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has brought unprecedented challenges to the protective efficiency of these COVID-19 vaccines. In particular, the recent emergence of Delta and Omicron variants, which are rapidly spreading worldwide, may bring many challenges to the medical systems. Interestingly, previous studies have shown that the Bacillus Calmette-Guerin (BCG) vaccine used to prevent tuberculosis can induce non-specific trained immunity, protecting against infectious diseases caused by respiratory viruses. Therefore, there is a hypothesis that BCG plays an essential role in reducing the incidence, severity, hospitalization, and mortality of COVID-19 and enhancing the protection efficiency of the COVID-19 vaccine. To confirm this hypothesis, 56 clinical trials have been conducted globally to assess BCG's protective effectiveness against COVID-19 infection. Herein, this review discussed the trained immunity induced by BCG and its underlying mechanisms and summarised BCG's latest research progress in preventing COVID-19, especially the ongoing clinical trials. We hope this review will provide new strategies for fighting against COVID-19.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"38 1","pages":"157"},"PeriodicalIF":3.1,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87173852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Koehler, J. Wingender, Michelle Lueling, Sven W. Meckelmann, U. Telgheder, O. Schmitz
BACKGROUND Cystic fibrosis (CF) is an autosomal recessive hereditary disease that leads to the production of thickened mucus in the lungs, favouring polymicrobial infections, such as chronic lung infections with the bacterial opportunistic pathogen Pseudomonas aeruginosa. METHOD A biofilm model in combination with an adapted sampling and GC-MS analysis method were applied to in vitro studies on different variables influencing the composition of the extracellular volatile metabolome of P. aeruginosa. RESULTS A significant influence on the metabolome could be demonstrated for the culture medium as well as the atmosphere during cultivation (aerobic or anaerobic). Furthermore, a significant influence of the mucoid (alginate-overproducing) phenotype of the bacterium on quantity and composition of volatile organic compounds could be observed. Based on the results a solid culture medium was developed to simulate the nutrient conditions in the lungs of a CF patient. The extracellular volatile metabolome of bacterial strains P. aeruginosa ATCC 10145, PAO1 and FRD1 was characterized under CF-like conditions. CONCLUSIONS Bacterial strain-dependent metabolites were identified. When P. aeruginosa PAO1 and FRD1 clinical isolates were compared, 36 metabolites showed significant variations in intensities. When the clinical isolates were compared with the reference strain (P. aeruginosa ATCC 10145), 28 metabolites (P. aeruginosa PAO1) and 70 metabolites (P. aeruginosa FRD1) were determined whose peaks showed significant deviation (p > 95%) in intensity. Furthermore, the bacterial strains could be differentiated from each other by means of two principal components.
{"title":"Characterization of the Extracellular Volatile Metabolome of Pseudomonas Aeruginosa Applying an in vitro Biofilm Model under Cystic Fibrosis-Like Conditions.","authors":"T. Koehler, J. Wingender, Michelle Lueling, Sven W. Meckelmann, U. Telgheder, O. Schmitz","doi":"10.31083/j.fbl2705156","DOIUrl":"https://doi.org/10.31083/j.fbl2705156","url":null,"abstract":"BACKGROUND\u0000Cystic fibrosis (CF) is an autosomal recessive hereditary disease that leads to the production of thickened mucus in the lungs, favouring polymicrobial infections, such as chronic lung infections with the bacterial opportunistic pathogen Pseudomonas aeruginosa.\u0000\u0000\u0000METHOD\u0000A biofilm model in combination with an adapted sampling and GC-MS analysis method were applied to in vitro studies on different variables influencing the composition of the extracellular volatile metabolome of P. aeruginosa.\u0000\u0000\u0000RESULTS\u0000A significant influence on the metabolome could be demonstrated for the culture medium as well as the atmosphere during cultivation (aerobic or anaerobic). Furthermore, a significant influence of the mucoid (alginate-overproducing) phenotype of the bacterium on quantity and composition of volatile organic compounds could be observed. Based on the results a solid culture medium was developed to simulate the nutrient conditions in the lungs of a CF patient. The extracellular volatile metabolome of bacterial strains P. aeruginosa ATCC 10145, PAO1 and FRD1 was characterized under CF-like conditions.\u0000\u0000\u0000CONCLUSIONS\u0000Bacterial strain-dependent metabolites were identified. When P. aeruginosa PAO1 and FRD1 clinical isolates were compared, 36 metabolites showed significant variations in intensities. When the clinical isolates were compared with the reference strain (P. aeruginosa ATCC 10145), 28 metabolites (P. aeruginosa PAO1) and 70 metabolites (P. aeruginosa FRD1) were determined whose peaks showed significant deviation (p > 95%) in intensity. Furthermore, the bacterial strains could be differentiated from each other by means of two principal components.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"3 1","pages":"156"},"PeriodicalIF":3.1,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78858985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND We obtained microelectrode recordings from four patients with intractable aggressivity who underwent surgery at posteromedial hypothalamus under general anaesthesia. We described two general types of extracellular action potentials (EAPs): typical/canonical and atypical. METHODS We analysed 337 units and 67 traces, which were characterized by the mean action potential (mAP). For the first phase, depolarization and repolarization, we computed amplitudes (VFP, VDep and VRep) and durations (dFP, dDep and dRep), maximum and minimum values of the first derivative (dVmax, dVmin), and amplitude and duration ratios. RESULTS Most of the canonical mAPs were positive (81.1%). EAPs with atypical mean action potentials (amAPs) were recorded in 42/337 cases. Only 35.6% of mAPs showed 2 phases. We identified the following types: N1P1N2 (38.3%), P1N1 (35.9%), amAP (12.5%), P1P2N1 (12.2%), N1P1 (4.7%), P1N1P2 (4.1%) and N1N2P1 (3.2%). We can define the properties of canonical forms as those units with (i) at least two opposite phases; (ii) VDep∈[1.2,2.7]×|VRep| and strongly related by this function VRep=-0.56(±0.01)VDep-1.83(±0.79); (iii) a very strong relationship between dVmax and dVmin, given by the equation dVmin=-0.91(±0.03)dVmax-0.37(±0.12), both of which were included in the depolarization phase; (iv) related with VDep by the equation dVmax=0.08(±0.001)VDep-0.28(±0.14); and (v) dDep~0.38dRep. However, the first phase does not pertain to the same dynamic process responsible for depolarization and repolarization. CONCLUSIONS Atypical units are described here for the first time and are true EAPs that differ strikingly from canonical forms. To date, they have been observed only in the hypothalamus, but future research is needed to assess their existence in other brain structures.
{"title":"Atypical Extracellular Action Potentials from Posteromedial Hypothalamus in Anesthetized Humans.","authors":"J. Pastor, L. Vega-Zelaya, Elena Martín-Abad","doi":"10.31083/j.fbl2705155","DOIUrl":"https://doi.org/10.31083/j.fbl2705155","url":null,"abstract":"BACKGROUND\u0000We obtained microelectrode recordings from four patients with intractable aggressivity who underwent surgery at posteromedial hypothalamus under general anaesthesia. We described two general types of extracellular action potentials (EAPs): typical/canonical and atypical.\u0000\u0000\u0000METHODS\u0000We analysed 337 units and 67 traces, which were characterized by the mean action potential (mAP). For the first phase, depolarization and repolarization, we computed amplitudes (VFP, VDep and VRep) and durations (dFP, dDep and dRep), maximum and minimum values of the first derivative (dVmax, dVmin), and amplitude and duration ratios.\u0000\u0000\u0000RESULTS\u0000Most of the canonical mAPs were positive (81.1%). EAPs with atypical mean action potentials (amAPs) were recorded in 42/337 cases. Only 35.6% of mAPs showed 2 phases. We identified the following types: N1P1N2 (38.3%), P1N1 (35.9%), amAP (12.5%), P1P2N1 (12.2%), N1P1 (4.7%), P1N1P2 (4.1%) and N1N2P1 (3.2%). We can define the properties of canonical forms as those units with (i) at least two opposite phases; (ii) VDep∈[1.2,2.7]×|VRep| and strongly related by this function VRep=-0.56(±0.01)VDep-1.83(±0.79); (iii) a very strong relationship between dVmax and dVmin, given by the equation dVmin=-0.91(±0.03)dVmax-0.37(±0.12), both of which were included in the depolarization phase; (iv) related with VDep by the equation dVmax=0.08(±0.001)VDep-0.28(±0.14); and (v) dDep~0.38dRep. However, the first phase does not pertain to the same dynamic process responsible for depolarization and repolarization.\u0000\u0000\u0000CONCLUSIONS\u0000Atypical units are described here for the first time and are true EAPs that differ strikingly from canonical forms. To date, they have been observed only in the hypothalamus, but future research is needed to assess their existence in other brain structures.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"1036 2","pages":"155"},"PeriodicalIF":3.1,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72433126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：