B. Sarg, Dhwani S Korde, J. Marksteiner, C. Humpel
BACKGROUND Platelets (thrombocytes) are small anuclear cells that play an important role in blood clotting. They are activated and dysfunctional in brain disorders, such as Alzheimer's disease (AD) and depression. Platelets express the amyloid-precursor protein (APP) and release beta-amyloid40 into the blood. Recent evidence reports that platelets also express the microtubule-associated protein tau. In this study, we further characterized the molecular appearance of tau and examined its alterations in patients with neurocognitive impairment. METHODS Platelets were isolated from patients with AD, mild cognitive impairment (MCI) or depression and compared to healthy controls. Subsequently, FACS analysis was employed to characterize platelets for platelet surface P-selectin (CD62P). In order to enhance the detection levels, samples were pooled (15 samples per group) and analyzed by Lumipulse Assay, Western blots, and mass spectrometry. RESULTS Tau is expressed in human platelets and tau levels were decreased in platelets isolated from patients with AD and depression. Additionally, phospho-tau-181 was slightly increased in patients with depression. We show that tau is highly fragmented (20-40 kDa) in the platelet extracts using Western blot analysis. The mass spectrometry data did not show a clear identification of tau in the pooled platelet samples. CONCLUSIONS Our data reveal that tau is found in platelets, possibly in a highly fragmented form. Tau levels may be used as a potential diagnostic approach to differentiate AD and depression from healthy controls.
背景血小板(血小板)是在血液凝固中起重要作用的小核细胞。它们在阿尔茨海默病(AD)和抑郁症等脑部疾病中被激活或功能失调。血小板表达淀粉样前体蛋白(APP)并将β -淀粉样蛋白40释放到血液中。最近有证据表明，血小板也表达微管相关蛋白tau。在这项研究中，我们进一步表征了tau蛋白的分子外观，并检查了其在神经认知障碍患者中的改变。方法从AD、轻度认知障碍(MCI)或抑郁症患者中分离血小板，并与健康对照进行比较。随后，采用FACS分析表征血小板表面p选择素(CD62P)。为了提高检测水平，将样品合并(每组15个样品)，并通过Lumipulse Assay, Western blots和质谱分析。结果tau蛋白在人血小板中表达，AD和抑郁症患者分离的血小板中tau蛋白水平降低。此外，在抑郁症患者中，磷酸化-tau-181略有升高。我们通过Western blot分析发现，tau蛋白在血小板提取物中高度碎片化(20-40 kDa)。质谱分析数据没有显示血小板样本中tau蛋白的明确鉴定。结论tau蛋白存在于血小板中，可能以高度碎片化的形式存在。Tau水平可作为区分AD和抑郁与健康对照的潜在诊断方法。
{"title":"Platelet TAU is Associated with Changes in Depression and Alzheimer's Disease.","authors":"B. Sarg, Dhwani S Korde, J. Marksteiner, C. Humpel","doi":"10.31083/j.fbl2705153","DOIUrl":"https://doi.org/10.31083/j.fbl2705153","url":null,"abstract":"BACKGROUND\u0000Platelets (thrombocytes) are small anuclear cells that play an important role in blood clotting. They are activated and dysfunctional in brain disorders, such as Alzheimer's disease (AD) and depression. Platelets express the amyloid-precursor protein (APP) and release beta-amyloid40 into the blood. Recent evidence reports that platelets also express the microtubule-associated protein tau. In this study, we further characterized the molecular appearance of tau and examined its alterations in patients with neurocognitive impairment.\u0000\u0000\u0000METHODS\u0000Platelets were isolated from patients with AD, mild cognitive impairment (MCI) or depression and compared to healthy controls. Subsequently, FACS analysis was employed to characterize platelets for platelet surface P-selectin (CD62P). In order to enhance the detection levels, samples were pooled (15 samples per group) and analyzed by Lumipulse Assay, Western blots, and mass spectrometry.\u0000\u0000\u0000RESULTS\u0000Tau is expressed in human platelets and tau levels were decreased in platelets isolated from patients with AD and depression. Additionally, phospho-tau-181 was slightly increased in patients with depression. We show that tau is highly fragmented (20-40 kDa) in the platelet extracts using Western blot analysis. The mass spectrometry data did not show a clear identification of tau in the pooled platelet samples.\u0000\u0000\u0000CONCLUSIONS\u0000Our data reveal that tau is found in platelets, possibly in a highly fragmented form. Tau levels may be used as a potential diagnostic approach to differentiate AD and depression from healthy controls.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"31 1","pages":"153"},"PeriodicalIF":3.1,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84112898","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 In this study, the entire mitochondrial genome (mitogenome) of Aleuroclava psidii (Singh, 1931) (Hemiptera: Aleyrodidae) was sequenced. The species A. psidii is currently classified in the subfamily Aleyrodinae. This mitogenome is the first representative from the genus Aleuroclava. METHODS Next-generation sequencing was used to obtain the molecular data. We conducted phylogenetic analyses with 18 existing mitogenomes of whiteflies and three outgroups of psyllids, under the Maximum likelihood and Bayesian inference criteria. RESULTS The arrangement of genes differed between the mitogenome of A. psidii and the putative ancestral insect mitogenome, and also differed from the mitogenomes of other whiteflies. Mitochondrial gene rearrangements involved the transpositions of trnQ, trnY, and the protein-coding gene nad1. Most hemipteran mitogenomes have the same mitochondrial gene order as that inferred to be ancestral for insects. However, there are an increased number of gene rearrangements in the mitogenomes of whiteflies. Phylogenetic reconstructions supported Aleurodicinae and Aleyrodinae as being monophyletic. CONCLUSIONS Comparison of the gene order of mitogenomes revealed a clade-specific evolutionary trend in whiteflies. This study demonstrates the potential of using structural rearrangements to resolve major phylogenetic relationships within Aleyrodidae.
{"title":"The Mitogenome of Aleuroclava Psidii (Singh, 1931) (Hemiptera: Aleyrodidae) and Increased Number of Mitochondrial Gene Rearrangements in Whiteflies.","authors":"Nan Song, Heng Zhang, Run-e Bai, Hao Meng","doi":"10.31083/j.fbl2705154","DOIUrl":"https://doi.org/10.31083/j.fbl2705154","url":null,"abstract":"BACKGROUND\u0000In this study, the entire mitochondrial genome (mitogenome) of Aleuroclava psidii (Singh, 1931) (Hemiptera: Aleyrodidae) was sequenced. The species A. psidii is currently classified in the subfamily Aleyrodinae. This mitogenome is the first representative from the genus Aleuroclava.\u0000\u0000\u0000METHODS\u0000Next-generation sequencing was used to obtain the molecular data. We conducted phylogenetic analyses with 18 existing mitogenomes of whiteflies and three outgroups of psyllids, under the Maximum likelihood and Bayesian inference criteria.\u0000\u0000\u0000RESULTS\u0000The arrangement of genes differed between the mitogenome of A. psidii and the putative ancestral insect mitogenome, and also differed from the mitogenomes of other whiteflies. Mitochondrial gene rearrangements involved the transpositions of trnQ, trnY, and the protein-coding gene nad1. Most hemipteran mitogenomes have the same mitochondrial gene order as that inferred to be ancestral for insects. However, there are an increased number of gene rearrangements in the mitogenomes of whiteflies. Phylogenetic reconstructions supported Aleurodicinae and Aleyrodinae as being monophyletic.\u0000\u0000\u0000CONCLUSIONS\u0000Comparison of the gene order of mitogenomes revealed a clade-specific evolutionary trend in whiteflies. This study demonstrates the potential of using structural rearrangements to resolve major phylogenetic relationships within Aleyrodidae.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"13 1","pages":"154"},"PeriodicalIF":3.1,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79528727","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}
V. Veljkovic, S. Glišić, V. Perovic, M. Veljkovic, S. Paessler
BACKGROUND A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the leading threat to global health. An effective antiviral could not only help those still vulnerable to the virus but could be a critical treatment if a virus emerges toward evading coronavirus disease 2019 (COVID-19) vaccines. Despite the significant efforts to test already-approved drugs for their potential to kill the virus, researchers found very few actually worked. METHODS The present report uses the electronic molecular descriptors, the quasi-valence number (AQVN), and the electron-ion interaction potential (EIIP), for the analysis of natural compounds with proven therapeutic activity against the COVID-19. RESULTS Based on the analysis of the electronic properties of natural compounds which are effective against SARS-CoV-2 virus the simple theoretical criterion for the selection of candidate compounds for the treatment of COVID-19 is proposed. CONCLUSIONS The proposed theoretical criterion can be used for the identification and optimization of new lead compounds for the treatment of the COVID-19 disease and for the selection of the food and food supplements which could have a beneficial effect on COVID-19 patients.
{"title":"Simple Theoretical Criterion for Selection of Natural Compounds with Anti-COVID-19 Activity.","authors":"V. Veljkovic, S. Glišić, V. Perovic, M. Veljkovic, S. Paessler","doi":"10.31083/j.fbl2705152","DOIUrl":"https://doi.org/10.31083/j.fbl2705152","url":null,"abstract":"BACKGROUND\u0000A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the leading threat to global health. An effective antiviral could not only help those still vulnerable to the virus but could be a critical treatment if a virus emerges toward evading coronavirus disease 2019 (COVID-19) vaccines. Despite the significant efforts to test already-approved drugs for their potential to kill the virus, researchers found very few actually worked.\u0000\u0000\u0000METHODS\u0000The present report uses the electronic molecular descriptors, the quasi-valence number (AQVN), and the electron-ion interaction potential (EIIP), for the analysis of natural compounds with proven therapeutic activity against the COVID-19.\u0000\u0000\u0000RESULTS\u0000Based on the analysis of the electronic properties of natural compounds which are effective against SARS-CoV-2 virus the simple theoretical criterion for the selection of candidate compounds for the treatment of COVID-19 is proposed.\u0000\u0000\u0000CONCLUSIONS\u0000The proposed theoretical criterion can be used for the identification and optimization of new lead compounds for the treatment of the COVID-19 disease and for the selection of the food and food supplements which could have a beneficial effect on COVID-19 patients.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"10 1","pages":"152"},"PeriodicalIF":3.1,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77033520","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}
Utilizing viruses in the treatment of cancer, or oncolytic viral therapy (OVT), began in the 1950s with the idea that viruses could invade and destroy cancer cells. Barriers to this approach included a lack of specificity towards cancer cells and intolerable toxicities. However, it was discovered that OVT increases cytokines such as interferon gamma and interleukins within the tumor microenvironment. This "priming" of the tumor microenvironment can lead to an improved innate immunologic response to tumor cells. An "OVT-as-monotherapy" approach has led to modest tumor response rates that have unfortunately not translated well in clinical trials. Currently, only one OVT agent-talimogene laherparevec (TVEC)-has been approved by the FDA for unresectable melanoma with limited visceral metastases. Further advancements in immunotherapy combined with improved viral engineering over the last decade have paved the way for a renewed focus on OVT. For example, various viruses have been modified to infiltrate and upregulate PD-L1 signaling within tumor cells. Upregulation of PD-L1 on tumor cells can increase tumor cell response to immunotherapies that utilize the interaction between PD-L1 on tumor cells and PD-1 on lymphocytes to allow for immune cell destruction of cancer cells. Combining OVT and immunotherapy offers more promise than OVT as monotherapy. Currently, several are actively investigating the combinatorial approach of OVT and immunotherapy in treating non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer, melanoma, pancreatic cancer, multiple myeloma, and head and neck squamous cell carcinoma. In this review, we will discuss the history of OVT including its limitations as a monotherapy. We will also discuss the background of combining OVT and immunotherapy including possible benefits and pitfalls of this approach. Lastly, we will review current clinical trials investigating OVT and immunotherapy in multiple cancers.
{"title":"Oncolytic Viruses as an Adjunct to Immune Checkpoint Inhibition.","authors":"J. Ripp, Stijn Hentzen, A. Saeed","doi":"10.31083/j.fbl2705151","DOIUrl":"https://doi.org/10.31083/j.fbl2705151","url":null,"abstract":"Utilizing viruses in the treatment of cancer, or oncolytic viral therapy (OVT), began in the 1950s with the idea that viruses could invade and destroy cancer cells. Barriers to this approach included a lack of specificity towards cancer cells and intolerable toxicities. However, it was discovered that OVT increases cytokines such as interferon gamma and interleukins within the tumor microenvironment. This \"priming\" of the tumor microenvironment can lead to an improved innate immunologic response to tumor cells. An \"OVT-as-monotherapy\" approach has led to modest tumor response rates that have unfortunately not translated well in clinical trials. Currently, only one OVT agent-talimogene laherparevec (TVEC)-has been approved by the FDA for unresectable melanoma with limited visceral metastases. Further advancements in immunotherapy combined with improved viral engineering over the last decade have paved the way for a renewed focus on OVT. For example, various viruses have been modified to infiltrate and upregulate PD-L1 signaling within tumor cells. Upregulation of PD-L1 on tumor cells can increase tumor cell response to immunotherapies that utilize the interaction between PD-L1 on tumor cells and PD-1 on lymphocytes to allow for immune cell destruction of cancer cells. Combining OVT and immunotherapy offers more promise than OVT as monotherapy. Currently, several are actively investigating the combinatorial approach of OVT and immunotherapy in treating non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer, melanoma, pancreatic cancer, multiple myeloma, and head and neck squamous cell carcinoma. In this review, we will discuss the history of OVT including its limitations as a monotherapy. We will also discuss the background of combining OVT and immunotherapy including possible benefits and pitfalls of this approach. Lastly, we will review current clinical trials investigating OVT and immunotherapy in multiple cancers.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"108 1","pages":"151"},"PeriodicalIF":3.1,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85673840","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 structures and activities of invertebrate sulfakinins that influence gut motility and heart rate are like the vertebrate cholecystokinin (CCK) peptides. Typical of sulfakinin precursors Drosophila melanogaster encodes non-sulfated drosulfakinin I (nsDSK I; FDDYGHMRF-NH2) and nsDSK II (GGDDQFDDYGHMRF-NH2) that bind DSK-R1 and DSK-R2. To explore the role of the nsDSK II N-terminal extension (GGDDQ) in gut we delineated its structure-activity relationship (SAR) and identified novel agonists. We then predicted the nsDSK II extension SAR is tissue specific consistent with cardiac CCK structure activity and signaling being different from gut. METHODS To evaluate our hypothesis, we tested single-substituted alanine and asparagine analogs in heart. RESULTS We found alanyl-substituted analogs were less active in heart than nsDSK II; in gut they include a super agonist and a protean agonist. Additionally, we discovered ns[N4]DSK II was more active than nsDSK II in pupal heart, while ns[N3]DSK II was inactive. In contrast, ns[N3]DSK II and ns[N4]DSK II were super agonists in adult heart, yet inactive in larva. Although we reported nsDSK II acts through DSK-R2 in gut, its identity in heart was unknown. CONCLUSIONS Here we reviewed ligand-receptor interactions in conjunction with SAR data to suggest nsDSK II acts through DSK-R1 in heart consistent with sulfakinin tissue-specific signaling.
背景:影响肠道运动和心率的无脊椎动物巯基缩氨酸的结构和活性与脊椎动物胆囊收缩素(CCK)肽相似。黑腹果蝇编码非磺化的磺胺基亚霉素I (nssdsk I;FDDYGHMRF-NH2)和nsDSK II (GGDDQFDDYGHMRF-NH2)结合DSK-R1和DSK-R2。为了探讨nssdsk II n端延伸(GGDDQ)在肠道中的作用，我们描述了它的构效关系(SAR)并鉴定了新的激动剂。然后我们预测nssdsk II扩展SAR具有组织特异性，与心脏CCK结构活性一致，信号传导不同于肠道。方法为了验证我们的假设，我们在心脏中测试了单取代丙氨酸和天冬酰胺类似物。结果alanyl-取代类似物在心脏中的活性低于nsDSK II;在肠道中，它们包括一种超级激动剂和一种变形激动剂。此外，我们发现ns[N4]DSK II在蛹心脏中比nsDSK II更活跃，而ns[N3]DSK II则不活跃。ns[N3]DSK II和ns[N4]DSK II在成虫心脏中表现为超级激动剂，而在幼虫中表现为无活性。尽管我们报道了nsDSK II在肠道中通过DSK-R2起作用，但其在心脏中的身份尚不清楚。本研究回顾了配体与受体的相互作用以及SAR数据，表明nsDSK II通过心脏中的DSK-R1起作用，与磺胺金素组织特异性信号传导一致。
{"title":"Structure-activity relationship data and ligand-receptor interactions identify novel agonists consistent with sulfakinin tissue-specific signaling in Drosophila melanogaster heart.","authors":"R. Nichols, C. Bass, C. Katanski","doi":"10.31083/j.fbl2705150","DOIUrl":"https://doi.org/10.31083/j.fbl2705150","url":null,"abstract":"BACKGROUND\u0000The structures and activities of invertebrate sulfakinins that influence gut motility and heart rate are like the vertebrate cholecystokinin (CCK) peptides. Typical of sulfakinin precursors Drosophila melanogaster encodes non-sulfated drosulfakinin I (nsDSK I; FDDYGHMRF-NH2) and nsDSK II (GGDDQFDDYGHMRF-NH2) that bind DSK-R1 and DSK-R2. To explore the role of the nsDSK II N-terminal extension (GGDDQ) in gut we delineated its structure-activity relationship (SAR) and identified novel agonists. We then predicted the nsDSK II extension SAR is tissue specific consistent with cardiac CCK structure activity and signaling being different from gut.\u0000\u0000\u0000METHODS\u0000To evaluate our hypothesis, we tested single-substituted alanine and asparagine analogs in heart.\u0000\u0000\u0000RESULTS\u0000We found alanyl-substituted analogs were less active in heart than nsDSK II; in gut they include a super agonist and a protean agonist. Additionally, we discovered ns[N4]DSK II was more active than nsDSK II in pupal heart, while ns[N3]DSK II was inactive. In contrast, ns[N3]DSK II and ns[N4]DSK II were super agonists in adult heart, yet inactive in larva. Although we reported nsDSK II acts through DSK-R2 in gut, its identity in heart was unknown.\u0000\u0000\u0000CONCLUSIONS\u0000Here we reviewed ligand-receptor interactions in conjunction with SAR data to suggest nsDSK II acts through DSK-R1 in heart consistent with sulfakinin tissue-specific signaling.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"96 1","pages":"150"},"PeriodicalIF":3.1,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85229742","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}
Rebecca McElroy, Ghazal Alipour Talesh, Christopher M. Harpur, R. Carzino, A. Corbett, D. Pellicci, S. Ranganathan, P. Sutton
BACKGROUND People with Cystic Fibrosis (CF) develop pulmonary inflammation, chronic infection and structural lung damage early in life, with these manifestations being prevalent among preschool children and infants. While early immune events are believed to play critical roles in shaping the progression, severity and disease burden later in life, T cells and their subsets are poorly studied in the CF lung, particularly during the formative early stages of disease. METHODS Using flow cytometry, we analyzed Mucosal Associated Invariant T (MAIT) cells, γδ T cells, and Natural Killer T (NKT)-like cells in bronchoalveolar lavage (BAL) samples from seventeen children with CF, aged two to six years old. The effect of age, sex and lung infections on the frequencies of these cells in BAL samples was analysed (grouped data were tested for normality and compared by t-test or Kruskal-Wallis analysis). RESULTS No difference was noted in the proportions of unconventional T cells related to the sex or age of the children. The frequency of γδ T cells and MAIT cells appeared unchanged by infection status. However, viral infections were associated with a significant increase in the proportion of NKT-like cells. CONCLUSIONS By evaluating T cells in the lungs of children during the early formative stages of CF, this study identified potentially important interactions between these cells and viral pathogens.
{"title":"Unconventional T Cell Immunity in the Lungs of Young Children with Cystic Fibrosis.","authors":"Rebecca McElroy, Ghazal Alipour Talesh, Christopher M. Harpur, R. Carzino, A. Corbett, D. Pellicci, S. Ranganathan, P. Sutton","doi":"10.31083/j.fbl2705149","DOIUrl":"https://doi.org/10.31083/j.fbl2705149","url":null,"abstract":"BACKGROUND\u0000People with Cystic Fibrosis (CF) develop pulmonary inflammation, chronic infection and structural lung damage early in life, with these manifestations being prevalent among preschool children and infants. While early immune events are believed to play critical roles in shaping the progression, severity and disease burden later in life, T cells and their subsets are poorly studied in the CF lung, particularly during the formative early stages of disease.\u0000\u0000\u0000METHODS\u0000Using flow cytometry, we analyzed Mucosal Associated Invariant T (MAIT) cells, γδ T cells, and Natural Killer T (NKT)-like cells in bronchoalveolar lavage (BAL) samples from seventeen children with CF, aged two to six years old. The effect of age, sex and lung infections on the frequencies of these cells in BAL samples was analysed (grouped data were tested for normality and compared by t-test or Kruskal-Wallis analysis).\u0000\u0000\u0000RESULTS\u0000No difference was noted in the proportions of unconventional T cells related to the sex or age of the children. The frequency of γδ T cells and MAIT cells appeared unchanged by infection status. However, viral infections were associated with a significant increase in the proportion of NKT-like cells.\u0000\u0000\u0000CONCLUSIONS\u0000By evaluating T cells in the lungs of children during the early formative stages of CF, this study identified potentially important interactions between these cells and viral pathogens.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"34 1","pages":"149"},"PeriodicalIF":3.1,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85412190","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}
Hong Liang, C. Baudouin, P. Daull, J. Garrigue, F. Brignole-Baudouin
BACKGROUND Benzalkonium chloride (BAK)-containing antiglaucoma therapies alter the ocular surface over the long term. We used an in vitro scraping model to compare the effects of preserved and unpreserved topical commercial prostaglandins (PGs) in a wound-healing model. METHODS Standardized mechanical scraping was performed in confluent immortalized human corneal/conjunctival epithelial cell layers. Cytotoxicity, cell migration and proliferation, as well as the percentage of closure, were analyzed 2 h and 1/2/3/6 days after a 30-min exposure to 1/10 dilutions in phosphate buffered saline (PBS) used also as control, BAK solutions at concentrations ranging from 0.0001% to 0.1%, latanoprost-0.02%BAK, travoprost-0.015%BAK, bimatoprost-0.005%BAK, BAK-free Tafluprost, latanoprost in cationic emulsion, and travoprost (Polyquad® and SofZia®). RESULTS PG eyedrop preparations with BAK preservative delayed corneal healing, which is primarily related to the presence of BAK, in a dose-dependent manner, especially at day 1, as evidenced through actin disorganization and decreased Ki-67-positive cell numbers. The PGs (BAK-free tafluprost, latanoprost in cationic emulsion,travoprost (Polyquad® and SofZia®)) maintained a normal healing process with results similar to those of control. Conjunctiva-derived cell layers healed more slowly than corneal cell layers and were more sensitive in in vitro cytotoxicity tests. CONCLUSIONS This novel in vitro scraping model mimics the damaged ocular surface epithelia observed in glaucoma patients affected by ocular surface disease, such as toxic-induced dry eye (TIDE) and offers a tool to assess the potential cytotoxic effects of PG formulations with or without BAK.
{"title":"In Vitro Corneal and Conjunctival Wound-Healing Assays as a Tool for Antiglaucoma Prostaglandin Formulation Characterization.","authors":"Hong Liang, C. Baudouin, P. Daull, J. Garrigue, F. Brignole-Baudouin","doi":"10.31083/j.fbl2705147","DOIUrl":"https://doi.org/10.31083/j.fbl2705147","url":null,"abstract":"BACKGROUND\u0000Benzalkonium chloride (BAK)-containing antiglaucoma therapies alter the ocular surface over the long term. We used an in vitro scraping model to compare the effects of preserved and unpreserved topical commercial prostaglandins (PGs) in a wound-healing model.\u0000\u0000\u0000METHODS\u0000Standardized mechanical scraping was performed in confluent immortalized human corneal/conjunctival epithelial cell layers. Cytotoxicity, cell migration and proliferation, as well as the percentage of closure, were analyzed 2 h and 1/2/3/6 days after a 30-min exposure to 1/10 dilutions in phosphate buffered saline (PBS) used also as control, BAK solutions at concentrations ranging from 0.0001% to 0.1%, latanoprost-0.02%BAK, travoprost-0.015%BAK, bimatoprost-0.005%BAK, BAK-free Tafluprost, latanoprost in cationic emulsion, and travoprost (Polyquad® and SofZia®).\u0000\u0000\u0000RESULTS\u0000PG eyedrop preparations with BAK preservative delayed corneal healing, which is primarily related to the presence of BAK, in a dose-dependent manner, especially at day 1, as evidenced through actin disorganization and decreased Ki-67-positive cell numbers. The PGs (BAK-free tafluprost, latanoprost in cationic emulsion,travoprost (Polyquad® and SofZia®)) maintained a normal healing process with results similar to those of control. Conjunctiva-derived cell layers healed more slowly than corneal cell layers and were more sensitive in in vitro cytotoxicity tests.\u0000\u0000\u0000CONCLUSIONS\u0000This novel in vitro scraping model mimics the damaged ocular surface epithelia observed in glaucoma patients affected by ocular surface disease, such as toxic-induced dry eye (TIDE) and offers a tool to assess the potential cytotoxic effects of PG formulations with or without BAK.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"39 1","pages":"147"},"PeriodicalIF":3.1,"publicationDate":"2022-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81152257","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}
Hypoxia is a typical characteristic of most solid malignancies, which has multiple effects on malignant phenotypes and biological behaviors of tumors including epithelial-mesenchymal-transition (EMT), invasion, migration, metastasis, autophagy, stem cell maintenance, pathological angiogenesis, drug resistance, and immunosuppression. Rcentlyumoand reversing the tumor hypoxic environment via nanotechnology has emerged as a novel therapeutic approach for the treatment of malignancies. The main strategies related to nanotechnology to alleviate or ameliorate hypoxic environment are as follows: (1) Bringing external oxygen to tumor hypoxic microenvironment; (2) Generating oxygen based on nanotechnology in situ; (3) Regulating the structure of the tumor microenvironment; (4) Decreasing oxygen consumption in the tumor microenvironment. In this review, we will discuss these nanotechnologies in detail.
{"title":"Recent Advancements of Nanotechnology-Based Strategies for Overcoming Tumor Microenvironment Hypoxia.","authors":"Jiangchao Wu, Jinyuan Song, Xianghong Yin, Jianghui Tang, Junlei Zhang, Xun Wang, Yongtao Ji, Yaxing Zhao, Dong-Xue Chen, Jianpeng Sheng, X. Bai, T. Liang","doi":"10.31083/j.fbl2705145","DOIUrl":"https://doi.org/10.31083/j.fbl2705145","url":null,"abstract":"Hypoxia is a typical characteristic of most solid malignancies, which has multiple effects on malignant phenotypes and biological behaviors of tumors including epithelial-mesenchymal-transition (EMT), invasion, migration, metastasis, autophagy, stem cell maintenance, pathological angiogenesis, drug resistance, and immunosuppression. Rcentlyumoand reversing the tumor hypoxic environment via nanotechnology has emerged as a novel therapeutic approach for the treatment of malignancies. The main strategies related to nanotechnology to alleviate or ameliorate hypoxic environment are as follows: (1) Bringing external oxygen to tumor hypoxic microenvironment; (2) Generating oxygen based on nanotechnology in situ; (3) Regulating the structure of the tumor microenvironment; (4) Decreasing oxygen consumption in the tumor microenvironment. In this review, we will discuss these nanotechnologies in detail.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"23 1","pages":"145"},"PeriodicalIF":3.1,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90524458","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}
J. Olloquequi, M. Ettcheto, A. Cano, E. Sánchez-López, M. Carrasco, Triana Espinosa, C. Beas‐Zárate, G. Gudiño-Cabrera, M. E. Ureña-Guerrero, E. Verdaguer, J. Folch, C. Auladell, A. Camins
The increases in population ageing and growth are leading to a boosting in the number of people living with dementia, Alzheimer's disease (AD) being the most common cause. In spite of decades of intensive research, no cure for AD has been found yet. However, some treatments that may change disease progression and help control symptoms have been proposed. Beyond the classical hypotheses of AD etiopathogenesis, i.e., amyloid beta peptide (Aβ) accumulation and tau hyperphosphorylation, a trend in attributing a key role to other molecular mechanisms is prompting the study of different therapeutic targets. Hence, drugs designed to modulate inflammation, insulin resistance, synapses, neurogenesis, cardiovascular factors and dysbiosis are shaping a new horizon in AD treatment. Within this frame, an increase in the number of candidate drugs for disease modification treatments is expected, as well as a focus on potential combinatory multidrug strategies.The present review summarizes the latest advances in drugs targeting Aβ and tau as major contributors to AD pathophysiology. In addition, it introduces the most important drugs in clinical studies targeting alternative mechanisms thought to be involved in AD's neurodegenerative process.
{"title":"Impact of New Drugs for Therapeutic Intervention in Alzheimer's Disease.","authors":"J. Olloquequi, M. Ettcheto, A. Cano, E. Sánchez-López, M. Carrasco, Triana Espinosa, C. Beas‐Zárate, G. Gudiño-Cabrera, M. E. Ureña-Guerrero, E. Verdaguer, J. Folch, C. Auladell, A. Camins","doi":"10.31083/j.fbl2705146","DOIUrl":"https://doi.org/10.31083/j.fbl2705146","url":null,"abstract":"The increases in population ageing and growth are leading to a boosting in the number of people living with dementia, Alzheimer's disease (AD) being the most common cause. In spite of decades of intensive research, no cure for AD has been found yet. However, some treatments that may change disease progression and help control symptoms have been proposed. Beyond the classical hypotheses of AD etiopathogenesis, i.e., amyloid beta peptide (Aβ) accumulation and tau hyperphosphorylation, a trend in attributing a key role to other molecular mechanisms is prompting the study of different therapeutic targets. Hence, drugs designed to modulate inflammation, insulin resistance, synapses, neurogenesis, cardiovascular factors and dysbiosis are shaping a new horizon in AD treatment. Within this frame, an increase in the number of candidate drugs for disease modification treatments is expected, as well as a focus on potential combinatory multidrug strategies.The present review summarizes the latest advances in drugs targeting Aβ and tau as major contributors to AD pathophysiology. In addition, it introduces the most important drugs in clinical studies targeting alternative mechanisms thought to be involved in AD's neurodegenerative process.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"61 1","pages":"146"},"PeriodicalIF":3.1,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75323368","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}
Substrates composition and surface features of materials rule adhesion control of cells to surfaces. As a result, most of the aspects of cell functions, such as spreading, migration, proliferation, and differentiation, can be significantly influenced in biomedical applications. Cell cultures make possible to understand cell biology, tissue morphology, mechanisms of diseases, drug action, and tissue engineering development, among others. Recent techniques related to culturing 3D cell aggregates in the presence of very low wettable surfaces represent an innovative field for in vitro experimentation aimed at more reliable conditions to investigate both tumor and non-tumor cell lines. Matching in particular cell biology to innovative materials, this work reviews the recent literature available on promoting cell aggregates formation strongly influenced by the high surface hydrophobicity. In particular, for spheroid formation, the highest water repellent coatings seem to be required for the significant effectiveness of the process. In this way, 3D cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions.
{"title":"Super Liquid-repellent Surfaces and 3D Spheroids Growth.","authors":"M. Ferrari, Francesca Cirisano, M. Morán","doi":"10.31083/j.fbl2705144","DOIUrl":"https://doi.org/10.31083/j.fbl2705144","url":null,"abstract":"Substrates composition and surface features of materials rule adhesion control of cells to surfaces. As a result, most of the aspects of cell functions, such as spreading, migration, proliferation, and differentiation, can be significantly influenced in biomedical applications. Cell cultures make possible to understand cell biology, tissue morphology, mechanisms of diseases, drug action, and tissue engineering development, among others. Recent techniques related to culturing 3D cell aggregates in the presence of very low wettable surfaces represent an innovative field for in vitro experimentation aimed at more reliable conditions to investigate both tumor and non-tumor cell lines. Matching in particular cell biology to innovative materials, this work reviews the recent literature available on promoting cell aggregates formation strongly influenced by the high surface hydrophobicity. In particular, for spheroid formation, the highest water repellent coatings seem to be required for the significant effectiveness of the process. In this way, 3D cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"9 1","pages":"144"},"PeriodicalIF":3.1,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79156524","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}
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