Pub Date : 2022-01-01DOI: 10.1177/03946320221130727
Jiying Wang, Zhaoying Sheng, Zhiyi Dong, Qiongya Wu, Yong Cai
Background: Lung cancer has the fastest increase in morbidity and mortality, and is one of the most threatening malignant tumors to human health and life. Both radiotherapy and targeted therapy are typical treatments after lung cancer surgery. Radiotherapy is a means of locally killing cancer lesions, and it plays an important role in the entire management of lung cancer. Gefitinib is one of the most commonly used targeted therapy drugs in the treatment of lung cancer. The purpose of this project is to explore the mechanism by which deacetylation of RBBP8 mediated by radiotherapy-promoting protein SIRT6 in lung adenocarcinoma enhances the sensitivity of targeted therapy.
Methods: In both the cell experiments and the animal experiments, the samples were divided into five groups: Model group, RT group, CT group, RT+CT group, and RT+CT+inhibitor group. The CCK8 method was used to detect the viability of each group of cells. The flow cytometry experiment was used to analyze the apoptotic characteristics of each group of cells. The scratch test was used to detect the migration ability of each group of cells. Transwell invasion test was used to determine the invasion ability of each group of cells. The lung tumor tissues of each group of mice were collected to analyze the tumor size, volume, and metastasis characteristics. The TUNEL experiment was used to detect the apoptosis characteristics of the cells in the lung cancer tissues of each group mice. Immunohistochemistry experiments were used to analyze the distribution and relative expression characteristics of protein SIRT6 in mouse lung cancer tissues. The colorimetric experiments were used to detect the activity of Caspase 3 and Caspase 8 in each group. Western blot method was used to detect the expression of SIRT6, RBBP8, and MYC in each group.
Results: In each experiment, the results of the experiment have mutually proven consistency, and there is no contradiction. In addition to the Model group, the other 4 groups used different treatment methods. The better the curative effect, the lower the cell viability of cancer cells and the higher the apoptotic ratio. This is reflected in the CCK8 test, flow cytometry analysis, cell scratch test, Transwell cell migration test, and TUNEL detection. At the same time, colorimetric detection and Western blot analysis also analyzed the levels of SIRT6, RBBP8 and other cancer-related proteins in each group at the molecular level, implying the importance of SIRT6 protein in the treatment process.
Conclusion: Our project has proved that radiotherapy can promote the protein SIRT6 to deacetylate RBBP8 proteins, and ultimately enhance targeted therapy drug sensitivity.
{"title":"The mechanism of radiotherapy for lung adenocarcinoma in promoting protein SIRT6-mediated deacetylation of RBBP8 to enhance the sensitivity of targeted therapy.","authors":"Jiying Wang, Zhaoying Sheng, Zhiyi Dong, Qiongya Wu, Yong Cai","doi":"10.1177/03946320221130727","DOIUrl":"https://doi.org/10.1177/03946320221130727","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer has the fastest increase in morbidity and mortality, and is one of the most threatening malignant tumors to human health and life. Both radiotherapy and targeted therapy are typical treatments after lung cancer surgery. Radiotherapy is a means of locally killing cancer lesions, and it plays an important role in the entire management of lung cancer. Gefitinib is one of the most commonly used targeted therapy drugs in the treatment of lung cancer. The purpose of this project is to explore the mechanism by which deacetylation of RBBP8 mediated by radiotherapy-promoting protein SIRT6 in lung adenocarcinoma enhances the sensitivity of targeted therapy.</p><p><strong>Methods: </strong>In both the cell experiments and the animal experiments, the samples were divided into five groups: Model group, RT group, CT group, RT+CT group, and RT+CT+inhibitor group. The CCK8 method was used to detect the viability of each group of cells. The flow cytometry experiment was used to analyze the apoptotic characteristics of each group of cells. The scratch test was used to detect the migration ability of each group of cells. Transwell invasion test was used to determine the invasion ability of each group of cells. The lung tumor tissues of each group of mice were collected to analyze the tumor size, volume, and metastasis characteristics. The TUNEL experiment was used to detect the apoptosis characteristics of the cells in the lung cancer tissues of each group mice. Immunohistochemistry experiments were used to analyze the distribution and relative expression characteristics of protein SIRT6 in mouse lung cancer tissues. The colorimetric experiments were used to detect the activity of Caspase 3 and Caspase 8 in each group. Western blot method was used to detect the expression of SIRT6, RBBP8, and MYC in each group.</p><p><strong>Results: </strong>In each experiment, the results of the experiment have mutually proven consistency, and there is no contradiction. In addition to the Model group, the other 4 groups used different treatment methods. The better the curative effect, the lower the cell viability of cancer cells and the higher the apoptotic ratio. This is reflected in the CCK8 test, flow cytometry analysis, cell scratch test, Transwell cell migration test, and TUNEL detection. At the same time, colorimetric detection and Western blot analysis also analyzed the levels of SIRT6, RBBP8 and other cancer-related proteins in each group at the molecular level, implying the importance of SIRT6 protein in the treatment process.</p><p><strong>Conclusion: </strong>Our project has proved that radiotherapy can promote the protein SIRT6 to deacetylate RBBP8 proteins, and ultimately enhance targeted therapy drug sensitivity.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/1d/10.1177_03946320221130727.PMC9523831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40380923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/03946320221092188
Iman Razeghian-Jahromi, Ali Karimi Akhormeh, M. Razmkhah, M. Zibaeenezhad
Coronary artery disease has remained a major health challenge despite enormous progress in prevention, diagnosis, and treatment strategies. Formation of atherosclerotic plaque is a chronic process that is developmentally influenced by intrinsic and extrinsic determinants. Inflammation triggers atherosclerosis, and the fundamental element of inflammation is the immune system. The immune system involves in the atherosclerosis process by a variety of immune cells and a cocktail of mediators. It is believed that almost all main components of this system possess a profound contribution to the atherosclerosis. However, they play contradictory roles, either protective or progressive, in different stages of atherosclerosis progression. It is evident that monocytes are the first immune cells appeared in the atherosclerotic lesion. With the plaque growth, other types of the immune cells such as mast cells, and T lymphocytes are gradually involved. Each cell releases several cytokines which cause the recruitment of other immune cells to the lesion site. This is followed by affecting the expression of other cytokines as well as altering certain signaling pathways. All in all, a mix of intertwined interactions determine the final outcome in terms of mild or severe manifestations, either clinical or subclinical. Therefore, it is of utmost importance to precisely understand the kind and degree of contribution which is made by each immune component in order to stop the growing burden of cardiovascular morbidity and mortality. In this review, we present a comprehensive appraisal on the role of immune cells in the atherosclerosis initiation and development.
{"title":"Immune system and atherosclerosis: Hostile or friendly relationship","authors":"Iman Razeghian-Jahromi, Ali Karimi Akhormeh, M. Razmkhah, M. Zibaeenezhad","doi":"10.1177/03946320221092188","DOIUrl":"https://doi.org/10.1177/03946320221092188","url":null,"abstract":"Coronary artery disease has remained a major health challenge despite enormous progress in prevention, diagnosis, and treatment strategies. Formation of atherosclerotic plaque is a chronic process that is developmentally influenced by intrinsic and extrinsic determinants. Inflammation triggers atherosclerosis, and the fundamental element of inflammation is the immune system. The immune system involves in the atherosclerosis process by a variety of immune cells and a cocktail of mediators. It is believed that almost all main components of this system possess a profound contribution to the atherosclerosis. However, they play contradictory roles, either protective or progressive, in different stages of atherosclerosis progression. It is evident that monocytes are the first immune cells appeared in the atherosclerotic lesion. With the plaque growth, other types of the immune cells such as mast cells, and T lymphocytes are gradually involved. Each cell releases several cytokines which cause the recruitment of other immune cells to the lesion site. This is followed by affecting the expression of other cytokines as well as altering certain signaling pathways. All in all, a mix of intertwined interactions determine the final outcome in terms of mild or severe manifestations, either clinical or subclinical. Therefore, it is of utmost importance to precisely understand the kind and degree of contribution which is made by each immune component in order to stop the growing burden of cardiovascular morbidity and mortality. In this review, we present a comprehensive appraisal on the role of immune cells in the atherosclerosis initiation and development.","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48378107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/03946320221095015
Seongkoo Kim, S. Han, J. Kang
Introduction: Although prolonged fever in patients with neutropenic fever (NF) during empirical antibiotic therapy could be caused by dysregulated immune responses, its association with cytokine concentrations has rarely been investigated. This study determined the kinetics of cytokine concentrations in pediatric patients with NF and bacteremia and evaluated the impact of cytokine concentration kinetics on prolonged fever. Methods: Concentrations of 13 cytokines were measured on the initial day of NF (Day 1) and 3 days (Day 4) and 7 days (Day 8) later in 10 patients with NF with bacteremia, and their kinetics was determined. The results for each cytokine concentration on each sampling day were compared for patients with fever that lasted ⩾3 days and those with fever that lasted <3 days. Results: Interleukin (IL)-6 (p < .001) and IL-10 (p = .001) concentrations were significantly higher on Day 1 than on Days 4 and 8. However, the increased IL-6 (p = 1.000) and IL-10 (p = 1.000) concentrations on Day 1 were not associated with prolonged fever (⩾3 days). For other cytokines, the concentrations measured on Days 1, 4, and 8 were similar regardless of fever duration. Conclusion: Prolonged fever in patients with NF and bacteremia was not associated with a prolonged increase in a specific cytokine concentration.
{"title":"Association between cytokine concentration kinetics and prolonged fever in febrile neutropenic children with bacteremia","authors":"Seongkoo Kim, S. Han, J. Kang","doi":"10.1177/03946320221095015","DOIUrl":"https://doi.org/10.1177/03946320221095015","url":null,"abstract":"Introduction: Although prolonged fever in patients with neutropenic fever (NF) during empirical antibiotic therapy could be caused by dysregulated immune responses, its association with cytokine concentrations has rarely been investigated. This study determined the kinetics of cytokine concentrations in pediatric patients with NF and bacteremia and evaluated the impact of cytokine concentration kinetics on prolonged fever. Methods: Concentrations of 13 cytokines were measured on the initial day of NF (Day 1) and 3 days (Day 4) and 7 days (Day 8) later in 10 patients with NF with bacteremia, and their kinetics was determined. The results for each cytokine concentration on each sampling day were compared for patients with fever that lasted ⩾3 days and those with fever that lasted <3 days. Results: Interleukin (IL)-6 (p < .001) and IL-10 (p = .001) concentrations were significantly higher on Day 1 than on Days 4 and 8. However, the increased IL-6 (p = 1.000) and IL-10 (p = 1.000) concentrations on Day 1 were not associated with prolonged fever (⩾3 days). For other cytokines, the concentrations measured on Days 1, 4, and 8 were similar regardless of fever duration. Conclusion: Prolonged fever in patients with NF and bacteremia was not associated with a prolonged increase in a specific cytokine concentration.","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47360965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/03946320221142793
Muhammad Azeem, Ghulam Mustafa, Hafiza S Mahrosh
Objective: Medicinal herbs are being investigated for medicationhg development against SARS-CoV-2 as a rich source of bioactive chemicals. One of the finest approaches for finding therapeutically effective drug molecules in real time is virtual screening scheme such as molecular docking in conjunction with molecular dynamics (MD) simulation. These virtual techniques provide an ample opportunity for the screening of plausible inhibitors of SARS-CoV-2 different target proteins from a comprehensive and extensive phytochemical library. The study was designed to identify potential phytochemicals by virtual screening against different receptor proteins.
Methods: In the current study, a library of plant secondary metabolites was created by manually curating 120 phytochemicals known to have antimicrobial as well as antiviral properties. In the current study, different potential phytochemicals were identified by virtual screening against various selected receptor proteins (i.e., viral main proteases, RNA-dependent RNA polymerase (RdRp), ADP ribose phosphatase, nonstructural proteins NSP7, NSP8, and NSP9) which are key proteins responsible for transcription, replication and maturation of SARS-CoV-2 in the host. Top three phytochemicals were selected against each viral receptor protein based on their best S-scores, RMSD values, molecular interactions, binding patterns and drug-likeness properties.
Results: The results of molecular docking study revealed that phytochemicals (i.e., baicalin, betaxanthin, epigallocatechin, fomecin A, gallic acid, hortensin, ichangin, kaempferol, limonoic acid, myricetin hexaacetat, pedalitin, quercetin, quercitrin, and silvestrol) have strong antiviral potential against SARS-CoV-2. Additionally, the reported preeminent reliable phytochemicals also revealed toxicity by no means during the evaluation through ADMET profiling. Moreover, the MD simulation study also exhibited thermal stability and stable binding affinity of the pedalitin with SARS-CoV-2 RdRp and SARS-CoV-2 main protease which suggests appreciable efficacy of the lead optimization.
Conclusion: The biological activity and pharmacologically distinguishing characteristics of these lead compounds also satisfied as repurposing antiviral drug contenders and are worth substantial evaluation in the biological laboratory for the recommendation of being plausible antiviral drug candidates against SARS-CoV-2.
{"title":"Virtual screening of phytochemicals by targeting multiple proteins of severe acute respiratory syndrome coronavirus 2: Molecular docking and molecular dynamics simulation studies.","authors":"Muhammad Azeem, Ghulam Mustafa, Hafiza S Mahrosh","doi":"10.1177/03946320221142793","DOIUrl":"10.1177/03946320221142793","url":null,"abstract":"<p><strong>Objective: </strong>Medicinal herbs are being investigated for medicationhg development against SARS-CoV-2 as a rich source of bioactive chemicals. One of the finest approaches for finding therapeutically effective drug molecules in real time is virtual screening scheme such as molecular docking in conjunction with molecular dynamics (MD) simulation. These virtual techniques provide an ample opportunity for the screening of plausible inhibitors of SARS-CoV-2 different target proteins from a comprehensive and extensive phytochemical library. The study was designed to identify potential phytochemicals by virtual screening against different receptor proteins.</p><p><strong>Methods: </strong>In the current study, a library of plant secondary metabolites was created by manually curating 120 phytochemicals known to have antimicrobial as well as antiviral properties. In the current study, different potential phytochemicals were identified by virtual screening against various selected receptor proteins (i.e., viral main proteases, RNA-dependent RNA polymerase (RdRp), ADP ribose phosphatase, nonstructural proteins NSP7, NSP8, and NSP9) which are key proteins responsible for transcription, replication and maturation of SARS-CoV-2 in the host. Top three phytochemicals were selected against each viral receptor protein based on their best S-scores, RMSD values, molecular interactions, binding patterns and drug-likeness properties.</p><p><strong>Results: </strong>The results of molecular docking study revealed that phytochemicals (i.e., baicalin, betaxanthin, epigallocatechin, fomecin A, gallic acid, hortensin, ichangin, kaempferol, limonoic acid, myricetin hexaacetat, pedalitin, quercetin, quercitrin, and silvestrol) have strong antiviral potential against SARS-CoV-2. Additionally, the reported preeminent reliable phytochemicals also revealed toxicity by no means during the evaluation through ADMET profiling. Moreover, the MD simulation study also exhibited thermal stability and stable binding affinity of the pedalitin with SARS-CoV-2 RdRp and SARS-CoV-2 main protease which suggests appreciable efficacy of the lead optimization.</p><p><strong>Conclusion: </strong>The biological activity and pharmacologically distinguishing characteristics of these lead compounds also satisfied as repurposing antiviral drug contenders and are worth substantial evaluation in the biological laboratory for the recommendation of being plausible antiviral drug candidates against SARS-CoV-2.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ee/f8/10.1177_03946320221142793.PMC9716588.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40710858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/20587384211073232
Sameh Chamkhi, Tarak Dhaouadi, Imen Sfar, Salma Mokni, Alia Jebri, Dhouha Mansouri, Salma Ghedira, Emna Ben Jemia, Samia Ben Boujemaa, Mohamed Houissa, Hichem Aouina, Taïeb Ben Abdallah, Yousr Gorgi
Background: To overcome the COVID-19 pandemic, serology assays are needed to identify past and ongoing infections. In this context, we evaluated the diagnostic performance of 6 immunoassays on samples from hospitalized patients for moderate to critical COVID-19.
Methods: 701 serum samples obtained from 443 COVID-19 patients (G1: 356 positive RT-PCR patients and G2: 87 negative RT-PCR cases) and 108 pre-pandemic sera from blood donors were tested with 6 commercial immunoassays: (1) Elecsys Anti-SARS-CoV-2, Roche (Nucleocapsid, N), (2) Elecsys Anti-SARS-CoV-2 S, Roche (Spike, S), (3) Vidas SARS-COV-2 IgM/IgG, BioMérieux (S), (4) SARS-CoV-2 IgG, Abbott (N), (5) Access SARS-CoV-2 IgG, Beckman Coulter (Receptor Binding Domain), and (6) Standard F COVID-19 IgM/IgG Combo FIA, SD Biosensor (N).
Results: Global sensitivities of the evaluated assays were as follows: (1) Roche anti-N = 74.5% [69.6-79.3], (2) Roche anti-S = 92.7% [84.7-100], (3) Vidas IgM = 74.9% [68.6-81.2], (4) Vidas IgG = 73.9% [67.6-80.1], (5) Abbott = 78.6% [63.4-93.8], (6) Beckman Coulter = 74.5% [62-86.9], (7) SD Biosensor IgM = 73.1% [61-85.1], and (8) SD Biosensor IgG = 76.9% [65.4-88.4]. Sensitivities increased gradually from week 1 to week 3 as follow: (1) Roche anti-N: 63.3%, 81% and 82.1%; (2) Vidas IgM: 68.2%, 83.2% and 85.9%; and (3) Vidas IgG: 66.7%, 79.1% and 86.6%. All immunoassays showed a specificity of 100%. Seropositivity was significantly associated with a higher frequency of critical COVID-19 (50.8% vs. 38.2%), p = 0.018, OR [95% CI] = 1.668 [1.09-2.553]. Inversely, death occurred more frequently in seronegative patients (28.7% vs. 13.6%), p=3.02 E-4, OR [95% CI] = 0.392 [0.233-0.658].
Conclusion: Evaluated serology assays exhibited good sensitivities and excellent specificities. Sensitivities increased gradually after symptoms onset. Even if seropositivity is more frequent in patients with critical COVID-19, it may predict a recovery outcome.
{"title":"Comparative study of six SARS-CoV-2 serology assays: Diagnostic performance and antibody dynamics in a cohort of hospitalized patients for moderate to critical COVID-19.","authors":"Sameh Chamkhi, Tarak Dhaouadi, Imen Sfar, Salma Mokni, Alia Jebri, Dhouha Mansouri, Salma Ghedira, Emna Ben Jemia, Samia Ben Boujemaa, Mohamed Houissa, Hichem Aouina, Taïeb Ben Abdallah, Yousr Gorgi","doi":"10.1177/20587384211073232","DOIUrl":"https://doi.org/10.1177/20587384211073232","url":null,"abstract":"<p><strong>Background: </strong>To overcome the COVID-19 pandemic, serology assays are needed to identify past and ongoing infections. In this context, we evaluated the diagnostic performance of 6 immunoassays on samples from hospitalized patients for moderate to critical COVID-19.</p><p><strong>Methods: </strong>701 serum samples obtained from 443 COVID-19 patients (G1: 356 positive RT-PCR patients and G2: 87 negative RT-PCR cases) and 108 pre-pandemic sera from blood donors were tested with 6 commercial immunoassays: (1) Elecsys Anti-SARS-CoV-2, Roche (Nucleocapsid, N), (2) Elecsys Anti-SARS-CoV-2 S, Roche (Spike, S), (3) Vidas SARS-COV-2 IgM/IgG, BioMérieux (S), (4) SARS-CoV-2 IgG, Abbott (N), (5) Access SARS-CoV-2 IgG, Beckman Coulter (Receptor Binding Domain), and (6) Standard F COVID-19 IgM/IgG Combo FIA, SD Biosensor (N).</p><p><strong>Results: </strong>Global sensitivities of the evaluated assays were as follows: (1) Roche anti-N = 74.5% [69.6-79.3], (2) Roche anti-S = 92.7% [84.7-100], (3) Vidas IgM = 74.9% [68.6-81.2], (4) Vidas IgG = 73.9% [67.6-80.1], (5) Abbott = 78.6% [63.4-93.8], (6) Beckman Coulter = 74.5% [62-86.9], (7) SD Biosensor IgM = 73.1% [61-85.1], and (8) SD Biosensor IgG = 76.9% [65.4-88.4]. Sensitivities increased gradually from week 1 to week 3 as follow: (1) Roche anti-N: 63.3%, 81% and 82.1%; (2) Vidas IgM: 68.2%, 83.2% and 85.9%; and (3) Vidas IgG: 66.7%, 79.1% and 86.6%. All immunoassays showed a specificity of 100%. Seropositivity was significantly associated with a higher frequency of critical COVID-19 (50.8% vs. 38.2%), <i>p</i> = 0.018, OR [95% CI] = 1.668 [1.09-2.553]. Inversely, death occurred more frequently in seronegative patients (28.7% vs. 13.6%), <i>p</i>=3.02 E-4, OR [95% CI] = 0.392 [0.233-0.658].</p><p><strong>Conclusion: </strong>Evaluated serology assays exhibited good sensitivities and excellent specificities. Sensitivities increased gradually after symptoms onset. Even if seropositivity is more frequent in patients with critical COVID-19, it may predict a recovery outcome.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/56/10.1177_20587384211073232.PMC8819577.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39884746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/20587384211069831
M. Cetkovic-Cvrlje, S. Rogan, Emily Barbaro
Objective T cells orchestrate an inflammatory response that destroys pancreatic insulin-producing β cells during the development of autoimmune type 1 diabetes (T1D). Garcinia kola Heckel (GK) is a plant widely exploited in West African traditional medicine. Some of the therapeutic effects of GK nut’s extract (GKE) have been suggested to be due to its anti-inflammatory potential. Since GKE has never been investigated in a T1D experimental model, nor in the T cells’ context, we aimed to determine whether GKE exhibits antidiabetic properties and affects T cells by its anticipated anti-inflammatory action. Methods The effect of aqueous GKE (aGKE) ingestion, 100 mg/kg daily by drinking water over the period of 6 weeks, has been tested in a low-dose streptozotocin-induced (LDSTZ) mouse model of autoimmune T1D. T cells were studied in vitro and in vivo in mice treated by aGKE. Results The results showed that aGKE treatment, which started a week before induction of disease, neither delayed the development of T1D, nor reduced glycemia severity. Interestingly, aGKE treatment did affect T cells and their function, significantly decreasing the frequency of helper (TH) and cytotoxic (TC) T cells, while elevating the levels of pro-inflammatory cytokines, TNF-α, IL-6, and IFN-γ, and suppressing IL-2. Conclusion In conclusion, our results did not confirm the antidiabetic property of GKE, while suggesting its therapeutic exploration in TH2-dependent pathologies that benefit from an aggravated TH1 response, such as allergies.
{"title":"Garcinia kola treatment exhibits immunomodulatory properties while not affecting type 1 diabetes development in an experimental mouse model","authors":"M. Cetkovic-Cvrlje, S. Rogan, Emily Barbaro","doi":"10.1177/20587384211069831","DOIUrl":"https://doi.org/10.1177/20587384211069831","url":null,"abstract":"Objective T cells orchestrate an inflammatory response that destroys pancreatic insulin-producing β cells during the development of autoimmune type 1 diabetes (T1D). Garcinia kola Heckel (GK) is a plant widely exploited in West African traditional medicine. Some of the therapeutic effects of GK nut’s extract (GKE) have been suggested to be due to its anti-inflammatory potential. Since GKE has never been investigated in a T1D experimental model, nor in the T cells’ context, we aimed to determine whether GKE exhibits antidiabetic properties and affects T cells by its anticipated anti-inflammatory action. Methods The effect of aqueous GKE (aGKE) ingestion, 100 mg/kg daily by drinking water over the period of 6 weeks, has been tested in a low-dose streptozotocin-induced (LDSTZ) mouse model of autoimmune T1D. T cells were studied in vitro and in vivo in mice treated by aGKE. Results The results showed that aGKE treatment, which started a week before induction of disease, neither delayed the development of T1D, nor reduced glycemia severity. Interestingly, aGKE treatment did affect T cells and their function, significantly decreasing the frequency of helper (TH) and cytotoxic (TC) T cells, while elevating the levels of pro-inflammatory cytokines, TNF-α, IL-6, and IFN-γ, and suppressing IL-2. Conclusion In conclusion, our results did not confirm the antidiabetic property of GKE, while suggesting its therapeutic exploration in TH2-dependent pathologies that benefit from an aggravated TH1 response, such as allergies.","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43968652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/03946320221106504
Sebastian Dwertmann Rico, Franziska Büscheck, David Dum, Andreas M Luebke, Martina Kluth, Claudia Hube-Magg, Andrea Hinsch, Doris Höflmayer, Daniel Perez, Jakob R Izbicki, Michael Neipp, Hamid Mofid, Thies Daniels, Christoph Isbert, Christoph Fraune, Katharina Möller, Anne Menz, Christian Bernreuther, Patrick Lebok, Till Clauditz, Guido Sauter, Ria Uhlig, Waldemar Wilczak, Ronald Simon, Stefan Steurer, Eike Burandt, Andreas Marx, Till Krech
Introduction: Mucin 5AC (MUC5AC) belongs to the family of secreted gel-forming mucins. It is physiologically expressed in some normal mucin producing epithelial cells but also in pancreatic, ovarian, and colon cancer cells. The role of MUC5AC expression in cancer is not fully understood. This study was designed to explore the role of MUC5AC for pancreatic cancer progression, its association to microsatellite instability, and its diagnostic utility. Methods: Mucin 5AC expression was studied immunohistochemically in a tissue microarray (TMA) from 532 pancreatic cancers, 61 cancers of the ampulla Vateri, six acinar cell carcinomas and 12 large sections of pancreatitis. Results: Mucin 5AC staining was interpretable in 476 of 599 (79%) arrayed cancers. Staining was completely absent in normal pancreas and pancreatitis, but frequent in pancreatic cancer. Membranous and cytoplasmic MUC5AC expression was most common in pancreatic adenocarcinomas (71% of 423), followed by carcinomas of the ampulla Vateri (43% of 47), and absent in six acinar cell carcinomas. Mucin 5AC expression was unrelated to tumor phenotype (tumor stage, tumor grade, lymph node, and distant metastasis), and microsatellite instability in ductal adenocarcinomas and carcinomas of the ampulla Vateri. Conclusion: Our study indicates that MUC5AC is an excellent biomarker for pancreatic cancer diagnosis, especially to support the sometimes-difficult diagnosis on small biopsies. Mucin 5AC expression is unrelated to pancreatic cancer aggressiveness.
{"title":"Mucin 5AC expression is common but unrelated to tumor progression in pancreatic adenocarcinoma.","authors":"Sebastian Dwertmann Rico, Franziska Büscheck, David Dum, Andreas M Luebke, Martina Kluth, Claudia Hube-Magg, Andrea Hinsch, Doris Höflmayer, Daniel Perez, Jakob R Izbicki, Michael Neipp, Hamid Mofid, Thies Daniels, Christoph Isbert, Christoph Fraune, Katharina Möller, Anne Menz, Christian Bernreuther, Patrick Lebok, Till Clauditz, Guido Sauter, Ria Uhlig, Waldemar Wilczak, Ronald Simon, Stefan Steurer, Eike Burandt, Andreas Marx, Till Krech","doi":"10.1177/03946320221106504","DOIUrl":"10.1177/03946320221106504","url":null,"abstract":"<p><p><b>Introduction:</b> Mucin 5AC (MUC5AC) belongs to the family of secreted gel-forming mucins. It is physiologically expressed in some normal mucin producing epithelial cells but also in pancreatic, ovarian, and colon cancer cells. The role of MUC5AC expression in cancer is not fully understood. This study was designed to explore the role of MUC5AC for pancreatic cancer progression, its association to microsatellite instability, and its diagnostic utility. <b>Methods:</b> Mucin 5AC expression was studied immunohistochemically in a tissue microarray (TMA) from 532 pancreatic cancers, 61 cancers of the ampulla Vateri, six acinar cell carcinomas and 12 large sections of pancreatitis. <b>Results:</b> Mucin 5AC staining was interpretable in 476 of 599 (79%) arrayed cancers. Staining was completely absent in normal pancreas and pancreatitis, but frequent in pancreatic cancer. Membranous and cytoplasmic MUC5AC expression was most common in pancreatic adenocarcinomas (71% of 423), followed by carcinomas of the ampulla Vateri (43% of 47), and absent in six acinar cell carcinomas. Mucin 5AC expression was unrelated to tumor phenotype (tumor stage, tumor grade, lymph node, and distant metastasis), and microsatellite instability in ductal adenocarcinomas and carcinomas of the ampulla Vateri. <b>Conclusion:</b> Our study indicates that MUC5AC is an excellent biomarker for pancreatic cancer diagnosis, especially to support the sometimes-difficult diagnosis on small biopsies. Mucin 5AC expression is unrelated to pancreatic cancer aggressiveness.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40407296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Niloticin is an active compound isolated from Cortex phellodendri with uncharacterized anti-inflammatory activity. We assessed the drug potential of niloticin and examined its ability to target myeloid differentiation protein 2 (MD-2) to ascertain the mechanism for its anti-inflammatory activity.
Methods: The Traditional Chinese Medicine Systems Pharmacology Database was used to evaluate niloticin. Bio-layer interferometry and molecular docking technologies were used to explore how niloticin targets MD-2, which mediates a series of toll-like receptor 4 (TLR4)-dependent inflammatory responses. The cytokines involved in the lipopolysaccharide (LPS)-TLR4/MD-2-NF-κB pathway were evaluated using ELISA, RT-qPCR, and western blotting.
Results: Niloticin could bind to MD-2 and had no evident effects on cell viability. Niloticin treatment significantly decreased the levels of NO, IL-6, TNF-α, and IL-1β induced by LPS (p < 0.01). IL-1β, IL-6, iNOS, TNF-α, and COX-2 mRNA expression levels were decreased by niloticin (all p < 0.01). Compared with that in the control group, the increase in TLR4, p65, MyD88, p-p65, and iNOS expression levels induced by LPS were suppressed by niloticin (all p < 0.01).
Conclusion: Our results suggest that niloticin has therapeutic potential and binds to MD-2. Niloticin binding to MD-2 antagonized the effects of LPS binding to the TLR4/MD-2 complex, resulting in the inhibition of the LPS-TLR4/MD-2-NF-κB signaling pathway.
{"title":"Niloticin binds to MD-2 to promote anti-inflammatory pathway activation in macrophage cells.","authors":"Guirong Chen, Chang Liu, Mingbo Zhang, Xiaobo Wang, Yubin Xu","doi":"10.1177/03946320221133017","DOIUrl":"https://doi.org/10.1177/03946320221133017","url":null,"abstract":"<p><strong>Objectives: </strong>Niloticin is an active compound isolated from <i>Cortex phellodendri</i> with uncharacterized anti-inflammatory activity. We assessed the drug potential of niloticin and examined its ability to target myeloid differentiation protein 2 (MD-2) to ascertain the mechanism for its anti-inflammatory activity.</p><p><strong>Methods: </strong>The Traditional Chinese Medicine Systems Pharmacology Database was used to evaluate niloticin. Bio-layer interferometry and molecular docking technologies were used to explore how niloticin targets MD-2, which mediates a series of toll-like receptor 4 (TLR4)-dependent inflammatory responses. The cytokines involved in the lipopolysaccharide (LPS)-TLR4/MD-2-NF-κB pathway were evaluated using ELISA, RT-qPCR, and western blotting.</p><p><strong>Results: </strong>Niloticin could bind to MD-2 and had no evident effects on cell viability. Niloticin treatment significantly decreased the levels of NO, IL-6, TNF-α, and IL-1β induced by LPS (<i>p</i> < 0.01). IL-1β, IL-6, iNOS, TNF-α, and COX-2 mRNA expression levels were decreased by niloticin (all <i>p</i> < 0.01). Compared with that in the control group, the increase in TLR4, p65, MyD88, p-p65, and iNOS expression levels induced by LPS were suppressed by niloticin (all <i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>Our results suggest that niloticin has therapeutic potential and binds to MD-2. Niloticin binding to MD-2 antagonized the effects of LPS binding to the TLR4/MD-2 complex, resulting in the inhibition of the LPS-TLR4/MD-2-NF-κB signaling pathway.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/dc/10.1177_03946320221133017.PMC9629566.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40439119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Macrophages play a critical role in atherosclerosis by contributing to plaque development, local inflammation, and thrombosis. Elucidation of the molecular cascades in atherosclerotic macrophages is important for preventing and treating atherosclerosis. This study aims to deepen the understanding of the mechanisms that regulate the function of aorta macrophage in atherosclerosis. Methods: In the current study, the expression and function of ETS variant transcription factor 6 (ETV6) in aorta macrophages in a mouse atherosclerosis model. Aorta macrophages were enriched by flow cytometry. ETV6 expression was analyzed by quantitative RT-PCR. The role of ETV6 in macrophage-mediated pro-inflammatory response was evaluated both in vitro and in vivo after ETV6 silencing. Results: A remarkable elevation of ETV6 in aorta macrophages of atherosclerotic mice was observed. In addition, in vitro analysis indicated that oxidized low-density lipoprotein (oxLDL) up-regulated ETV6 in macrophages via the NF-κB pathway. ETV6 silencing suppressed oxLDL-induced expression of IL-1β, IL-6, and TNF-α in macrophages in vitro. However, ETV6 silencing did not impact the uptake of either oxLDL or cholesterol by macrophages. Furthermore, ETV6 silencing suppressed oxLDL-induced activation of the NF-κB pathway in macrophages, as evidenced by less phosphorylation of IKKβ and NF-κB p65, more cytoplasmic IκBα, and lower nuclear NF-κB p65. Moreover, ETV6 silencing inhibited the production of IL-1β and TNF-α in aorta macrophages in vivo. Conclusion: ETV6 supports macrophage-mediated inflammation in atherosclerotic aortas. This is a novel mechanism regulating the pro-inflammatory activity of atherosclerotic macrophages.
{"title":"ETS variant transcription factor 6 enhances oxidized low-density lipoprotein-induced inflammatory response in atherosclerotic macrophages via activating NF-κB signaling.","authors":"Xiaofang Xiong, Zheng Yan, Wei Jiang, Xuejun Jiang","doi":"10.1177/20587384221076472","DOIUrl":"10.1177/20587384221076472","url":null,"abstract":"<p><p><b>Objectives</b>: Macrophages play a critical role in atherosclerosis by contributing to plaque development, local inflammation, and thrombosis. Elucidation of the molecular cascades in atherosclerotic macrophages is important for preventing and treating atherosclerosis. This study aims to deepen the understanding of the mechanisms that regulate the function of aorta macrophage in atherosclerosis. <b>Methods</b>: In the current study, the expression and function of ETS variant transcription factor 6 (ETV6) in aorta macrophages in a mouse atherosclerosis model. Aorta macrophages were enriched by flow cytometry. ETV6 expression was analyzed by quantitative RT-PCR. The role of ETV6 in macrophage-mediated pro-inflammatory response was evaluated both <i>in vitro</i> and <i>in vivo</i> after ETV6 silencing. <b>Results:</b> A remarkable elevation of ETV6 in aorta macrophages of atherosclerotic mice was observed. In addition, <i>in vitro</i> analysis indicated that oxidized low-density lipoprotein (oxLDL) up-regulated ETV6 in macrophages via the NF-κB pathway. ETV6 silencing suppressed oxLDL-induced expression of IL-1β, IL-6, and TNF-α in macrophages <i>in vitro</i>. However, ETV6 silencing did not impact the uptake of either oxLDL or cholesterol by macrophages. Furthermore, ETV6 silencing suppressed oxLDL-induced activation of the NF-κB pathway in macrophages, as evidenced by less phosphorylation of IKKβ and NF-κB p65, more cytoplasmic IκBα, and lower nuclear NF-κB p65. Moreover, ETV6 silencing inhibited the production of IL-1β and TNF-α in aorta macrophages <i>in vivo</i>. <b>Conclusion:</b> ETV6 supports macrophage-mediated inflammation in atherosclerotic aortas. This is a novel mechanism regulating the pro-inflammatory activity of atherosclerotic macrophages.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48656444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/03946320221112433
Mi Hee Kwack, Dae-Lyong Ha, Weon Ju Lee
Objectives: Particulate matter (PM) is an air pollutant that can damage human skin; antioxidants have shown some efficacy in alleviating PM-induced skin inflammation. We investigated the antioxidant effects of punicalagin, epigallocatechin-3-gallate (EGCG), and resveratrol on PM-induced changes in cultured human sebocytes, outer root sheath (ORS) cells, and Cutibacterium acnes-pretreated mice.
Methods: Sebocytes and ORS cells were cultured with 100 μg/mL PM10 and 5 μM punicalagin, 1 μM EGCG, or 1 μM resveratrol for 24 h. In C. acnes-pretreated mice, inflammatory nodules were treated with 100 μg/mL PM10 and 5 μM punicalagin, 1 μM EGCG, or 1 μM resveratrol. Cell viability was measured using an MTT assay. Antioxidant effects were analyzed according to RNA expression, using real-time PCR, as well as reactive oxygen species (ROS) and sebum measurements.
Results: Antioxidants inhibited the upregulation of inflammatory cytokines, matrix metalloproteinase, aryl hydrocarbon receptor, and NF-kB as well as the production of ROS induced by PM10 in cultured sebocytes and ORS cells. The preventative effects of punicalagin and EGCG on biomarker expression in cultured sebocytes and ORS cells were slightly greater than those of resveratrol, though the difference was not significant. In C. acnes-pretreated mice, the antioxidants inhibited inflammatory cytokine and matrix metalloproteinase expression as well as sebum production.
Conclusions: Antioxidants effectively reduced the expression of inflammatory biomarkers and sebum production in cultured sebocytes, ORS cells, and C. acnes-pretreated mice.
{"title":"Preventative effects of antioxidants on changes in sebocytes, outer root sheath cells, and <i>Cutibacterium acnes</i>-pretreated mice by particulate matter: No significant difference among antioxidants.","authors":"Mi Hee Kwack, Dae-Lyong Ha, Weon Ju Lee","doi":"10.1177/03946320221112433","DOIUrl":"10.1177/03946320221112433","url":null,"abstract":"<p><strong>Objectives: </strong>Particulate matter (PM) is an air pollutant that can damage human skin; antioxidants have shown some efficacy in alleviating PM-induced skin inflammation. We investigated the antioxidant effects of punicalagin, epigallocatechin-3-gallate (EGCG), and resveratrol on PM-induced changes in cultured human sebocytes, outer root sheath (ORS) cells, and <i>Cutibacterium acnes</i>-pretreated mice.</p><p><strong>Methods: </strong>Sebocytes and ORS cells were cultured with 100 μg/mL PM10 and 5 μM punicalagin, 1 μM EGCG, or 1 μM resveratrol for 24 h. In <i>C</i>. <i>acnes</i>-pretreated mice, inflammatory nodules were treated with 100 μg/mL PM10 and 5 μM punicalagin, 1 μM EGCG, or 1 μM resveratrol. Cell viability was measured using an MTT assay. Antioxidant effects were analyzed according to RNA expression, using real-time PCR, as well as reactive oxygen species (ROS) and sebum measurements.</p><p><strong>Results: </strong>Antioxidants inhibited the upregulation of inflammatory cytokines, matrix metalloproteinase, aryl hydrocarbon receptor, and NF-kB as well as the production of ROS induced by PM10 in cultured sebocytes and ORS cells. The preventative effects of punicalagin and EGCG on biomarker expression in cultured sebocytes and ORS cells were slightly greater than those of resveratrol, though the difference was not significant. In <i>C</i>. <i>acnes</i>-pretreated mice, the antioxidants inhibited inflammatory cytokine and matrix metalloproteinase expression as well as sebum production.</p><p><strong>Conclusions: </strong>Antioxidants effectively reduced the expression of inflammatory biomarkers and sebum production in cultured sebocytes, ORS cells, and <i>C</i>. <i>acnes</i>-pretreated mice.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/bc/10.1177_03946320221112433.PMC9252012.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40577143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}