Pub Date : 2022-04-21eCollection Date: 2022-01-01DOI: 10.1155/2022/5735546
Eman T Ali, Azza Sajid Jabbar, Hadeel S Al Ali, Saad Shaheen Hamadi, Majid S Jabir, Salim Albukhaty
Background: Tissue damage caused by COVID-19 could be detected by several clinical indicators including hematological, immunological, biochemical, and inflammatory markers. This study was to detect these clinical parameters to reveal the correlation between the factors and their roles in the development of COVID-19, to explore the hazard factors in severe cases.
Materials and methods: A total of 200 participants of both sexes were included in the study, with an age range of (25-72) years, categorized into three main groups: 50 healthy individuals, 62 mild infected patients, and 88 severe infected patients with pneumonia. Different hematological and clinical parameters were included in the analysis (Basrah city, Iraq). Serum levels of interleukin-6 (IL-6), ferritin, and high-sensitivity C-reactive protein (hs-CRP) were assessed for all participants using an enzyme-linked immunosorbent assay (ELISA). The liver, renal, and cardiac functions were assessed by clinical chemistry testing.
Results: COVID-19 patients had leukocytosis, with an increased number of neutrophils and a decreased lymphocyte count, according to our findings. In regard to inflammatory parameters, both ESR and hs-CRP showed significant differences between the two groups, whereas IL-6 was significantly higher in the total severe group compared to the other two groups. Biochemical results revealed that each lactate dehydrogenase (LDH), ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) had significant changes in the total severe group. Among pneumonic with an O2 requirement and pneumonic without an O2 requirement, there were significant differences in immunological and inflammatory markers (p > 0.05). The neutrophils-lymphocytes ratio (NLR) was highly elevated in severe who required O2. Moreover, IL-6, lymphocytes, and neutrophils were possible risk factors for COVID-19 infection, with the strongest influence of IL-6 with a high odds ratio (OR: 24.138, 95% CI: 8.437-30.65, p < 0.01). Furthermore, there were significant correlations among the indicators.
Conclusion: Each of IL-6, lymphocytes, and neutrophils might represent major factors in the severity of COVID-19 and IL-6 plays the main role in inducing the inflammatory and pathophysiology process that is known as the cytokine storm.
{"title":"Extensive Study on Hematological, Immunological, Inflammatory Markers, and Biochemical Profile to Identify the Risk Factors in COVID-19 Patients.","authors":"Eman T Ali, Azza Sajid Jabbar, Hadeel S Al Ali, Saad Shaheen Hamadi, Majid S Jabir, Salim Albukhaty","doi":"10.1155/2022/5735546","DOIUrl":"https://doi.org/10.1155/2022/5735546","url":null,"abstract":"<p><strong>Background: </strong>Tissue damage caused by COVID-19 could be detected by several clinical indicators including hematological, immunological, biochemical, and inflammatory markers. This study was to detect these clinical parameters to reveal the correlation between the factors and their roles in the development of COVID-19, to explore the hazard factors in severe cases.</p><p><strong>Materials and methods: </strong>A total of 200 participants of both sexes were included in the study, with an age range of (25-72) years, categorized into three main groups: 50 healthy individuals, 62 mild infected patients, and 88 severe infected patients with pneumonia. Different hematological and clinical parameters were included in the analysis (Basrah city, Iraq). Serum levels of interleukin-6 (IL-6), ferritin, and high-sensitivity <i>C</i>-reactive protein (hs-CRP) were assessed for all participants using an enzyme-linked immunosorbent assay (ELISA). The liver, renal, and cardiac functions were assessed by clinical chemistry testing.</p><p><strong>Results: </strong>COVID-19 patients had leukocytosis, with an increased number of neutrophils and a decreased lymphocyte count, according to our findings. In regard to inflammatory parameters, both ESR and hs-CRP showed significant differences between the two groups, whereas IL-6 was significantly higher in the total severe group compared to the other two groups. Biochemical results revealed that each lactate dehydrogenase (LDH), ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) had significant changes in the total severe group. Among pneumonic with an O2 requirement and pneumonic without an O2 requirement, there were significant differences in immunological and inflammatory markers (<i>p</i> > 0.05). The neutrophils-lymphocytes ratio (NLR) was highly elevated in severe who required O2. Moreover, IL-6, lymphocytes, and neutrophils were possible risk factors for COVID-19 infection, with the strongest influence of IL-6 with a high odds ratio (OR: 24.138, 95% CI: 8.437-30.65, <i>p</i> < 0.01). Furthermore, there were significant correlations among the indicators.</p><p><strong>Conclusion: </strong>Each of IL-6, lymphocytes, and neutrophils might represent major factors in the severity of COVID-19 and IL-6 plays the main role in inducing the inflammatory and pathophysiology process that is known as the cytokine storm.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":" ","pages":"5735546"},"PeriodicalIF":2.0,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40041517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Fesahat, Efat Norouzi, S. Seifati, Saeideh Hamidian, A. Hosseini, F. Zare
Immune system disorders and increased inflammation in the male reproductive system can lead to fetal risk in the early stages of development and implantation. Antioxidants such as vitamin C can play a protective role against sperm inflammatory reactions. This study aimed to evaluate the effect of vitamin C on the expression of inflammatory and anti-inflammatory cytokine genes in the male partners of couples with recurrent pregnancy loss. In this randomized clinical trial, twenty male partners of couples with RPL were examined for sperm parameters and expression profile of some inflammatory and anti-inflammatory cytokine genes before and after treatment with vitamin C. There was a statistically significant higher rate of normal morphology and sperm concentration in each patient before and after treatment with vitamin C (p ≤ 0.05). The mRNA levels of interleukin 6 and tumor necrosis factor-alpha were significantly decreased in the sperm of patients after treatment with vitamin C compared to before treatment. In contrast, the gene expression levels of interleukin 4 and transforming growth factor-beta showed a significant increase in the sperm of patients after treatment with vitamin C. Oral daily administration of vitamin C may be effective in the fertility potential of male partners of couples with RPL not only through the improvement of the sperm parameters but also by modulating the expression profile of inflammatory and anti-inflammatory genes. Further studies on protein levels are needed to clarify the role of TNF-⍺ and IFN-γ as a prognostic value in evaluating the recurrent abortion risk in infertile male partners. This trial is registered with IRCT20180312039059N1.
{"title":"Impact of Vitamin C on Gene Expression Profile of Inflammatory and Anti-Inflammatory Cytokines in the Male Partners of Couples with Recurrent Pregnancy Loss","authors":"F. Fesahat, Efat Norouzi, S. Seifati, Saeideh Hamidian, A. Hosseini, F. Zare","doi":"10.1155/2022/1222533","DOIUrl":"https://doi.org/10.1155/2022/1222533","url":null,"abstract":"Immune system disorders and increased inflammation in the male reproductive system can lead to fetal risk in the early stages of development and implantation. Antioxidants such as vitamin C can play a protective role against sperm inflammatory reactions. This study aimed to evaluate the effect of vitamin C on the expression of inflammatory and anti-inflammatory cytokine genes in the male partners of couples with recurrent pregnancy loss. In this randomized clinical trial, twenty male partners of couples with RPL were examined for sperm parameters and expression profile of some inflammatory and anti-inflammatory cytokine genes before and after treatment with vitamin C. There was a statistically significant higher rate of normal morphology and sperm concentration in each patient before and after treatment with vitamin C (p ≤ 0.05). The mRNA levels of interleukin 6 and tumor necrosis factor-alpha were significantly decreased in the sperm of patients after treatment with vitamin C compared to before treatment. In contrast, the gene expression levels of interleukin 4 and transforming growth factor-beta showed a significant increase in the sperm of patients after treatment with vitamin C. Oral daily administration of vitamin C may be effective in the fertility potential of male partners of couples with RPL not only through the improvement of the sperm parameters but also by modulating the expression profile of inflammatory and anti-inflammatory genes. Further studies on protein levels are needed to clarify the role of TNF-⍺ and IFN-γ as a prognostic value in evaluating the recurrent abortion risk in infertile male partners. This trial is registered with IRCT20180312039059N1.","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"31 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81873765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction Recurrent extreme hyperferritinemia (ferritin >10,000 ng/mL) was noted in 4 critically ill adolescents prior to death, though this association has not previously been described. Methods A retrospective review of the medical records of 4 critically ill adolescents with recurrent extreme hyperferritinemia and systemic inflammation was performed to identify additional common epidemiologic factors. Results Systemic inflammation was characterized as cytokine storm syndrome in 2 patients and hemophagocytic lymphohistiocytosis in 2 patients. Episodes of extreme hyperferritinemia were noted on at least 2 different dates in all patients; these episodes (n = 10) were separated by an interval of 2 weeks to several months and were usually (in 8 of 10 episodes) associated with the onset or worsening of multiple organ dysfunction syndrome. Death occurred within 2 weeks of the onset of an episode of recurrent extreme hyperferritinemia. Lymphocytopenia and cachexia were noted in all patients. Conclusions Recurrent extreme hyperferritinemia—often with multiple organ dysfunction syndrome—was noted in 4 adolescents with systemic inflammation who did not survive their critical illness. Recurrent extreme hyperferritinemia may be a novel biomarker of increased mortality in patients with the syndrome of persistent inflammation, immunosuppression, and catabolism.
{"title":"Mortality Associated with Recurrent Extreme Hyperferritinemia in Critically Ill Adolescents","authors":"J. Baird","doi":"10.1155/2022/6207417","DOIUrl":"https://doi.org/10.1155/2022/6207417","url":null,"abstract":"Introduction Recurrent extreme hyperferritinemia (ferritin >10,000 ng/mL) was noted in 4 critically ill adolescents prior to death, though this association has not previously been described. Methods A retrospective review of the medical records of 4 critically ill adolescents with recurrent extreme hyperferritinemia and systemic inflammation was performed to identify additional common epidemiologic factors. Results Systemic inflammation was characterized as cytokine storm syndrome in 2 patients and hemophagocytic lymphohistiocytosis in 2 patients. Episodes of extreme hyperferritinemia were noted on at least 2 different dates in all patients; these episodes (n = 10) were separated by an interval of 2 weeks to several months and were usually (in 8 of 10 episodes) associated with the onset or worsening of multiple organ dysfunction syndrome. Death occurred within 2 weeks of the onset of an episode of recurrent extreme hyperferritinemia. Lymphocytopenia and cachexia were noted in all patients. Conclusions Recurrent extreme hyperferritinemia—often with multiple organ dysfunction syndrome—was noted in 4 adolescents with systemic inflammation who did not survive their critical illness. Recurrent extreme hyperferritinemia may be a novel biomarker of increased mortality in patients with the syndrome of persistent inflammation, immunosuppression, and catabolism.","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78143601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-10eCollection Date: 2022-01-01DOI: 10.1155/2022/8632245
Shyam Dheda, David A Vesey, Carmel Hawley, David W Johnson, Magid Fahim
Background: People receiving hemodialysis (HD) treatment have higher cardiovascular morbidity and mortality, ascribed to an increased prevalence of traditional cardiovascular risk factors. However, the role of nontraditional risk factors, such as inflammation, has become increasingly recognized. The origin of this inflammation remains elusive and one putative cause is elevated levels of circulating bacterial endotoxin.
Methods: In this study, serum concentrations of endotoxin and inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-1β (IL1β), ferritin and tumor necrosis factor (TNF), were measured in 30 adults receiving HD and 10 healthy individuals without kidney disease. In people receiving HD, samples were collected immediately before dialysis (preHD), after dialysis (postHD), and 48 hours after (postHD48hrs).
Results: Endotoxin was detectable in only 1 of 90 samples analyzed. There were no significant differences in serum hsCRP, IL1β, and IL6 levels, before and after dialysis. Serum TNF levels decreased significantly from 30.9 (8.0, 39.5) pg/mL preHD to 13.9 (8.5, 17.3) pg/mL post-HD (p=0.002) and then increased back to 27.37 (14.5, 35) pg/mL 2 days later (p < 0.001). Ferritin increased from 1153 ng/mL (782, 1458) preHD to 1313 ng/mL (657, 1638) post HD (p < 0.001) and then decreased back to 1186 ng/mL (754, 1597) (p=0.66) postHD48hrs. Compared to controls, people receiving HD had significantly elevated levels of hsCRP [6.16 mg/L (2.1, 16.8) vs. 1.1 mg/L (0.81, 3.63) p=0.015], IL1β [1.5 pg/mL (0.05, 2.51) vs. 0.5 pg/mL (1.81, 2.95) p ≤ 0.001], and ferritin [1153 (782, 1458) vs. 132.9 (111, 257) ng/mL p ≤ 0.001], but comparable levels of in IL6 [6.15 pg/mL (4.82, 9.12) vs. 7.49 pg/mL (4.56, 10.39), p=0.77] and TNF [27.35 pg/mL ± 17.48 vs. 17.87 pg/mL ± 12.28, p < 0.12]. In conclusion, people on HD have elevated levels of inflammatory biomarkers, which are not associated with endotoxemia (which is rare) or the dialysis procedure.
{"title":"Effect of a Hemodialysis Session on Markers of Inflammation and Endotoxin.","authors":"Shyam Dheda, David A Vesey, Carmel Hawley, David W Johnson, Magid Fahim","doi":"10.1155/2022/8632245","DOIUrl":"https://doi.org/10.1155/2022/8632245","url":null,"abstract":"<p><strong>Background: </strong>People receiving hemodialysis (HD) treatment have higher cardiovascular morbidity and mortality, ascribed to an increased prevalence of traditional cardiovascular risk factors. However, the role of nontraditional risk factors, such as inflammation, has become increasingly recognized. The origin of this inflammation remains elusive and one putative cause is elevated levels of circulating bacterial endotoxin.</p><p><strong>Methods: </strong>In this study, serum concentrations of endotoxin and inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-1<i>β</i> (IL1<i>β</i>), ferritin and tumor necrosis factor (TNF), were measured in 30 adults receiving HD and 10 healthy individuals without kidney disease. In people receiving HD, samples were collected immediately before dialysis (preHD), after dialysis (postHD), and 48 hours after (postHD<sub>48hrs</sub>).</p><p><strong>Results: </strong>Endotoxin was detectable in only 1 of 90 samples analyzed. There were no significant differences in serum hsCRP, IL1<i>β,</i> and IL6 levels, before and after dialysis. Serum TNF levels decreased significantly from 30.9 (8.0, 39.5) pg/mL preHD to 13.9 (8.5, 17.3) pg/mL post-HD (<i>p</i>=0.002) and then increased back to 27.37 (14.5, 35) pg/mL 2 days later (<i>p</i> < 0.001). Ferritin increased from 1153 ng/mL (782, 1458) preHD to 1313 ng/mL (657, 1638) post HD (<i>p</i> < 0.001) and then decreased back to 1186 ng/mL (754, 1597) (<i>p</i>=0.66) postHD<sub>48hrs.</sub> Compared to controls, people receiving HD had significantly elevated levels of hsCRP [6.16 mg/L (2.1, 16.8) vs. 1.1 mg/L (0.81, 3.63) <i>p</i>=0.015], IL1<i>β</i> [1.5 pg/mL (0.05, 2.51) vs. 0.5 pg/mL (1.81, 2.95) <i>p</i> ≤ 0.001], and ferritin [1153 (782, 1458) vs. 132.9 (111, 257) ng/mL <i>p</i> ≤ 0.001], but comparable levels of in IL6 [6.15 pg/mL (4.82, 9.12) vs. 7.49 pg/mL (4.56, 10.39), <i>p</i>=0.77] and TNF [27.35 pg/mL ± 17.48 vs. 17.87 pg/mL ± 12.28, <i>p</i> < 0.12]. In <i>conclusion</i>, people on HD have elevated levels of inflammatory biomarkers, which are not associated with endotoxemia (which is rare) or the dialysis procedure.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":" ","pages":"8632245"},"PeriodicalIF":2.0,"publicationDate":"2022-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8930269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40309079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Castoldi, G. Romagnoli, M. de Assis Golim, O. Ribeiro, Olga Célia Martinez Ibañez, D. Maria, Andréa Vanessa Pinto Domeneghini, M. C. Gameiro, P. R. Martins, M. Mischan, R. Kaneno
AIRmax and AIRmin mice strains were selected according to the intensity of their acute inflammatory responsiveness. Previous studies have shown that AIR mice differ in their resistance to chemically induced skin tumors and in the development of melanoma metastases, in addition to differences in neutrophil and NK cells activity. In the present work, we aimed to evaluate whether the difference of susceptibility to murine melanoma is associated with NK cytotoxic activity against Yac.1 cells and lymphocyte subsets. Mice were subcutaneously inoculated with B16F10 or S91 melanoma cells. After 7, 14, or 30 days, the animals were euthanized to analyze the number of lymphocyte subsets, cytotoxic activity, and number of cytokine-producing spleen cells. AIRmax mice presented a higher number of CD4+/CD25+ cells than that of AIRmin mice following inoculation of B16F10 cells, whereas inoculation of S91 cells reduced CD4+/CD25+ and increased TCD8+ cell subsets in the AIRmax mice. AIRmax mice had a higher number of interleukin (IL)-10- and IL-12-producing cells and a lower number of interferon-γ–producing cells than those of AIRmin mice at 30 days. The cytotoxic activity of nonadherent spleen cells was similar in both the AIR strains. These results suggest that melanoma cells can induce different responses in AIR mice, possibly owing to alterations in regulatory mechanisms, such as the action of CD4+/CD25+ regulatory T cells and IL-10, in AIRmax mice.
{"title":"Cytotoxic Activity and Lymphocyte Subtypes in Mice Selected for Maximal and Minimal Inflammatory Response after Transplantation of B16F10 and S91 Melanoma Cells","authors":"L. Castoldi, G. Romagnoli, M. de Assis Golim, O. Ribeiro, Olga Célia Martinez Ibañez, D. Maria, Andréa Vanessa Pinto Domeneghini, M. C. Gameiro, P. R. Martins, M. Mischan, R. Kaneno","doi":"10.1155/2022/3298542","DOIUrl":"https://doi.org/10.1155/2022/3298542","url":null,"abstract":"AIRmax and AIRmin mice strains were selected according to the intensity of their acute inflammatory responsiveness. Previous studies have shown that AIR mice differ in their resistance to chemically induced skin tumors and in the development of melanoma metastases, in addition to differences in neutrophil and NK cells activity. In the present work, we aimed to evaluate whether the difference of susceptibility to murine melanoma is associated with NK cytotoxic activity against Yac.1 cells and lymphocyte subsets. Mice were subcutaneously inoculated with B16F10 or S91 melanoma cells. After 7, 14, or 30 days, the animals were euthanized to analyze the number of lymphocyte subsets, cytotoxic activity, and number of cytokine-producing spleen cells. AIRmax mice presented a higher number of CD4+/CD25+ cells than that of AIRmin mice following inoculation of B16F10 cells, whereas inoculation of S91 cells reduced CD4+/CD25+ and increased TCD8+ cell subsets in the AIRmax mice. AIRmax mice had a higher number of interleukin (IL)-10- and IL-12-producing cells and a lower number of interferon-γ–producing cells than those of AIRmin mice at 30 days. The cytotoxic activity of nonadherent spleen cells was similar in both the AIR strains. These results suggest that melanoma cells can induce different responses in AIR mice, possibly owing to alterations in regulatory mechanisms, such as the action of CD4+/CD25+ regulatory T cells and IL-10, in AIRmax mice.","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"26 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78319643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Habas, Srinivasa Reddy Natala, Jon K. Bowden-Verhoek, E. Stocking, D. Price, W. Wrasidlo, D. Bonhaus, Martin B. Gill
Toll-like receptors (TLRs) play a critical role in innate immune system responses to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). A growing body of evidence suggests that excessive TLR-mediated innate immune system activation can lead to neuronal damage and precipitate or perpetuate neurodegenerative diseases. Among TLR subtypes, both TLR2 and TLR9 have been implicated in neurodegenerative disorders with increased expression of these receptors in the central nervous system being associated with pro-inflammatory signaling and increased burdens of pathologic aggregated proteins. In the current study, we characterized the actions of a combined TLR2/TLR9 antagonist, NPT1220-312, on pro-inflammatory signaling and cytokine release in monocyte/macrophage-derived heterologous cells, human microglia, and murine and human whole blood. NPT1220-312 potently blocked TLR2- and TLR9-mediated release of inflammatory cytokines in monocyte/macrophage cells and in human microglia. NPT1220-312 also blocked TLR2-mediated activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome including IL-1β, IL-18, and apoptosis-associated speck-like protein containing a CARD (ASC) release to the culture medium of human differentiated macrophages. The ability of NPT1220-312 to inhibit TLR2 mediated pro-inflammatory release of chemokines and cytokines in situ was demonstrated using murine and human whole blood. Together, these findings suggest that blockade of TLR2 and TLR9 may reduce inappropriate production of pro-inflammatory cytokines and chemokines from peripheral and central immune cells and thus potentially provide therapeutic benefit in neuroinflammatory/neurodegenerative disorders.
{"title":"NPT1220-312, a TLR2/TLR9 Small Molecule Antagonist, Inhibits Pro-Inflammatory Signaling, Cytokine Release, and NLRP3 Inflammasome Activation","authors":"A. Habas, Srinivasa Reddy Natala, Jon K. Bowden-Verhoek, E. Stocking, D. Price, W. Wrasidlo, D. Bonhaus, Martin B. Gill","doi":"10.1155/2022/2337363","DOIUrl":"https://doi.org/10.1155/2022/2337363","url":null,"abstract":"Toll-like receptors (TLRs) play a critical role in innate immune system responses to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). A growing body of evidence suggests that excessive TLR-mediated innate immune system activation can lead to neuronal damage and precipitate or perpetuate neurodegenerative diseases. Among TLR subtypes, both TLR2 and TLR9 have been implicated in neurodegenerative disorders with increased expression of these receptors in the central nervous system being associated with pro-inflammatory signaling and increased burdens of pathologic aggregated proteins. In the current study, we characterized the actions of a combined TLR2/TLR9 antagonist, NPT1220-312, on pro-inflammatory signaling and cytokine release in monocyte/macrophage-derived heterologous cells, human microglia, and murine and human whole blood. NPT1220-312 potently blocked TLR2- and TLR9-mediated release of inflammatory cytokines in monocyte/macrophage cells and in human microglia. NPT1220-312 also blocked TLR2-mediated activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome including IL-1β, IL-18, and apoptosis-associated speck-like protein containing a CARD (ASC) release to the culture medium of human differentiated macrophages. The ability of NPT1220-312 to inhibit TLR2 mediated pro-inflammatory release of chemokines and cytokines in situ was demonstrated using murine and human whole blood. Together, these findings suggest that blockade of TLR2 and TLR9 may reduce inappropriate production of pro-inflammatory cytokines and chemokines from peripheral and central immune cells and thus potentially provide therapeutic benefit in neuroinflammatory/neurodegenerative disorders.","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"54 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82104267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-27eCollection Date: 2022-01-01DOI: 10.1155/2022/4071472
Hasmik Yepiskoposyan, Manuel C Peitsch, Marja Talikka
Virtually any stressor that alters the cellular homeostatic state may result in an inflammatory response. As a critical component of innate immunity, inflammasomes play a prominent role in the inflammatory response. The information on inflammasome biology is rapidly growing, thus creating the need for structuring it into a model that can help visualize and enhance the understanding of underlying biological processes. Causal biological network (CBN) models provide predictive power for novel disease mechanisms and treatment outcomes. We assembled the available literature information on inflammasome activation into the CBN model and scored it with publicly available transcriptomic datasets that address viral infection of the lungs, osteo- and rheumatoid arthritis, psoriasis, and aging. The scoring inferred pathway activation leading to NLRP3 inflammasome activation in these diverse conditions, demonstrating that the CBN model provides a platform for interpreting transcriptomic data in the context of inflammasome activation.
{"title":"Causal Biological Network Model for Inflammasome Signaling Applied for Interpreting Transcriptomic Changes in Various Inflammatory States.","authors":"Hasmik Yepiskoposyan, Manuel C Peitsch, Marja Talikka","doi":"10.1155/2022/4071472","DOIUrl":"https://doi.org/10.1155/2022/4071472","url":null,"abstract":"<p><p>Virtually any stressor that alters the cellular homeostatic state may result in an inflammatory response. As a critical component of innate immunity, inflammasomes play a prominent role in the inflammatory response. The information on inflammasome biology is rapidly growing, thus creating the need for structuring it into a model that can help visualize and enhance the understanding of underlying biological processes. Causal biological network (CBN) models provide predictive power for novel disease mechanisms and treatment outcomes. We assembled the available literature information on inflammasome activation into the CBN model and scored it with publicly available transcriptomic datasets that address viral infection of the lungs, osteo- and rheumatoid arthritis, psoriasis, and aging. The scoring inferred pathway activation leading to NLRP3 inflammasome activation in these diverse conditions, demonstrating that the CBN model provides a platform for interpreting transcriptomic data in the context of inflammasome activation.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":" ","pages":"4071472"},"PeriodicalIF":2.0,"publicationDate":"2022-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39756473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abnormal scar formation during wound healing can result in keloid and hypertrophic scars, which is a major global health challenge. Such abnormal scars can cause significant physiological pain and psychological distress and become a financial burden. Due to the biological complexity of scar formation, the pathogenesis of such scars and how to prevent them from forming remains elusive. In this review paper, we delve into the world of "omics" approaches to study abnormal scars and provide examples of genomics, transcriptomics, proteomics, epigenomics, and metabolomics. The benefits of "omics" approaches are that they allow for high-throughput studies and the analysis of 100s to 1000s of genes and proteins with the accumulation of large quantities of data. Currently in the field, there is a lack of "omics" review articles describing pathological scars. In this review, we summarize genome-wide linkage analysis, genome-wide association studies, and microarray data to name a few omics technologies. Such data can provide novel insights into different molecular pathways and identify novel factors which may not be captured through small-scale laboratory techniques.
{"title":"OMICS Approaches Evaluating Keloid and Hypertrophic Scars.","authors":"Nazihah Bakhtyar, Saeid Amini-Nik, Marc G Jeschke","doi":"10.1155/2022/1490492","DOIUrl":"https://doi.org/10.1155/2022/1490492","url":null,"abstract":"<p><p>Abnormal scar formation during wound healing can result in keloid and hypertrophic scars, which is a major global health challenge. Such abnormal scars can cause significant physiological pain and psychological distress and become a financial burden. Due to the biological complexity of scar formation, the pathogenesis of such scars and how to prevent them from forming remains elusive. In this review paper, we delve into the world of \"omics\" approaches to study abnormal scars and provide examples of genomics, transcriptomics, proteomics, epigenomics, and metabolomics. The benefits of \"omics\" approaches are that they allow for high-throughput studies and the analysis of 100s to 1000s of genes and proteins with the accumulation of large quantities of data. Currently in the field, there is a lack of \"omics\" review articles describing pathological scars. In this review, we summarize genome-wide linkage analysis, genome-wide association studies, and microarray data to name a few omics technologies. Such data can provide novel insights into different molecular pathways and identify novel factors which may not be captured through small-scale laboratory techniques.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2022 ","pages":"1490492"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9462234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Defensin Alpha 4 (DEFA4) is the fourth member of the Alpha Defensins family known as a part of antimicrobial peptides in the innate immune system. DEFA4 has a strong preference to kill Gram-negative bacteria more than Gram-positive bacteria. In addition, DEFA4 exhibits antiviral activity against human immunodeficiency virus type 1 (HIV-1) in vitro. Moreover, DEFA4 can act as an inhibitor of corticosterone production (Corticostatin). On the other hand, alternations in DEFA4 gene expression have been reported in different disorders such as diseases related to inflammation and immunity dysfunction, brain-related disorders, and various cancers. The up-regulation of DEFA4 appears to be involved in the malignant transformation or aggressive form of cancer. Interestingly, the modified version of DEFA4 fragment (1-11) was potent and efficient against antibiotic-resistant bacteria. This review provides a general background abSaudi Arabia out DEFA4 and sheds light on changes in DEFA4 gene expression in different diseases. The paper also discusses other aspects related to DEFA4 as an antimicrobial and antiviral agent. The research was conducted based on available articles obtained from databases starting from 1988 to the present.
{"title":"Alterations in Immune-Related Defensin Alpha 4 (<i>DEFA4</i>) Gene Expression in Health and Disease.","authors":"Fatemah Basingab, Abeer Alsaiary, Shahad Almontashri, Aisha Alrofaidi, Mona Alharbi, Sheren Azhari, Khloud Algothmi, Safiah Alhazmi","doi":"10.1155/2022/9099136","DOIUrl":"https://doi.org/10.1155/2022/9099136","url":null,"abstract":"<p><p>Defensin Alpha 4 (DEFA4) is the fourth member of the Alpha Defensins family known as a part of antimicrobial peptides in the innate immune system. DEFA4 has a strong preference to kill Gram-negative bacteria more than Gram-positive bacteria. In addition, DEFA4 exhibits antiviral activity against human immunodeficiency virus type 1 (HIV-1) <i>in vitro</i>. Moreover, DEFA4 can act as an inhibitor of corticosterone production (Corticostatin). On the other hand, alternations in <i>DEFA4</i> gene expression have been reported in different disorders such as diseases related to inflammation and immunity dysfunction, brain-related disorders, and various cancers. The up-regulation of <i>DEFA4</i> appears to be involved in the malignant transformation or aggressive form of cancer. Interestingly, the modified version of DEFA4 fragment (1-11) was potent and efficient against antibiotic-resistant bacteria. This review provides a general background abSaudi Arabia out <i>DEFA4</i> and sheds light on changes in <i>DEFA4</i> gene expression in different diseases. The paper also discusses other aspects related to DEFA4 as an antimicrobial and antiviral agent. The research was conducted based on available articles obtained from databases starting from 1988 to the present.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2022 ","pages":"9099136"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10619834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Pulmonary toxicity induced by CCl4, a model of idiopathic pulmonary fibrosis (IPF), leads to tissue remodeling and inflammation. Human umbilical cord mesenchymal cell-conditioned medium (hMSC-CM) is a potent anti-inflammatory, antioxidative, and antifibrotic agent.
Methods: Forty male Wistar rats were assigned to the control (C), olive oil control (C.O) (hMSC-CM), control (C.Ms), fibrosis (fb), and fibrosis with hMSC-CM (f.Ms) treatment groups. The groups C, C.O, and C.Ms received PBS (200 µl), olive oil (1 ml/kg), and hMSC-CM (100 μg protein/kg), respectively. The fibrosis group was administered with only CCl4 (1 ml/kg). The last group, f.Ms was treated with CCl4 (1 ml/kg) and 100 μg protein/kg IV hMSC-CM. While the treatment with olive oil and CCl4 was performed for 2 days/week from the first week for 12 weeks, the treatment with PBS and hMSC-CM was carried out 2 days/week from week 4th to week 12th. The effect of the UC-MSC culture medium treatment on the lung was evaluated by assessing lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-β1 (TGF-β1) genes, and proteins expression by real-time RCR and western blotting, respectively.
Results: Lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-α), transforming growth factor-b1 (TGF-β1), malondialdehyde (MDA), and oxidative stress levels were markedly higher in the fibrosis group than in the control groups (p ≤ 0.001). Additionally, glutathione (GSH) in the fibrosis group was markedly lower than those in the control groups (p ≤ 0.001). Fibrosis in the UC-MSC treatment group had milder histopathological injuries than in the fibrosis group.
Conclusion: hMSC-MSC as a strong anti-inflammatory, antioxidative, and antifibrotic decreases the level of oxidative stress, proinflammatory cytokines, and MDA causing a restoring effect against CCl4-induced pulmonary fibrosis.
{"title":"The Restoring Effect of Human Umbilical Cord-Derived Mesenchymal Cell-Conditioned Medium (hMSC-CM) against Carbon Tetrachloride-Induced Pulmonary Fibrosis in Male Wistar Rats.","authors":"Maryam Khajvand-Abedini, Mahdi Bahmani, Nasrin Ziamajidi, Alireza Nourian, Parisa Habibi, Shirin Heidarisasan, Roghayeh Abbasalipourkabir","doi":"10.1155/2022/7179766","DOIUrl":"https://doi.org/10.1155/2022/7179766","url":null,"abstract":"<p><strong>Objective: </strong>Pulmonary toxicity induced by CCl<sub>4</sub>, a model of idiopathic pulmonary fibrosis (IPF), leads to tissue remodeling and inflammation. Human umbilical cord mesenchymal cell-conditioned medium (hMSC-CM) is a potent anti-inflammatory, antioxidative, and antifibrotic agent.</p><p><strong>Methods: </strong>Forty male Wistar rats were assigned to the control (C), olive oil control (C.O) (hMSC-CM), control (C.Ms), fibrosis (fb), and fibrosis with hMSC-CM (f.Ms) treatment groups. The groups C, C.O, and C.Ms received PBS (200 <i>µ</i>l), olive oil (1 ml/kg), and hMSC-CM (100 <i>μ</i>g protein/kg), respectively. The fibrosis group was administered with only CCl4 (1 ml/kg). The last group, f.Ms was treated with CCl<sub>4</sub> (1 ml/kg) and 100 <i>μ</i>g protein/kg IV hMSC-CM. While the treatment with olive oil and CCl<sub>4</sub> was performed for 2 days/week from the first week for 12 weeks, the treatment with PBS and hMSC-CM was carried out 2 days/week from week 4<sup>th</sup> to week 12<sup>th</sup>. The effect of the UC-MSC culture medium treatment on the lung was evaluated by assessing lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-<i>α</i>), and transforming growth factor-<i>β</i>1 (TGF-<i>β</i>1) genes, and proteins expression by real-time RCR and western blotting, respectively.</p><p><strong>Results: </strong>Lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-<i>α</i>), transforming growth factor-b1 (TGF-<i>β</i>1), malondialdehyde (MDA), and oxidative stress levels were markedly higher in the fibrosis group than in the control groups (<i>p</i> ≤ 0.001). Additionally, glutathione (GSH) in the fibrosis group was markedly lower than those in the control groups (<i>p</i> ≤ 0.001). Fibrosis in the UC-MSC treatment group had milder histopathological injuries than in the fibrosis group.</p><p><strong>Conclusion: </strong>hMSC-MSC as a strong anti-inflammatory, antioxidative, and antifibrotic decreases the level of oxidative stress, proinflammatory cytokines, and MDA causing a restoring effect against CCl<sub>4</sub>-induced pulmonary fibrosis.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2022 ","pages":"7179766"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10466857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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