Pub Date : 2024-11-01Epub Date: 2024-09-28DOI: 10.1007/s00011-024-01947-9
Marie Martin, Emie Debenay, Jeanne Bardinet, Adrien Peltier, Line Pourtau, David Gaudout, Sophie Layé, Véronique Pallet, Anne-Laure Dinel, Corinne Joffre
Objective and design: Neuroinflammation is a protective mechanism but can become harmful if chronic and/or unregulated, leading to neuronal damage and cognitive alterations. Limiting inflammation and promoting resolution could be achieved with nutrients such as grapes and blueberries polyphenols, saffron carotenoids, and omega-3, which have anti-inflammatory and proresolutive properties.
Methods: This study explored the impact of 18-day supplementation with plant extracts (grape, blueberry and saffron), omega-3 or both (mix) on neuroinflammation induced by lipopolysaccharide (LPS, 250 µg/kg) in 149 mice at different time points post-LPS treatment (30 min, 2 h, 6 h). Inflammatory, oxidative and neuroprotective gene expression; oxylipin quantification; and fatty acid composition were analyzed at each time point. PCA analysis was performed with all these biomarkers.
Results: Mix supplementation induced changes in the resolution of inflammation. In fact, the production of proinflammatory mediators in the hippocampus started earlier in the supplemented group than in the LPS group. Pro-resolving mediators were also found in higher quantities in supplemented mice. These changes were associated with increased hippocampal antioxidant status at 6 h post-LPS.
Conclusions: These findings suggest that such dietary interventions with plant extracts, and omega-3 could be beneficial in preventing neuroinflammation and, consequently, age-related cognitive decline. Further research is needed to explore the effects of these supplements on chronic inflammation in the context of aging.
{"title":"Plant extracts and omega-3 supplementation modulate hippocampal oxylipin profile in response to LPS-induced neuroinflammation.","authors":"Marie Martin, Emie Debenay, Jeanne Bardinet, Adrien Peltier, Line Pourtau, David Gaudout, Sophie Layé, Véronique Pallet, Anne-Laure Dinel, Corinne Joffre","doi":"10.1007/s00011-024-01947-9","DOIUrl":"10.1007/s00011-024-01947-9","url":null,"abstract":"<p><strong>Objective and design: </strong>Neuroinflammation is a protective mechanism but can become harmful if chronic and/or unregulated, leading to neuronal damage and cognitive alterations. Limiting inflammation and promoting resolution could be achieved with nutrients such as grapes and blueberries polyphenols, saffron carotenoids, and omega-3, which have anti-inflammatory and proresolutive properties.</p><p><strong>Methods: </strong>This study explored the impact of 18-day supplementation with plant extracts (grape, blueberry and saffron), omega-3 or both (mix) on neuroinflammation induced by lipopolysaccharide (LPS, 250 µg/kg) in 149 mice at different time points post-LPS treatment (30 min, 2 h, 6 h). Inflammatory, oxidative and neuroprotective gene expression; oxylipin quantification; and fatty acid composition were analyzed at each time point. PCA analysis was performed with all these biomarkers.</p><p><strong>Results: </strong>Mix supplementation induced changes in the resolution of inflammation. In fact, the production of proinflammatory mediators in the hippocampus started earlier in the supplemented group than in the LPS group. Pro-resolving mediators were also found in higher quantities in supplemented mice. These changes were associated with increased hippocampal antioxidant status at 6 h post-LPS.</p><p><strong>Conclusions: </strong>These findings suggest that such dietary interventions with plant extracts, and omega-3 could be beneficial in preventing neuroinflammation and, consequently, age-related cognitive decline. Further research is needed to explore the effects of these supplements on chronic inflammation in the context of aging.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2023-2042"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345966","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 : 2024-11-01Epub Date: 2024-09-05DOI: 10.1007/s00011-024-01940-2
Jinmei Xue, Zhizhen Liu, Bailing Xie, Rui Dong, Juan Wu, Yisha Wu, Zhihan Xu, Yuhe Tian, Yao Wei, Zhigang Geng, Lei Lu, Yu Liu, Jun Xie, Pingchang Yang
Background: Dysfunctional immune regulation plays a crucial role in the pathogenesis of airway allergies. Macrophages are one of the components of the immune regulation cells. The aim of this study is to elucidate the role of lysine demethylase 5 A (KDM5A) in maintaining macrophages' immune regulatory ability.
Methods: DNA was extracted from Lactobacillus rhamnosus GG to be designated as LgDNA. LgDNA was administered to the mice through nasal instillations. M2 macrophages (M2 cells) were isolated from the airway tissues using flow cytometry.
Results: We found that airway M2 cells of mice with airway Th2 polarization had reduced amounts of IL-10 and KDM5A. Mice with Kdm5a deficiency in M2 cells showed the airway Th2 polarization. The expression of Kdm5a in airway M2 cells was enhanced by nasal instillations containing LgDNA. KDM5A mediated the effects of LgDNA on inducing the Il10 expression in airway M2 cells. Administration of LgDNA mitigated experimental airway allergy.
Conclusions: M2 macrophages in the airway tissues of mice with airway allergy show low levels of KDM5A. By upregulating KDM5A expression, LgDNA can increase Il10 expression and reconcile airway Th2 polarization.
{"title":"Probiotic nucleotides increase IL-10 expression in airway macrophages to mitigate airway allergy.","authors":"Jinmei Xue, Zhizhen Liu, Bailing Xie, Rui Dong, Juan Wu, Yisha Wu, Zhihan Xu, Yuhe Tian, Yao Wei, Zhigang Geng, Lei Lu, Yu Liu, Jun Xie, Pingchang Yang","doi":"10.1007/s00011-024-01940-2","DOIUrl":"10.1007/s00011-024-01940-2","url":null,"abstract":"<p><strong>Background: </strong>Dysfunctional immune regulation plays a crucial role in the pathogenesis of airway allergies. Macrophages are one of the components of the immune regulation cells. The aim of this study is to elucidate the role of lysine demethylase 5 A (KDM5A) in maintaining macrophages' immune regulatory ability.</p><p><strong>Methods: </strong>DNA was extracted from Lactobacillus rhamnosus GG to be designated as LgDNA. LgDNA was administered to the mice through nasal instillations. M2 macrophages (M2 cells) were isolated from the airway tissues using flow cytometry.</p><p><strong>Results: </strong>We found that airway M2 cells of mice with airway Th2 polarization had reduced amounts of IL-10 and KDM5A. Mice with Kdm5a deficiency in M2 cells showed the airway Th2 polarization. The expression of Kdm5a in airway M2 cells was enhanced by nasal instillations containing LgDNA. KDM5A mediated the effects of LgDNA on inducing the Il10 expression in airway M2 cells. Administration of LgDNA mitigated experimental airway allergy.</p><p><strong>Conclusions: </strong>M2 macrophages in the airway tissues of mice with airway allergy show low levels of KDM5A. By upregulating KDM5A expression, LgDNA can increase Il10 expression and reconcile airway Th2 polarization.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1919-1930"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132621","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 : 2024-10-26DOI: 10.1007/s00011-024-01963-9
Lidiane Isabel Filippin, María José Cuevas, Elena Lima, Norma Possa Marroni, Javier Gonzalez Gallego, Ricardo Machado Xavier
{"title":"Retraction Note: The role of nitric oxide during healing of trauma to the skeletal muscle.","authors":"Lidiane Isabel Filippin, María José Cuevas, Elena Lima, Norma Possa Marroni, Javier Gonzalez Gallego, Ricardo Machado Xavier","doi":"10.1007/s00011-024-01963-9","DOIUrl":"https://doi.org/10.1007/s00011-024-01963-9","url":null,"abstract":"","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499587","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 : 2024-10-26DOI: 10.1007/s00011-024-01962-w
Lei Wang, Rui Hu, Pei Xu, Pengkai Gao, Bin Mo, Liya Dong, Fengqing Hu
Background: Vascularization after rib fracture is a crucial physiological process that is essential for the repair and healing of the rib. Studies have shown that CD90 plays a critical role in regulating rib fracture healing, but the underlying mechanism of its role has not been fully elucidated.
Methods: CD90 adenovirus knockout mice were used to construct a rib injury model. The bone healing was observed by micro-CT. CD31/EMCN immunofluorescence staining was performed on bone tissue to observe the density of H-shaped and L-shaped blood vessels at the site of bone injury. CD31 and EMCN dual-stained single cells from the rib fracture sites were detected by flow cytometry. The periosteal stem cells transfected with CD90 or Notch1 overexpression and silencing vector were co-cultured with osteoblast MC3T3-E1 in osteogenic induction medium. Moreover, bone microvascular endothelial cells were extracted from the rib injury and co-cultured with the periosteal stem cells transfected with CD90. CCK-8 was used to detect cell viability, RT-qPCR and Western blot were used to detect Notch1, Notch2, Notch3, Notch4, CD31, HIF-1α, CD90, RUNX2, OCN and OPN expression. Alkaline phosphatase (ALP) staining and alizarin red staining were used to observe mineralized nodules. Immunofluorescence staining was used to detect the expression of Dll4, Notch, and CD90 in each group of cells. The angiogenesis experiment was conducted to observe cellular vascular formation.
Results: Compared with the Adsh-NC group, the bone healing in the Adsh-CD90 group was significantly impaired, with a marked reduction in the number and volume of blood vessels at the rib fracture site, as evidenced by CD31/EMCN immunofluorescence staining, which showed a reduction in the number of H type vessels at the site of bone injury. It was found that CD90 depletion can inhibit the signaling of Dll4/Notch in the rib fracture site. Furthermore, we found that overexpression of Notch1 reverses the impairment of tubule formation in bone microvascular endothelial cells caused by CD90 suppression.r.Dll4 protein reverses the inhibitory effect of CD90 deletion on periosteal stem cells and MC3T3-E1 cell viability and osteogenesis. In the end, we found that overexpression of Notch1 and CD90 can promote angiogenesis of bone microvascular endothelial cells and Notch pathway activation.
Conclusion: CD90 can affect vascular formation in mouse rib fractures, and CD90 may be regulated by Dll4/Notch.
{"title":"CD90's role in vascularization and healing of rib fractures: insights from Dll4/notch regulation.","authors":"Lei Wang, Rui Hu, Pei Xu, Pengkai Gao, Bin Mo, Liya Dong, Fengqing Hu","doi":"10.1007/s00011-024-01962-w","DOIUrl":"https://doi.org/10.1007/s00011-024-01962-w","url":null,"abstract":"<p><strong>Background: </strong>Vascularization after rib fracture is a crucial physiological process that is essential for the repair and healing of the rib. Studies have shown that CD90 plays a critical role in regulating rib fracture healing, but the underlying mechanism of its role has not been fully elucidated.</p><p><strong>Methods: </strong>CD90 adenovirus knockout mice were used to construct a rib injury model. The bone healing was observed by micro-CT. CD31/EMCN immunofluorescence staining was performed on bone tissue to observe the density of H-shaped and L-shaped blood vessels at the site of bone injury. CD31 and EMCN dual-stained single cells from the rib fracture sites were detected by flow cytometry. The periosteal stem cells transfected with CD90 or Notch1 overexpression and silencing vector were co-cultured with osteoblast MC3T3-E1 in osteogenic induction medium. Moreover, bone microvascular endothelial cells were extracted from the rib injury and co-cultured with the periosteal stem cells transfected with CD90. CCK-8 was used to detect cell viability, RT-qPCR and Western blot were used to detect Notch1, Notch2, Notch3, Notch4, CD31, HIF-1α, CD90, RUNX2, OCN and OPN expression. Alkaline phosphatase (ALP) staining and alizarin red staining were used to observe mineralized nodules. Immunofluorescence staining was used to detect the expression of Dll4, Notch, and CD90 in each group of cells. The angiogenesis experiment was conducted to observe cellular vascular formation.</p><p><strong>Results: </strong>Compared with the Adsh-NC group, the bone healing in the Adsh-CD90 group was significantly impaired, with a marked reduction in the number and volume of blood vessels at the rib fracture site, as evidenced by CD31/EMCN immunofluorescence staining, which showed a reduction in the number of H type vessels at the site of bone injury. It was found that CD90 depletion can inhibit the signaling of Dll4/Notch in the rib fracture site. Furthermore, we found that overexpression of Notch1 reverses the impairment of tubule formation in bone microvascular endothelial cells caused by CD90 suppression.r.Dll4 protein reverses the inhibitory effect of CD90 deletion on periosteal stem cells and MC3T3-E1 cell viability and osteogenesis. In the end, we found that overexpression of Notch1 and CD90 can promote angiogenesis of bone microvascular endothelial cells and Notch pathway activation.</p><p><strong>Conclusion: </strong>CD90 can affect vascular formation in mouse rib fractures, and CD90 may be regulated by Dll4/Notch.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499584","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 : 2024-10-26DOI: 10.1007/s00011-024-01961-x
Ruixue Kong, Lijun Peng, Honggang Bao, Lulu Sun, Yan Feng, Hua Li, Dashan Wang
Background: G proteins are a class of important signal transducers in mammalians. G proteins can corpoarated with G proteincoupled receptors (GPCRs) and transmit signals from extracellular stimuli into intracellular response, which will regulate a series of biological functions. G-proteins are heterotrimeric proteins composed of Gα, Gβ, and Gγ subunits. Based on structural and functional similarity of their α-subunits, G proteins are typically grouped into four classes (Gi, Gs, Gq/11, and G12/13). The Gq/11 subfamily consists of Gq, G11, G14, and G15/16 proteins. Gαq is the α-subunit of Gq protein and encoded by GNAQ. Our previous studies revealed that Gαq play an important role in regulating T cell survival and T cell differentiation. Inflammasomes are multiprotein complexes that play a critical role in modulating innate inflammatory response. NLRP3 inflammasome is currently the most extensively studied inflammasome.
Methods: We found that Gαq suppressed NLRP3 inflammasome activation in macrophage, Gαq also suppressed NLRP3 inflammasome activation in a LPS-induced sepsis mouse model. Gαq can locate to mitochondria and Gαq was required for the maintenance of mitochondrial homeostasis. Gαq regulated NLRP3 inflammasome activation by modulating mitochondrial reactive oxygen species (mtROS).
Results: We found that Gαq suppressed NLRP3 inflammasome activation in macrophage, Gαq also suppressed NLRP3 inflammasome activation in a LPS-induced sepsis mouse model. Gαq can locate to mitochondria and Gαq was required for the maintenance of mitochondrial homeostasis. Gαq regulated NLRP3 inflammasome activation by modulating mitochondrial reactive oxygen species (mtROS).
Conclusion: Our results indicate that Gαq regulates NLRP3 inflammasome activation by modulating mitochondrial ROS production. Our research provides new mechanistic insight into the activation of NLRP3 inflammasome. As it has been proved that NLRP3 inflammasome plays an important role in the pathogenesis many diseases such as Alzheimer's disease, cancer, and inflammatory bowel disease, Gαq might become a novel drug target for these diseases in future.
{"title":"The role of Gαq in regulating NLRP3 inflammasome activation.","authors":"Ruixue Kong, Lijun Peng, Honggang Bao, Lulu Sun, Yan Feng, Hua Li, Dashan Wang","doi":"10.1007/s00011-024-01961-x","DOIUrl":"https://doi.org/10.1007/s00011-024-01961-x","url":null,"abstract":"<p><strong>Background: </strong>G proteins are a class of important signal transducers in mammalians. G proteins can corpoarated with G proteincoupled receptors (GPCRs) and transmit signals from extracellular stimuli into intracellular response, which will regulate a series of biological functions. G-proteins are heterotrimeric proteins composed of Gα, Gβ, and Gγ subunits. Based on structural and functional similarity of their α-subunits, G proteins are typically grouped into four classes (Gi, Gs, Gq/11, and G12/13). The Gq/11 subfamily consists of Gq, G11, G14, and G15/16 proteins. Gαq is the α-subunit of Gq protein and encoded by GNAQ. Our previous studies revealed that Gαq play an important role in regulating T cell survival and T cell differentiation. Inflammasomes are multiprotein complexes that play a critical role in modulating innate inflammatory response. NLRP3 inflammasome is currently the most extensively studied inflammasome.</p><p><strong>Methods: </strong>We found that Gαq suppressed NLRP3 inflammasome activation in macrophage, Gαq also suppressed NLRP3 inflammasome activation in a LPS-induced sepsis mouse model. Gαq can locate to mitochondria and Gαq was required for the maintenance of mitochondrial homeostasis. Gαq regulated NLRP3 inflammasome activation by modulating mitochondrial reactive oxygen species (mtROS).</p><p><strong>Results: </strong>We found that Gαq suppressed NLRP3 inflammasome activation in macrophage, Gαq also suppressed NLRP3 inflammasome activation in a LPS-induced sepsis mouse model. Gαq can locate to mitochondria and Gαq was required for the maintenance of mitochondrial homeostasis. Gαq regulated NLRP3 inflammasome activation by modulating mitochondrial reactive oxygen species (mtROS).</p><p><strong>Conclusion: </strong>Our results indicate that Gαq regulates NLRP3 inflammasome activation by modulating mitochondrial ROS production. Our research provides new mechanistic insight into the activation of NLRP3 inflammasome. As it has been proved that NLRP3 inflammasome plays an important role in the pathogenesis many diseases such as Alzheimer's disease, cancer, and inflammatory bowel disease, Gαq might become a novel drug target for these diseases in future.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499588","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 : 2024-10-26DOI: 10.1007/s00011-024-01960-y
Anand Ubhe
Objective: This article is aims to provide an overview of studies reported in the literature to investigate the etiological role of IL-1/IL-1ra in various disease conditions and the different drug delivery systems developed to achieve IL-1ra as a possible therapeutic option.
Methods: Studies reported in PubMed, Google scholar, and other open-source literature related to etiological involvement of IL-1ra in pathophysiological conditions and various drug delivery schemes developed for IL-1ra for its efficacy evaluation as a possible treatment for different disease conditions were surveyed.
Results and conclusions: The pathophysiological conditions involving IL-1/IL-1 ra spanned CNS-related disorders, Diabetes, Cardiac disorders, Ocular disease conditions, Gastrointestinal conditions, Tumor growth & metastasis, and miscellaneous conditions. The drug delivery systems developed for IL-1ra included a commercial drug product, Gene therapy, Antibody fusions, Extended-release delivery systems, and Pegylated-IL-1ra systems.
{"title":"IL-1 receptor antagonist: etiological and drug delivery systems overview.","authors":"Anand Ubhe","doi":"10.1007/s00011-024-01960-y","DOIUrl":"https://doi.org/10.1007/s00011-024-01960-y","url":null,"abstract":"<p><strong>Objective: </strong>This article is aims to provide an overview of studies reported in the literature to investigate the etiological role of IL-1/IL-1ra in various disease conditions and the different drug delivery systems developed to achieve IL-1ra as a possible therapeutic option.</p><p><strong>Methods: </strong>Studies reported in PubMed, Google scholar, and other open-source literature related to etiological involvement of IL-1ra in pathophysiological conditions and various drug delivery schemes developed for IL-1ra for its efficacy evaluation as a possible treatment for different disease conditions were surveyed.</p><p><strong>Results and conclusions: </strong>The pathophysiological conditions involving IL-1/IL-1 ra spanned CNS-related disorders, Diabetes, Cardiac disorders, Ocular disease conditions, Gastrointestinal conditions, Tumor growth & metastasis, and miscellaneous conditions. The drug delivery systems developed for IL-1ra included a commercial drug product, Gene therapy, Antibody fusions, Extended-release delivery systems, and Pegylated-IL-1ra systems.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499585","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 : 2024-10-24DOI: 10.1007/s00011-024-01942-0
Ahmed Ramzi, Subhia Maya, Nadeen Balousha, Mufreh Amin, Mostafa Ramzi Shiha
Introduction: Pentoxifylline (PTX) affects most blood components and the blood vessels, potentially modulating various conditions. Due to its impact on markers linked to COVID-19 severity, research has explored PTX for acute COVID-19. Following the widespread administration of COVID-19 vaccinations, there has been a notable and consistently growing increase in research focusing on long COVID. Consequently, our examination of relevant acute COVID-19 data shall additionally be contextualized into long COVID research.
Methods: Various Databases were searched until July 2024 for all primary clinical studies on Pentoxifylline (PTX) in COVID-19.
Results: Studies were on acute infection with SARS-CoV-2 where PTX was an adjuvant to standard therapy for ethical and practical reasons under the circumstance. PTX generally reduced hospitalization duration and improved some inflammatory markers, but its impact on mortality was inconsistent. Adverse events were minimal. Meta-analysis revealed a significant reduction in hospitalization duration.
Conclusion: This systematic review and meta-analysis suggest that adding pentoxifylline (PTX) to standard COVID-19 therapy may significantly reduce hospitalization duration and improve some inflammatory markers. However, its impact on mortality rates is inconclusive. Adverse events are minimal. PTX can be favorable as an add-on in managing acute COVID-19 and could reduce the risk of long COVID, as well as assist in managing many of its most common symptoms.
{"title":"Pentoxifylline in COVID-19 and considerations for its research in long COVID.","authors":"Ahmed Ramzi, Subhia Maya, Nadeen Balousha, Mufreh Amin, Mostafa Ramzi Shiha","doi":"10.1007/s00011-024-01942-0","DOIUrl":"https://doi.org/10.1007/s00011-024-01942-0","url":null,"abstract":"<p><strong>Introduction: </strong>Pentoxifylline (PTX) affects most blood components and the blood vessels, potentially modulating various conditions. Due to its impact on markers linked to COVID-19 severity, research has explored PTX for acute COVID-19. Following the widespread administration of COVID-19 vaccinations, there has been a notable and consistently growing increase in research focusing on long COVID. Consequently, our examination of relevant acute COVID-19 data shall additionally be contextualized into long COVID research.</p><p><strong>Methods: </strong>Various Databases were searched until July 2024 for all primary clinical studies on Pentoxifylline (PTX) in COVID-19.</p><p><strong>Results: </strong>Studies were on acute infection with SARS-CoV-2 where PTX was an adjuvant to standard therapy for ethical and practical reasons under the circumstance. PTX generally reduced hospitalization duration and improved some inflammatory markers, but its impact on mortality was inconsistent. Adverse events were minimal. Meta-analysis revealed a significant reduction in hospitalization duration.</p><p><strong>Conclusion: </strong>This systematic review and meta-analysis suggest that adding pentoxifylline (PTX) to standard COVID-19 therapy may significantly reduce hospitalization duration and improve some inflammatory markers. However, its impact on mortality rates is inconclusive. Adverse events are minimal. PTX can be favorable as an add-on in managing acute COVID-19 and could reduce the risk of long COVID, as well as assist in managing many of its most common symptoms.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499586","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 : 2024-10-21DOI: 10.1007/s00011-024-01953-x
April L Raftery, Céline Pattaroni, Nicola L Harris, Evelyn Tsantikos, Margaret L Hibbs
Background: Crohn's disease and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases that affect the gut and lung respectively and can occur comorbidly.
Methods: Using the SHIP-1-/- model of Crohn's-like ileitis and chronic lung inflammation, the two diseases were co-investigated.
Results: Contrary to prior literature, Crohn's-like ileitis was not fully penetrant in SHIP-1-/- mice, and housing in a specific pathogen-free facility was completely protective. Indeed, ileal tissue from SHIP-1-/- mice without overt ileitis was similar to control ilea. However, SHIP-1-/- mice with ileitis exhibited increased granulocytes in ileal tissue together with T cell lymphopenia and they lacked low abundance Bifidobacteria, suggesting this bacterium protects against ileitis. Lung disease, as defined by inflammation in lung washes, emphysema, and lung consolidation, was present in SHIP-1-/- mice regardless of ileitis phenotype; however, there was a shift in the nature of lung inflammation in animals with ileitis, with increased G-CSF and neutrophils, in addition to type 2 cytokines and eosinophils. Deficiency of G-CSF, which protects against lung disease, protected against the development of ileitis in SHIP-1-/- mice.
Conclusions: These studies have defined environmental, immune, and inflammatory factors that predispose to ileitis, and have identified that comorbid lung disease correlates with a granulocyte signature.
背景:克罗恩病和慢性阻塞性肺疾病(COPD)是分别影响肠道和肺部的慢性炎症性疾病,可同时发生:方法:利用SHIP-1-/-克罗恩回肠炎和慢性肺部炎症模型,对这两种疾病进行联合研究:结果:与之前的文献相反,克罗恩病样回肠炎在SHIP-1-/-小鼠中并不具有完全的渗透性,而饲养在特定的无病原体设施中则具有完全的保护性。事实上,没有明显回肠炎的SHIP-1-/-小鼠的回肠组织与对照组回肠组织相似。然而,患有回肠炎的 SHIP-1-/- 小鼠回肠组织中的粒细胞增多,同时出现 T 细胞淋巴细胞减少症,而且它们缺乏低丰度双歧杆菌,这表明双歧杆菌对回肠炎有保护作用。无论回肠炎表型如何,SHIP-1-/-小鼠都会出现肺部疾病,表现为肺洗液中的炎症、肺气肿和肺固缩;然而,回肠炎动物肺部炎症的性质发生了变化,除了 2 型细胞因子和嗜酸性粒细胞外,G-CSF 和中性粒细胞也增加了。G-CSF对肺部疾病有保护作用,而SHIP-1-/-小鼠缺乏G-CSF则可防止回肠炎的发生:这些研究确定了易导致回肠炎的环境、免疫和炎症因素,并发现合并肺部疾病与粒细胞特征相关。
{"title":"Environmental and inflammatory factors influencing concurrent gut and lung inflammation.","authors":"April L Raftery, Céline Pattaroni, Nicola L Harris, Evelyn Tsantikos, Margaret L Hibbs","doi":"10.1007/s00011-024-01953-x","DOIUrl":"https://doi.org/10.1007/s00011-024-01953-x","url":null,"abstract":"<p><strong>Background: </strong>Crohn's disease and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases that affect the gut and lung respectively and can occur comorbidly.</p><p><strong>Methods: </strong>Using the SHIP-1<sup>-/-</sup> model of Crohn's-like ileitis and chronic lung inflammation, the two diseases were co-investigated.</p><p><strong>Results: </strong>Contrary to prior literature, Crohn's-like ileitis was not fully penetrant in SHIP-1<sup>-/-</sup> mice, and housing in a specific pathogen-free facility was completely protective. Indeed, ileal tissue from SHIP-1<sup>-/-</sup> mice without overt ileitis was similar to control ilea. However, SHIP-1<sup>-/-</sup> mice with ileitis exhibited increased granulocytes in ileal tissue together with T cell lymphopenia and they lacked low abundance Bifidobacteria, suggesting this bacterium protects against ileitis. Lung disease, as defined by inflammation in lung washes, emphysema, and lung consolidation, was present in SHIP-1<sup>-/-</sup> mice regardless of ileitis phenotype; however, there was a shift in the nature of lung inflammation in animals with ileitis, with increased G-CSF and neutrophils, in addition to type 2 cytokines and eosinophils. Deficiency of G-CSF, which protects against lung disease, protected against the development of ileitis in SHIP-1<sup>-/-</sup> mice.</p><p><strong>Conclusions: </strong>These studies have defined environmental, immune, and inflammatory factors that predispose to ileitis, and have identified that comorbid lung disease correlates with a granulocyte signature.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464295","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}
Background: Sepsis represents a significant global health and hygiene challenge. Excessive activation of macrophages in sepsis can result in certain patients displaying characteristics akin to those observed in Macrophage Activation Syndrome (MAS). MAS represents a grave immune system disorder characterized by persistent and severe inflammation within the body. In the context of sepsis, MAS presents atypically, leading some researchers to refer to it as Macrophage Activation-Like Syndrome (MALS). However, there are currently no effective treatment measures for this situation. The purpose of this article is to explore potential treatment methods for sepsis-associated MALS.
Objective: The objective of this review is to synthesize the specific pathophysiological mechanisms and treatment strategies of MAS to investigate potential therapeutic approaches for sepsis-associated MALS.
Method: We searched major databases (including PubMed, Web of Science, and Google Scholar etc.) for literature encompassing macrophage activation syndrome and sepsis up to Mar 2024 and combined with studies found in the reference lists of the included studies.
Conclusion: We have synthesized the underlying pathophysiological mechanism of MALS in sepsis, and then summarized the diagnostic criteria and the effects of various treatment modalities utilized in patients with MAS or MALS. In both scenarios, heterogeneous treatment responses resulting from identical treatment approaches were observed. The determination of whether the patient is genuinely experiencing MALS significantly impacts the ultimate outcomes of therapeutic efficacy. In order to tackle this concern, additional clinical trials and research endeavors are imperative.
背景:败血症是全球健康和卫生方面的重大挑战。败血症中巨噬细胞的过度活化会导致某些患者表现出类似巨噬细胞活化综合征(MAS)的特征。巨噬细胞活化综合征是一种严重的免疫系统疾病,其特征是体内持续存在严重的炎症。在败血症中,巨噬细胞活化综合征的表现并不典型,因此一些研究人员将其称为巨噬细胞活化样综合征(MALS)。然而,目前还没有针对这种情况的有效治疗措施。本文旨在探讨脓毒症相关 MALS 的潜在治疗方法:本综述旨在综合 MAS 的特定病理生理机制和治疗策略,以探讨脓毒症相关 MALS 的潜在治疗方法:我们检索了主要数据库(包括PubMed、Web of Science和Google Scholar等)中截至2024年3月有关巨噬细胞活化综合征和脓毒症的文献,并结合纳入研究参考文献列表中的研究:我们归纳了脓毒症中巨噬细胞活化综合征的潜在病理生理机制,然后总结了MAS或巨噬细胞活化综合征患者的诊断标准和各种治疗方法的效果。在这两种情况下,相同的治疗方法会产生不同的治疗反应。判断患者是否真正患有 MALS 会对最终疗效产生重大影响。为了解决这一问题,必须开展更多的临床试验和研究工作。
{"title":"Macrophage activation syndrome in Sepsis: from pathogenesis to clinical management.","authors":"Shunyao Chen, Cong Zhang, Jialiu Luo, Zhiqiang Lin, Teding Chang, Liming Dong, Deng Chen, Zhao-Hui Tang","doi":"10.1007/s00011-024-01957-7","DOIUrl":"https://doi.org/10.1007/s00011-024-01957-7","url":null,"abstract":"<p><strong>Background: </strong>Sepsis represents a significant global health and hygiene challenge. Excessive activation of macrophages in sepsis can result in certain patients displaying characteristics akin to those observed in Macrophage Activation Syndrome (MAS). MAS represents a grave immune system disorder characterized by persistent and severe inflammation within the body. In the context of sepsis, MAS presents atypically, leading some researchers to refer to it as Macrophage Activation-Like Syndrome (MALS). However, there are currently no effective treatment measures for this situation. The purpose of this article is to explore potential treatment methods for sepsis-associated MALS.</p><p><strong>Objective: </strong>The objective of this review is to synthesize the specific pathophysiological mechanisms and treatment strategies of MAS to investigate potential therapeutic approaches for sepsis-associated MALS.</p><p><strong>Method: </strong>We searched major databases (including PubMed, Web of Science, and Google Scholar etc.) for literature encompassing macrophage activation syndrome and sepsis up to Mar 2024 and combined with studies found in the reference lists of the included studies.</p><p><strong>Conclusion: </strong>We have synthesized the underlying pathophysiological mechanism of MALS in sepsis, and then summarized the diagnostic criteria and the effects of various treatment modalities utilized in patients with MAS or MALS. In both scenarios, heterogeneous treatment responses resulting from identical treatment approaches were observed. The determination of whether the patient is genuinely experiencing MALS significantly impacts the ultimate outcomes of therapeutic efficacy. In order to tackle this concern, additional clinical trials and research endeavors are imperative.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464296","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}
Psoriasis (Ps) is a chronic inflammatory disorder marked by skin plaque formation, driven by immune dysregulation and genetic factors. Despite the available treatments, incidence of Ps is increasing in the dermatology patients. Novel strategies are crucial due to current treatment limitations. The interleukin 17 (IL-17) pathway is pivotal in Ps pathogenesis, however the expression of its putative target gene placenta expressed transcript 1 (Plet1) remains unstudied in Ps. Considering the potential anti-inflammatory properties of N-Acetylglucosamine (GlcNAc), our study explored its role in modulating Plet1 expression in an imiquimod (IMQ)-induced Ps mouse model. Our data demonstarted a significant reduction of inflammation and Psoriasis Area and Severity Index (PASI) scores, downregulation of growth factors (GFs), IL-17 A, and MAPK expression after GlcNAc treatment. In addition, GlcNAc treatment reduced neutrophils, monocyte-dendritic cells (Mo-DC) and conventional T cells (Tcons) while increasing monocyte-macrophages (Mo-Macs) and regulatory T cells (Tregs). GlcNAc treatment also downregulated Plet1 overexpression in psoriatic mouse skin and in vitro, reduced proliferation and apoptosis in IL-17 A stimulated human dermal fibroblasts (HDF), along with IL-17 A and TGF-β mRNA expression. Together, these data suggest that, GlcNAc interferes with downstream mechanisms in IL-17 pathway and downregulating Plet1 expression, presenting a promising strategy for Ps treatment.
银屑病(Ps)是一种以皮肤斑块形成为特征的慢性炎症性疾病,由免疫调节失调和遗传因素引起。尽管有多种治疗方法,但银屑病在皮肤科患者中的发病率仍在上升。由于目前治疗方法的局限性,新策略至关重要。白细胞介素 17(IL-17)通路在 Ps 发病机制中起着关键作用,但其假定靶基因胎盘表达转录本 1(Plet1)在 Ps 中的表达仍未得到研究。 考虑到 N-乙酰葡糖胺(GlcNAc)潜在的抗炎特性,我们的研究探讨了它在咪喹莫特(IMQ)诱导的 Ps 小鼠模型中调节 Plet1 表达的作用。我们的数据显示,GlcNAc治疗后,炎症和银屑病面积和严重程度指数(PASI)评分明显降低,生长因子(GFs)、IL-17 A和MAPK表达下调。此外,GlcNAc 处理还减少了中性粒细胞、单核-树突状细胞(Mo-DC)和传统 T 细胞(Tcons),同时增加了单核-巨噬细胞(Mo-Macs)和调节性 T 细胞(Tregs)。GlcNAc 处理还能下调银屑病小鼠皮肤中 Plet1 的过表达,并在体外减少 IL-17 A 刺激的人真皮成纤维细胞(HDF)的增殖和凋亡,以及 IL-17 A 和 TGF-β mRNA 的表达。这些数据共同表明,GlcNAc 可干扰 IL-17 通路的下游机制并下调 Plet1 的表达,从而为 Ps 治疗提供了一种有前景的策略。
{"title":"Modulation of Plet1 expression by N-Acetylglucosamine through the IL-17 A-MAPK pathway in an imiquimod-induced psoriasis mouse model.","authors":"Balachandar Selvakumar, Bilal Rah, Jayalakshmi Jagal, Priyadarshini Sekar, Raneem Moustafa, Rakhee Kizhuvappat Ramakrishnan, Mohamed Haider, Saleh Mohamed Ibrahim, Rani Samsudin","doi":"10.1007/s00011-024-01958-6","DOIUrl":"https://doi.org/10.1007/s00011-024-01958-6","url":null,"abstract":"<p><p>Psoriasis (Ps) is a chronic inflammatory disorder marked by skin plaque formation, driven by immune dysregulation and genetic factors. Despite the available treatments, incidence of Ps is increasing in the dermatology patients. Novel strategies are crucial due to current treatment limitations. The interleukin 17 (IL-17) pathway is pivotal in Ps pathogenesis, however the expression of its putative target gene placenta expressed transcript 1 (Plet1) remains unstudied in Ps. Considering the potential anti-inflammatory properties of N-Acetylglucosamine (GlcNAc), our study explored its role in modulating Plet1 expression in an imiquimod (IMQ)-induced Ps mouse model. Our data demonstarted a significant reduction of inflammation and Psoriasis Area and Severity Index (PASI) scores, downregulation of growth factors (GFs), IL-17 A, and MAPK expression after GlcNAc treatment. In addition, GlcNAc treatment reduced neutrophils, monocyte-dendritic cells (Mo-DC) and conventional T cells (Tcons) while increasing monocyte-macrophages (Mo-Macs) and regulatory T cells (Tregs). GlcNAc treatment also downregulated Plet1 overexpression in psoriatic mouse skin and in vitro, reduced proliferation and apoptosis in IL-17 A stimulated human dermal fibroblasts (HDF), along with IL-17 A and TGF-β mRNA expression. Together, these data suggest that, GlcNAc interferes with downstream mechanisms in IL-17 pathway and downregulating Plet1 expression, presenting a promising strategy for Ps treatment.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464297","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}