M. Haist, H. Stege, Verena Maikranz, Maria Halley Blanco, S. Grabbe, C. Loquai
The advent of immune-checkpoint inhibitors (ICIs) led to significant improvements in the treatment of patients with advanced melanoma and resulted in durable tumor responses in a considerable number of advanced melanoma patients. Next to the immune-mediated anti-neoplastic effects, ICIs may cause various immune-related adverse events (irAEs), often requiring early discontinuation of therapy. By contrast, cutaneous irAE rarely enforce treatment discontinuation but may represent simple and robust predictive markers for treatment response. The relevance of irAEs as clinical markers for an improved response to immunotherapy is still debated. We report here on two patients with multifocal metastatic melanoma who developed the rare event of generalized poliosis during combined immunotherapy with ipilimumab plus nivolumab, followed by a near-complete and durable response. Our observations suggest that poliosis may be a useful and simple clinical indicator of anti-tumor immunity, clinical response and favorable survival outcome in advanced melanoma patients treated with ICI.
{"title":"Poliosis Is Associated with Response to Checkpoint-Inhibitor Therapy: A Case Report of Two Patients with Multifocal Metastatic Melanoma","authors":"M. Haist, H. Stege, Verena Maikranz, Maria Halley Blanco, S. Grabbe, C. Loquai","doi":"10.3390/immuno2020020","DOIUrl":"https://doi.org/10.3390/immuno2020020","url":null,"abstract":"The advent of immune-checkpoint inhibitors (ICIs) led to significant improvements in the treatment of patients with advanced melanoma and resulted in durable tumor responses in a considerable number of advanced melanoma patients. Next to the immune-mediated anti-neoplastic effects, ICIs may cause various immune-related adverse events (irAEs), often requiring early discontinuation of therapy. By contrast, cutaneous irAE rarely enforce treatment discontinuation but may represent simple and robust predictive markers for treatment response. The relevance of irAEs as clinical markers for an improved response to immunotherapy is still debated. We report here on two patients with multifocal metastatic melanoma who developed the rare event of generalized poliosis during combined immunotherapy with ipilimumab plus nivolumab, followed by a near-complete and durable response. Our observations suggest that poliosis may be a useful and simple clinical indicator of anti-tumor immunity, clinical response and favorable survival outcome in advanced melanoma patients treated with ICI.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87498356","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}
Thirumurugan Rathinasabapathy, Jade Lomax, Kavin Srikanth, D. Esposito, C. Kay, S. Komarnytsky
Wild blueberries (Vaccinium angustifolium Aiton.) are a rich source of dietary fiber and (poly)phenols with gastrointestinal and immune health-promoting properties, however, their mechanisms of action on the intestinal epithelial cells and transient tissue macrophages remain to be elucidated. In this study, we evaluated the individual effects of anthocyanins, short-chain fatty acids (metabolites derived from fiber), and a series of hydroxycinnamic and hydroxybenzoic acid metabolites common to anthocyanins and other polyphenols on epithelial gut homeostasis in human colon epithelial CCD-18 cells and murine RAW 264.7 macrophages. Gastrointestinal cell migration was enhanced in response to anthocyanin glucosides with the maximum effect observed for malvidin-3-glucoside, and a structural subset of hydroxybenzoic acids, especially 2-hydroxybenzoic acid. Enhanced staining for ZO-1 protein in the junctional complexes was observed in CCD-18 cells treated with malvidin and butyrate, as well as several phenolic metabolites, including hydroxybenzoic and hydroxycinnamic acids. Nitric oxide production and pro-inflammatory gene expression profiles in the LPS-stimulated macrophages were mostly affected by treatments with 3-caffeoylquinic (chlorogenic) and 3,4-dihydroxycinnamic (caffeic) acids, as well as 2-hydroxybenzoic acid. This study lays the foundation for future investigations evaluating the effects of dietary interventions on managing gastrointestinal and inflammatory pathophysiological outcomes.
{"title":"Effect of Wild Blueberry Metabolites on Biomarkers of Gastrointestinal and Immune Health In Vitro","authors":"Thirumurugan Rathinasabapathy, Jade Lomax, Kavin Srikanth, D. Esposito, C. Kay, S. Komarnytsky","doi":"10.3390/immuno2020019","DOIUrl":"https://doi.org/10.3390/immuno2020019","url":null,"abstract":"Wild blueberries (Vaccinium angustifolium Aiton.) are a rich source of dietary fiber and (poly)phenols with gastrointestinal and immune health-promoting properties, however, their mechanisms of action on the intestinal epithelial cells and transient tissue macrophages remain to be elucidated. In this study, we evaluated the individual effects of anthocyanins, short-chain fatty acids (metabolites derived from fiber), and a series of hydroxycinnamic and hydroxybenzoic acid metabolites common to anthocyanins and other polyphenols on epithelial gut homeostasis in human colon epithelial CCD-18 cells and murine RAW 264.7 macrophages. Gastrointestinal cell migration was enhanced in response to anthocyanin glucosides with the maximum effect observed for malvidin-3-glucoside, and a structural subset of hydroxybenzoic acids, especially 2-hydroxybenzoic acid. Enhanced staining for ZO-1 protein in the junctional complexes was observed in CCD-18 cells treated with malvidin and butyrate, as well as several phenolic metabolites, including hydroxybenzoic and hydroxycinnamic acids. Nitric oxide production and pro-inflammatory gene expression profiles in the LPS-stimulated macrophages were mostly affected by treatments with 3-caffeoylquinic (chlorogenic) and 3,4-dihydroxycinnamic (caffeic) acids, as well as 2-hydroxybenzoic acid. This study lays the foundation for future investigations evaluating the effects of dietary interventions on managing gastrointestinal and inflammatory pathophysiological outcomes.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85607445","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}
Yashwanth Subbannayya, Ankit Bhatta, S. Pinto, K. Fitzgerald, R. K. Kandasamy
Short open reading frames (sORFs) encoding functional peptides have emerged as important mediators of biological processes. Recent studies indicate that sORFs of long non-coding RNAs (lncRNAs) can encode functional micropeptides regulating immunity and inflammation. However, large-scale identification of potential micropeptide-encoding sequences is a significant challenge. We present a data analysis pipeline that uses immune cell-derived mass spectrometry-based proteomic data reanalyzed using a rigorous proteogenomics-based workflow. Our analysis resulted in the identification of 2815 putative lncRNA-encoded micropeptides across three human immune cell types. Stringent score cut-off and manual verification confidently identified 185 high-confidence putative micropeptide-coding events, of which a majority have not been reported previously. Functional validation revealed the expression and localization of lnc-MKKS in both nucleus and cytoplasmic compartments. Our pilot analysis serves as a resource for future studies focusing on the role of micropeptides in immune cell response.
{"title":"Proteogenomics Analysis Reveals Novel Micropeptides in Primary Human Immune Cells","authors":"Yashwanth Subbannayya, Ankit Bhatta, S. Pinto, K. Fitzgerald, R. K. Kandasamy","doi":"10.3390/immuno2020018","DOIUrl":"https://doi.org/10.3390/immuno2020018","url":null,"abstract":"Short open reading frames (sORFs) encoding functional peptides have emerged as important mediators of biological processes. Recent studies indicate that sORFs of long non-coding RNAs (lncRNAs) can encode functional micropeptides regulating immunity and inflammation. However, large-scale identification of potential micropeptide-encoding sequences is a significant challenge. We present a data analysis pipeline that uses immune cell-derived mass spectrometry-based proteomic data reanalyzed using a rigorous proteogenomics-based workflow. Our analysis resulted in the identification of 2815 putative lncRNA-encoded micropeptides across three human immune cell types. Stringent score cut-off and manual verification confidently identified 185 high-confidence putative micropeptide-coding events, of which a majority have not been reported previously. Functional validation revealed the expression and localization of lnc-MKKS in both nucleus and cytoplasmic compartments. Our pilot analysis serves as a resource for future studies focusing on the role of micropeptides in immune cell response.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90307270","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}
In the past few years, a renowned interest in the interplay between the immune system and central nervous systems (CNS) has sparked a wealth of new experimental studies. Two recent publications in Science shed new light on the “resident” immune cell populations in the CNS and their functions in homeostasis and pathological status, with potential implications in understanding CNS disease mechanisms and in designing new “intelligent” therapies.
{"title":"The New Anatomy of Neuroimmunology","authors":"C. Solaro, D. Barratt, M. Vaccarezza","doi":"10.3390/immuno2010016","DOIUrl":"https://doi.org/10.3390/immuno2010016","url":null,"abstract":"In the past few years, a renowned interest in the interplay between the immune system and central nervous systems (CNS) has sparked a wealth of new experimental studies. Two recent publications in Science shed new light on the “resident” immune cell populations in the CNS and their functions in homeostasis and pathological status, with potential implications in understanding CNS disease mechanisms and in designing new “intelligent” therapies.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89547889","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}
H. Yasmin, Anureeta Adhikary, M. Al-Ahdal, Syamal Roy, U. Kishore
Leishmaniasis is a zoonotic and vector-borne infectious disease that is caused by the genus Leishmania belonging to the trypanosomatid family. The protozoan parasite has a digenetic life cycle involving a mammalian host and an insect vector. Leishmaniasisis is a worldwide public health problem falling under the neglected tropical disease category, with over 90 endemic countries, and approximately 1 million new cases and 20,000 deaths annually. Leishmania infection can progress toward the development of species–specific pathologic disorders, ranging in severity from self-healing cutaneous lesions to disseminating muco-cutaneous and fatal visceral manifestations. The severity and the outcome of leishmaniasis is determined by the parasite’s antigenic epitope characteristics, the vector physiology, and most importantly, the immune response and immune status of the host. This review examines the nature of host–pathogen interaction in leishmaniasis, innate and adaptive immune responses, and various strategies that have been employed for vaccine development.
{"title":"Host–Pathogen Interaction in Leishmaniasis: Immune Response and Vaccination Strategies","authors":"H. Yasmin, Anureeta Adhikary, M. Al-Ahdal, Syamal Roy, U. Kishore","doi":"10.3390/immuno2010015","DOIUrl":"https://doi.org/10.3390/immuno2010015","url":null,"abstract":"Leishmaniasis is a zoonotic and vector-borne infectious disease that is caused by the genus Leishmania belonging to the trypanosomatid family. The protozoan parasite has a digenetic life cycle involving a mammalian host and an insect vector. Leishmaniasisis is a worldwide public health problem falling under the neglected tropical disease category, with over 90 endemic countries, and approximately 1 million new cases and 20,000 deaths annually. Leishmania infection can progress toward the development of species–specific pathologic disorders, ranging in severity from self-healing cutaneous lesions to disseminating muco-cutaneous and fatal visceral manifestations. The severity and the outcome of leishmaniasis is determined by the parasite’s antigenic epitope characteristics, the vector physiology, and most importantly, the immune response and immune status of the host. This review examines the nature of host–pathogen interaction in leishmaniasis, innate and adaptive immune responses, and various strategies that have been employed for vaccine development.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79553482","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}
Johanna Kusnick, Alix Bruneau, F. Tacke, L. Hammerich
Ferroptosis is a recently recognized iron-dependent form of non-apoptotic regulated cell death (RCD) characterized by lipid peroxide accumulation to lethal levels. Cancer cells, which show an increased iron dependency to enable rapid growth, seem vulnerable to ferroptosis. There is also increasing evidence that ferroptosis might be immunogenic and therefore could synergize with immunotherapies. Hepatocellular carcinoma (HCC) is the most common primary liver tumor with a low survival rate due to frequent recurrence and limited efficacy of conventional chemotherapies, illustrating the urgent need for novel drug approaches or combinatorial strategies. Immunotherapy is a new treatment approach for advanced HCC patients. In this setting, ferroptosis inducers may have substantial clinical potential. However, there are still many questions to answer before the mystery of ferroptosis is fully unveiled. This review discusses the existing studies and our current understanding regarding the molecular mechanisms of ferroptosis with the goal of enhancing response to immunotherapy of liver cancer. In addition, challenges and opportunities in clinical applications of potential candidates for ferroptosis-driven therapeutic strategies will be summarized. Unraveling the role of ferroptosis in the immune response could benefit the development of promising anti-cancer therapies that overcome drug resistance and prevent tumor metastasis.
{"title":"Ferroptosis in Cancer Immunotherapy—Implications for Hepatocellular Carcinoma","authors":"Johanna Kusnick, Alix Bruneau, F. Tacke, L. Hammerich","doi":"10.3390/immuno2010014","DOIUrl":"https://doi.org/10.3390/immuno2010014","url":null,"abstract":"Ferroptosis is a recently recognized iron-dependent form of non-apoptotic regulated cell death (RCD) characterized by lipid peroxide accumulation to lethal levels. Cancer cells, which show an increased iron dependency to enable rapid growth, seem vulnerable to ferroptosis. There is also increasing evidence that ferroptosis might be immunogenic and therefore could synergize with immunotherapies. Hepatocellular carcinoma (HCC) is the most common primary liver tumor with a low survival rate due to frequent recurrence and limited efficacy of conventional chemotherapies, illustrating the urgent need for novel drug approaches or combinatorial strategies. Immunotherapy is a new treatment approach for advanced HCC patients. In this setting, ferroptosis inducers may have substantial clinical potential. However, there are still many questions to answer before the mystery of ferroptosis is fully unveiled. This review discusses the existing studies and our current understanding regarding the molecular mechanisms of ferroptosis with the goal of enhancing response to immunotherapy of liver cancer. In addition, challenges and opportunities in clinical applications of potential candidates for ferroptosis-driven therapeutic strategies will be summarized. Unraveling the role of ferroptosis in the immune response could benefit the development of promising anti-cancer therapies that overcome drug resistance and prevent tumor metastasis.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"356 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76501455","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}
N. Kaneko, M. Moriyama, T. Maehara, Hu Chen, Yuka Miyahara, Seiji Nakamura
This review summarizes recent progress in understanding the pathogenesis of IgG4-related disease (IgG4-RD), with a focus on fibrosis. Several studies reported that CD4+ T cells with cytotoxic activity promoted by the secretion of granzyme and perforin, cytotoxic CD4+ T cells (CD4+CTLs), and disease-specific activated B cells, infiltrated inflamed tissues and cooperated to induce tissue fibrosis in autoimmune fibrotic diseases such as IgG4-RD, systemic sclerosis, and fibrosing mediastinitis. An accumulation of cells undergoing apoptotic cell death induced by CD4+CTLs and CD8+CTLs followed by macrophage-mediated clearing and finally tissue remodeling driven by cytokines released by CD4+CTLs, activated B cells, and M2 macrophages may contribute to the activation of fibroblasts and collagen production. In IgG4-RD, this process likely involves the apoptosis of non-immune, non-endothelial cells of mesenchymal origin and subsequent tissue remodeling. In summary, CD4+CTLs infiltrate affected tissues where they may cooperate with activated B cells, CD8+CTLs, and M2 macrophages, to induce apoptosis by secreting cytotoxic cytokines. These immune cells also drive fibrosis by secreting pro-fibrotic molecules in IgG4-RD.
{"title":"Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related Disease","authors":"N. Kaneko, M. Moriyama, T. Maehara, Hu Chen, Yuka Miyahara, Seiji Nakamura","doi":"10.3390/immuno2010013","DOIUrl":"https://doi.org/10.3390/immuno2010013","url":null,"abstract":"This review summarizes recent progress in understanding the pathogenesis of IgG4-related disease (IgG4-RD), with a focus on fibrosis. Several studies reported that CD4+ T cells with cytotoxic activity promoted by the secretion of granzyme and perforin, cytotoxic CD4+ T cells (CD4+CTLs), and disease-specific activated B cells, infiltrated inflamed tissues and cooperated to induce tissue fibrosis in autoimmune fibrotic diseases such as IgG4-RD, systemic sclerosis, and fibrosing mediastinitis. An accumulation of cells undergoing apoptotic cell death induced by CD4+CTLs and CD8+CTLs followed by macrophage-mediated clearing and finally tissue remodeling driven by cytokines released by CD4+CTLs, activated B cells, and M2 macrophages may contribute to the activation of fibroblasts and collagen production. In IgG4-RD, this process likely involves the apoptosis of non-immune, non-endothelial cells of mesenchymal origin and subsequent tissue remodeling. In summary, CD4+CTLs infiltrate affected tissues where they may cooperate with activated B cells, CD8+CTLs, and M2 macrophages, to induce apoptosis by secreting cytotoxic cytokines. These immune cells also drive fibrosis by secreting pro-fibrotic molecules in IgG4-RD.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"448 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72427122","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}
Rigorous peer-reviews are the basis of high-quality academic publishing [...]
严格的同行评议是高质量学术出版的基础[…]
{"title":"Acknowledgment to Reviewers of Immuno in 2021","authors":"","doi":"10.3390/immuno2010011","DOIUrl":"https://doi.org/10.3390/immuno2010011","url":null,"abstract":"Rigorous peer-reviews are the basis of high-quality academic publishing [...]","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75209462","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}
O. Said, I. Khamaysi, Abdalsalam Kmail, O. Sadiq, Besan Saied, S. Fulder, Basheer Abofarekh, Mahmud Masalha, R. Amin, B. Saad
Nigella sativa, Conyza bonariensis, and Alchemilla vulgaris are highly recommended in Greco-Arab traditional medicine as anti-hemorrhoid medicinal plants. The efficacy and safety of a topical cream (HPC) consisting of water–ethanol extracts of these three plants were evaluated here in vitro and in a randomized, double-blind, placebo-controlled study (RDBPC). HPC showed no significant cytotoxic effects in fibroblast cell line 3T3 (LDH-release and MTT assay); it inhibited the nitric oxide production by cultured monocyte cell line THP-1 in a dose-dependent manner (reaching the control levels of untreated cells at a concentration of 100 μg/mL). HPC showed a dose-dependent antibacterial activity against Escherichia coli (60% inhibition compared to Ampicillin at 5 mg/disc) and a significant vasoconstriction effect on intestinal vein rings (40% increase compared to phenylephrine). In a RDBPC with 77 hemorrhoidal disease (patients ages 19–61 years with a median grade of hemorrhoids of 2.0), we determined the anti-hemorrhoid efficacy and safety of HPC. The patients were randomly assigned to the HPC group (54 patients) or the placebo group (23 patients). They were asked to apply 2–3 mL of HPC or placebo twice daily for 6 days. The degree of hemorrhoidal disease severity, hemorrhage severity, pain, and itching served as an evaluation of the HPC efficacy. Compared to the placebo group, the obtained results showed that 6 days of treatment with HPC reduced the indexes of hemorrhage severity, severity of pain, and severity of itching to 0–1, 1, and 1 after 6 days, respectively. In conclusion, patients treated with HPC had a significant clinical improvement in all disease severity parameters compared to placebo. In vitro evaluations proved HPC to have significant antimicrobial, anti-inflammatory, and vasoconstriction effects. Therefore, HPC represents an interesting alternative treatment for hemorrhoidal disease.
{"title":"Anti-Inflammatory, Antimicrobial, and Vasoconstriction Activities of an Anti-Hemorrhoidal Mixture of Alchemilla vulgaris, Conyza bonariensis, and Nigella sativa: In Vitro and Clinical Evaluations","authors":"O. Said, I. Khamaysi, Abdalsalam Kmail, O. Sadiq, Besan Saied, S. Fulder, Basheer Abofarekh, Mahmud Masalha, R. Amin, B. Saad","doi":"10.3390/immuno2010010","DOIUrl":"https://doi.org/10.3390/immuno2010010","url":null,"abstract":"Nigella sativa, Conyza bonariensis, and Alchemilla vulgaris are highly recommended in Greco-Arab traditional medicine as anti-hemorrhoid medicinal plants. The efficacy and safety of a topical cream (HPC) consisting of water–ethanol extracts of these three plants were evaluated here in vitro and in a randomized, double-blind, placebo-controlled study (RDBPC). HPC showed no significant cytotoxic effects in fibroblast cell line 3T3 (LDH-release and MTT assay); it inhibited the nitric oxide production by cultured monocyte cell line THP-1 in a dose-dependent manner (reaching the control levels of untreated cells at a concentration of 100 μg/mL). HPC showed a dose-dependent antibacterial activity against Escherichia coli (60% inhibition compared to Ampicillin at 5 mg/disc) and a significant vasoconstriction effect on intestinal vein rings (40% increase compared to phenylephrine). In a RDBPC with 77 hemorrhoidal disease (patients ages 19–61 years with a median grade of hemorrhoids of 2.0), we determined the anti-hemorrhoid efficacy and safety of HPC. The patients were randomly assigned to the HPC group (54 patients) or the placebo group (23 patients). They were asked to apply 2–3 mL of HPC or placebo twice daily for 6 days. The degree of hemorrhoidal disease severity, hemorrhage severity, pain, and itching served as an evaluation of the HPC efficacy. Compared to the placebo group, the obtained results showed that 6 days of treatment with HPC reduced the indexes of hemorrhage severity, severity of pain, and severity of itching to 0–1, 1, and 1 after 6 days, respectively. In conclusion, patients treated with HPC had a significant clinical improvement in all disease severity parameters compared to placebo. In vitro evaluations proved HPC to have significant antimicrobial, anti-inflammatory, and vasoconstriction effects. Therefore, HPC represents an interesting alternative treatment for hemorrhoidal disease.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86292658","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}
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. This clinically heterogeneous neurological disorder is closely related to Guillain–Barré syndrome and is considered the chronic counterpart of that acute disease. Currently available treatments are mostly empirical; they include corticosteroids, intravenous immunoglobulins, plasma exchange and chronic immunosuppressive agents, either alone or in combination. Recent advances in the understanding of the underlying pathogenic mechanisms in CIDP have brought a number of novel ways of possible intervention for use in CIDP. This review summarizes selected pre-clinical and clinical findings, highlights the importance of using adapted animal models to evaluate the efficacy of novel treatments, and proposes the outlines of future directions to ameliorate the conditions of patients with CIDP.
{"title":"CIDP: Current Treatments and Identification of Targets for Future Specific Therapeutic Intervention","authors":"S. Brun, J. de Seze, S. Muller","doi":"10.3390/immuno2010009","DOIUrl":"https://doi.org/10.3390/immuno2010009","url":null,"abstract":"Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. This clinically heterogeneous neurological disorder is closely related to Guillain–Barré syndrome and is considered the chronic counterpart of that acute disease. Currently available treatments are mostly empirical; they include corticosteroids, intravenous immunoglobulins, plasma exchange and chronic immunosuppressive agents, either alone or in combination. Recent advances in the understanding of the underlying pathogenic mechanisms in CIDP have brought a number of novel ways of possible intervention for use in CIDP. This review summarizes selected pre-clinical and clinical findings, highlights the importance of using adapted animal models to evaluate the efficacy of novel treatments, and proposes the outlines of future directions to ameliorate the conditions of patients with CIDP.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"115 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74784033","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}