14,840 results
Search Results
2. Review Paper. Variation in Immune Defence as a Question of Evolutionary Ecology
- Author
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Schmid-Hempel, Paul
- Published
- 2003
3. The possible importance of the antioxidants and oxidative stress metabolism in the emerging monkeypox disease: An opinion paper
- Author
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Duygu Aydemir and Nuriye Nuray Ulusu
- Subjects
antioxidant molecules ,monkeypox ,MPXV infection ,oxidative stress ,immune response ,antioxidant enzymes ,Public aspects of medicine ,RA1-1270 - Published
- 2022
- Full Text
- View/download PDF
4. Immunologically relevant aspects of the new COVID-19 vaccines—an ÖGAI (Austrian Society for Allergology and Immunology) and AeDA (German Society for Applied Allergology) position paper
- Author
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Hans F. Merk, Randolf Brehler, Wolfgang Wehrmann, Kathrin Eller, Ursula Wiedermann, Kaan Boztug, Wolfgang Pfützner, Winfried F. Pickl, Michael Bonelli, Karl-Christian Bergmann, Thomas Eiwegger, Natalija Novak, Birgit Pfaller, Thomas Fuchs, Norbert Mülleneisen, Johannes Ring, Elisabeth Förster-Waldl, Wolfram Hötzenecker, Lisa Göschl, Holger Wrede, Eva Untersmayr, Patrick M. Brunner, Ludger Klimek, Katharina Grabmeier-Pfistershammer, Galateja Jordakieva, Erika Jensen-Jarolim, Alexander R. Moschen, Wolfgang Schlenter, Walter Reinisch, and Uta Rabe
- Subjects
0301 basic medicine ,medicine.medical_specialty ,COVID-19 vaccination ,medicine.medical_treatment ,Population ,Immunomodulation ,03 medical and health sciences ,0302 clinical medicine ,Pandemic ,medicine ,Immunology and Allergy ,media_common.cataloged_instance ,ddc:610 ,030212 general & internal medicine ,Immune response ,European union ,Intensive care medicine ,education ,media_common ,education.field_of_study ,business.industry ,Immunosuppression ,Review article ,Vaccination ,030104 developmental biology ,Tolerability ,Position Article ,Position paper ,Vaccination effect ,business - Abstract
Allergo journal international 30(5), 155-168 (2021). doi:10.1007/s40629-021-00178-2, Published by Urban & Vogel, München
- Published
- 2021
5. Identifying the anti-inflammatory response to lipid lowering therapy: a position paper from the working group on atherosclerosis and vascular biology of the European Society of Cardiology
- Author
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Daniel F. J. Ketelhuth, José Tuñón, Imo E. Hoefer, Paul C. Evans, Esther Lutgens, Bertrand Cariou, Jesús Egido, Claudia Monaco, Sabine Steffens, Magnus Bäck, Christian Weber, Marie-Luce Bochaton-Piallat, Cécile Vindis, Erik Stroes, Christian M. Matter, Lina Badimon, Mat J.A.P. Daemen, University of Zurich, Tuñón, José, Pathology, ACS - Atherosclerosis & ischemic syndromes, Vascular Medicine, and ACS - Heart failure & arrhythmias
- Subjects
0301 basic medicine ,Physiology ,Anti-Inflammatory Agents ,030204 cardiovascular system & hematology ,ddc:616.07 ,Bioinformatics ,PCSK9 ,11459 Center for Molecular Cardiology ,PCSK9 Gene ,chemistry.chemical_compound ,0302 clinical medicine ,2737 Physiology (medical) ,Risk Factors ,Medicine ,Hypolipidemic Agents ,PCSK9 Inhibitors ,Position Paper from European Society of Cardiology Working Group ,Lipids ,3. Good health ,Treatment Outcome ,10209 Clinic for Cardiology ,lipids (amino acids, peptides, and proteins) ,Inflammation Mediators ,Proprotein Convertase 9 ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Serine Proteinase Inhibitors ,Inflammation ,610 Medicine & health ,Lipid-lowering therapy ,2705 Cardiology and Cardiovascular Medicine ,03 medical and health sciences ,Immune system ,Physiology (medical) ,Animals ,Humans ,Immune response ,Dyslipidemias ,business.industry ,Cholesterol ,Statins ,Lipid metabolism ,1314 Physiology ,Atherosclerosis ,030104 developmental biology ,chemistry ,Position paper ,business ,Biomarkers - Abstract
Dysregulated lipid metabolism induces an inflammatory and immune response leading to atherosclerosis. Conversely, inflammation may alter lipid metabolism. Recent treatment strategies in secondary prevention of atherosclerosis support beneficial effects of both anti-inflammatory and lipid-lowering therapies beyond current targets. There is a controversy about the possibility that anti-inflammatory effects of lipid-lowering therapy may be either independent or not of a decrease in low-density lipoprotein cholesterol. In this Position Paper, we critically interpret and integrate the results obtained in both experimental and clinical studies on anti-inflammatory actions of lipid-lowering therapy and the mechanisms involved. We highlight that: (i) besides decreasing cholesterol through different mechanisms, most lipid-lowering therapies share anti-inflammatory and immunomodulatory properties, and the anti-inflammatory response to lipid-lowering may be relevant to predict the effect of treatment, (ii) using surrogates for both lipid metabolism and inflammation as biomarkers or vascular inflammation imaging in future studies may contribute to a better understanding of the relative importance of different mechanisms of action, and (iii) comparative studies of further lipid lowering, anti-inflammation and a combination of both are crucial to identify effects that are specific or shared for each treatment strategy.
- Published
- 2019
6. The Immunomodulatory Effect of Nigella sativa.
- Author
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Ciesielska-Figlon, Klaudia, Wojciechowicz, Karolina, Wardowska, Anna, and Lisowska, Katarzyna Aleksandra
- Subjects
ESSENTIAL oils ,FOOD preservatives ,BLACK cumin ,CONFERENCE papers ,TRADITIONAL medicine ,OILSEEDS ,IMMUNE response - Abstract
Background: For thousands of years till nowadays, Nigella sativa (NS) has served as a common spice and food preservative. Its seed extracts, seed oil, and essential oil in traditional medicine have been used to remedy many ailments such as headaches, fever, gastric complaints, and even rheumatism. In addition, the antibacterial, virucidal, fungicidal, and antiparasitic properties of NS are well known. However, studies on the possible immunomodulatory effects of black cumin are relatively scarce. This article discusses in vitro and in vivo research supporting the immunomodulatory role of NS. Methods: The review is based on articles, books, and conference papers printed until September 2022, found in the Web of Science, PubMed, Wiley Online Library, and Google Scholar databases. Results: Experimental findings were reported concerning the ability of NS to modulate inflammation and immune responses or cytotoxic activity. Conclusions: All results suggest that NS can potentially be employed in developing effective therapeutic agents for regulating immune reactions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Immune trypanolysis test with blood spotted on filter paper for epidemiological surveillance of sleeping sickness.
- Author
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Camara, Oumou, Camara, Mamadou, Lejon, Veerle, Ilboudo, Hamidou, Sakande, Hassane, Léno, Mamadou, Büscher, Philippe, Bucheton, Bruno, and Jamonneau, Vincent
- Subjects
- *
IMMUNE response , *BLOOD filtration , *FILTER paper , *EPIDEMIOLOGY , *PATIENT monitoring , *IMMUNOGLOBULINS - Abstract
Objectives The immune trypanolysis test ( TL) is an accurate sero-diagnostic tool increasingly implemented for sleeping sickness medical surveillance, but it is restricted to the reference laboratories. To facilitate storage and transport of the test specimen, we developed a protocol for the examination of blood spotted on filter paper ( TL-fp) that can be stored and shipped at ambient temperature. We compared its performance with the classical TL on plasma ( TL-pl) that needs to be kept frozen until use. Methods The study was conducted in active foci of the Republic of Guinea. In total, 438 specimens from treated and untreated sleeping sickness patients and serological suspects were tested with both methods. Result TL-fp gave significantly less positive results than TL-pl, but all the confirmed sleeping sickness cases were positive with the TL-fp protocol. Conclusion TL-fp appears to offer a good compromise between feasibility and sensitivity to detect currently infected subjects who play a role in the transmission of Trypanosoma brucei gambiense and is useful for contributing to the elimination of gambiense sleeping sickness. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
8. Identifying the anti-inflammatory response to lipid lowering therapy: a position paper from the working group on atherosclerosis and vascular biology of the European Society of Cardiology.
- Author
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Tuñón, José, Badimón, Lina, Bochaton-Piallat, Marie-Luce, Cariou, Bertrand, Daemen, Mat J, Egido, Jesus, Evans, Paul C, Hoefer, Imo E, Ketelhuth, Daniel F J, Lutgens, Esther, Matter, Christian M, Monaco, Claudia, Steffens, Sabine, Stroes, Erik, Vindis, Cécile, Weber, Christian, and Bäck, Magnus
- Abstract
Dysregulated lipid metabolism induces an inflammatory and immune response leading to atherosclerosis. Conversely, inflammation may alter lipid metabolism. Recent treatment strategies in secondary prevention of atherosclerosis support beneficial effects of both anti-inflammatory and lipid-lowering therapies beyond current targets. There is a controversy about the possibility that anti-inflammatory effects of lipid-lowering therapy may be either independent or not of a decrease in low-density lipoprotein cholesterol. In this Position Paper, we critically interpret and integrate the results obtained in both experimental and clinical studies on anti-inflammatory actions of lipid-lowering therapy and the mechanisms involved. We highlight that: (i) besides decreasing cholesterol through different mechanisms, most lipid-lowering therapies share anti-inflammatory and immunomodulatory properties, and the anti-inflammatory response to lipid-lowering may be relevant to predict the effect of treatment, (ii) using surrogates for both lipid metabolism and inflammation as biomarkers or vascular inflammation imaging in future studies may contribute to a better understanding of the relative importance of different mechanisms of action, and (iii) comparative studies of further lipid lowering, anti-inflammation and a combination of both are crucial to identify effects that are specific or shared for each treatment strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
9. Paper de l’exonucleasa TREX2 en la biología i patologia de la pell
- Author
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Manils Pacheco, Joan, Soler Prat, Concepció, and Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental
- Subjects
Enfermedades de la piel ,Psoriasi ,616.5 ,Pell ,Respuesta inmune ,Cáncer ,Ciències de la Salut ,Skin diseases ,Resposta immunitària ,Malalties de la pell ,Psoriasis ,Immune response ,Càncer ,Piel ,Skin ,Cancer - Abstract
[cat] TREX2 (three-prime repair exonuclease 2) és una exonucleasa no processiva 3'-5', expressada específicament en la pell que pot estar implicada en el manteniment de la integritat del genoma editant els extrems 3' del DNA en diversos processos, des de la replicació a la reparació del dany passant per la degradació en l'apoptosi. L'estudi de TREX2 mitjançant immunohistofluorescència de mostres humanes de lesions precanceroses (queratosis actínica) i tumors derivats de queratinòcits, incloent cSCC (cutaneous squamous cell carcinomas) i HNSCCs (head and neck SCC), revela que en les carcinogènesis escamoses l'expressió de TREX2 pateix es troba alterada. La deleció de Trex2 en ratolins provoca un augment de la susceptibilitat de tumors induïts en pell provocats per radiació ultraviolada B (UVB). TREX2 promou l'eliminació del DNA danyat i l'apoptosi dels queratinòcits en les pells de ratolí irradiades amb UVB. Les lesions al DNA induïdes per UVB (CPD: cyclobutane pyrimidine_dimers), són més persistents en les pells dels ratolins Trex21- respecte els wt, paral• lelament també es dóna una menor activació de la caspasa 3, indicador d'apoptosi, en les pells Trex21-. Els resultat obtinguts en queratinòcits wt i deficients en TREX2 in vitxo reflexen una multifuncionalitat de la proteïna TREX2 intervenint en la reparació del dany al DNA en resposta a la radiació UV i promovent l'apoptosi de forma irreversible, essent aquesta última funció la que preval. TREX2 pot ser reclutada diferencialment a diferents localitzacions subnuclears en funció de l'estat de la cromatina, com per exemple els micronuclis i les regions de cromatina poc condensada. Els estudis de co-immunoprecipitació demostren que TREX2 interacciona amb yH2AX, així TREX2 pot accedir als extrems lliures del DNA interaccionant amb la proteïna H2AX fosforilada, preferentment en la cromatina destinada a ser degradada. L'estudi histopatològic de les pells de ratolins irradiats amb UVB, revela que els ratolins Trex21- són més resistents que els wt a la inflamació de la pell induïda per UVB. Addicionalment, en les pells irradiades repetidament del ratolí Trex2-/, l'augment en el nombre de capes cel• lulars en l'epidermis com a mesura de protecció de la pell contra la irradiació, és menor que en el wt. En resum, les nostres dades subratllen la rellevància de TREX2 a l'hora de promoure la resposta inflamatòria contra la UVB. Per altra part, a lesions psoriàsiques es dóna un fort increment i canvis en el patró d'expressió de TREX2 respecte la pell sana. La deficiència de TREX2 a ratolins disminueix el fenotip psoriàsic induït per l'Imiquimod. Concretament, TREX2 afavoreix la mort cel• lular i la resposta inflamatòria inicial. A més a més, TREX2 està implicada en la degradació del DNA durant la diferenciació terminal dels corneòcits, disminuint la paraqueratosi. Així, TREX2 té un paper actiu i rellevant en el desenvolupament de la patogènesi associada a la psoriasi., [eng] TREX2 is a 3 '-DNA exonuclease specifically expressed in keratinocytes that acts as tumor suppressor in skin carcinogenesis, but the importance in human pathologies like carcinogenesis and psoriasis and the underlying mechanisms remained unknown. Here, we investigated the relevance and molecular events of TREX2 in the DNA damage skin response. TREX2 expression was up-regulated by chronic exposure to ultraviolet (UV) radiation, whereas was de-regulated or lost in human squamous cell carcinomas (SCCs). TREX2 deficiency in mice enhanced the susceptibility to UVB-induced skin carcinogenesis, which was associated with alterations in DNA damage removal and degradation, cell death and inflammation, indicating multifaceted functions of TREX2. Notably, TREX2 deficiency diminished the up-regulation of key cytokines related to DNA repair and antitumor immunity. Interestingly, TREX2 was recruited to low-density chromatin regions in nuclei that were beginning to condensate chromatin and to micronuclei, interacting with phosphorylated H2AX histone (yH2AX). Altogether, our data establish cell and non-cell autonomous functions of TREX2 in the defense against UV-induced skin carcinogenesis. Moreover TREX2 is overexpressed in psoriasic lesions. To elucidate the importance of this exonuclease in the development of the disease, we induced a skin inflammation in mice by topical application of Imiquimod. The Trex24- mice were more resistant to the Imiquimod-induced skin inflammation than wt. Thus, clinical parameters like skin thickness, erythema and scaling were lower in the Trex24- mice compared to the wt, whereas parakeratosis was more abundant in the Trex24- skins. Altogether, our results show thatTREX2 contribute to the pathologic features of psoriasis by enhancing the keratinocyte apoptosis and the inflammation in response to Imiquimod application.
- Published
- 2015
10. Systematic review and meta-analysis of 50 years of coral disease research visualized through the scope of network theory.
- Author
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Montilla, Luis M., Ascanio, Alfredo, Verde, Alejandra, and Croquer, Aldo
- Subjects
CORAL diseases ,CONFERENCE papers ,COMMUNITY organization ,META-analysis ,SOCIAL network theory ,TRENDS ,ECOLOGICAL regions ,IMMUNE response - Abstract
Coral disease research encompasses five decades of undeniable progress. Since the first descriptions of anomalous signs, we have come to understand multiple processes and environmental drivers that interact with coral pathologies. In order to gain a better insight into the knowledge we already have, we explored how key topics in coral disease research have been related to each other using network analysis. We reviewed 719 papers and conference proceedings published from 1965 to 2017. From each study, four elements determined our network nodes: (1) studied disease(s); (2) host genus; (3) marine ecoregion(s) associated with the study site; and (4) research objectives. Basic properties of this network confirmed that there is a set of specific topics comprising the majority of research. The top five diseases, genera, and ecoregions studied accounted for over 48% of the research effort in all cases. The community structure analysis identified 15 clusters of topics with different degrees of overlap among them. These clusters represent the typical sets of elements that appear together for a given study. Our results show that while some coral diseases have been studied considering multiple aspects, the overall trend is for most diseases to be understood under a limited range of approaches, e.g., bacterial assemblages have been considerably studied in Yellow and Black band diseases while immune response has been better examined for the aspergillosis-Gorgonia system. Thus, our challenge in the near future is to identify and resolve potential gaps in order to achieve a more comprehensive progress on coral disease research. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
11. Sometimes you’re the scooper, and sometimes you get scooped: How to turn both into something good.
- Author
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Kim, Jin-Soo and Corn, Jacob E.
- Subjects
EXPERIMENTAL design ,BIOTECHNOLOGY ,GENETICS ,GENOMICS ,GRASSES - Abstract
Fast-moving, competitive fields often inadvertently duplicate research. In a research environment that values being first over being robust, this results in one manuscript “scooping” ongoing research from other groups. Opportunities to demonstrate the solidity of a result through coincidental reproduction are thus lost. Here, two group leaders, one the scooper and one the scoopee, discuss their experiences under PLOS Biology’s new “complementary research” policy. In this case, submission of the second article followed publication of the first by mere days. Scooper and scoopee discuss how complementary research is good for everyone by expanding the scientific reach of studies that are overlapping but not identical, demonstrating the robustness of related results, increasing readership for both authors, and making “replication” studies cost effective by creatively using resources that have already been spent. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
12. Oral administration of Clostridium butyricum rescues streptomycin-exacerbated respiratory syncytial virus-induced lung inflammation in mice
- Author
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Na Zhao, Weiwei Liu, Jia Wang, Wenwen Zhu, Beixing Liu, Rui Zheng, and Dalu Wang
- Subjects
Microbiology (medical) ,Immunology ,Pneumonia, Viral ,Macrophage polarization ,Administration, Oral ,Inflammation ,rsv ,Respiratory Syncytial Virus Infections ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,immune response ,Interferon-gamma ,Mice ,Immune system ,Lactobacillus ,medicine ,Animals ,Clostridium butyricum ,Mice, Inbred BALB C ,Lung ,gastrointestinal microbiota ,biology ,Interleukin-17 ,biology.organism_classification ,medicine.disease ,butyrate ,Gastrointestinal Microbiome ,macrophages ,Infectious Diseases ,medicine.anatomical_structure ,Respiratory Syncytial Virus, Human ,clostridium butyricum ,Streptomycin ,Dysbiosis ,Parasitology ,medicine.symptom ,Interleukin-5 ,Respiratory tract ,Research Article ,Research Paper - Abstract
Changes in the intestinal microbiota indirectly impact the health of mucosa distal to the intestine, particularly the respiratory tract. However, the effects of intestinal microbiota dysbiosis on the regulation of respiratory syncytial virus (RSV) infection are not clear. In this study, we examined the effects of altering the intestinal microbiota on the pulmonary immune response against RSV infection. BALB/c mice were treated with streptomycin before infection with RSV to study the altered immune response. The ingestion of streptomycin led to a marked alteration in the intestinal microbiota with a reduced abundance of Lactobacillus and Clostridium genera, followed by greatly aggravated pulmonary inflammation in response to RSV infection. This aggravated inflammation was associated with a dysregulated immune response against RSV infection, characterized by the increased expression of IFN-γ and IL-17 and increased pulmonary M1-like macrophage polarization, and decreased expression of IL-5. Supplementation of Clostridium butyricum (CB) prevented aggravated inflammation and the dysregulated immune response characterized by greater M2 polarization of pulmonary macrophages and decreased release of IFN-γ and IL-17 as well as increased IL-5 levels. Furthermore, in vitro and in vivo experiments identified that butyrate, the main metabolite produced by CB, promoted M2 polarization of macrophages in RSV-infected mice exposed to streptomycin. Together, these results demonstrate the mechanism by which intestinal microbiota modulate the pulmonary immune response to RSV infection.
- Published
- 2021
13. Profiling the immune response to Mycobacterium tuberculosis Beijing family infection: a perspective from the transcriptome
- Author
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Rodríguez-Castillo Juan Germán, Murcia Martha Isabel, Barrios Payan Jorge, Mata-Espinosa Dulce Adriana, Bobadilla del Valle Myriam, López-Leal Gamaliel, Ochoa-Leyva Adrian, Zatarain-Barrón Zyanya Lucía, Cerezo-Cortés María Irene, Bini Estela Isabel, Cornejo-Granados Fernanda, Marquina–Casitllo Brenda Nohemí, and Hernandez-Pando Rogelio
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Tuberculosis ,m. tuberculosis ,Immunology ,Virulence ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,immune response ,Transcriptome ,Mycobacterium tuberculosis ,Mice ,Necrosis ,transcriptomics ,Immune system ,beijing ,Beijing ,colombia ,medicine ,Profiling (information science) ,Animals ,Genetics ,Mice, Inbred BALB C ,biology ,Public health ,Immunity ,medicine.disease ,biology.organism_classification ,virulence ,Infectious Diseases ,beijing-like ,Parasitology ,Research Article ,Research Paper - Abstract
Tuberculosis continues to be an important public health problem. Particularly considering Beijing-family strains of Mycobacterium tuberculosis, which have been associated with drug-resistance and hypervirulence. The Beijing-like SIT190 (BL) is the most prevalent Beijing strain in Colombia. The pathogenic mechanism and immune response against this pathogen is unknown. Thus, we compared the course of pulmonary TB in BALB/c mice infected with Classical-Beijing strain 391 and BL strain 323. The disease course was different among infected animals with Classical-Beijing and BL strain. Mice infected with BL had a 100% mortality at 45 days post-infection (dpi), with high bacillary loads and massive pneumonia, whereas infected animals with Classical-Beijing survived until 60 dpi and showed extensive pneumonia and necrosis. Lung RNA extraction was carried out at early (day 3 dpi), intermediate (day 14 dpi), and late (days 28 and 60 dpi) time points of infection. Transcriptional analysis of infected mice with Classical-Beijing showed several over-expressed genes, associated with a pro-inflammatory profile, including those for coding for CCL3 and CCL4 chemokines, both biomarkers of disease severity. Conversely, mice infected with BL displayed a profile which included the over-expression of several genes associated with immune-suppression, including Nkiras, Dleu2, and Sphk2, highlighting an anti-inflammatory milieu which would allow high bacterial replication followed by an intense inflammatory response. In summary, both Beijing strains induced a non-protective immune response which induced extensive tissue damage, BL strain induced rapidly extensive pneumonia and death, whereas Classical-Beijing strain produced slower extensive pneumonia later associated with extensive necrosis. Abbreviations Mtb: Mycobacterium tuberculosis; SIT: Spoligotype International Type; TB: Tuberculosis; CTB: Classical-typical Beijing; BL: Beijing-Like; CCL3: Chemokine (C-C motif) ligand 3 (CCL3); CCL4: Chemokine (C-C motif) ligand four (CCL4); WHO: World health Organization; DR: Direct Repeats; IFN-γ: Interferon Gamma; IL: Interleukin; TGF-β: Transforming Growth Factor Beta; XDR: Extremely Drug Resistant; MDR: Multi Drug Resistant; MIRU-VNTR: Mycobacterial Interspersed Repetitive Units–Variable Number Tandem repeats; OADC: Oleic Albumin Dextrose Catalase; ATCC: American Type Culture Collection; MOI: Multiplicity of Infection; CFUs: Colony Forming Units; ELISA: enzyme-linked immunosorbent assay; qRT-PCR: Real-Time Quantitative Reverse Transcription PCR; RNA-seq: Ribonucleic Acid sequencing; RIN: RNA Integrity Number; RNA: Ribonucleic Acid; DNA: Deoxyribonucleic Acid; dsDNA HS: Double stranded Deoxyribonucleic Acid High Sensitivity; RAI: Red de Apoyo à la Investigacion, Mexico City, Mexico; DEG: Differential Expressed Genes; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; ORA: Over-Representation Analysis; SNPs: Single Nucleotide Polymorphisms; TNFα: Tumoral necrosis factor alpha; DE: Differential Expression; EPA: Enrichment Pathways Analysis; TLR: Toll-Like receptor; NLRP: NOD-like receptor with Pyrin domain; tRNA: Transfer RNA; MAPK: Mitogen-Activated Protein Kinase; NK: Natural killer; ATP: Adenosine Triphosphate; DGC: dystrophin-glycoprotein complex; PDIM: Ptiocerol Dimicocerosate; NCBI: National Center for Bioinformatics Information
- Published
- 2021
14. Genomic mutation features identify distinct BRCA-associated mutation characteristics in endometrioid carcinoma and endometrioid ovarian carcinoma
- Author
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Xiaoxue Zhang, Yu Xia, Canhui Cao, Wenjian Gong, Qinglei Gao, Ruidi Yu, Wei Zhang, Dan Liu, and Yong Fang
- Subjects
Aging ,Veliparib ,endocrine system diseases ,endometrioid ovarian carcinoma ,genome mutation ,BRCA ,Biology ,immune response ,Olaparib ,chemistry.chemical_compound ,Germline mutation ,Ovarian carcinoma ,Carcinoma ,medicine ,Humans ,Rucaparib ,BRCA2 Protein ,Ovarian Neoplasms ,BRCA1 Protein ,BRCA mutation ,Cell Biology ,medicine.disease ,Endometrial Neoplasms ,chemistry ,Mutation (genetic algorithm) ,Mutation ,Cancer research ,Female ,Transcriptome ,Carcinoma, Endometrioid ,Research Paper ,endometrioid carcinoma - Abstract
Although endometrioid carcinoma (EC) and endometrioid ovarian carcinoma (EnOC) display similar pathological features, their molecular characteristics remain to be determined. Somatic mutation data from 2777 EC, 423 EnOC, and 57 endometriosis patients from the Catalogue of Somatic Mutations in Cancer (COSMIC) dataset were analyzed and showed similar profiles with different mutation frequencies among them. By using 275 overlapping mutated genes, EC was clustered into two groups with different disease outcomes and different clinical characteristics. Although BRCA-associated mutation characteristics were identified in both EC and EnOC, the mutation frequencies of BRCA1 (P=0.0146), BRCA2 (P=0.0321), ATR (P=3.25E-11), RAD51 (P=3.95E-08), RAD1 (P=0.0003), TP53 (P=6.11E-33), and BRIP1 (P=2.90E-09) were higher in EnOC. Further analysis showed that EnOC cell lines with BRCA-associated mutation characteristics were more sensitive to poly ADP-ribose polymerase (PARP) inhibitors than EC cell lines, including olaparib, talazoparib, rucaparib, and veliparib. Moreover, based on BRCA-associated mutational and transcriptomic profiles, EC with BRCA-associated mutational burdens shows lower levels of immune cell infiltration, higher expression of immunosuppressive checkpoint molecules and worse prognosis than EC without BRCA mutation. Our study comprehensively analyzed the genome mutation features of EC and EnOC and provide insights into the molecular characteristics of EC and EnOC.
- Published
- 2021
15. TBK1 is paradoxical in tumor development: a focus on the pathway mediating IFN-I expression.
- Author
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Banglu Wang, Fan Zhang, Xiaoyu Wu, and Mei Ji
- Subjects
TYPE I interferons ,CANCER invasiveness ,NATURAL immunity ,IMMUNE response ,CELLULAR signal transduction - Abstract
TANK-binding kinase 1 (TBK1) is a member of the IKK family and plays a crucial role in the activation of non-canonical NF-kB signaling and type I interferon responses. The aberrant activation of TBK1 contributes to the proliferation and survival of various types of tumor cells, particularly in specific mutational or tumorous contexts. Inhibitors targeting TBK1 are under development and application in both in vivo and in vitro settings, yet their clinical efficacy remains limited. Numerous literatures have shown that TBK1 can exhibit both tumor promoting and tumor inhibiting effects. TBK1 acts as a pivotal node within the innate immune pathway, mediating anti-tumor immunity through the activation of innate immune responses. Facilitating interferon-I (IFN-I) production represents a critical mechanism through which TBK1 bridges these processes. IFN has been shown to exert both beneficial and detrimental effects on tumor progression. Hence, the paradoxical role of TBK1 in tumor development may necessitate acknowledgment in light of its downstream IFNI signaling cascade. In this paper, we review the signaling pathways mediated by TBK1 in various tumor contexts and summarize the dual roles of TBK1 and the TBK1-IFN pathways in both promoting and inhibiting tumor progression. Additionally, we highlight the significance of the TBK1-IFN pathway in clinical therapy, particularly in the context of immune response. We anticipate further advancements in the development of TBK1 inhibitors as part of novel cancer treatment strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
16. Determination of Deamidation in Adjuvanted Vaccine Antigens through Isoaspartic Acid Quantification.
- Author
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Hasija, Manvi, Ma, Jian, Li, Bing, Rahman, Nausheen, Strahlendorf, Kirsten A., and Ausar, Salvador Fernando
- Subjects
DEAMINATION ,POST-translational modification ,VACCINE development ,IMMUNE response ,VACCINES - Abstract
Deamidation is a post-translational chemical modification that occurs within proteins and can be influenced by many factors, including temperature and pH. In vaccines, deamidation is considered undesirable as it may lead to changes in structure, function, stability, and immunogenicity. Detecting deamidation in vaccines, especially adjuvanted vaccines, can be challenging due to the lack of simple quantitative techniques. In this study, the quantification of isoaspartic acid (isoAsp) was used to assess deamidation in model antigens in the presence and absence of common vaccine adjuvants. This study shows that the detection of isoAsp was possible in the presence of various types of adjuvants with little to no interference. High levels of isoAsp were detected in thermally and pH-stressed adjuvanted vaccines, suggesting significant deamidation and highlighting the stability-indicating capabilities of the assay. The quantification of isoAsp in stability programs of a vaccine drug product could possibly find applications in product shelf-life determination, using thermal kinetic modeling to predict deamidation over time. The ability to detect deamidation early in vaccine development enhances process improvements and ultimately improves the vaccine's stability. To summarize, this paper describes a rapid and simple method to determine deamidation in adjuvanted vaccines. This method could be applicable to formulation development, stability assessment, or shelf-life determination. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
17. Multiple Functions of Hepatitis E Virus ORF3.
- Author
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Jiao, Fengyuan, Zhao, Yu, Zhou, Gengxu, Meng, Chi, Wang, Lingjie, Wu, Shengping, Li, Jixiang, Cao, Liting, Zhou, Bo, Luo, Yichen, and Jiao, Hanwei
- Subjects
CHRONIC active hepatitis ,HEPATITIS E ,HEPATITIS A ,GROWTH factors ,IMMUNE response - Abstract
Hepatitis E (Hepatitis E, HE) is an acute and chronic infectious hepatitis caused by hepatitis E virus (Hepatitis E Virus, HEV) infection, which is responsible for most acute hepatitis in the world and is a significant public health problem. The pathogen, HEV, has three Open Reading Frames (ORFs) ORF1, ORF2, and ORF3, each of which has a different function. Most of the current research is focused on ORF1 and ORF2, while the research on ORF3 is still relatively small. To provide more ideas for the study of HEV pathogenesis and the prevention and treatment of HE, this paper reviews the effects of ORF3 on the ERK pathway, growth factors, immune response, and virus release. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
18. Immunotherapy in the context of sepsis-induced immunological dysregulation.
- Author
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Yiqi Wu, Lu Wang, Yun Li, Yuan Cao, Min Wang, Zihui Deng, and Hongjun Kang
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IMMUNOTHERAPY ,IMMUNOSUPPRESSION ,NEONATAL sepsis ,SEPSIS ,IMMUNE response ,IMMUNE system ,IMMUNE reconstitution inflammatory syndrome - Abstract
Sepsis is a clinical syndrome caused by uncontrollable immune dysregulation triggered by pathogen infection, characterized by high incidence, mortality rates, and disease burden. Current treatments primarily focus on symptomatic relief, lacking specific therapeutic interventions. The core mechanism of sepsis is believed to be an imbalance in the host's immune response, characterized by early excessive inflammation followed by late immune suppression, triggered by pathogen invasion. This suggests that we can develop immunotherapeutic treatment strategies by targeting and modulating the components and immunological functions of the host's innate and adaptive immune systems. Therefore, this paper reviews the mechanisms of immune dysregulation in sepsis and, based on this foundation, discusses the current state of immunotherapy applications in sepsis animal models and clinical trials. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Global Stability Analysis of CHIKV Dynamics Model with Adaptive Immunity and Distributed Time Delays.
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Alade, Taofeek O., Olaniyi, Samson, Idris, Hassan A., Al Rahbi, Yaqoob, and Alnegga, Mohammad
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CHIKUNGUNYA virus ,LYAPUNOV stability ,DYNAMICAL systems ,VIRUS diseases ,IMMUNE response - Abstract
The application of mathematical biology and dynamical systems has proven to be an effective approach for studying viral infection models. To contribute to this research, our paper proposes a new CHIKV model that takes into account an adaptive immune response and distributed time delays, which accurately reflects the time lag between initial viral contacts and the production of new active CHIKV particles. By analyzing the model’s qualitative behavior, we establish a biological threshold number that can predict whether CHIKV will be cleared from or persist in the body. We demonstrate the global stability of both CHIKV-present and CHIKV-free steady states using the Lyapunov functional method and LaSalle’s invariance principle. In addition, we conduct numerical simulations to examine how time delays can affect the stability of the steady states. Through these simulations, we gain insights into how varying time delays can influence the persistence or clearance of CHIKV within the host. [ABSTRACT FROM AUTHOR]
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- 2024
20. Research status of receptor-interacting protein kinase 1 in regulating cancer progression and immune response.
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ZHANG Yong, LI Weihong, CHENG Zhipeng, WANG bin, WANG Siheng, and WANG Yubin
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Receptor-interacting protein kinase 1 (RIPK1) is a multi-domain serine/threonine protein kinase that causes downstream signal transduction and biological effects by phosphorylating specific proteins. In recent years, with the in-depth study of RIPK1, scholars have found that it is of great significance in autoimmune diseases, neurodegenerative diseases, and a variety of solid tumors and hematological tumors. On the one hand, RIPK1 promotes cell survival and inflammatory responses by activating specific pathways such as nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). On the other hand, RIPK1 promotes apoptosis by interacting with cysteinyl aspartate specific proteinase-8 (caspase-8), or promotes necroptosis by interacting with RIPK3 and mixed lineage kinase domain-like protein (MLKL). As an upstream signal, RIPK1 has different expression levels in patients with different tumors. Its scaffold function and kinase activity can regulate cancer progression, initiate adaptive immunity, inhibit tumor progression, and generate an immunosuppressive tumor microenvironment to promote tumor development. Its dual role has been demonstrated in regulating the occurrence and development of tumors and the body's immune response, and can be used as a new therapeutic target to control cancer progression. This paper starts with the structure of RIPK1 to further explore its function in regulating cancer progression and immune response, and to provide new ideas for the development of cancer-targeted drugs. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Stability analysis for a HIV model with cell-to-cell transmission, two immune responses and induced apoptosis.
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Ru Meng, Yantao Luo, and Tingting Zheng
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GLOBAL asymptotic stability ,BASIC reproduction number ,HOPFIELD networks ,IMMUNE response ,APOPTOSIS ,HIV - Abstract
In this paper, a dynamic HIV model with cell-to-cell transmission, two immune responses, and induced apoptosis is proposed and studied. First, the non-negativity and boundedness of the solutions of the model are given, and then the exact expression of the basic reproduction number R0 is obtained by using the next generation matrix method. Second, criteria are obtained for the local stability of the disease-free equilibrium, immune response-free equilibrium, and the infected equilibrium with both humoral and cellular immune responses. Furthermore, the threshold conditions are also derived for the global asymptotic stability of the disease-free equilibrium, immune responsefree equilibrium, and the infected equilibrium with both humoral and cellular immune responses by constructing the suitable Lyapunov function. Finally, some numerical simulations are conducted to verify the theoretical results; the numerical simulation results show that the increase of apoptosis rate had a positive role in the control of viral infection. [ABSTRACT FROM AUTHOR]
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- 2024
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22. The Immune Response of Cancer Cells in Breast and Gynecologic Neoplasms.
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Rakoczy, Katarzyna, Kaczor, Justyna, Sołtyk, Adam, Szymańska, Natalia, Stecko, Jakub, Drąg-Zalesińska, Małgorzata, and Kulbacka, Julita
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BREAST tumors ,CANCER cells ,IMMUNE response ,BREAST cancer ,BREAST ,PHENOTYPIC plasticity - Abstract
Cancer diseases constitute a major health problem which leads to the death of millions of people annually. They are unique among other diseases because cancer cells can perfectly adapt to the environment that they create themselves. This environment is usually highly hostile and for normal cells it would be hugely difficult to survive, however neoplastic cells not only can survive but also manage to proliferate. One of the reasons is that they can alter immunological pathways which allow them to be flexible and change their phenotype to the one needed in specific conditions. The aim of this paper is to describe some of these immunological pathways that play significant roles in gynecologic neoplasms as well as review recent research in this field. It is of high importance to possess extensive knowledge about these processes, as greater understanding leads to creating more specialized therapies which may prove highly effective in the future. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Modeling the Nonmonotonic Immune Response in a Tumor–Immune System Interaction.
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Liu, Yu, Ma, Yuhang, Yang, Cuihong, Peng, Zhihang, Takeuchi, Yasuhiro, Banerjee, Malay, and Dong, Yueping
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IMMUNE response ,HOPF bifurcations ,ORBITS (Astronomy) ,IMMUNE system ,CELL physiology - Abstract
Tumor–immune system interactions are very complicated, being highly nonlinear and not well understood. A large number of tumors can potentially weaken the immune system through various mechanisms such as secreting cytokines that suppress the immune response. In this paper, we propose a tumor–immune system interaction model with a nonmonotonic immune response function and adoptive cellular immunotherapy (ACI). The model has a tumor-free equilibrium and at most three tumor-presence equilibria (low, moderate and high ones). The stability of all equilibria is studied by analyzing their characteristic equations. The consideration of nonmonotonic immune response results in a series of bifurcations such as the saddle-node bifurcation, transcritical bifurcation, Hopf bifurcation and Bogdanov–Takens bifurcation. In addition, numerical simulation results show the coexistence of periodic orbits and homoclinic orbits. Interestingly, along with various bifurcations, we also found two bistable scenarios: the coexistence of a stable tumor-free as well as a high-tumor-presence equilibrium and the coexistence of a stable-low as well as a high-tumor-presence equilibrium, which can show symmetric and antisymmetric properties in a range of model parameters and initial cell concentrations. The new findings indicate that under ACI, patients can possibly reach either a stable tumor-free state or a low-tumor-presence state in the presence of nonmonotonic immune response once the immune system is activated. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Development of a BoHV-4 viral vector expressing tgD of BoHV-1 and evaluation of its immunogenicity in mouse model
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Zeynep Akkutay Yoldar, S. Bilge-Dagalp, Feray Alkan, Aykut Ozkul, Gaetano Donofrio, Fırat Doğan, and Touraj Aligholipour Farzani
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Booster dose ,Bacterial, Fungal and Virus Molecular Biology - Research Paper ,TgD ,Antibodies, Viral ,Microbiology ,Viral vector ,Mice ,Viral Proteins ,Immune system ,Antigen ,Bovine herpesvirus 1 ,Media Technology ,Animals ,Bovine herpesvirus 4 ,Immune response ,Herpesvirus 1, Bovine ,Mice, Inbred BALB C ,Bacterial artificial chromosome ,biology ,Immunogenicity ,biology.organism_classification ,Antibodies, Neutralizing ,Virology ,Herpesvirus 4, Bovine ,biology.protein ,Antibody - Abstract
In recent years, Bovine herpesvirus 4 (BoHV-4) has emerged as an attractive gene delivery viral vector, mainly for vaccination purposes in the veterinary field. In the present study, a new infectious clone of the BoHV-4 genome carrying a bacterial artificial chromosome vector (BoHV-4-BAC) was developed by homologous recombination in mammalian cell culture and bacterial systems, and exploited to express a truncated form of glycoprotein D (tgD) of Bovine herpesvirus 1 (BoHV-1) (BoHV-4-tgD∆TK) as a vaccine candidate. This construct's immunogenicity was compared to a DNA vector expressing the same antigen (pC-tgD) in a BALB/c mouse model. After the mice were immunized, total and specific antibody responses, cytokine responses, total splenocyte cells proliferation/cytotoxicity, and virus neutralization assays were conducted to analyze the immune response elicited by both constructs. Mice from both vaccine groups developed significant humoral and cellular immune responses after a booster dose regime was conducted on day 28 post-injection. In almost all immunological assays, BoHV-4-tgDΔTK induced as high an immune response as pC-tgD. In both vaccine constructs, neutralizing antibodies were a significant determining factor in protection against BoHV-1, even after the first injection. We conclude that a BoHV-4-based viral vector offers an effective immunization strategy as an alternative to DNA-based immunization platforms, at least to combat BoHV-1.
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- 2021
25. Mitochondrial DNA Heteroplasmy as an Informational Reservoir Dynamically Linked to Metabolic and Immunological Processes Associated with COVID-19 Neurological Disorders
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George B. Stefano and Richard M. Kream
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Mitochondrial DNA ,Cell type ,Somatic cell ,Mitochondrion ,Biology ,Heteroplasmy ,DNA, Mitochondrial ,Genome ,Cellular and Molecular Neuroscience ,Immune system ,Animals ,Humans ,Immune response ,Genetics ,Review Paper ,Gut microbiome ,SARS-CoV-2 ,Immunity ,COVID-19 ,Cell Biology ,General Medicine ,Mitochondria ,Nuclear DNA ,Central nervous system ,Nervous System Diseases - Abstract
Mitochondrial DNA (mtDNA) heteroplasmy is the dynamically determined co-expression of wild type (WT) inherited polymorphisms and collective time-dependent somatic mutations within individual mtDNA genomes. The temporal expression and distribution of cell-specific and tissue-specific mtDNA heteroplasmy in healthy individuals may be functionally associated with intracellular mitochondrial signaling pathways and nuclear DNA gene expression. The maintenance of endogenously regulated tissue-specific copy numbers of heteroplasmic mtDNA may represent a sensitive biomarker of homeostasis of mitochondrial dynamics, metabolic integrity, and immune competence. Myeloid cells, monocytes, macrophages, and antigen-presenting dendritic cells undergo programmed changes in mitochondrial metabolism according to innate and adaptive immunological processes. In the central nervous system (CNS), the polarization of activated microglial cells is dependent on strategically programmed changes in mitochondrial function. Therefore, variations in heteroplasmic mtDNA copy numbers may have functional consequences in metabolically competent mitochondria in innate and adaptive immune processes involving the CNS. Recently, altered mitochondrial function has been demonstrated in the progression of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Accordingly, our review is organized to present convergent lines of empirical evidence that potentially link expression of mtDNA heteroplasmy by functionally interactive CNS cell types to the extent and severity of acute and chronic post-COVID-19 neurological disorders.
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- 2021
26. Correction: Wang et al. A VLP-Based Vaccine Displaying HBHA and MTP Antigens of Mycobacterium tuberculosis Induces Potentially Protective Immune Responses in M. tuberculosis H37Ra Infected Mice. Vaccines 2023, 11 , 941.
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Wang, Juan, Xie, Tao, Ullah, Inayat, Mi, Youjun, Li, Xiaoping, Gong, Yang, He, Pu, Liu, Yuqi, Li, Fei, Li, Jixi, Lu, Zengjun, and Zhu, Bingdong
- Subjects
MYCOBACTERIUM tuberculosis ,IMMUNE response ,TUBERCULOSIS ,MICE ,ANTIGENS - Abstract
Graph: Figure 7 Immunization schedule and protective efficacy of immunization with LV20 in adjuvant DP against M. tuberculosis H37Ra infection. A VLP-Based Vaccine Displaying HBHA and MTP Antigens of Mycobacterium tuberculosis Induces Potentially Protective Immune Responses in M. tuberculosis H37Ra Infected Mice. After conducting an investigation in collaboration with the academic editors, the authors wish to make the following corrections to this paper: We changed the title of the paper from "A VLP-Based Vaccine Displaying HBHA and MTP Antigens of I Mycobacterium tuberculosis i Induces Protective Immune Responses in I M. tuberculosis i H37Ra Infected Mice" to "A VLP-Based Vaccine Displaying HBHA and MTP Antigens of I Mycobacterium tuberculosis i Induces Potentially Protective Immune Responses in I M. tuberculosis i H37Ra Infected Mice". [Extracted from the article]
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- 2023
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27. COVID-19 vaccination in patients with multiple sclerosis: What we have learnt by February 2021
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Shay Menascu, Diana Guber, Anat Achiron, Uri Givon, Michael Gurevich, Shlomo Flechter, Daniela Noa Zohar, Yael Stern, David Magalashvili, Mark Dolev, Shmuel Miron, Rina Falb, Michael Polliack, Emanuel Shirbint, and Sapir Dreyer-Alster
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,COVID-19 Vaccines ,Multiple Sclerosis ,Adolescent ,immune response ,Cohort Studies ,03 medical and health sciences ,Patient safety ,Disability Evaluation ,Young Adult ,0302 clinical medicine ,Immune system ,Recurrence ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,Young adult ,Adverse effect ,acute relapse ,BNT162 Vaccine ,Aged ,business.industry ,Multiple sclerosis ,Vaccination ,Age Factors ,COVID-19 ,Middle Aged ,medicine.disease ,adverse events ,Neurology ,Female ,Neurology (clinical) ,Patient Safety ,business ,Original Research Papers ,030217 neurology & neurosurgery ,Cohort study - Abstract
Background: Since vaccination against coronavirus disease 2019 (COVID-19) became available, risks related to vaccinating patients with multiple sclerosis (MS) need to be carefully assessed. Objective: Characterize safety and occurrence of immediate relapses following COVID-19 vaccination in a large cohort of MS patients. Methods: We assessed the safety of BNT162b2 COVID-19 vaccination in adult MS patients. Results: Between 20 December 2020 and 25 January 2021, 555 MS patients received the first dose of BNT162b2 vaccine and 435 received the second dose. There were three cases of COVID-19 infection encountered after the first dose. Safety profile of COVID-19 vaccine was characterized by pain at the injection site, fatigue, and headache. No increased risk of relapse activity was noted over a median follow-up of 20 and 38 days after first and second vaccine doses, respectively. The rate of patients with acute relapse was 2.1% and 1.6% following the first and second doses, respectively, similar to the rate in non-vaccinating patients during the corresponding period. Mild increase in the rate of adverse events was noted in younger patients (18–55 years), among patients with lower disability (Expanded Disability Status Scale (EDSS) ⩽3.0), and in patients treated with immunomodulatory drugs. Conclusion: COVID-19 BNT162b2 vaccine proved safe for MS patients. No increased risk of relapse activity was noted.
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- 2021
28. Single-cell transcriptomes of peripheral blood cells indicate and elucidate severity of COVID-19
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Mengyao Liu, Ping Zhu, Gaoxiang Wang, Tao Cheng, Hui Cheng, Xiaowei Xie, Biao Zhang, Xuelian Cheng, Liting Chen, Sha Hao, and Jianfeng Zhou
- Subjects
CD4-Positive T-Lymphocytes ,0301 basic medicine ,medicine.medical_treatment ,Cell ,severity ,CD8-Positive T-Lymphocytes ,Biology ,Severity of Illness Index ,Peripheral blood mononuclear cell ,immune response ,General Biochemistry, Genetics and Molecular Biology ,Proinflammatory cytokine ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Humans ,General Environmental Science ,single-cell RNA-seq ,SARS-CoV-2 ,Effector ,COVID-19 ,Killer Cells, Natural ,030104 developmental biology ,medicine.anatomical_structure ,Cytokine ,Case-Control Studies ,030220 oncology & carcinogenesis ,PBMCs ,Immunology ,Leukocytes, Mononuclear ,Single-Cell Analysis ,General Agricultural and Biological Sciences ,CD8 ,Research Paper - Abstract
The blood and immune system of coronavirus disease 2019 (COVID-19) infected patients are dysfunctional, and numerous studies have been conducted to resolve their characteristics and pathogenic mechanisms. Nevertheless, the variations of immune responses along with disease severity have not been comprehensively documented. Here, we profiled the single-cell transcriptomes of 96,313 peripheral blood mononuclear cells (PBMCs) derived from 12 COVID-19 patients (including four moderate, four severe and four critical cases) and three healthy donors. We showed that proliferative CD8 effector T cells with declined immune functions and cytotoxicity accumulated in the critical stage. By contrast, the quantity of natural killer (NK) cells was significantly reduced, while they exhibited enhanced immune activities. Notably, a gradually attenuated responseto COVID-19 along with disease severity was observed in monocytes, in terms of cellular composition, transcriptional discrepancy and transcription factor regulatory network. Furthermore, we identified immune cell-type dependent cytokine signatures distinguishing the severity of COVID-19 patients. In addition, cell interactions between CD8 effector T/NK cells and monocytes mediated by inflammatory cytokines were enhanced in moderate and severe stages, but weakened in critical cases. Collectively, our work uncovers the cellular and molecular players underlying the disordered and heterogeneous immune responses associated with COVID-19 severity, which could provide valuable insights for the treatment of critical COVID-19 patients. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s11427-020-1880-y and is accessible for authorized users.
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- 2021
29. NLRC4 gene silencing-dependent blockade of NOD-like receptor pathway inhibits inflammation, reduces proliferation and increases apoptosis of dendritic cells in mice with septic shock
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Jun-Ming Luo, Chun-Song Yan, and Shi-Sheng Wang
- Subjects
CD86 ,NLRC4 ,Aging ,Chemistry ,Septic shock ,inflammatory reaction ,Inflammation ,Cell Biology ,Cell cycle ,Lung injury ,medicine.disease ,immune response ,NOD-like receptor pathway ,Apoptosis ,Cancer research ,medicine ,septic shock ,Viability assay ,medicine.symptom ,Research Paper - Abstract
Septic shock is one of the most significant health concerns across the world, involving hypo-perfusion and defects in tissue energy. The current study investigates the role of NLR family CARD domain containing protein 4 (NLRC4) in septic shock-induced inflammatory reactions, lung tissue injuries, and dendritic cell (DC) apoptosis. Septic shock mice models were established by modified cecal ligation and puncture and injected with retroviral vector expressing siRNA-NLRC4. DCs were then isolated and transfected with siRNA-NLRC4. The degree of lung tissue injury, cell cycle distribution, cell apoptosis and cell viability of DCs were assessed. NLRC4 was found to be expressed at high levels in mice with septic shock. NLRC4 silencing inhibited the activation of the NOD-like receptor (NLR) pathway as evidenced by the decreased levels of NOD1, NOD2, RIP2, and NF-κB. In addition, NLRC4 silencing reduced the inflammatory reaction as attributed by reduced levels of IL-1β, TNF-α and IL-6. Suppressed NLRC4 levels inhibited cell viability and promoted cell apoptosis evidenced by inhibited induction of DC surface markers (CD80, CD86, and MHC II), along with alleviated lung tissue injury. In conclusion, NLRC4 silencing ameliorates lung injury and inflammation induced by septic shock by negatively regulating the NLR pathway.
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- 2021
30. Mitochondria-targeted and ultrasound-responsive nanoparticles for oxygen and nitric oxide codelivery to reverse immunosuppression and enhance sonodynamic therapy for immune activation
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Hao Xu, Yan Xu, Jingxing Si, Hao Ren, Changwei Ji, Yaqian Yang, Xiaozhou Mou, Wenjing Zhang, Hongqian Guo, and Xin He
- Subjects
China ,Ultrasonic Therapy ,medicine.medical_treatment ,Mitochondria-targeted ,Medicine (miscellaneous) ,Nitric Oxide ,Theranostic Nanomedicine ,Nitric oxide ,Oxygen and nitric oxide codelivery ,Mice ,chemistry.chemical_compound ,Drug Delivery Systems ,Immune system ,Cancer immunotherapy ,Cell Line, Tumor ,Immune Tolerance ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Immune response ,Hypoxia ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Ultrasonography ,Tumor microenvironment ,Chemistry ,Sonodynamic therapy ,Immunity ,Immunosuppression ,Immunotherapy ,Macrophage Activation ,Mitochondria ,Oxygen ,Reverse immunosuppression ,Cancer research ,Nanoparticles ,Immunogenic cell death ,Reactive Oxygen Species ,Research Paper - Abstract
Background: Sonodynamic therapy (SDT) is a promising strategy to inhibit tumor growth and activate antitumor immune responses for immunotherapy. However, the hypoxic and immunosuppressive tumor microenvironment limits its therapeutic efficacy and suppresses immune response. Methods: In this study, mitochondria-targeted and ultrasound-responsive nanoparticles were developed to co-deliver oxygen (O2) and nitric oxide (NO) to enhance SDT and immune response. This system (PIH-NO) was constructed with a human serum albumin-based NO donor (HSA-NO) to encapsulate perfluorodecalin (FDC) and the sonosensitizer (IR780). In vitro, the burst release of O2 and NO with US treatment to generate reactive oxygen species (ROS), the mitochondria targeting properties and mitochondrial dysfunction were evaluated in tumor cells. Moreover, in vivo, tumor accumulation, therapeutic efficacy, the immunosuppressive tumor microenvironment, immunogenic cell death, and immune activation after PIH-NO treatment were also studied in 4T1 tumor bearing mice. Results: PIH-NO could accumulate in the mitochondria and relive hypoxia. After US irradiation, O2 and NO displayed burst release to enhance SDT, generated strongly oxidizing peroxynitrite anions, and led to mitochondrial dysfunction. The release of NO increased blood perfusion and enhanced the accumulation of the formed nanoparticles. Owing to O2 and NO release with US, PIH-NO enhanced SDT to inhibit tumor growth and amplify immunogenic cell death in vitro and in vivo. Additionally, PIH-NO promoted the maturation of dendritic cells and increased the number of infiltrating immune cells. More importantly, PIH-NO polarized M2 macrophages into M1 phenotype and depleted myeloid-derived suppressor cells to reverse immunosuppression and enhance immune response. Conclusion: Our findings provide a simple strategy to co-deliver O2 and NO to enhance SDT and reverse immunosuppression, leading to an increase in the immune response for cancer immunotherapy.
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- 2021
31. Interleukin IL-5 alleviates sepsis-induced acute lung injury by regulating the immune response in rats
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Wangmei Zhou, Beichun Wei, Xu Li, Lei Shi, Yu Chen, and Shengwu Liao
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0301 basic medicine ,Male ,medicine.medical_specialty ,Bioengineering ,Lung injury ,HMGB1 ,Applied Microbiology and Biotechnology ,immune response ,Sepsis ,Rats, Sprague-Dawley ,sepsis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,il-5 ,Animals ,Interleukin 5 ,Lung ,biology ,business.industry ,Interleukin ,General Medicine ,medicine.disease ,Peripheral blood ,Rats ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,acute lung injury ,030220 oncology & carcinogenesis ,biology.protein ,Cytokines ,Interleukin-5 ,business ,CD8 ,TP248.13-248.65 ,Research Article ,Research Paper ,Biotechnology - Abstract
To study the effect of IL-5 on the immune response and lung injury in rats with sepsis. We constructed a rat model of sepsis by cecal ligation and puncture (CLP). The rats were randomly divided into the control group, the sham group, the CLP group and the IL-5 group, with 6 rats in each group. With the induction of CLP, the lung tissue of rats was severely injured, and the water content of lung tissue was significantly increased. Moreover, the ratio of CD4+/CD8+ was significantly decreased and Th1/Th2 was significantly increased in the peripheral blood. The content of IL-6, TNF-α, and HMGB1 was found to be increased in the CLP group. However, with the injection of IL-5, the degree of lung tissue injury in CLP rats was alleviated and the water content of lung tissue was significantly reduced. The ratio of CD4+/CD8+ was increased and Th1/Th2 was significantly down-regulated in the peripheral blood and the levels of IL-6, TNF-α, and HMGB1 in serum were significantly decreased. In conclusion, IL-5 can alleviate lung injury by regulating the immune response and inhibiting the systemic inflammatory response induced by sepsis., Graphical abstract
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- 2021
32. Brain-derived neurotrophic factor precursor in the immune system is a novel target for treating multiple sclerosis
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Xin-Fu Zhou, Chang-Qi Li, Kang Chen, Cong Luo, Ru-Ping Dai, Junmei Xu, Hui Li, Yang Liu, Plinio R Hurtado, Zhao-Lan Hu, Bo Hu, Shiqing Feng, Shuang Wang, Ernesto Hurtado-Perez, Hu, Zhao Lan, Luo, Cong, Hurtado, Plinio Reinaldo, Li, Hui, Wang, Shuang, Hu, Bo, Xu, Jun Mei, Liu, Yang, Feng, Shi Qing, Hurtado-Perez, Ernesto, Chen, Kang, Zhou, Xin Fu, Li, Chang Qi, and Dai, Ru Ping
- Subjects
Encephalomyelitis, Autoimmune, Experimental ,medicine.medical_treatment ,Medicine (miscellaneous) ,multiple sclerosis ,Peripheral blood mononuclear cell ,immune response ,Multiple sclerosis ,Mice ,Immune system ,Neurotrophic factors ,Leukocytes ,Animals ,Humans ,Medicine ,antibodies ,Protein Precursors ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,B cell ,Brain-derived neurotrophic factor ,business.industry ,Experimental autoimmune encephalomyelitis ,brain-derived neurotrophic factor ,Brain ,Immunotherapy ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,proBDNF ,medicine.anatomical_structure ,Spinal Cord ,Case-Control Studies ,Immunology ,Leukocytes, Mononuclear ,immunotherapy ,business ,Research Paper - Abstract
Rationale: Brain-derived neurotrophic factor precursor (proBDNF) is expressed in the central nervoussystem (CNS) and the immune system. However, the role of proBDNF in the pathogenesis of multiplesclerosis (MS) is unknown. Methods: Peripheral blood and post-mortem brain and spinal cord specimens were obtained from multiple sclerosis patients to analyze proBDNF expression in peripheral lymphocytes and infiltrating immune cells in the lesion site. The proBDNF expression profile was also examined in the experimental autoimmune encephalomyelitis (EAE) mouse model, and polyclonal and monoclonal anti-proBDNF antibodies were used to explore their therapeutic effect in EAE. Finally, the role of proBDNF in the inflammatory immune activity of peripheral blood mononuclear cells (PBMCs) was verified in vitro experiments. Results: High proBDNF expression was detected in the circulating lymphocytes and infiltrated inflammatory cells at the lesion sites of the brain and spinal cord in MS patients. In the EAE mouse model, proBDNF was upregulated in CNS and in circulating and splenic lymphocytes. Systemic but not intracranial administration of anti-proBDNF blocking antibodies attenuated clinical scores, limited demyelination, and inhibited proinflammatory cytokines in EAE mice. Immuno-stimulants treatment increased the proBDNF release and upregulated the expression of p75 neurotrophic receptors (p75NTR) in lymphocytes. The monoclonal antibody against proBDNF inhibited the inflammatory response of PBMCs upon stimulations. Conclusion: The findings suggest that proBDNF from immune cells promotes the immunopathogenesis of MS. Monoclonal Ab-proB may be a promising therapeutic agent for treating MS. Refereed/Peer-reviewed
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- 2021
33. The role of vitamin A and vitamin D in the modulation of the immune response with focus on innate lymphoid cells
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Vladimir Jurisic, Biljana Božić-Nedeljković, and Tanja Džopalić
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Vitamin ,animal diseases ,Immunology ,Population ,Cell ,innate lymphoid cells ,vitamin D ,chemical and pharmacologic phenomena ,Biology ,vitamin A ,immune response ,chemistry.chemical_compound ,Immune system ,Vitamin D and neurology ,medicine ,Immunology and Allergy ,education ,Review Paper ,education.field_of_study ,Innate immune system ,Innate lymphoid cell ,biochemical phenomena, metabolism, and nutrition ,Acquired immune system ,medicine.anatomical_structure ,chemistry ,Medicine ,bacteria - Abstract
The immune system with its numerous and complex interactions helps to protect the host from pathogenic microorganisms, and enables cleaning of damaged tissues. It is also associated with constant “monitoring” of the appearance of malignant cells and their elimination that can occur in the human body. Such a role depends on many factors including adequate intake of nutrients, including vitamins. The effect of vitamin supplementation on the modulation of the immune response has always been the focus of numerous studies. Vitamins A and D have been shown to have the greatest immune-modulatory effect. In this review, we discuss and consider the possible roles of vitamins A and D on the immune response through innate and adaptive immune cells, with special focus on the cell population recently characterized as innate lymphoid cells. Recent literature data indicate that vitamin A and its metabolites modulate the balance between Th1 and Th2 immunity. In addition, vitamin D expresses protective effects on the innate immune system and inhibitory effects on adaptive immunity.
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- 2021
34. Effect of a Large-sized Cage with a Low Metabolizable Energy and Low Crude Protein Diet on Growth Performance, Feed Cost, and Blood Parameters of Growing Layers
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Ma Ruiyu, Li Yan, Zhan Kai, Wei Liu, Wan Yi, and Li Junying
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growth performance ,blood parameter ,Protein diet ,Triglyceride ,040301 veterinary sciences ,Blood biochemistry ,layer ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,Full Papers ,Biology ,Body weight ,040201 dairy & animal science ,immune response ,0403 veterinary science ,chemistry.chemical_compound ,large cage ,Antibody response ,Animal science ,chemistry ,Standard diet ,Animal Science and Zoology ,Cage ,Blood parameters - Abstract
Effects of a large-sized cage with a low metabolizable energy and low crude protein (LME-LCP) diet on growth performance, feed cost, blood biochemistry, and antibody response of growing layers were evaluated. A total of 668 one-day-old female Gushi chicks were randomly allocated into three different cages, namely, large, medium, and small cages, referred to as Group A, Group B, and Group C, respectively, and fed LME-LCP diets. A fourth group of birds raised in small cages and fed a standard diet (STD) was designated Group D i.e. the control. Equal stocking densities were maintained among the four groups throughout the experiment, from 50–20 birds/m2. Large cages with LME-LCP diet (Group A) increased the shank length and girth as chicks grew, improved the activities of serum creatine kinase, and reduced serum triglyceride and cholesterol concentrations. The total feed intake in birds from Group A was higher than those from the other groups at every stage. The total cost (rmb/bird) of feed was 6.70% lower in Group A than that in Group D, which indicated the cost-effectiveness of large cages. In conclusion, large cages with LME-LCP diets have positive effects on body weight, shank growth, and serum biochemical indices of growing Gushi chicks, and can reduce feed costs.
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- 2021
35. A TP53-based immune prognostic model for muscle-invasive bladder cancer
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Huayi Lu, Wanli Cui, Yufan Huang, Xuefei Jin, and Hongyan Li
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Oncology ,Aging ,medicine.medical_specialty ,LAG3 ,Programmed Cell Death 1 Receptor ,Kaplan-Meier Estimate ,T-Lymphocytes, Regulatory ,immune response ,MIBC ,Immune system ,Immunophenotyping ,TIGIT ,Antigens, CD ,Internal medicine ,Databases, Genetic ,medicine ,Humans ,CTLA-4 Antigen ,Neoplasm Invasiveness ,TP53 ,Receptors, Immunologic ,Hepatitis A Virus Cellular Receptor 2 ,Proportional Hazards Models ,Carcinoma, Transitional Cell ,Bladder cancer ,Proportional hazards model ,business.industry ,Macrophages ,Reproducibility of Results ,Muscle, Smooth ,Dendritic Cells ,Cell Biology ,immune checkpoints ,Nomogram ,immune prognostic model ,Prognosis ,medicine.disease ,Lymphocyte Activation Gene 3 Protein ,Survival Rate ,Nomograms ,Urinary Bladder Neoplasms ,Mutation ,Cohort ,Tumor Suppressor Protein p53 ,business ,Research Paper - Abstract
Background Muscle-invasive bladder cancer (MIBC) patients are subject to unfavorable treatment options and a high recurrence rate. The status of TP53 mutations played an essential role in the progression and the prognosis of MIBC. The present study proposed to investigate the association between TP53 mutations and immunophenotype in MIBC. Results We established an immune prognostic model (IPM) ground on the immune-associated genes derived from variation analysis between wild-type TP53 and mutated TP53 TCGA-MIBC patients, and validated in another cohort from GEO database. Based on IPM, we divided MIBC patients into low and high risk subgroups. The high risk MIBC patients had higher proportions of macrophages M1, and lower proportions of T cells regulatory (Tregs) and activated dendritic cells than the low risk MIBC patients. Moreover, the expression of immune checkpoints genes (PD1, CTLA4, LAG3, HAVCR2 and TIGIT) was higher in the high risk patients than the low risk patients. In clinical application, IPM exhibited better survival prediction than conventional clinical characteristics. Conclusions Our investigation presented practical prognostic significance for MIBC patients and displayed the overarching landscape of the immune response in the MIBC microenvironment. Methods Data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) analysis between the TP53 mutated and wild-type MIBC patients was conducted. The CIBERSORT algorithm was performed to evaluate the proportion of immune cell types. Gene expression profiles from the TCGA and GEO were used as training and testing cohorts to build and validate an immune-related prognostic model (IPM). Genes in the IPM model were first screened by univariate Cox analysis, then filtered by the least absolute shrinkage and selection operator (LASSO) Cox regression. A nomogram was finally established and evaluated by combining both the IPM and other clinical factors.
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- 2020
36. The impact of physical frailty on the response to inactivated influenza vaccine in older adults
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Uma R. Chandran, Krissy K. Moehling, Mary Patricia Nowalk, Marianna A. Ortiz, Bo Zhai, John F. Alcorn, Michael Susick, Richard K. Zimmerman, David A. Nace, Min Z. Levine, Chyongchiou J. Lin, and William E. Schwarzmann
- Subjects
Male ,Aging ,Influenza vaccine ,T-Lymphocytes ,frailty ,Peripheral blood mononuclear cell ,immune response ,Immune system ,Assisted Living Facilities ,Influenza, Human ,peripheral cell mediated immunity ,Humans ,Medicine ,Seroconversion ,Aged ,Cell Proliferation ,Aged, 80 and over ,Hemagglutination assay ,business.industry ,Interleukin-8 ,Antibody titer ,virus diseases ,Cell Biology ,Hemagglutination Inhibition Tests ,Middle Aged ,Vaccination ,Oxidative Stress ,Titer ,Vaccines, Inactivated ,Influenza Vaccines ,Case-Control Studies ,Antibody Formation ,Immunology ,Leukocytes, Mononuclear ,Female ,Independent Living ,Interferons ,antibody titers ,influenza ,business ,Research Paper - Abstract
Physical frailty’s impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log2 HAI titers, and fold-rise in log2 HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.
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- 2020
37. Exploring the landscape of Babesia bovis vaccines: progress, challenges, and opportunities.
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Santos, John Harvey M., Siddle, Hannah V., Raza, Ali, Stanisic, Danielle I., Good, Michael F., and Tabor, Ala E.
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BABESIA ,ERYTHROCYTES ,ASEXUAL reproduction ,GENETIC vectors ,VIRAL vaccines - Abstract
Bovine babesiosis, caused by different Babesia spp. such as B. bovis, B. bigemina, B. divergens, and B. major, is a global disease that poses a serious threat to livestock production. Babesia bovis infections are associated with severe disease and increased mortality in adult cattle, making it the most virulent agent of bovine babesiosis. Babesia bovis parasites undergo asexual reproduction within bovine red blood cells, followed by sexual reproduction within their tick vectors, which transmit the parasite transovarially. Current control methods, including therapeutic drugs (i.e., imidocarb) have been found to lead to drug resistance. Moreover, changing environmental factors add complexity to efficient parasite control. Understanding the fundamental biology, host immune responses, and host–parasite interactions of Babesia parasites is critical for developing next-generation vaccines to control acute disease and parasite transmission. This systematic review analyzed available research papers on vaccine development and the associated immune responses to B. bovis. We compiled and consolidated the reported vaccine strategies, considering the study design and rationale of each study, to provide a systematic review of knowledge and insights for further research. Thirteen studies published since 2014 (inclusive) represented various vaccine strategies developed against B. bovis such as subunit, live attenuated, and viral vector vaccines. Such strategies incorporated B. bovis proteins or whole live parasites with the latter providing the most effective prophylaxis against bovine babesiosis. Incorporating novel research approaches, such as "omics" will enhance our understanding of parasite vulnerabilities. [ABSTRACT FROM AUTHOR]
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- 2023
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38. ILC3: a case of conflicted identity.
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Koprivica, Ivan, Stanisavljević, Suzana, Mićanović, Dragica, Jevtić, Bojan, Stojanović, Ivana, and Miljković, Đorđe
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INNATE lymphoid cells ,FLOW cytometry ,IMMUNE response ,IN vivo studies ,INFLAMMATION - Abstract
Innate lymphoid cells type 3 (ILC3s) are the first line sentinels at the mucous tissues, where they contribute to the homeostatic immune response in a major way. Also, they have been increasingly appreciated as important modulators of chronic inflammatory and autoimmune responses, both locally and systemically. The proper identification of ILC3 is of utmost importance for meaningful studies on their role in immunity. Flow cytometry is the method of choice for the detection and characterization of ILC3. However, the analysis of ILC3-related papers shows inconsistency in ILC3 phenotypic definition, as different inclusion and exclusion markers are used for their identification. Here, we present these discrepancies in the phenotypic characterization of human and mouse ILC3s. We discuss the pros and cons of using various markers for ILC3 identification. Furthermore, we consider the possibilities for the efficient isolation and propagation of ILC3 from different organs and tissues for in-vitro and in-vivo studies. This paper calls upon uniformity in ILC3 definition, isolation, and propagation for the increased possibility of confluent interpretation of ILC3's role in immunity. [ABSTRACT FROM AUTHOR]
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- 2023
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39. Single domain Camelid antibody fragments for molecular imaging and therapy of cancer.
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Shulin Li, Hoefnagel, Sanne Johanna Maria, and Krishnadath, Kausilia Krishnawatie
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CANCER treatment ,CANCER prognosis ,PHOTODYNAMIC therapy ,IMMUNOGLOBULINS ,IMMUNE response - Abstract
Despite innovations in cancer therapeutics, cancer remains associated with high mortality and is one of biggest health challenges worldwide. Therefore, developing precise cancer imaging and effective treatments is an unmet clinical need. A relatively novel type of therapeutics are heavy chain variable domain antibody fragments (VHHs) derived from llamas. Here, we explored the suitability of VHHs for cancer imaging and therapy through reviewing the existing literature. We searched the MEDLINE, EMBASE and Cochrane databases and identified 32 papers on molecular imaging and 41 papers on therapy that were suitable for comprehensive reviewing. We found that VHHs harbor a higher specificity and affinity compared to mAbs, which contributes to high-quality imaging and less side-effects on healthy cells. The employment of VHHs in cancer imaging showed remarkably shorter times between administration and imaging. Studies showed that 18F and 99mTc are two optimal radionuclides for imaging with VHHs and that site-specific labelling is the optimal conjugation modality for VHHs with radionuclide or fluorescent molecules. We found different solutions for reducing kidney retention and immunogenicity of VHHs. VHHs as anticancer therapeutics have been tested in photodynamic therapy, targeted radionuclide therapy, immunotherapy and molecular targeted therapy. These studies showed that VHHs target unique antigen epitopes, which are distinct from the ones recognized by mAbs. This advantage means that VHHs may be more effective for targeted anticancer therapy and can be combined with mAbs. We found that high cellular internalization and specificity of VHHs contributes to the effectiveness and safety of VHHs as anticancer therapeutics. Two clinical trials have confirmed that VHHs are effective and safe for cancer imaging and therapy. Together, VHHs seem to harbor several advantages compared to mAbs and show potential for application in personalized treatment for cancer patients. VHH-based imaging and therapy are promising options for improving outcomes of cancer patients. [ABSTRACT FROM AUTHOR]
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- 2023
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40. Senescent cell-derived vaccines: A new concept towards an immune response against cancer and aging?
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IMMUNE response ,AGING ,VACCINES ,BIOLOGICAL products ,CANCER vaccines - Abstract
A new review paper published in Aging explores the concept of using senescent cell-derived vaccines as a potential immune response against cancer and aging. The paper discusses the role of tumor-associated senescent cells in cancer progression and regression and highlights the potential use of senolytics, drugs that eliminate senescent cells, in cancer treatment. The researchers also propose the idea of designing an adaptive anti-aging vaccine. The paper provides valuable insights into the current knowledge in this field. [Extracted from the article]
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- 2024
41. Intra-tumoral heterogeneity and immune responses predicts prognosis of gastric cancer
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Yue Wang, Wanjing Feng, Xiao-Dong Zhu, and Siyuan Chen
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Adult ,Male ,Oncology ,Aging ,medicine.medical_specialty ,medicine.medical_treatment ,Sequencing data ,Risk Assessment ,immune response ,Decision Support Techniques ,Genetic Heterogeneity ,Lymphocytes, Tumor-Infiltrating ,Immune system ,Pharmacotherapy ,Gastrectomy ,Predictive Value of Tests ,Risk Factors ,Stomach Neoplasms ,Internal medicine ,Cancer genome ,Databases, Genetic ,Tumor-Associated Macrophages ,Exome Sequencing ,Genetic variation ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,Humans ,mutant-allele tumor heterogeneity ,Genetic Testing ,RNA-Seq ,Aged ,Aged, 80 and over ,Hazard ratio ,intra-tumor heterogeneity ,Cell Biology ,Middle Aged ,Confidence interval ,Phenotype ,Treatment Outcome ,Chemotherapy, Adjuvant ,Drug Resistance, Neoplasm ,Mutation ,Female ,Transcriptome ,Research Paper - Abstract
Chemotherapy resistance eventually develops in patients with gastric cancer (GC). Intra-tumoral heterogeneity (ITH) refers to the intercellular genetic variations and phenotypic diversity that affect responses to drug therapy. We measured ITH using mutant-allele tumor heterogeneity (MATH) derived from whole-exome sequencing data of patients with GC in The Cancer Genome Atlas (TCGA) database. The study included 385 patients from the TCGA database with available data regarding gastrectomy, survival, and whole-exome sequencing. Further analysis was performed in 171 GC patients with available data regarding adjuvant chemotherapy. Multiple factor analysis showed that MATH was an independent predictor of OS (hazard ratio [HR], 1.432; 95% confidence interval [CI], 1.073–1.913; P = 0.015) in patients with GC. Moreover, MATH was also an independent predictor of OS among the 171 GC patients who received adjuvant chemotherapy (HR, 2.016; 95% CI, 1.236–3.289; P = 0.005). Pathway enrichment and immune cell analyses revealed significantly higher infiltration by 20 types of immune cells in the low/intermediate group, compared to the group with high MATH scores. In conclusion, low/intermediate MATH scores predicted longer OS, when compared to those with high MATH scores. The immune response was obviously upregulated in patients with GC and low/intermediate MATH scores.
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- 2020
42. TNF-α response in macrophages depends on clinical
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Johann, Guillemot, Christophe, Ginevra, Camille, Allam, Elisabeth, Kay, Christophe, Gilbert, Patricia, Doublet, Sophie, Jarraud, and Annelise, Chapalain
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sequence type ,Genotype ,ST1 ,Tumor Necrosis Factor-alpha ,clinical isolates ,Macrophages ,immune response ,Legionella pneumophila ,macrophages ,cell death ,ST47 ,TNF-α ,Humans ,Tumor Necrosis Factor Inhibitors ,Legionnaires' Disease ,Research Article ,Research Paper - Abstract
Legionnaires’ Disease (LD) is a severe pneumonia mainly caused in Europe by Legionella pneumophila serogroup 1 (Lp1). Sequence-based typing methods reveal that some sequence types (ST) are overrepresented in clinical samples such as ST1 and ST47, suggesting that some strains are more fit for infection than others. In the present study, a collection of 108 Lp1 clinical isolates were used to evaluate the strain-dependent immune responses from human macrophages. Clinical Lp1 isolates induced differential TNFα secretion from macrophages. ST1 isolates induced a significantly higher TNF-α secretion than non-ST1, whereas ST47 isolates induced a significantly lower TNF-α secretion than non-ST47 isolates. ST1 isolates induced a significantly higher cell death than ST47 isolates evaluated by lactate dehydrogenase activity (cytotoxicity) and caspase-3 activity (apoptosis). Treatment of macrophages with anti-TNF-α antibodies significantly reduced the cell death in macrophages infected with ST1 or ST47 strains. The TNF-α secretion was neither explained by a differential bacterial replication nor by the number or type (bystander or infected) of TNF-α producing cells following infection but by a differential response from macrophages. The Paris ST1 reference strain elicited a significantly higher TNF-α gene transcription and a higher induction of NF-κB signaling pathway than the Lorraine ST47 reference strain. Clinical Lp1 isolates induce a diverse immune response and cell death, which could be related to the genotype. The two predominant sequence-types ST1 and ST47 trigger opposite inflammatory response that could be related to the host susceptibility.
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- 2022
43. Absent immune response to SARS-CoV-2 in a 3-month recurrence of coronavirus disease 2019 (COVID-19) case
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Lingyan Fan, Qiaoyun Shi, Qifa Song, Zuoan Huang, Shuyuan Ye, Yedan Sun, Guosheng Gao, and Zhe Zhu
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0301 basic medicine ,Male ,Disease ,Long-term viral shedding ,Gastroenterology ,0302 clinical medicine ,COVID-19 Testing ,Recurrence ,Medicine ,030212 general & internal medicine ,Reverse Transcriptase Polymerase Chain Reaction ,Novel coronavirus (SARS-CoV-2) ,General Medicine ,Viral Load ,Interleukin-10 ,Virus Shedding ,Hospitalization ,Elevated serum creatinine ,Infectious Diseases ,C-Reactive Protein ,Creatinine ,Tumor necrosis factor alpha ,Viral load ,Microbiology (medical) ,medicine.medical_specialty ,Fever ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,030106 microbiology ,Antiviral Agents ,Virus ,03 medical and health sciences ,Interferon-gamma ,Immune system ,Internal medicine ,Lymphopenia ,Humans ,Viral shedding ,Immune response ,Aged ,Original Paper ,business.industry ,Interleukin-6 ,SARS-CoV-2 ,Tumor Necrosis Factor-alpha ,Immunity ,COVID-19 ,Coronavirus disease 2019 (COVID-19) ,Interleukin-2 ,business ,Tomography, X-Ray Computed ,Biomarkers - Abstract
Background The viral persistence in patients with Coronavirus Disease 2019 (COVID-19) remains to be investigated. Methods We investigated the viral loads, therapies, clinical features, and immune responses in a 70-year patient tested positive for SARS-CoV-2 for 3 months. Findings The patient exhibited the highest prevalence of abnormal indices of clinical features and immune responses at the first admission, including fever (38.3 ℃), decreased lymphocytes (0.83 × 109/L) and serum potassium (3.1 mmol/L), as well as elevated serum creatinine (115 µmol/L), urea (8.6 mmol/L), and C-reactive protein (80 mg/L). By contrast, at the second and the third admission, these indices were all normal. Through three admissions, IL-2 increased from 0.14 pg/mL, 0.69 pg/mL, to 0.91 pg/mL, while IL-6 decreased from 11.78 pg/mL, 1.52 pg/mL, to 0.69 pg/mL, so did IL-10 from 5.13 pg/mL, 1.85 pg/mL, to 1.75 pg/mL. The steady declining trend was also found in TNF-α (1.49, 1.15, and 0.85 pg/mL) and IFN-γ (0.64, 0.42, and 0.27 pg/mL). The threshold cycle values of RT-PCR were 26.1, 30.5, and 23.5 for ORFlab gene, and 26.2, 30.6, and 22.7 for N gene, showing the patient had higher viral loads at the first and the third admission than during the middle term of the disease. The patient also showed substantially improved acute exudative lesions on the chest CT scanning images. Conclusions The patient displayed declining immune responses in spite of the viral shedding for 3 months. We inferred the declining immune responses might result from the segregation of the virus from the immune system.
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- 2020
44. PDIA3 correlates with clinical malignant features and immune signature in human gliomas
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Fangkun Liu, Fan Fan, Zeyu Wang, Quan Cheng, Ziyu Dai, Yulai Zhou, Hui Cao, Hao Zhang, and Biqi Cui
- Subjects
Aging ,Protein Disulfide-Isomerases ,PDIA3 ,Biology ,immune response ,Transcriptome ,Immune system ,Biomarkers, Tumor ,PTEN ,tumor microenvironment ,Humans ,Correlation of Data ,Tumor microenvironment ,Brain Neoplasms ,Cell Biology ,Glioma ,Gene Expression Regulation, Neoplastic ,Isocitrate dehydrogenase ,Single cell sequencing ,Mutation ,biology.protein ,Cancer research ,Biomarker (medicine) ,prognosis ,Research Paper - Abstract
Since therapeutic strategies are limited in gliomas, new molecules or biomarkers are essential for diagnosis and therapy. Here, we investigated expression of protein disulfide isomerase family A member 3 (PDIA3) in gliomas to evaluate its potential as a promising immune target or biomarker. Transcriptome level, genomic profiles and its association with clinical practice from TCGA and CGGA databases were analyzed. All statistical analyses were performed using R project. In gliomas with high PDIA3 expression, somatic mutations showed the correlation with loss of PTEN and amplification of EGFR; meanwhile, in PDIA3 low gliomas, mutations in isocitrate dehydrogenase (IDH) took 80%. Moreover, PDIA3 was found to positively correlate with ESTIMATE scores and diverse infiltrating immune and stromal cell types localizing in tumor microenvironment. PDIA3 was found to be highly correlated with macrophage and T cells based on single cell sequencing. Additionally, PDIA3 was also involved in suppression of anti-tumor immunity via multiple immune regulatory processes. Finally, PDIA3 was observed to correlate with other immune checkpoint inhibitors and associated with inflammation. Our findings identified the significance of PDIA3 in the process of gliomas and demonstrated the potential of PDIA3 as a molecular target in prognosis and immune related treatment of gliomas.
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- 2020
45. Exosomes Transmit Viral Genetic Information and Immune Signals may cause Immunosuppression and Immune Tolerance in ALV-J Infected HD11 cells
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Yan Wang, Yu Heling, Can Cui, Zhu Shiliang, Hengyong Xu, Diyan Li, Qing Zhu, Qijian He, Hua Li, Xiaoling Zhao, Huadong Yin, Fei Ye, and Yuxiang Lu
- Subjects
Herpesvirus 4, Human ,macrophage cells ,Proteome ,Secondary infection ,Exosomes ,Real-Time Polymerase Chain Reaction ,Applied Microbiology and Biotechnology ,Exosome ,immune response ,Immune tolerance ,Cell Line ,Transcriptome ,03 medical and health sciences ,Phosphatidylinositol 3-Kinases ,Immune system ,Retrovirus ,exosome ,Humans ,RNA, Messenger ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,biology ,Antigen processing ,Sequence Analysis, RNA ,Macrophages ,Cell Biology ,biology.organism_classification ,Microvesicles ,Endocytosis ,Cell biology ,retrovirus ,Retroviridae ,RNA, Long Noncoding ,Proto-Oncogene Proteins c-akt ,Developmental Biology ,Research Paper ,Signal Transduction - Abstract
Avian leukosis virus (ALV) is oncogenic retrovirus that not only causes immunosuppression but also enhances the host's susceptibility to secondary infection. Exosomes play vital role in the signal transduction cascades that occur in response to viral infection. We want to explore the function of exosomes in the spread of ALV and the body's subsequent immunological response. RNA-sequencing and the isobaric tags for relative and absolute quantitation (iTRAQ) method were used to detect differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in exosomes secreted by macrophage cells in response to injection with ALV subgroup J (ALV-J). RNA-sequencing identified 513 DEGs in infected cells, with specific differential regulation in mRNA involved in tight junction signaling, TNF signaling, salmonella infection response, and immune response, among other important cellular processes. Differential regulation was observed in 843 lncRNAs, with particular enrichment in those lncRNA targets involved in Rap1 signaling, HTLV-I infection, tight junction signaling, and other signaling pathways. A total of 50 DEPs were identified in the infected cells by iTRAQ. The proteins enriched are involved in immune response, antigen processing, the formation of both MHC protein and myosin complexes, and transport. Combined analysis of the transcriptome and proteome revealed that there were 337 correlations between RNA and protein enrichment, five of which were significant. Pathways that were enriched on both the RNA and protein levels were involved in pathways in cancer, PI3K-Akt signaling pathway, Endocytosis, Epstein-Barr virus infection. These data show that exosomes are transmitters of intercellular signaling in response to viral infection. Exosomes can carry both viral nucleic acids and proteins, making it possible for exosomes to be involved in the viral infection of other cells and the transmission of immune signals between cells. Our sequencing results confirme previous studies on exosomes and further find exosomes may cause immunosuppression and immune tolerance.
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- 2020
46. Molecular cloning of Gibel carp (Carassius auratus gibelio) complement component C3 and its expression profile after Cyprinid herpesvirus 2 infection
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Yong Zhou, Yuding Fan, Xueping Zhang, Wenzhi Liu, Nan Jiang, and Lingbing Zeng
- Subjects
Lipopolysaccharides ,040301 veterinary sciences ,Immunology ,cloning ,Molecular cloning ,Cyprinid herpesvirus 2 (CyHV-2) ,immune response ,Cell Line ,complement component C3 ,0403 veterinary science ,Fish Diseases ,03 medical and health sciences ,Common carp ,Goldfish ,Complementary DNA ,Gibel carp (Carassius auratus gibelio) ,Animals ,Cloning, Molecular ,Carp ,Gene ,Peptide sequence ,Herpesviridae ,Phylogeny ,030304 developmental biology ,0303 health sciences ,Innate immune system ,Full Paper ,General Veterinary ,biology ,Gene Expression Profiling ,Complement C3 ,Herpesviridae Infections ,04 agricultural and veterinary sciences ,biology.organism_classification ,Molecular biology ,Immunity, Innate ,Grass carp ,sense organs - Abstract
The complement systems play an important role in innate and adaptive immunity. In this study, the complement C3 gene, designated CagC3, was cloned and sequenced from Gibel carp (Carassius auratus gibelio). The expression pattern of CagC3 in different tissues of healthy Gibel carp and after challenge with Cyprinid herpesvirus 2 (CyHV-2) were evaluated using quantitative real-time PCR. The full-length CagC3 cDNA was 5131 bp with an ORF of 4950 bp, encoding a predicted protein of 1649 amino acids. The deduced amino acid sequence showed that CagC3 has conserved domains and residues known to be critical for C3 function. Phylogenetic analysis demonstrated that CagC3 clustered with homologs from common carp and grass carp (Ctenopharyngodon idella). CagC3 is expressed in all examined tissues of healthy Gibel carp, with the highest expression in liver. In vivo, after CyHV-2 challenge, CagC3 transcription was significantly upregulated in liver, spleen and kidney with the peaks at 24 hr, 2 d, and 2 d, respectively. In vitro, CagC3 expression in the Gibel carp brain cell line showed the same pattern as that in vivo after stimulation with CyHV-2 or poly(I:C). However, CagC3 expression was downregulated at 24 hr after induction with lipopolysaccharide (LPS), and then reached the peak at 2 d. These results suggest that CagC3 is involved in the innate immune response of Gibel carp to viral infection.
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- 2020
47. Survival correlation of immune response in human cancers
- Author
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Yuexin Liu
- Subjects
Oncology ,medicine.medical_specialty ,overall survival ,Immunogenicity ,immunogenicity ,Biology ,Gene signature ,immune response ,3. Good health ,Clinical trial ,Correlation ,progression-free interval ,Immune system ,Internal medicine ,Gene density ,medicine ,Overall survival ,cancer ,Human genome ,Research Paper - Abstract
Background: The clinical benefit of immune response is largely unknown. We systematically explored the correlation of immune response with patient outcome in human cancers. Results: The global immune gene signature was primarily located on the plasma membrane with a high gene density at 6p21 and 1q23-1q24. Immune responses varied with a wide range in human cancers. A total of 11 cancer types exhibited significant correlation of immune response with overall survival. Higher immune response was significantly associated with longer overall survival in 7 types and with shorter overall survival in 4 types. In addition, 11 cancer types exhibited significant correlation of immune response with progression-free interval. Higher immune response was significantly associated with longer progression-free interval in 7 types and with shorter progression-free interval in 4 types. Methods: The Ingenuity Knowledge Base and human genome assembly GRCh38 were used to annotate the immune gene signature by cellular components and genomic coordinates, respectively. We devised an mRNA-based metric of pre-existing immune conditions by using the gene signature, and calculated the metric for 10,062 The Cancer Genome Atlas tumor samples across 32 different cancer types. The Kaplan-Meier method was used to evaluate the overall survival and progression-free interval differences between dichotomic groups stratified by the median metric for each cancer type. Conclusions: Immune responses have different impacts on patient outcome in different human cancers. Prospective verification is needed before the findings can be applied for clinical trial development.
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- 2019
48. Arabidopsis MAPKKK δ-1 is required for full immunity against bacterial and fungal infection
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Hideo Nakashita, Tomoya Asano, Michiko Yasuda, Yasir Sidiq, Thi Hang-Ni Nguyen, Kohji Nishimura, and Takumi Nishiuchi
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Physiology ,Trichothecene ,Arabidopsis ,Plant Science ,MAPK cascade ,MAPKKK ,immune response ,proteomics ,Fusarium ,Gene Expression Regulation, Plant ,Pseudomonas syringae ,Protein phosphorylation ,Mitogen-Activated Protein Kinase Kinases ,Disease resistance ,MAP kinase kinase kinase ,biology ,AcademicSubjects/SCI01210 ,Arabidopsis Proteins ,Phosphoproteomics ,biology.organism_classification ,MAP Kinase Kinase Kinases ,Fusarium sporotrichioides ,Research Papers ,Cell biology ,protein phosphorylation ,Mycoses ,Plant—Environment Interactions ,Raf kinase - Abstract
MKD1, a novel mitogen activated protein kinase kinase kinase, is part of the transcription factor AtNFXL1 complex and required for full immune responses against both bacterial and fungal infection., The genome of Arabidopsis encodes more than 60 mitogen-activated protein kinase kinase (MAPKK) kinases (MAPKKKs); however, the functions of most MAPKKKs and their downstream MAPKKs are largely unknown. Here, MAPKKK δ-1 (MKD1), a novel Raf-like MAPKKK, was isolated from Arabidopsis as a subunit of a complex including the transcription factor AtNFXL1, which is involved in the trichothecene phytotoxin response and in disease resistance against the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (PstDC3000). A MKD1-dependent cascade positively regulates disease resistance against PstDC3000 and the trichothecene mycotoxin-producing fungal pathogen Fusarium sporotrichioides. MKD1 expression was induced by trichothecenes derived from Fusarium species. MKD1 directly interacted with MKK1 and MKK5 in vivo, and phosphorylated MKK1 and MKK5 in vitro. Correspondingly, mkk1 mutants and MKK5RNAi transgenic plants showed enhanced susceptibility to F. sporotrichioides. MKD1 was required for full activation of two MAPKs (MPK3 and MPK6) by the T-2 toxin and flg22. Finally, quantitative phosphoproteomics suggested that an MKD1-dependent cascade controlled phosphorylation of a disease resistance protein, SUMO, and a mycotoxin-detoxifying enzyme. Our findings suggest that the MKD1–MKK1/MKK5–MPK3/MPK6-dependent signaling cascade is involved in the full immune responses against both bacterial and fungal infection.
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- 2019
49. Genomic, proteomic, and immunologic associations with a durable complete remission of measurable metastatic melanoma induced by a patient-specific dendritic cell vaccine
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Gabriel Nistor, Robert O. Dillman, and Aleksandra J. Poole
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Proteomics ,Dendritic cell vaccine ,030231 tropical medicine ,Immunology ,Cancer Vaccines ,immune response ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,Antigens, Neoplasm ,Humans ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Serum amyloid A ,Melanoma ,Pharmacology ,business.industry ,biomarkers ,Histology ,Dendritic Cells ,In vitro ,Histocompatibility ,Vaccination ,Female ,business ,CD8 ,Research Paper ,metastatic melanoma - Abstract
This report describes efforts to understand the immune mechanism of action that led to a complete response in a patient with progressive, refractory, metastatic melanoma after treatment with a therapeutic vaccine consisting of autologous dendritic cells (DC) loaded with autologous tumor antigens (ATA) derived from cells that were self-renewing in cell culture. Her histocompatibility type proved to be HLA B27 with extensive mutations in the HLA-A locus. Exomic analysis of proliferating tumor cells revealed more than 2800 non-synonymous mutations compared to her leukocytes. Histology of resected tumor lesions showed no evidence of an existing or suppressed immune response. In in vitro mixed cell cultures, DC loaded with ATA induced increased IL-22 expression, and a four-fold increase in CD8 + T lymphocytes. Cryopreserved blood samples obtained at week-0, 1 week before the first of three-weekly vaccine injections, and at week-4, 1 week after the third dose, were analyzed by protein array and compared for 110 different serum markers. At baseline, she had marked elevations of amyloid A, IL-12p40, IL21, IL-22, IL-10, IL-16, GROa, TNF-alpha, IL-3, and IL-2, and a lesser elevation of IL-15. One week after 3 weekly vaccinations she had a further 80% increase in amyloid A, a further 66% increase in IL-22, a 92% decrease in IL12p40, a 45% decrease in TGF-β and 26% decrease in IL-10. The data suggested that by 3 weeks after the first DCV injection, vaccine-induced changes in this particular patient were most consistent with enhanced innate and Th1 immune responses rather than Th2 or Th17.
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- 2019
50. The anti-carcinogenesis properties of erianin in the modulation of oxidative stress-mediated apoptosis and immune response in liver cancer
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Anhui Yang, Xin Li, Di Wang, Zhiwen Li, Xinrui Zhang, and Yingwu Wang
- Subjects
Aging ,Mice, Nude ,Apoptosis ,Mitochondrion ,medicine.disease_cause ,immune response ,liver cancer ,Mice ,Immune system ,Nude mouse ,Bibenzyls ,medicine ,Animals ,Anticarcinogenic Agents ,Humans ,erianin ,Mice, Inbred BALB C ,biology ,Phenol ,Chemistry ,Liver Neoplasms ,Cancer ,Cell Biology ,biology.organism_classification ,medicine.disease ,Xenograft Model Antitumor Assays ,mitochondria ,Oxidative Stress ,Cancer cell ,Cancer research ,Carcinogenesis ,Oxidative stress ,Research Paper - Abstract
In this study, erianin was found to reduce the viability of cancer cells, inhibit their proliferation and migration, induce G2/M phase arrest, enhance cancer cell apoptosis, promote an increase in levels of intracellular reactive oxygen species and a decrease in mitochondrial membrane potential, and regulate the expression levels of anti- and pro-apoptosis-related proteins in HepG2 and SMMC-7721 cells. Erianin inhibited tumor growth in HepG2- and SMMC-7721-xenograft tumor nude mouse models, reduced the expression levels of anti-apoptosis proteins and enhanced the expression levels of pro-apoptosis proteins in tumor tissues. Erianin inhibited tumor growth in immunosuppressed BALB/c mice bearing heterotopic tumors. Among 111 types of cytokines detected in proteome profiling of tumor tissues, erianin substantially influenced levels of 38 types of cytokines in HepG2-xenografted tumors and of 15 types of cytokines in SMMC-7721-xenografted tumors, most of which are related to immune functions. Erianin strongly affected the serum levels of cytokines, and regulated the activation of nuclear factor-kappa B (NF-κB), and the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins in spleen. The anti-liver cancer properties of erianin were found to be related mostly to its modulation of oxidative stress-mediated mitochondrial apoptosis and immune response.
- Published
- 2019
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