RESUMO
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving many systems and organs, and individuals with SLE exhibit unique cancer risk characteristics. The significance of the basement membrane (BM) in the occurrence and progression of human autoimmune diseases and tumors has been established through research. However, the roles of BM-related genes and their protein expression mechanisms in the pathogenesis of SLE and pan-cancer development has not been elucidated. Methods: In this study, we applied bioinformatics methods to perform differential expression analysis of BM-related genes in datasets from SLE patients. We utilized LASSO logistic regression, SVM-RFE, and RandomForest to screen for feature genes and construct a diagnosis model for SLE. In order to attain a comprehensive comprehension of the biological functionalities of the feature genes, we conducted GSEA analysis, ROC analysis, and computed levels of immune cell infiltration. Finally, we sourced pan-cancer expression profiles from the TCGA and GTEx databases and performed pan-cancer analysis. Results: We screened six feature genes (AGRN, PHF13, SPOCK2, TGFBI, COL4A3, and COLQ) to construct an SLE diagnostic model. Immune infiltration analysis showed a significant correlation between AGRN and immune cell functions such as parainflammation and type I IFN response. After further gene expression validation, we finally selected AGRN for pan-cancer analysis. The results showed that AGRN's expression level varied according to distinct tumor types and was closely correlated with some tumor patients' prognosis, immune cell infiltration, and other indicators. Discussion: In conclusion, BM-related genes play a pivotal role in the pathogenesis of SLE, and AGRN shows immense promise as a target in SLE and the progression of multiple tumors.
Assuntos
Doenças Autoimunes , Interferon Tipo I , Lúpus Eritematoso Sistêmico , Neoplasias , Humanos , Biologia Computacional , Proteínas de Ligação a DNA , Interferon Tipo I/fisiologia , Neoplasias/genética , Proteoglicanas , Fatores de Risco , Fatores de Transcrição , Agrina/metabolismoRESUMO
Chronic prostatitis/chronic pelvic pain syndromes (CP/CPPS) is a clinical tricky problem due to its enigmatic etiology, low cure rate, and high recurrence rate. The research on its pathogenesis has never stopped. In this experimental autoimmune prostatitis (EAP) model, male C57BL/6 mice were subcutaneously immunized with prostate extracts in an adequate adjuvant. For mice in the antibody intervention group, anti-T2 polyclonal antibodies were intraperitoneally injected during the induction of EAP. Animals were periodically monitored for pelvic pain. Hematoxylin and eosin staining was used to assess prostate inflammation. Tumor necrosis factor-α (TNF-α) levels in serum were measured by ELISA kits. The immunized animals developed prostatitis as a consequence of the immune response against prostate antigens. Pelvic pain thresholds were gradually decreased and TNF-α expression significantly increased. T2 plays an important role in the disease since polyclonal antibodies to T2 greatly ameliorated symptoms in animals induced for EAP. T2 peptide may represent the major autoantigen epitope in EAP, which could serve for a better understanding of the etiology of CP/CPPS.
Assuntos
Autoantígenos/sangue , Doenças Autoimunes/sangue , Epitopos/sangue , Dor Pélvica/sangue , Fragmentos de Peptídeos/antagonistas & inibidores , Prostatite/sangue , Sequência de Aminoácidos , Animais , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/prevenção & controle , Epitopos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dor Pélvica/imunologia , Dor Pélvica/prevenção & controle , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/imunologia , Prostatite/imunologia , Prostatite/prevenção & controle , CoelhosRESUMO
The most commonly used administration methods in clinics and life are oral administration, intravenous injection, and other systemic administration methods. Targeted administration must be an essential long-term development direction due to the limited availability and a high incidence of systemic side effects. Cardiovascular diseases (CVD) are the leading cause of death all over the world. Targeted drug delivery (TDD) methods with the heart as the target organ have developed rapidly and are diversified. This article reviews the research progress of various TDD methods around the world with a heart as the target organ. It is mainly divided into two parts: the targeting vector represented by nanoparticles and various TDD methods such as intracoronary injection, ventricular wall injection, pericardial injection, and implantable medical device therapy and put forward some suggestions on the development of targeting. Different TDD methods described in this paper have not been widely used in clinical practice, and some have not even completed preclinical studies. Targeted drug delivery still requires long-term efforts by many researchers to realize the true meaning of the heart. HIGHLIGHTS Targeted administration can achieve a better therapeutic effect and effectively reduce the occurrence of adverse reactions. Parenteral administration or medical device implantation can be used for targeted drug delivery. Combined with new dosage forms or new technologies, better-targeted therapy can be achieved. Clinical trials have confirmed the safety and effectiveness of several administration methods.