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关键词： genomic sequence   HLA-DQ   new allele   Saudi Arabia  

摘要： The novel allele HLA-DQB1*05:351 differs from DQB1*05:03:01:01 by a single nucleotide substitution in exon 3.

关键词： HLA-B*35:186   sequence-based typing   the novel allele  

摘要： HLA-B*35:186 differs from HLA-B*35:01:01:01 by 12 nucleotide substitutions in exon 2.

关键词： HLA   HLA-DQB1*05:311:02   novel allele   sequencing-based typing  

摘要： HLA-DQB1*05:311:02 differs from HLA-DQB1*05:02:01:01 by one nucleotide substitution in codon 188 in Exon 3.

关键词： Cancer drug delivery   Tumor microenvironment (TME) targeting   Tumor-associated macrophages (TAMs)   targeting   cancer immunotherapy   M2 macrophages polarization   Liposomal IFN-gamma   M2 macrophage-targeting peptide-modified   liposomes  

摘要： While liposomes enhance the safety and pharmacokinetic profile of free drugs, they have not significantly improved therapeutic efficacy. To overcome this challenge, targeted depletion of tumor-associated macrophages (TAMs) shows significant potential as an effective antitumor therapy, reducing off-target effects in comparison to non-targeted liposomes. In the context of peptide-mediated targeted cancer therapy, we evaluated the reprogramming activity of IFN-gamma liposomes on TAMs, as well as that of IFN-gamma liposomes modified with an M2 macrophage-targeting peptide, which binds preferentially to murine anti-inflammatory M2 macrophages/M2like TAMs. Flow cytometry analysis showed significantly enhanced cellular uptake of m2-peptide-targeted liposomes in J774.1 macrophage cell lines compared to non-targeted liposomes. In BALB/c mice bearing C-26 murine carcinoma, the m2-peptide-targeted liposome groups exhibited significantly higher IFN-gamma concentrations compared to non-targeted counterparts within the tumor environment. Furthermore, m2-peptide-targeted F2 liposomes at doses of 25 mu g IFN-gamma/kg resulted in superior tumor growth inhibition and greater tumor accumulation, indicating the potential of macrophage-targeted therapy in cancer growth inhibition. However, they failed to improve the overall therapeutic efficacy compared to Doxil. This study proposes a combination therapy of m2peptide-targeted IFN-gamma liposomes with successful chemotherapeutic liposomes such as Doxil.

关键词： Osteoarthritis   Inflammation   GUSBP11   miR-122-5p   Biomarker  

摘要： Studies have demonstrated that several lncRNAs exhibit abnormal expression levels in patients suffering from osteoarthritis, and in-depth investigation of these aberrantly expressed lncRNAs may pave the way for innovative therapeutic strategies targeting OA. The aim of this study was to examine the expression of glucuronidase beta pseudogene 11 (GUSBP11) in OA patients and to elucidate its potential molecular mechanism. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect GUSBP11 levels on cartilage tissues and serum samples obtained from OA patients. To establish an in vitro OA cell model, interleukin-1(3 (IL- 1(3) was utilized to induce CHON-001 and ATDC5 cell lines. Cell counting kit-8 (CCK-8) assay and flow cytometry were performed to evaluate cell viability and apoptosis, and enzyme-linked immunosorbent assay (ELISA) was employed to qualify the levels of inflammatory factors. StarBase database predicted that miR-122-5p was the target gene of GUSBP11. Subsequently, luciferase reporter genes were conducted to validate this interaction. Potential target genes of miR-122-5p were predicted, followed by gene function annotation and correlation analysis of these targets. Our findings revealed that GUSBP11 expression was markedly decreased in both the cartilage tissues and serum of OA patients. Diminished levels of GUSBP11 showed high diagnostic accuracy for OA. In the IL-1(3-induced OA cell model, GUSBP11 expression was notably reduced, leading to decreased cell viability, an increase in apoptotic cells, and elevated levels of inflammatory factors. Up-regulation of GUSBP11 significantly ameliorated these adverse effects. Luciferase reporter genes confirmed the interaction between GUSBP11 and miR-122-5p, indicating that an increase in miR-122-5p drastically inhibited cell viability while promoting apoptosis and inflammation. In conclusion, within the context of the in vitro OA cell model, GUSBP11 appears to exacerbate IL-1(3-induced

关键词： HLA   HLA-DPA1*01:03:61   novel allele   sequencing-based typing  

摘要： HLA-DPA1*01:03:61 differs from HLA-DPA1*01:03:01:02 by one nucleotide substitution in codon 81 in exon 2.

关键词： CD47   cervical cancer   IL-37   immunotherapy   macrophage phagocytosis   STAT3  

摘要： As a promising therapeutic approach, immunotherapy is being extensively investigated in cervical cancer. Although immunotherapy has been validated to improve progression-free survival and overall survival in clinical trials, the overall response rate for cervical cancer remains inadequate, necessitating further improvement. Interleukin (IL)-37, an emerging immunomodulator, exhibits antitumour potentials by inhibiting tumour progression and regulating tumour-associated macrophage recognition. We found a significant downregulation of IL-37 expression in cervical cancer, correlated with a poor prognosis. Moreover, the upregulation of IL-37 expression exhibited a suppressive effect on various tumorigenic processes, suppressing the proliferation, invasion, migration, apoptosis and angiogenesis of tumour cells. We also found that the upregulation of IL-37 suppressed cluster of differentiation 47 (CD47) expression in tumour cells via suppression of the signal transducer and activator of transcription 3 (STAT3) expression and phosphorylation, thereby enhancing macrophage recognition and phagocytosis to tumour cells, ultimately reducing immune evasion. Overall, our study highlighted the crucial role of IL-37 in antitumour efficacy and downregulating the expression of CD47 in tumour cells to reduce immune evasion, suggesting the potential of IL-37 as a prognostic biomarker in cervical cancer and offering innovative therapeutic strategies to improve cancer treatment outcomes.

关键词： C*02:231   HLA   IPD-IMGT/HLA  

摘要： HLA-C*02:231 differs from C*02:02:02:79 by a single non-synonymous nucleotide change in codon 124 (ATC>GTC).

关键词： Heart failure   Mitochondrial permeability transition-driven   necrosis   Biomarkers   Predictive and diagnostic efficacy   Enrichment pathways   Regulatory networks  

摘要： Background: Heart failure is linked to increased hospitalization and mortality. Mitochondrial permeability transition-driven necrosis is associated with cardiovascular diseases, but its role in heart failure is unclear. This study aimed to identify and validate genes related to mitochondrial permeability transition-driven necrosis in heart failure, potentially leading to new drug targets and signaling pathways. Methods: We identified differentially expressed genes related to heart failure from the gene expression omnibus database and identified module genes related to mitochondrial permeability transition-driven necrosis from the gene set enrichment analysis database. Key genes were determined by intersecting these two gene groups using least absolute shrinkage and selection operator and support vector machine algorithms. Pathways, diagnostic efficacy, gene interactions, immune infiltration, and regulatory networks were analyzed. Small interfering RNAs were used for validation. Real-time-quantitative polymerase chain reaction, flow cytometry, and JC-1 assays were performed in vitro. Results: Forty-six differentially expressed genes, and 3439 module genes were identified. LYVE1, IL1RL1, and SERPINA3 were identified as significantly downregulated key genes, with IL1RL1 and SERPINA3 associated with heart failure risk. Benzo(a) pyrene, bisphenol A, estradiol, and particulate matter were found to simultaneously increase the expression of three key genes. In clinical samples, only LYVE1 and IL1RL1 were downregulated, as expected. Knockdown of these genes in cells led to increased necrosis and decreased mitochondrial membrane potential. Only estradiol reduced brain natriuretic peptide protein levels in hypertrophic cells. Conclusions: LYVE1 and IL1RL1 were validated as key genes linked to mitochondrial permeability transitiondriven necrosis in heart failure. Estradiol may have a therapeutic effect on heart failure.