课程文献中心 更多>>

关键词： blood lipids   exercise and diet intervention   inflammation   obesity  

摘要： : This study piloted a 24-week bodybuilding program combining resistance training (RT) with a dietary bulk-and-cut protocol in middle-aged adult males. : Seven untrained males (33 ± 3.0 years; BMI = 35.0 ± 4.6 kg/m; body fat = 36 ± 5%) completed a 24-week intervention combining RT with a dietary protocol consisting of 12-week cycles of caloric bulking (0-12 weeks) and cutting (12-24 weeks). The participant retention rate was 64%, while compliance with training was 96.7%, and adherence to dietary cycles was over 93%. To assess the preliminary efficacy of the intervention, venous blood samples and measurements of body composition (BodPod), muscle strength, and VOmax (cycle ergometer) were collected at baseline (week 0) and following the bulking (week 12) and cutting (week 24) cycles. Circulating lipids (triglycerides, total, low-density, and high-density cholesterol), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured in serum. : The training led to significant increases in muscle strength, especially in the deadlift (+46%, < 0.001) and squat (+65%, < 0.001). Improvements in body composition were characterized by an increase in fat-free mass and a decrease in body fat percentage over the 24-week intervention (+3% and -6%, respectively, < 0.05). Lipids, CRP, IL-6, and IL-10 did not change significantly, but there was a notable reduction in TNF-α (time effect = 0.05, η = 0.39), with 15% lower concentrations at week 24 compared to baseline, indicating reduced inflammation. : Overall, the pilot intervention achieved high compliance and adherence rates, leading to improvements in body composition and lower resting TNF-α concentrations in a group of middle-aged males with obesity.

摘要： INTRODUCTION:Previously, we reported that interleukin-8 (IL-8) was associated with poor prognosis of basal like breast cancer patients and has been identified as a pro-tumorigenic factor, facilitating cell invasion and migration. Here, we investigated the pharmacological impact of inhibitors targeting the chemokine receptors, CXCR1 and CXCR2, which are activated by IL-8. METHODS:The survival rates of TNBC patients by IL-8 were analyzed by the Kaplan-Meier plotter. The levels of mRNA and protein expression were analyzed by real-time PCR and western blotting. The alteration of apoptotic cell death-related proteins by SB225002 was analyzed by the Proteome Profiler Human Apoptosis Array. Cell growth was analyzed by MTT and colony forming assay. Apoptosis and cell cycle were analyzed by FACS. RESULTS:Aberrant IL-8 expression is involved with the prognosis of triple-negative breast cancer (TNBC) patients. Basal IL-8 levels are markedly elevated in TNBC cells compared to those in HER2+ and/or ER+ breast cancer cells. Furthermore, recombinant human IL-8 treatment enhanced cell invasiveness in TNBC cells. To counteract the tumor-promoting effects of IL-8, we assessed the therapeutic potential of CXCR1 and CXCR2 inhibitors. Notably, while reparixin, a CXCR1-specific inhibitor, exhibited no impact on cell viability, SB225002, a CXCR2-specific inhibitor, significantly reduced cell viability in a dose-dependent manner. There was a noticeable reduction in the levels of anti-apoptotic biomarkers, including Bcl-2, cIAP-1, cIAP-2, Survivin, XIAP, HIF-1α, and HO-1, following SB225002 treatment. Our findings indicate an increase in the apoptotic cell population with SB225002 treatment in TNBC cells. In xenograft models, SB225002 effectively diminished the metastatic potential of 4T1 cells, which are known to metastasize to the lung and liver. CONCLUSION:Our results underscore the significant role of the IL-8/CXCR2 signaling axis in the metastasis of TNBC and suggest that CXCR2 inhibit

关键词： Crohn's disease   Anti-TNF alpha   Preoperative treatment   Postoperative recurrence   Loss of response  

摘要： Anti-TNF alpha antibodies are effective in controlling intestinal inflammation caused by Crohn's disease. However, many patients undergo surgery due to diminished efficacy of the antibodies during maintenance therapy. Currently, the decision between intensification of TNF alpha therapy and surgery is difficult to make. The purpose of this study was to determine the effect of preoperative treatment with anti-TNF alpha antibodies on postoperative recurrence of Crohn's disease. One hundred and fourteen consecutive patients with Crohn's disease who underwent bowel resection with anastomosis between 2009 and 2021 were retrospectively analyzed on the preoperative treatment history and perioperative information. Of the 74 patients who used anti-TNF alpha antibodies preoperatively, 43 underwent surgery after intensification of therapy following attenuation of anti-TNF alpha antibody efficacy. Time to postoperative endoscopic recurrence was significantly shorter in the group using anti-TNF alpha antibodies than in the group not using them (p = 0.0055). We found no difference in time to postoperative endoscopic recurrence between patients who underwent intensified therapy and those who underwent immediate surgery. Patients who received preoperative anti-TNF alpha antibody had a shorter time to postoperative endoscopic recurrence, but the presence or absence of intensified treatment after weakening of the anti-TNF alpha antibody effects did not affect the time to postoperative endoscopic recurrence.

关键词： HLA evolutionary divergence   Human leukocyte antigen   SARS-CoV-2  

摘要： Immunogenetic factors such as human leukocyte antigen (HLA) alleles, have yielded contrasting associations with protection or increased chances of hospitalization due to COVID-19 worldwide. This case-control study included 834 patients with confirmed COVID-19 diagnosis from five Brazilian states: Ceará (n = 110), Mato Grosso (n = 192), Pará (n = 209), Rio de Janeiro (n = 211) and Rio Grande do Sul (n = 112). Genotyping was performed using the Axiom™ Human Genotyping SARS-CoV-2 array, targeting single nucleotide polymorphisms in HLA class I and II genes; HLA alleles were imputed for eight loci. Among the 15 preselected candidate alleles, only DQA1∗05:01 (p = 0.015) in the state of Ceará remained significantly associated with hospitalization. The meta-analysis of the most frequent alleles in all states revealed that HLA-DPA1∗01:03 (p = 0.0229, OR = 0.76, 95 % CI = 0.60-0.96) and HLA-DPB1∗04:01 (p = 0.0474, OR = 0.78, 95 % CI = 0.611.00) were associated with protection against hospitalization, whereas HLA-DPA1∗02:01 (p = 0.0259, OR = 1.37, 95 % CI = 1.04-1.80), HLA-DQA1∗05:01 (p = 0.0133, OR = 1.40, 95 % CI = 1.07-1.82), and HLA-DRB1∗03:01 (p = 0.0276, OR: 1.59, 95 % CI: 1.05-2.40) associated with increased risk of hospitalization. HLA evolutionary divergence (HED) scores were significantly higher among the non-hospitalized group for the HLA-A locus, which has been shown to be a protective factor for the most severe forms and consequently hospitalization due to COVID-19.

关键词： Immunomodulation   L-17 inhibition   Personalized therapy   Secukinumab   Type 1 diabetes mellitus  

摘要： We report the case of a 30-year-old male with psoriatic arthritis treated with secukinumab (anti-IL-17A) who developed new-onset type 1 diabetes mellitus (T1DM). During follow-up, a consistent reduction in insulin requirements and glycemic variability was observed in the two weeks following each dose of secukinumab. This suggests a possible immunomodulatory effect of IL-17 inhibition on beta-cell function and glycemic control. To our knowledge, this is the first report describing clinical benefits of secukinumab in the early stages of T1DM, highlighting its potential as a therapeutic tool in modulating autoimmune processes involved in disease progression.

关键词： coronary artery disease   cytokines   inflammation   ischemic heart disease  

摘要： Ischemic heart disease (CAD), a leading global health burden, arises primarily from atherosclerosis, an inflammatory condition characterized by lipid accumulation and metabolic dysregulation. The precise contribution of inflammatory cytokines (IL-2, IL-6, and TNF-α) to CAD pathogenesis remains an area of significant research. The primary aim of this study is to examine the IL-2, IL-6, and TNF-α in patients with coronary artery disease (CAD) and compare them with Non-CAD individuals to evaluate their potential as diagnostic biomarkers for CAD. A prospective observational study was conducted over 3 years, involving 100 participants divided into CAD and non-CAD groups. Blood samples were isolated and analyzed for IL-2, IL-6, and TNF-α levels utilizing ELISA kits. Biochemical parameters, including lipid profiles, were also assessed. This study observed significantly elevated IL-6 in patients with CAD compared with controls, while IL-2 and TNF-α levels did not reach statistical significance. The CAD group exhibited dyslipidemia characterized by elevated triglycerides and reduced HDL. Furthermore, the CAD group demonstrated alterations in biochemical parameters, including lower albumin and calcium levels, higher urea and uric acid levels, and an elevated erythrocyte sedimentation rate. These findings suggest a systemic inflammatory state and metabolic disturbances in patients with CAD. This study highlights IL-6 as a potential biomarker and key player in CAD pathogenesis. These findings warrant further investigation into the therapeutic potential of targeting inflammatory pathways for cardiovascular risk reduction.

关键词： HBV   HLA-Ib   rs41551813   HIF-1   genetic association   HBV outcome  

摘要： Background The natural history of HBV infection is highly heterogeneous. Failure to clear the virus during the acute phase of infection allows for viral persistence and progression to chronicity. Investigating the immune mechanisms involved in this process is crucial for effectively managing infection outcome. HLA-Ib molecules (HLA-G, HLA-E and HLA-F) play a critical role in regulating the immune response. Objectives: Primary objective we investigate the potential impact of functional polymorphisms in HLA-F*01:03 (rs1736924), HLA-E*01:01/01:03 (rs1264457), and two selected HLA-G polymorphisms in Exon 2 (+292 A > T (rs41551813) and +372 G > A (rs1130355)) on HBV infection outcome. Secondary objective: we evaluate the expression of soluble HLA-E in our cohort. Methods We evaluated these polymorphisms in a cohort of 200 patients with chronic HBV infection and 100 individuals who spontaneously resolved the infection, using SSP-PCR and Sanger sequencing. Additionally, we measured soluble HLA-E (sHLA-E) levels using ELISA. Results Our results showed a significant association of HLA-G (rs41551813) and HLA-E (rs1264457) polymorphisms with HBV infection outcome, where carriers of the A allele in both HLA-G (rs41551813) and HLA-E (rs1264457) had a significantly higher likelihood of spontaneous HBV clearance (all p < 0.01). Furthermore, we demonstrate that elevated sHLA-E expression favours HBV persistence. Additionally, our findings has revealed that the HLA-G + 292 A > T polymorphism (rs41551813) is associated with regulation of sHLA-G expression. Haplotype analysis further identified the 'TAAA' haplotype as linked to spontaneous HBV clearance. Conclusion this study demonstrates, for the first time, the critical role of HLA-Ib on HBV infection outcome, providing insights for potential therapeutic interventions.

关键词： Breast neoplasms   Cancer vaccines   Epitopes   T-Lymphocyte   Histocompatibility antigen class II   Neoantigen  

摘要： BackgroundThe high occurrence of treatment resistance in patients with hormone receptor-positive (HR +) breast cancer is a global health concern. Thus, effective immunotherapy must be developed. The public neoantigens, estrogen receptor 1 (ESR1) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), shared by HR + and endocrine-resistant breast cancer, could be ideal targets for immunotherapy;however, their presentation by human leukocyte antigen class II (HLA II) and recognition by CD4 + T cells remain largely *** mutations in ESR1 and ten mutations in PIK3CA were subjected to major histocompatibility complex (MHC)-peptide binding analysis and enzyme-linked immunospot (ELISPOT) assays using peripheral blood mononuclear cells (PBMCs) from healthy donors carrying DRB4*01:03, or DRB4*01:03 and DPA1*02:02-DPB1*05:01 (DP5). DRB4*01:03- or DP5-restricted peptides were inferred from binding measurements and ELISPOT assays. Other DRB1 alleles that can also present these mutant peptides were identified using binding *** IFN-gamma responses by CD4 + T cells were detected for most peptides. The peptides that contain ESR1 (E380Q) and PIK3CA (N345K, E542K, E545K/A, E726K, H1047R/L/Y, and G1049R) are presumably restricted by DRB4*01:03, which is frequently found globally (carrier frequency: 35-63%), or by DRB4*01:03 and DRB1*04 alleles. Some PIK3CA (H1047R/L/Y) peptides can also be presented by DRB1*01:01, DRB1*09:01, DRB1*11:01, and DRB1*15:02. ESR1 (Y537S/N, D538G) peptides are potentially restricted by DP5, a frequently found allele in East Asian populations, and DRB1*01:01 and DRB1*15:*** in ESR1 and PIK3CA were recognized by CD4 + T cells from healthy donors through potential restriction by common HLA II alleles. Further studies are warranted to elucidate the landscape of HLA II presentation and validate the clinical applicability of these mutations for the immunotherapy of patients

关键词： CCR6   IFN-g   IL-17   ILC1   ILC3   Innate lymphoid cells (ILCs)   Leprosy  

摘要： Leprosy is a skin disease caused by Mycobacterium leprae, characterized by both localized and generalized immune responses. Th1/17 lymphocytes play a crucial role in the immune response against M. leprae. However, adaptive immunity alone is not sufficient to completely eradicate the pathogen, suggesting the involvement of other innate immune cells in pathogen removal. Therefore, we investigated innate lymphoid cells (ILCs), which are the innate counterparts of helper T cells in adaptive immunity and are known to produce IFN-γ and IL-17. In the present study, we evaluated the expression of ILC1 and ILC3 in borderline tuberculoid (BT) and lepromatous leprosy (LL) lesional skin by flow cytometry and real time PCR. Further, the expression of various in-situ genes, including cytokines, chemokines, cytokine receptors chemokine receptors, and transcription factors by qPCR in skin lesions of leprosy patients were analyzed. The phenotypes of ILC1 and ILC3 cells were determined as CD3CCR6CD19IFN-γ and CD3CCR6CD19IL-17A, respectively, by flow-cytometry analysis. BT skin lesions represents high CCR6 expression on total ILCs as compared to LL patients. Our results clearly indicate that ILC1 and ILC3 were highly expressed in skin lesions of BT as compared to LL leprosy patients. Moreover, we observed that double positive (DP) CD3CCR6CD19IFN-γIL-17A ILCs were up-regulated in LL and showed a pathogenic role. The gene expression of IL-17A and IFN-γ were found to be significantly positively correlated with the percentage of CCR6 ILCs. On the other hand, CCR6 ILCs were negatively correlated with ILC1 and ILC3 associated markers. Summarily our results clearly suggest that both ILC1 and ILC3 are important and immune-protective, on the contrary DP (IFN-γIL-17A) ILCs may promote progression and immunopathology of leprosy.

关键词： Rheumatoid arthritis   Growth arrest and DNA damage 45 gamma   Interleukin 10   Collagen-induced arthritis   C-Jun N-terminal kinases  

摘要： It has been shown that Gadd45 beta alleviated K/BxN serum-induced arthritis, but in collagen-induced arthritis (CIA), it exacerbated joint inflammatory response, clinical signs, and symptoms. So far, the function of Gadd45 gamma in arthritis remains to be explored. This study aimed to investigate the role and immune regulatory mechanism of Gadd45 gamma in arthritis by intra-articular injection of a lentiviral vector encoding the Gadd45 gamma gene (LV-Gadd45 gamma) or lentiviral vectors (LV). The experiments showed that CIA increased the level of Gadd45 gamma, overexpression of Gadd45 gamma inhibited the symptoms and articular destruction of CIA, reduced the pro-inflammatory cytokine IL-1 beta, IL-6, and matrix metalloproteinases-13 (MMP-13), and increased the anti-inflammatory cytokine IL-10. In turn, high levels of IL- 10 elevated Gadd45 gamma in CIA mice, human rheumatoid synovial fibroblasts (HRSF), and RAW cell lines. Furthermore, the increasing expression of Gadd45 gamma dramatically raised IL-10 and diminished the phosphorylation of c-Jun N-terminal kinase (JNK) in CIA mice and HRSF. Mechanistic analysis showed that the attenuating effect of Gadd45 gamma on CIA may be attributed to the mutual enhancement of the expression of Gadd45 gamma and IL-10 and the inhibition of JNK activity through downregulating IL-1 beta and IL-6. The results indicate that Gadd45 gamma can act as an inflammatory suppressor and joint damage attenuator in CIA mice. Increased IL-10 levels through a positive feedback circuit between Gadd45 gamma and IL-10 and the inhibitory effect of Gadd45 gamma on JNK activity endows this protein with the ability to inhibit CIA.