American journal of clinical and experimental immunology最新文献

Chronic obstructive pulmonary disease (COPD) is marked by both lung-related and systemic symptoms, notably chronic inflammation. Despite pulmonary rehabilitation (PR) being a critical treatment for COPD, its influence on systemic inflammation remains unclear. This meta-analysis was conducted to assess PR's effect on circulating inflammatory markers in COPD patients. We systematically reviewed databases like PubMed, EMBASE, and Web of Science to select randomized controlled trials and observational studies that investigated the impact of PR on systemic inflammation. We calculated the mean differences (MD) in inflammatory markers before and after PR using a random-effects model and assessed the risk of bias with established tools. Our study included six investigations (four RCTs, two observational) with 147 COPD patients. Our findings show notable increases in IL-6 (MD 0.44, 95% CI 0.17-0.70, P = 0.001), CRP (MD 0.56, 95% CI 0.31-0.81, P<0.00001), and TNF-alpha (MD 0.41, 95% CI 0.12-0.70, P = 0.005) following PR. However, sensitivity analysis pinpointed the study by El-Kader et al. as a key influence on these results. Excluding this study led to nonsignificant changes. Thus, our meta-analysis uncovers an unanticipated rise in inflammatory markers post-PR in COPD patients, questioning the assumed anti-inflammatory benefits of PR.

Objective: The aim of this study was to explore the laboratory results in severe as asthma patients with omalizumab therapy and provide evidence for estimating omalizumab efficacy.

Methods: Retrospective study of 18 patients with severe asthma received omalizumab therapy in Shanghai General Hospital from 2020 to 2022 was performed. The basic data of patients were collected. The absolute number and the percentage of basophil and eosinophil in peripheral blood, total IgE level in serum, and as pulmonary function were detected at the beginning of treatment and 4 months after treatment. Differences between two groups were analyzed using Paired T test.

Results: The most common allergens collected from patients with moderate to severe asthma were dust mite (positive ratio 55.56%), mixed mold (16.67%), cat and dog dander, and Aspergillus fumigatus (11.11%). There was no significant difference in eosinophil and basophil counts in peripheral blood between the two groups. However, serum total IgE levels increased from (437.55±279.35) KU/L to (1071.42±721.28) KU/L (P=0.004), and FEV1/FVC ratio increased from (65.53±14.15)% to (73.91±13.63)% (P=0.005) after 4 months of treatment.

Conclusions: The existing laboratory indicators for evaluation of omalizumab efficacy are still very limited, and new biomarkers need to be further developed. Elevated serum IgE levels at four weeks of treatment and FEV1/FVC may be potential indicators for omalizumab monitoring.

Sarcopenia, characterized by the insidious reduction of skeletal muscle mass and strength, detrimentally affects the quality of life in elderly cohorts. Present therapeutic strategies are confined to physiotherapeutic interventions, signaling a critical need for elucidation of the etiological underpinnings to facilitate the development of innovative pharmacotherapies. Recent scientific inquiries have associated mitochondrial dysfunction and inflammation with the etiology of sarcopenia. Mitochondria are integral to numerous fundamental cellular processes within muscle tissue, including but not limited to apoptosis, autophagy, signaling via reactive oxygen species, and the maintenance of protein equilibrium. Deviations in mitochondrial dynamics, coupled with compromised oxidative capabilities, autophagic processes, and protein equilibrium, result in disturbances to muscular architecture and functionality. Mitochondrial dysfunction is particularly detrimental as it diminishes oxidative phosphorylation, escalates apoptotic activity, and hinders calcium homeostasis within muscle cells. Additionally, deleterious feedback loops of deteriorated respiration, exacerbated oxidative injury, and diminished quality control mechanisms precipitate the acceleration of muscular senescence. Notably, mitochondria exhibiting deficient energetic metabolism are pivotal in precipitating the shift from normative muscle aging to a pathogenic state. This analytical review meticulously examines the complex interplay between mitochondrial dysfunction, persistent inflammation, and the pathogenesis of sarcopenia. It underscores the imperative to alleviate inflammation and amend mitochondrial anomalies within geriatric populations as a strategy to forestall and manage sarcopenia. An initial overview provides a succinct exposition of sarcopenia and its clinical repercussions. The discourse then progresses to an examination of the direct correlation between mitochondrial dysfunction and the genesis of sarcopenia. Concomitantly, it accentuates potential synergistic effects between inflammatory responses and mitochondrial insufficiencies during the aging of skeletal muscle, thereby casting light upon emergent therapeutic objectives. In culmination, this review distills the prevailing comprehension of the mitochondrial and inflammatory pathways implicated in sarcopenia and delineates extant lacunae in knowledge to orient subsequent scientific inquiry.

This study aimed to improve Knee Osteoarthritis (KOA) therapy by evaluating the knowledge framework and investigating research trends in inflammatory mechanisms. Conducting a thorough search on July 31, 2023, using the Science Citation Index Expanded of the Web of Science Core Collection, we identified 1,083 articles authored by 6,159 individuals from 3,610 institutions across 299 countries. China led in productivity with 377 papers, followed by the United States (253) and Japan (60). The University of California System (20 publications), Guangzhou University of Science and Technology (19), Duke University (18), and Shanghai Jiao Tong University (18) were the top institutions. Notably, the USA and Southern Medical University China held significant centrality in countries and institutions, respectively. Among 1,084 co-occurring keywords, "expression", "rheumatoid arthritis", "articular cartilage", "F kappa b", and "Synovial fluid" emerged as highly correlated topics. Analyzing inflammatory mechanisms in KOA through visualization tools offers insights into the knowledge framework, aiding in identifying future trends for better pain control. The study employed CiteSpace, VOS Viewer, and Tableau to analyze research hotspots and frontiers in inflammation mechanisms in KOA. It focused on essential signaling pathways in articular cartilage, synovial membrane, subchondral bone, and synovial fluids of OA patients and animal models, along with potential therapeutic reagents. Future exploration of the interaction between mechanisms can elucidate key factors in different pathways and the efficacy of injection therapy on inflammation.

Objective: This randomized controlled trial aims to compare the effects of high versus low dose extracorporeal shockwave therapy (ESWT) on immune system activation and regulation in elderly patients with osteoarthritis.

Methods: 120 patients aged 65 years and older with knee osteoarthritis will be randomly allocated to receive either high dose (0.25 mJ/mm²) or low dose (0.10 mJ/mm²) ESWT administered weekly for 4 weeks. Serum cytokines, stimulated immune cell subsets, and T regulatory cells will be measured at baseline, 4 weeks after intervention and at 1-month follow-up.

Results: High dose ESWT will increase pro-inflammatory cytokines and decrease immunosuppressive T regulatory cells compared to low dose ESWT in elderly osteoarthritis patients may be the outcome mainly.

Conclusion: This study will provide evidence on ESWT dosing protocols and their differential immunomodulatory effects, which can guide optimal use for musculoskeletal conditions in geriatric populations.

Currently, hepatitis C virus (HCV) infects nearly 3% of the global population, the majority of whom are chronically infected; however, hepatitis C vaccines are still in the developmental stage. Numerous studies suggest that the spontaneous resolution of HCV infection and the design of its vaccine are reliant on vital contributions from CTL cell responses and T regulatory cells. Multiple researchers have identified both Core and nonstructural protein 3 (NS3) proteins as crucial immune genes and potential candidates for HCV DNA vaccine design. In this study, Core and NS3 were subcloned and inserted into pcDNA3.1 to construct HCV DNA vaccines administered in mouse models. Furthermore, the effects of Core and NS3 on the induction of CTL and NK were compared in spleen mouse models using the LDH method. Additionally, flow cytometry was employed to investigate the percentage of T regulatory cells (Treg cells) and cells expressing PD-1 in the spleens of the mouse models. Our data indicated that pcDNA3.1+NS3 and pcDNA3.1+Core could enhance CTL and NK activity in mouse models. Importantly, the Treg and PD-1 analysis in mouse models revealed a substantial reduction in the proportions of CD4+/CD25+/Foxp3+ T cells and PD-1+ cells in experimental subjects treated with HCV NS3 along with 5 mg/kg of lenalidomide, utilized as a novel adjuvant, compared to those administered an equivalent dosage of lenalidomide in conjunction with HCV Core. In conclusion, our observations indicated that the NS3-HCV gene had a limited impact on the activation of inhibitory factors. Therefore, NS3 is considered a more suitable candidate for DNA vaccine design compared to Core HCV.

Griscelli syndrome is a rare inherited autosomal recessive syndrome that causes immunodeficiency. Hemophagocytic lymphohistiocytosis (HLH), which is characterized by a high mortality rate, may develop because of Griscelli syndrome type 2 (GS2). We aimed to share our experience with the diagnosis and treatment methods of patients who developed HLH secondary to GS2. Patients with GS2 who were diagnosed and treated for HLH between 2017 and 2022 at the Cukurova University Division of Pediatric Allergy & Immunology and Division of Pediatric Hematology were included in the study. Microscopic examination of the hair shaft and next-generation sequencing for molecular genetic testing of RAB27A helped in the diagnosis of GS2. The first clinical presentation of 8 patients was HLH. One patient presented with CNS involvement and two patients presented with recurrent fever. Over 5 years, GS2 was diagnosed in 15 patients, of whom 11 (73.3%) developed HLH. The HLH-2004 protocol was used to treat these patients. Hematopoietic stem cell transplantation (HSCT) was performed in five patients who were matched with suitable donors. While all patients who underwent HSCT were alive, three patients who could not undergo HSCT because no donor could be found died. Deletion of CAAGC at nucleotides 514_518 in GS2 patients is associated with CNS involvement and a poor prognosis. HLH may be the first sign of presentation in patients with GS2. Although further research is needed, regardless of the conditioning regimen utilized, early HSCT remains the primary therapy option for preventing GS2-induced mortality in HLH.

Bladder cancer is the most common malignancy in the urinary tract, and is biologically and clinically quite heterogeneous. Around 90% of diagnoses are made in the 6^th decade, being more prevalent in males. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) axis play a putative role in immune checkpoint and as a means through which cancer evades the immune system. Inhibition of the glicogênio synthase kinase (GSK) 3 leads to the downregulation of PD-1 via upregulation of the transcription factor Tbet. The use of biomarkers PD-L1 and GSK-3β and evaluation of the immune infiltrate have very promising correlations with urothelial carcinoma prognosis and treatment prediction.

Objective: To investigate the protein expression of PD-L1 and GSK-3β and the CD8-positive immune infiltrates in bladder carcinomas.

Materials and methods: This was a cross-sectional study of 140 samples of urothelial carcinomas from 2015 to 2018. Automated digitally assisted scoring and conventional analyses of the markers of GSK-3β (27C10), CD8 (7103β) and PDL-1 (22c3), were reviewed by two pathologists independently and a histologic score was calculated. The density of CD8 was also measured.

Results: The immunoexpression of GSK-3β (91%) was presented in most samples, PD-L1 in 62.9% and CD8 cells present in 46.3% of cases. When analyzed in conjunction, the levels of GSK-3β and PD-L1 (P = 0.033), and CD8 and PD-L1 (P<0.002) showed significant correlations. No significant associations were observed between GSK-3β and CD8. The positivity of GSK-3β and PD-L1 was predominant in high-grade tumors.

Conclusion: Despite the tumor microenvironment heterogeneity, the expression of CD8, GSK-3β and PDL1 could be valuable and GSK-3β could be a potential target in advanced bladder cancer, especially in the context of immunotherapy.

Objective: To explore the distribution and epidemiological characteristics of patients with syphilis in a first-class tertiary hospital and to evaluate the coincidence rate between chemiluminescence immunoassay (CLIA) and Treponema pallidum particle agglutination assay (TPPA).

Methods: The medical records of 247,501 outpatients and inpatients were retrospectively analyzed. TPPA was used to verify positive and suspected cases, and the coincidence rate between CLIA and TPPA was evaluated. Receiver operating characteristic (ROC) curve was used to determine optimal diagnostic thresholds.

Results: Of the 247,501 serum samples, 5,173 were detected positive for syphilis using CLIA, with a detection rate of 2.09% and a men-to-women ratio of 1.39. The chi-square test showed that sex and age were both factors that affected the detection rate (χ²=229.51, P < 0.0001). In addition, urology, orthopedics, cardiology, general surgery, gastroenterology, and gynecology represented the top six departments with the highest numbers of positive cases. Comparative analysis showed that the overall coincidence rate between CLIA and TPPA was 80.24%. Analysis of the ROC curve showed that the area under the curve (AUC) was 0.936 (95% confidence interval [CI]: 0.929-0.942, P < 0.0001) using sample/cut-off value (S/CO) as a diagnostic indicator. The results showed that an S/CO value of 3.945 was the best diagnostic value for the CLIA method, with a diagnostic specificity of 93.64% and a sensitivity of 81.90%.

Conclusions: Syphilis is widely distributed in various hospital departments and primarily affects middle-aged and older individuals. For cases that have been initially screened as positive or suspicious, TPPA and other tests should be used for verification to avoid misdiagnosis and missed diagnosis.