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关键词： IL10   B cells   STAT3   regulatory SNP   autoimmune diseases   immunoregulation  

摘要： Interleukin 10 (IL10) is a major anti-inflammatory cytokine that acts as a master regulator of the immune response. A single nucleotide polymorphism rs3024505(C/T), located downstream of the IL10 gene, is associated with several aggressive inflammatory diseases, including systemic lupus erythematosus, Sj & ouml;gren's syndrome, Crohn's disease, and ulcerative colitis. In such autoimmune pathologies, IL10-producing B cells play a protective role by decreasing the level of inflammation and restoring immune homeostasis. This study demonstrates that rs3024505 is located within an enhancer that augments the activity of the IL10 promoter in a reporter system based on a human B cell line. The common rs3024505(C) variant creates a functional binding site for the transcription factor STAT3, whereas the risk allele rs3024505(T) disrupts STAT3 binding, thereby reducing the IL10 promoter activity. Our findings indicate that B cells from individuals carrying the minor rs3024505(T) allele may produce less IL10 due to the disrupted STAT3 binding site, contributing to the progression of inflammatory pathologies.

关键词： Major histocompatibility complex class II molecule   Lung adenocarcinoma   Subtyping   Immune landscape   Immunotherapy  

摘要： Introduction: Major histocompatibility complex class II molecule (MHC-II) is pivotal in anti-tumor immunity, and targeting MHC-II in tumors may help improve patient survival. But function of MHC-II in the immunotherapy and prognosis of lung adenocarcinoma (LUAD) patients has not been thoroughly studied and reported. Methods: We selected LUAD-related MHC-II genes from public databases based on previous literature reports. We identified different subtypes according to expression differences of these genes in different LUAD samples through cluster analysis. We used R package to conduct a series of analyses on different subtypes, exploring their survival differences, gene expression differences, pathway enrichment differences, and differences in immune characteristics and immune therapy. Finally, we screened potential drugs from the cMAP database. Results: We identified two MHC-II-related LUAD subtypes. Our analyses presented that patients with cluster2 subtype showed better prognosis, higher immune scores, higher levels of immune cell infiltration and immune function activation. In addition, patients with this subtype had higher immunophenoscore, lower TIDE scores, and DEPTH scores. We also identified 10 small molecule drugs, such as lenalidomide, VX-745, and tyrphostin-AG-1295. Conclusion: Overall, MHC-II is not only a potential biomarker for accurately distinguishing LUAD subtypes but also a predictive factor for their survival. Our study offers novel insights into understanding of impact of MHC-II in LUAD and offers a new perspective for improving the accurate classification of LUAD patients and enhancing drug treatment.

关键词： Inflammatory cytokines   Lung cancer   Mendelian randomization  

摘要： Background: In recent years, relevant studies have reported that inflammatory cytokines are related to the occurrence of cancer. However, the correlation with lung cancer is not clear. This study used the Mendelian random grouping method to investigate the correlation between inflammatory factors and lung cancer in different populations. Methods: We obtained the single nucleotide polymorphisms (SNPs) of inflammatory cytokines through the open database and the SNPs of lung cancer (European and East Asian) through the IEU OpenGWAS project. Inverse variance-weighted (IVW) MR analyses were used to determine the causalities of exposures and outcomes. Supplementary analyses were also performed using weighted median and MR-Egger regressions. Afterward, sensitivity analyses were performed to test the robustness. Search the ChEMBL database for target drugs and indications for CTACK, IL-2, and IL-13. Results: By IVW method, we found that CTACK, IL-2, and IL-13 were associated with an increased risk of lung cancer in the European population (CTACK, OR = 1.098, 95 % CI 1.001-1.204, P = 0.047;IL-2, OR = 1.112, 95 % CI 1.009-1.225, P = 0.032;IL-13, OR = 1.068, 95 % CI 1.007-1.132, P = 0.029), while only IL-13 was associated with an increased risk of lung cancer in the East Asian population (IL-13, OR = 1.110, 95 % CI 1.010-1.220, P = 0.030). The weighted median and MR-Egger regression methods were in the same direction as the IVW effect sizes. Furthermore, no evidence of multidirectionality was detected using the MR-Egger intercept as a sensitivity analysis. Currently, there are no approved or phase III studied indications for CTACK, IL-2, and IL13 targets in lung cancer. Conclusion: The study outcomes supported that the inflammatory cytokines CTACK, IL-2, and IL-13 increase the risk of lung cancer. There is a lack of indications for drugs in these three targets. We explored the causal relationship between inflammatory cytokines and lung cancer, providing a basis for future cance

关键词： Post COVID-19 syndrome   dyspnoea   fatigue   exercise intolerance   low-intensivity rehabilitation setting   Spa rehabilitation setting  

摘要： Background. Post COVID-19 syndrome is a frequent disabling outcome, leading to a delay in social reintegration and return to working life. Study design. This was a prospective observational cohort study. The main objective was to explore the effectiveness of a Spa rehabilitation treatment on the improvement of post COVID-19 dyspnoea and fatigue, also analyzing the relationship between such symptoms. Additionally, it was assessed if different clinical characteristics could predispose patients in experiencing post COVID-19 symptoms or could influence the effectiveness of a Spa intervention. Methods. From July to November 2021, 187 post COVID-19 patients were enrolled in the study. All the patients complained persisting dyspnoea, whose impact on daily activities was assessed using the modified Medical Research Council dyspnoea scale. 144 patients (77.0%) reported also fatigue. The Spa treatment was started at least 3 months after COVID-19 acute phase. At the end of the treatment, patients were asked to rate the improvement in the dyspnoea and fatigue sensation. 118 patients also underwent the modified Borg Dyspnoea Scale for severity estimation of Exertion Dyspnoea and the Barthel index for severity estimation of Physical Limitation. Results. 165 out of 187 patients (88.2%) reported an improvement in dyspnoea, while 116 out 144 patients (80.6%) reported an improvement in both dyspnoea and fatigue. On a total of 118 subjects, a clinically significant improvement in the modified Borg Dyspnoea Scale (i.e. Delta Borg equal or more than -2.0 points) was reached by the 50.8% of patients, while a clinically significant improvement in the Barthel index (i.e. Delta Barthel equal or more than +10.0 points) was reached by the 51.7% of them. The 31.4% of patients reached a minimal clinically important improvement in both the modified Borg Dyspnoea Scale and the Barthel index. No risk factors were associated to a clinically impacting dyspnoea at entry, while a BMI>30 Kg/m(2) was th

关键词： cytokine   macular edema   age-related macular degeneration   interleukin  

摘要： P URPOSE . To evaluate the effect of intravitreal bevacizumab on aqueous levels of a panel of 12 inflammatory cytokines in patients with neovascular age-related macular degeneration (nAMD) and correlate response to treatment, as measured by change in the central subfovea thickness (CST), with cytokine levels. M ETHODS . Thirty-three treatment-na & iuml;ve patients with nAMD received a loading dose of intravitreal bevacizumab consisting of three injections at six weekly intervals. The aqueous samples prior to the first (baseline), second (week 6), and third (week 12) injections were analyzed for cytokine levels. Participants were subgrouped based on changes in CST on spectral-domain optical coherence tomography (SD-OCT) at 12 weeks. Group 1 included patients with a decrease in CST (responders;n = 27). Group 2 included patients who had no decrease in CST (poor responders;n = 6). R ESULTS . Aqueous IL-8 was the only cytokine to demonstrate a significant difference in levels between responders and poor responders, with higher interleukin-8 (IL-8) at week 12 in the poor responder group. Aqueous IL-6 and IL-8 levels showed a positive correlation with CST on SD-OCT (Spearman r = 0.45 and 0.55, respectively). There was a temporal increase overall in cytokine concentration accompanying bevacizumab treatment. C ONCLUSIONS . Aqueous IL-6 and IL-8 may be important markers of treatment response or poor response in nAMD. Future therapeutic strategies may include targeted treatment against both vascular endothelial cell growth factor (VEGF) and IL-6 and/or IL-8 in patients who do not respond to anti-VEGF treatment alone.

关键词： clinical chemistry test   cost   cost analysis   suitable prescription   Inappropriate prescription   hidden cost   cost calculation   immunology   TDABC  

摘要： The relevant and correct prescribing of medical biology is a major public health issue. Correct prescribing is a legal obligation under article L6211-8 of the French Public Health Code and is an integral part of the biologist's daily work, already specified in the 2012 (section 4.7) and 2022 (section 5.3.3) versions of the NF EN ISO 15189 standard. COFRAC document SH REF 02 v08 specifies the requirements for consultancy services. The adaptation of the prescriptions is a revision of the contract with the prescriber, which makes it possible to optimize patient care and ensure the satisfaction of the laboratory users. Although essential, accurate prescribing is time consuming. "Chronophage" is the term that has been used for almost a decade. At present, the work of biologists in this area is not valued. In fact, there is no evaluation system to highlight this regulation control activity. To date, no work has been published to estimate this time, this chronophagy, and to evaluate its impact. Cost measurement using Time-Driven Activity-Based Costing (TDABC), a variant of Activity-Based Costing (ABC), is based on a process approach. The main contribution of TDABC is that it uses a single cost driver: time. Serum immunofixation is a test used to confirm and monitor plasma cell dyscrasias, the archetype of which is multiple myeloma. The learned societies and the IMWG provide explicit diagnostic criteria, but the guidelines do not address the frequency of follow-up. In particular, the frequency of repeat and follow-up serum immunofixation remains unaddressed from an evidence-based medicine perspective. This work has made it possible to highlight the savings made between 1st January and 31th August 2023 thanks to the involvement of the biologist and to highlight his essential role in the process of controlling the overall expenditure (reagents, human resources, time and money) in the specialized biochemistry sector (bench: proteins) and to strengthen the role of the biologist

关键词： Cervical cancer   IL-32   miR-205   Migration   Invasion  

摘要： Human papillomavirus (HPV) infection is a major contributor to cervical cancer. Persistent HPV infection can trigger the expression of IL-32, yet the precise role of IL-32 in the occurrence and development of cervical cancer remains elusive. To investigate this, qRT-PCR and western blotting were utilized to measure the mRNA and protein expression levels;bioinformatics analysis was used to screen differentially expressed miRNAs;wound healing and transwell assays were conducted to evaluate cell migration and invasion capabilities. Comparative analysis revealed significantly elevated IL-32 expression in cervical cancer tissues and cell lines compared to control groups. In SiHa and/or HeLa, overexpression of IL-32 and IL-32 exposure markedly upregulated miR-205, whereas its knockdown resulted in a substantial downregulation of miR-205. Furthermore, miR-205 also could significantly regulate the expression of IL-32 in HeLa and SiHa cells. Upregulation and downregulation of IL-32 led to a significant increase or decrease in NF kappa B expression, respectively. Treatment with BAY11-7082 (an NF kappa B inhibitor) notably decreased miR-205 expression but had no effect on IL-32 levels. qRT-PCR and western blotting analyses demonstrated that both overexpression and underexpression of IL-32 and miR-205 significantly enhanced or reduced MMP2 and MMP9 expression in cervical cancer cells, respectively. Knockdown of IL-32 significantly inhibited the migration and invasion of HeLa and SiHa;conversely, treatment with rIL-32 alpha and rIL-32 gamma notably promoted their migration and invasion. In brief, IL-32 is highly expressed via the formation of a positive regulatory loop with NF kappa B/miR-205, contributing to the persistence of inflammation and promoting the progression of cervical cancer.

关键词： robotics   rehabilitation   interleukin-1   brain injuries   brain-derived neurotrophic factor  

摘要： Acquired brain injury (ABI) is becoming increasingly common in Malaysia as a result of a rise in both strokes and accidents. The present review aims to explore the levels of serum inflammatory markers of interleukin-1 (IL-1) and brain-derived neurotrophic factor (BDNF) following conventional and robotic rehabilitation regimes among ABI patients and the association between serum biomarkers with the Medical Research Council (MRC) scale for muscle strength. Online databases, namely ScienceDirect, PubMed, and Google Scholar were utilized by using search terms such as 'Definition of brain injury', 'Epidemiology of brain injury', 'Interleukin-1 in stroke', 'BDNF in stroke', 'Interleukin-1 in traumatic brain injury', 'BDNF in traumatic brain injury', 'Interleukin-1 level and robotic rehabilitation', 'BDNF and robotic rehabilitation', 'Interleukin-1 level and neurorehabilitation', and 'BDNF and neurorehabilitation'. All types of articles with different levels of evidence were included along with other relevant review articles. Articles that were not in English and were not available in the full text were excluded. The review identifies similar and no significant improvement in the treatment between conventional rehabilitation and robotic rehabilitation concerning serum biomarkers IL-1 and BDNF. This review also identifies that muscle strength and endurance training improved the level of serum BDNF in brain injury patients. Therefore, this review provides evidence of the levels of IL-1 and BDNF in noninvasive conventional rehabilitation and robotic rehabilitation among brain injury patients, as well as their relation with the MRC scale, to give a good functional outcome that will enhance the quality of life of these groups of individuals.

关键词： aging   inflammation   immune system   oxidative stress   T cells  

摘要： Cytokines are the primary mediators of age-related disorders. The IL-17/IL-10 axis plays a crucial role in bone destruction and neuro-inflammation. Additionally, a new Th2 cytokine-IL-33-has gained attention for its potential implications in aging-associated conditions. However, the involvement of IL-33 in aging-mediated bone loss and memory impairment remains unclear and needs further investigation. This study reveals the impact of IL-33 on various aspects of the immune system, bone health, and neural functions. To induce senescence, we used d-galactose for its convenience and fewer side effects. The experimental design involved treating 20-week-old C57BL/6J mice with d-galactose subcutaneously for 10 weeks to induce aging-like effects. Thereafter, IL-33 recombinant protein was administered intraperitoneally for 15 days to evaluate its impact on various immune, skeletal, and neural parameters. The results demonstrated that d-galactose-induced aging led to bone loss and compromised osteogenic parameters, accompanied by increased oxidative stress and neurodegeneration in specific brain regions. Behavioral activities were also affected. However, supplementation with IL-33 mitigated these effects, elevating osteogenic parameters and reducing senescence markers in osteoblast cells in an aging mouse model and exerted neuroprotective potential. Notably d-galactose-induced aging was characterized by high bone turnover, reflected by altered serum levels of CTX, PTH, beta-galactosidase, and P1NP. IL-33 treatment attenuated these effects, suggesting its role in regulating bone metabolism. Furthermore, d-galactose-induced aging was associated with increased differentiation of Th17 cells and upregulation of associated markers, such as STAT-3 and ROR-gamma t, while downregulating Foxp3, which antagonizes Th17 cell differentiation. IL-33 treatment countered these effects by suppressing Th17 cell differentiation and promoting IL-10-producing T-regulatory cells. Overall, these find