Damage-mediated macrophage polarization in sterile inflammation

Most of the leading causes of death, such as cardiovascular diseases, cancer, dementia, neurodegenerative diseases, and many more, are associated with sterile inflammation, either as a cause or a consequence of these conditions. The ability to control the progression of inflammation toward tissue resolution before it becomes chronic holds significant clinical potential. During sterile inflammation, the initiation of inflammation occurs through damage-associated molecular patterns (DAMPs) in the absence of pathogen-associated molecules. Macrophages, which are primarily localized in the tissue, play a pivotal role in sensing DAMPs. Furthermore, macrophages can also detect and respond to resolution-associated molecular patterns (RAMPs) and specific pro-resolving mediators (SPMs) during sterile inflammation. Macrophages, being highly adaptable cells, are particularly influenced by changes in the microenvironment. In response to the tissue environment, monocytes, pro-inflammatory macrophages, and pro-resolution macrophages can modulate their differentiation state. Ultimately, DAMP and RAMP-primed macrophages, depending on the predominant subpopulation, regulate the balance between inflammatory and resolving processes. While sterile injury and pathogen-induced reactions may have distinct effects on macrophages, most studies have focused on macrophage responses induced by pathogens. In this review, which emphasizes available human data, we illustrate how macrophages sense these mediators by examining the expression of receptors for DAMPs, RAMPs, and SPMs. We also delve into the signaling pathways induced by DAMPs, RAMPs, and SPMs, which primarily contribute to the regulation of macrophage differentiation from a pro-inflammatory to a pro-resolution phenotype. Understanding the regulatory mechanisms behind the transition between macrophage subtypes can offer insights into manipulating the transition from inflammation to resolution in sterile inflammatory diseases

Hungarian Linguistic, Cross-Cultural and Age Adaptation of Transition Specific Questionnaires in Patients with Inflammatory Bowel Disease

Objective: In the TRANS–IBD clinical trial, the outcomes are measured with selected validated questionnaires. Cross-cultural and age adaptations of the Self-Efficacy Scale for adolescents and young adults (IBD–SES), the Transition Readiness Assessment Questionnaire (TRAQ), and the Self-Management and Transition Readiness Questionnaire (STARx) were performed. Methods: Linguistic and cultural adaptation was carried out with the usage of reliability coefficients (Cronbach’s α coefficients, Spearman’s rank correlation), and with confirmatory factor analysis (CFA; root Mean Square Error of Approximation [RMSEA], Comparative Fit Index [CFI], and Tucker-Lewis Index [TLI]). Results: 112 adolescents participated in the study (45.5% male, mean age 17 ± 1.98 years). CFA was acceptable in the IBD–SES and the TRAQ. Internal consistency was acceptable in IBD–SES and good in TRAQ (0.729; 0.865, respectively). Test–retest reliability was good in IBD–SES, but below the acceptable threshold in TRAQ (ρ = 0.819; ρ = 0.034). In STARx tools, RMSEA showed poor fit values, CFI and TLI were below acceptable fit values, and internal consistency was not satisfied (0.415; 0.693, respectively), while test–retest reliabilities were acceptable (ρ = 0.787; ρ = 0.788, respectively). Conclusions: Cross-cultural, age-specific adaptation was successfully completed with IBD–SES and TRAQ. Those are comparable to the original validated versions. The adaption of the STARx tools was not successful

Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL)

Modern treatment strategies have improved the prognosis of childhood ALL; however, treatment still fails in 25–30% of patients. Further improvement of treatment may depend on the development of targeted therapies. mTOR kinase, a central mediator of several signaling pathways, has recently attracted remarkable attention as a potential target in pediatric ALL. However, limited data exists about the activity of mTOR. In the present study, the amount of mTOR activity dependent phospho-proteins was characterized by ELISA in human leukemia cell lines and in lymphoblasts from childhood ALL patients (n = 49). Expression was measured before and during chemotherapy and at relapses. Leukemia cell lines exhibited increased mTOR activity, indicated by phospho-S6 ribosomal protein (p-S6) and phosphorylated eukaryotic initiation factor 4E binding protein (p-4EBP1). Elevated p-4EBP1 protein levels were detected in ALL samples at diagnosis; efficacy of chemotherapy was followed by the decrease of mTOR activity dependent protein phosphorylation. Optical density (OD) for p-4EBP1 (ELISA) was significantly higher in patients with poor prognosis at diagnosis, and in the samples of relapsed patients. Our results suggest that measuring mTOR activity related phospho-proteins such as p-4EBP1 by ELISA may help to identify patients with poor prognosis before treatment, and to detect early relapses. Determining mTOR activity in leukemic cells may also be a useful tool for selecting patients who may benefit from future mTOR inhibitor treatments

N-glycan analysis via capillary electrophoresis

A szénhidrátoknak az élő szervezetekben számos funkciót töltenek be, mint energiaforrás, szignalizációs molekulák, támasztó szerkezetek. A legjobban kutatott glikokonjugátum csoport az N-glikán. Munkám során azt vizsgáltam, hogy a PNGase F enzimmel történő N-glikánok emésztése során, mely puffer komponenseket érdemes alkalmazni. Főként az ammónium-só tartalmú pufferekre koncentrálva. Standard immunoglobulin G1, humán szérum és saját biológiai szérum mintákat feldolgozva. A minta előkészítés után kapilláris elektroforetikus módszerrel szeparáltam a szénhidrát struktúrákat.BSc/BABiológi

An unusual case of childhood osteoarticular tuberculosis from the Árpádian Age cemetery of Győrszentiván-Révhegyi tag (Győr-Moson-Sopron county, Hungary).

Ancient human remains exhibiting bony changes consistent with osteoarticular tuberculosis (OATB) indicate that the disease has afflicted mankind for millennia. Nonetheless, not many pediatric OATB cases have been published in the paleopathological literature-from Hungary, only three cases have been described up to now. In our paper, we demonstrate a child (S0603) from the Árpádian Age cemetery of Győrszentiván-Révhegyi tag (northwestern Hungary), who represents a unique case of OATB regarding both the pattern and severity of the observed bony changes. During the macromorphological and radiological investigations, the most serious alterations were discovered in the upper thoracic spine-the development of osteolytic lesions led to severe bone loss and consequent collapse and fusion of several adjacent vertebrae. The pathological process terminated in a sharp, rigid angular kyphosis. Disruption of the normal spine curvature resulted in consequent deformation of the whole thoracic wall-it became "rugby-ball-shaped". The overall nature and pattern of the detected alterations, as well as their resemblance to those of described in previously published archaeological and modern cases from the pre-antibiotic era indicate that they are most consistent with OATB. Based on the severity and extent of the lesions, as well as on the evidence of secondary healing, S0603 suffered from TB for a long time prior to death. Besides body deformation, OATB resulted in consequent disability in daily activities, which would have required regular and significant care from others to survive. It implies that in the Árpádian Age community of Győrszentiván-Révhegyi tag, there was a willingness to care for people in need. Detailed archaeological case studies can give us a unique insight into the natural history and different presentations of OATB. Furthermore, they can provide paleopathologists with a stronger basis for diagnosing TB and consequently, with a more sensitive means of assessing TB frequency in past populations

The amount of mTOR activity dependent phospho-proteins (p-4EBP1 and p-S6) in lymphoma/leukemia cells (ELISA).

<p>(a.) P-4EBP1 ODs are shown for normal control peripheral blood mononuclear cells (N1, N2, N3), isolated peripheral normal B- and T-cells (B, T), isolated peripheral blood mononuclear cells and isolated bone marrow mononuclear cells from non-leukemic patients (NL) and isolated primary childhood ALL cells from representative patient samples, and from leukemia (Jurkat, CEM, Mn60, Nalm6) and lymphoma cell lines (KMH2). (b.) Relative p-4EBP1 and p-S6 expression was determined in samples from ALL patients (n = 10) and in leukemia/lymphoma cell lines (Jurkat, CEM, Mn60, Nalm6, KMH2); expression of normal lymphoid cells is considered to be 1. (OD: optical density; MNC: mononuclear cells. Equal cell numbers and equal protein concentrations were confirmed for comparisons.).</p

Multivariate analysis of various standard independent prognostic factors in ALL cases.

*<p>Cutoff value is 1.1 p-4EBP1 OD.</p><p>RR – relative risk, 95% CI –95% confidence interval.</p><p>na – not applicable.</p