Samoocena jakości życia seniorów ze schorzeniami neurologicznymi

Introduction. Quality of life and old age are closely related. Aging is perceived as a destructive, progressive, and irreversible process. This process is caused by biological factors related to physical involution as well as psychosocial factors. Elderly people have difficulties related to deteriorating health.Aim. The study aims to determine the quality of life of elderly people with neurological disorders.Material and Methods. The research was conducted in the Lublin Voivodeship, in a group of 111 elderly people diagnosed with neurological diseases. 51.35% of participants were female. The age of the respondents was in the range of 65–95 years. A standardized questionnaire: the WHOQOL-BREF constituted the research tool.Results. In the examined group of patients, the general quality of life was assessed at an average level of 3.11 ± 1.12, and the assessment of health at the level of 2.81 ± 1.00. The respondents rated the highest the environmental domain (57.05 ± 16.23). The social relationship domain was at an average level; 54.00 ± 24.08, while the psychological one was 46.38 ± 13.16. The physical health domain received the lowest scores (44.53 ± 12.42).Conclusions. The self-evaluation of the quality of life completed by elderly people with neurological disorders was at a low level. Marital status differentiated the quality of life in the social domain. The residence of the studied seniors influenced the assessment of their overall quality of life. (JNNN 2019;8(1):11–15)Wstęp. Jakość życia i starość są ze sobą ściśle związane. Starzenie się postrzegane jest jako proces destrukcyjny, postępujący i nieodwracalny. Proces ten powodują czynniki biologiczne związane z inwolucją fizyczną jak i czynniki psychospołeczne. Osoby starsze mają trudności związane z pogarszającym się stanem zdrowia.Cel. Celem badań było określenie jakości życia osób w podeszłym wieku ze schorzeniami neurologicznymi.Materiał i metody. Badania przeprowadzono na terenie województwa lubelskiego, w grupie 111 osób w podeszłym wieku, u których stwierdzono występowanie chorób neurologicznych. W badanej grupie było 51.35% kobiet. Wiek badanych zawierał się w przedziale 65–95 lat. W pracy wykorzystano wystandaryzowane narzędzie badawcze: skalę WHOQOL-Bref.Wyniki. W badanej grupie pacjentów ogólna jakość życia oceniona została na poziomie średniej 3,11 ± 1,12, a ocena stanu zdrowia na poziomie 2,81 ± 1,00. Badani najlepiej ocenili dziedzinę środowiskową (57,05 ± 16,23). Dziedzina społeczna kształtowała się na poziomie średniej 54,00 ± 24,08, natomiast dziedzina psychologiczna na poziomie 46,38 ± 13,16. Najniżej badani ocenili dziedzinę somatyczną (44,53 ± 12,42).Wnioski. Samoocena jakości życia dokonana przez osoby starsze ze schorzeniami neurologicznymi kształtowała się na obniżonym poziomie. Stan cywilny różnicował jakość życia w zakresie dziedziny społecznej. Miejsce zamieszkania badanych seniorów wpływało na ocenę ich ogólnej jakości życia. (PNN 2019;8(1):11–15

CXCR4 upregulation is an indicator of sensitivity to B-cell receptor/PI3K blockade and a potential resistance mechanism in B-cell receptor-dependent diffuse large B-cell lymphomas

B-cell receptor (BCR) signaling pathway components represent promising treatment targets in multiple B-cell malignancies including diffuse large B-cell lymphoma (DLBCL). In in vitro and in vivo model systems, a subset of DLBCLs depend upon BCR survival signals and respond to proximal BCR/phosphoinositide 3 kinase (PI3K) blockade. However, single-agent BCR pathway inhibitors have had more limited activity in patients with DLBCL, underscoring the need for indicators of sensitivity to BCR blockade and insights into potential resistance mechanisms. Here, we report highly significant transcriptional upregulation of C-X-C chemokine receptor 4 (CXCR4) in BCR-dependent DLBCL cell lines and primary tumors following chemical spleen tyrosine kinase (SYK) inhibition, molecular SYK depletion or chemical PI3K blockade. SYK or PI3K inhibition also selectively upregulated cell surface CXCR4 protein expression in BCR-dependent DLBCLs. CXCR4 expression was directly modulated by fork-head box O1 via the PI3K/protein kinase B/forkhead box O1 signaling axis. Following chemical SYK inhibition, all BCR-dependent DLBCLs exhibited significantly increased stromal cell-derived factor-1α (SDF-1α) induced chemotaxis, consistent with the role of CXCR4 signaling in B-cell migration. Select PI3K isoform inhibitors also augmented SDF-1α induced chemotaxis. These data define CXCR4 upregulation as an indicator of sensitivity to BCR/PI3K blockade and identify CXCR4 signaling as a potential resistance mechanism in BCR-dependent DLBCLs

BCR signaling inhibitors differ in their ability to overcome Mcl-1-mediated resistance of CLL B cells to ABT-199

The Bcl-2 antagonist ABT-199 has demonstrated promising clinical activity in patients with CLL. ABT-199 is strongly cytotoxic against unstimulated peripheral blood CLL cellsin vitro, but is much less effective against CLL cells that have received survival signals from the microenvironment. In particular, stimulation of CLL cells with CD40L results in substantial resistance that is mediated by induction of the antiapoptotic Bcl-2 family proteins Bcl-xLand Bfl-1. In the present study we investigated whether resistance to ABT-199 can be conferred by B-cell receptor (BCR) stimulation, which is another important survival signal from the leukemic microenvironment. We show that sustained BCR stimulation results in significant ABT-199-resistance, which correlates with induction of the antiapoptotic protein Mcl-1 and less consistently with downregulation of proapoptotic Bmf, Hrk and BimEL A major role for Mcl-1 in conferring ABT-199 resistance is additionally supported by knockdown and enforced expression experiments with primary CLL cells. We further show that SYK, BTK and PI3K\u3b4 inhibitors significantly downregulate Mcl-1, but with different efficacy. Complete Mcl-1 downregulation was consistently achieved only with the SYK inhibitors R406 and GS-9973, whereas the BTK inhibitor ibrutinib and the PI3K\u3b4 inhibitor idelalisib in more than half of the cases had only a partial effect. The greater ability of SYK inhibitors to downregulate Mcl-1 correlated with their greater capacity to block BCR-mediated inactivation of GSK-3, a major negative regulator of Mcl-1. The finding that BCR-signaling inhibitors differ in their ability to target Mcl-1 is relevant for the design of clinical trials combining these agents with ABT-199

The Mutual Interactions between Mesenchymal Stem Cells and Myoblasts in an Autologous Co-Culture Model

<div><p>Both myoblasts and mesenchymal stem cells (MSC) take part in the muscle tissue regeneration and have been used as experimental cellular therapy in muscular disorders treatment. It is possible that co-transplantation approach could improve the efficacy of this treatment. However, the relations between those two cell types are not clearly defined. The aim of this study was to determine the reciprocal interactions between myoblasts and MSC <i>in vitro</i> in terms of the features important for the muscle regeneration process. Primary caprine muscle-derived cells (MDC) and bone marrow-derived MSC were analysed in autologous settings. We found that MSC contribute to myotubes formation by fusion with MDC when co-cultured directly, but do not acquire myogenic phenotype if exposed to MDC-derived soluble factors only. Experiments with exposure to hydrogen peroxide showed that MSC are significantly more resistant to oxidative stress than MDC, but a direct co-culture with MSC does not diminish the cytotoxic effect of H₂O₂ on MDC. Cell migration assay demonstrated that MSC possess significantly greater migration ability than MDC which is further enhanced by MDC-derived soluble factors, whereas the opposite effect was not found. MSC-derived soluble factors significantly enhanced the proliferation of MDC, whereas MDC inhibited the division rate of MSC. To conclude, presented results suggest that myogenic precursors and MSC support each other during muscle regeneration and therefore myoblasts-MSC co-transplantation could be an attractive approach in the treatment of muscular disorders.</p></div

MDC and MSC proliferation rate.

<p>Proliferation of MDC (A) and MSC (B) derived from the same donors (n = 6) was measured with BrdU assay. Data presented as means, SEM, SD. The graphs present proliferation of cells cultured in standard GM (CTRL), GM supplemented with bFGF and cells cultured in 100% conditioned medium (cond) derived either from MDC or MSC. Data analysed with Wilcoxon test for related groups. Values that differed significantly (p<0.05) were indicated as following: * in comparison to CTRL group; # in comparison to bFGF group; ^ in comparison to the second conditioned group. Tests were performed in triplicates.</p