Combination regimens of Bifidobacterium infantis and Lactobacillus acidophilus have been demonstrated to prevent necrotizing enterocolitis (NEC) in clinical trials. However, the molecular mechanisms ...responsible for this protective effect are not well understood. Additionally, conditioned media from individual cultures of these two probiotics show strain specific modulation of inflammation using in vitro human intestinal NEC models. Here we report a transcription profiling analysis of gene expression in immature human fetal intestinal epithelial cells (H4 cells) pretreated with conditioned media from B. infantis (BCM) or L. acidophilus (LCM) prior to IL-1 beta stimulation. Compared with control media, the two probiotic-conditioned media (PCM) treatments altered the expression of hundreds of genes involved in the immune response, apoptosis and cell survival, cell adhesion, the cell cycle, development and angiogenesis. In IL-1 beta -stimulated cells, PCM treatment decreased the upregulation of genes in the NF- Kappa B activation pathway and downregulated genes associated with extracellular matrix (ECM) remodeling. Compared with LCM, BCM showed more significant modulatory effects on ECM remodeling, reflected by a lower p value. IL-6 and IL-8 production was significantly reduced in IL-1 beta -stimulated cells pretreated with PCM (p<0.05), which was consistent with their altered gene expression. Western blot analysis showed that compared with IL-1 beta stimulation alone, PCM treatment attenuated the decrease of cytoplasmic I Kappa B alpha and NF- Kappa B p65 levels as well as the increase of nuclear NF- Kappa B p65 levels in the stimulated cells (p<0.05). In conclusion, PCM treatment exerted anti-inflammatory effects in immature human fetal enterocytes primarily by modulating genes in the NF- Kappa B signaling and ECM remodeling pathways. Additionally, some components of these signaling pathways, particularly the ECM remodeling pathway, were more profoundly affected by BCM than LCM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this thesis we take network biology approaches using large scale microarray expression data in order to gain insight in three biological problems. First, using a compendium of cancer microarray ...expression profiles, we show that reverse-engineered gene networks can be combined with expression profiles to compute the likelihood that genes and associated pathways are mediators of a disease. We apply our method to non-recurrent primary and metastatic prostate cancer data, and identify the androgen receptor gene (AR) among the top genetic mediators and the AR pathway as a highly enriched pathway for metastatic prostate cancer. These results were not obtained on the basis of expression change alone. We further demonstrate that the AR gene, in the context of the network, can be used as a marker to detect the aggressiveness of primary prostate cancers. Next, we use a T-cell expression compendia in order to identify the regulators of the T-regulatory (Treg) cells, key mediators of immune tolerance. Using a transcriptional regulatory network, we show that there are multiple regulators of this signature, in contrast to the well established notion that FOXP3 is the master regulator. We identify IKZF2 as another regulator of the Treg signature. By experimentally perturbing FOXP3 and IKZF2, we show that both transcription factors contribute to the regulation of genes in the Treg signature. Finally, using matched microRNA-mRNA expression profiles from the NCI-60 collection of cancer cell lines, we probe the microRNA regulatory networks in cancer. We identify miRNA-224 as a potential regulator of gene-expresion changes involved in cell cycle regulation and demonstrate that alterations in miRNA-224 impact the phenotype of lung cancer cell lines in-vitro, suggesting a potential role for this microRNA in lung carcinogenesis. These findings demonstrate that network based systems biology approaches applied to large scale expression profiles can be used advantageously to identify genetic mediators associated with disease.
Leveraging TCGA’s multi-dimensional data in glioblastoma (GBM), we inferred the putative regulatory network between microRNA and mRNA using the Context-Likelihood-Relatedness (
1
) modeling ...algorithm. Interrogation of the network in context of defined molecular subtypes identified 8 microRNAs with a strong discriminatory potential between proneural and mesenchymal subtypes. Integrative
in silico
analyses, functional genetic screen and experimental validation identified miR-34a as a tumor suppressor in proneural subtype GBM. Mechanistically, in addition to its direct regulation of PDGFRA, promoter enrichment analysis of CLR-inferred mRNA nodes established miR-34a as a novel regulator of a Smad4 transcriptional network. Clinically, miR-34a expression level is shown to be prognostic, where miR-34a low-expressing GBMs exhibited better overall survival. This work illustrates the potential of comprehensive multi-dimensional cancer genomic data combined with computational and experimental models in enabling mechanistic exploration of relationships among different genetic elements across the genome space in cancer.
Aim: Bell's palsy is a form of deficiency in the face and paralysis related to peripheral- nerve dysfunction. Our study investigates the role of the inflammatory values in predicting Bell’s palsy ...prognosis.
Methods: A total of 58 Bell’s palsy ≥ III patients, according to the House Brackman classification, on the first presentation were taken as the study group, and 60 age and gender-matched healthy people without any disease formed the control group. The success of the corticosteroid treatment was accepted as House Brackmann grades I and II in the post-treatment follow-up, and grades III to VI patients were evaluated as partial-not meaningful recovery. In addition, pretreatment hemogram and biochemistry tests were recorded, and the C-reactive protein (CRP)/albumin ratio, Neutrophil to lymphocyte ratio (NLR), red blood cell distribution width (RDW), and mean platelet volume (MPV) of the patients were compared.
Results: In the study group, the CRP/albumin ratio and the mean RDW were statistically significantly higher than the control group (0.958 ± 0.91 vs. 0.478 ± 0.322, p = 0.029; 13.89 ± 1.27 vs. 12.98 ± 0.72, p 0.05).
Conclusion: Higher CRP/albumin, RDW, NLR, MPV were related to a poor prognosis for Bell’s palsy. RDW, which to date has been a widely used marker for inflammation, could be a potentially promising marker for use in predicting prognosis in Bell’s palsy.
Stone monuments are important symbols of cultural heritage of countries. However, many environmental factors negatively affect these monuments. The increasing damage on the stone monuments and the ...danger of irreversible loss of cultural heritage have resulted in growing efforts for the preservation of the monuments. Eflatunpınar Hittite Water Monument in Beyşehir, Konya, Turkey, is a unique Hittite cultural monument that has survived for nearly 3200 years even though it has been exposed to many environmental effects. In this study, non-destructive testing (NDT) was used to detect the degradation on the building stones of the Eflatunpınar Hittite Water Monument and change-deterioration maps were prepared subsequently. It was also investigated whether the chemistry of the Eflatunpınar spring water may cause deterioration. Additionally, the petrographic, chemical, and physico-mechanical properties of the rocks taken from the ancient stone quarry were determined in order to compare with the properties of the monument’s building stones. Based on the physico-chemical characteristics of the Eflatunpınar spring water and XRD results of crusts in building stone surface of the monument, it was identified that water can be effective on the formation of calcite and gypsum crusts especially in the lower parts of the monument. However, applied NDT methods and change-deterioration maps indicated that the deterioration as well as neglect and abandonment in the monument are mostly associated with the capillary effect of the flowing water through the structure and the deterioration effect is more apparent in contact points between the building stone and the flowing water. Additionally, in the building stones above the capillary front, the conservation condition is significantly better.
Internalized stigma, adoption of negative attitudes and stereotypes of the society regarding persons' illness, has not been studied previously in pediatric psoriasis patients.
We aimed to investigate ...the internalized stigma in pediatric psoriasis patients and to determine differences according to factors affecting internalized stigma compared to adult psoriasis patients.
This multicenter, cross-sectional, comparative study included 125 pediatric (55 female, 70 male; mean age±standard deviation SD, 14.59±2.87 years) and 1,235 adult psoriasis patients (577 female, 658 male; mean age±SD, 43.3±13.7 years). Psoriasis Internalized Stigma Scale (PISS), Dermatology Life Quality Index (DLQI), Perceived Health Status (PHS), and the General Health Questionnaire (GHQ)-12 were the scales used in the study.
The mean PISS was 58.48±14.9 in pediatric group. When PISS subscales of groups were compared, the pediatric group had significantly higher stigma resistance (
=0.01) whereas adult group had higher scores of alienation (
=0.01) and stereotype endorsement (
=0.04). There was a strong correlation between mean values of PISS and DLQI (r=0.423,
=0.001). High internalized stigma scores had no relation to either the severity or localization of disease in pediatric group. However, poor PHS (
=0.007) and low-income levels (
=0.03) in both groups, and body mass index (r=0.181,
=0.04) in the pediatric group were related to high PISS scores.
Internalized stigma in pediatric patients is as high as adults and is related to poor quality of life, general health, and psychological illnesses. Unlike adults, internalized stigma was mainly determined by psoriasis per se, rather than disease severity or involvement of visible body parts, genitalia or folds.
Background: Internalized stigma, adoption of negative attitudes and stereotypes of the society regarding persons’ illness, has not been studied previously in pediatric psoriasis patients. Objective: ...We aimed to investigate the internalized stigma in pediatric psoriasis patients and to determine differences according to factors affecting internalized stigma compared to adult psoriasis patients. Methods: This multicenter, cross-sectional, comparative study included 125 pediatric (55 female, 70 male; mean age±standard deviation SD, 14.59±2.87 years) and 1,235 adult psoriasis patients (577 female, 658 male; mean age±SD, 43.3±13.7 years). Psoriasis Internalized Stigma Scale (PISS), Dermatology Life Quality Index (DLQI), Perceived Health Status (PHS), and the General Health Questionnaire (GHQ)-12 were the scales used in the study. Results: The mean PISS was 58.48±14.9 in pediatric group. When PISS subscales of groups were compared, the pediatric group had significantly higher stigma resistance (p=0.01) whereas adult group had higher scores of alienation (p=0.01) and stereotype endorsement (p=0.04). There was a strong correlation between mean values of PISS and DLQI (r=0.423, p=0.001). High internalized stigma scores had no relation to either the severity or localization of disease in pediatric group. However, poor PHS (p=0.007) and low-income levels (p=0.03) in both groups, and body mass index (r=0.181, p=0.04) in the pediatric group were related to high PISS scores. Conclusion: Internalized stigma in pediatric patients is as high as adults and is related to poor quality of life, general health, and psychological illnesses. Unlike adults, internalized stigma was mainly determined by psoriasis per se, rather than disease severity or involvement of visible body parts, genitalia or folds. (Ann Dermatol 32(3) 181∼188, 2020)
INTRODUCTION:Musical hallucinations are complex auditory hallucinations. The term covers the clinical phenomenon of hearing tunes and melodies that are uncontrollable and not related to external ...stimuli. Musical hallucinations may be experienced in a variety of conditions including diseases of the ear and neurologic, psychiatric, infectious, and toxic states. When the underlying pathology resolves, musical hallucinations tend to disappear.
CASE REPORT:We present an elderly man with musical hallucinations and without any conditions known to be related with its occurrence, except for Parkinson disease.
CONCLUSION:Musical hallucinations in the elderly occur predominantly in women with a hearing impairment. Parkinson disease is usually accompanied by visual hallucinations. Auditory hallucinations are rare in Parkinson disease and most of them are accompanied by visual hallucinations. Isolated auditory hallucinations are rarer in Parkinson disease and mostly consist of human voices.
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