Terapia neurologopedyczna dziecka z chorobą moyamoya

Introduction. Moyamoya is a rare disease of unknown etiology which leads to strokes resultant from occlusions of intracranial arteries. As a result of the blockage of the arteries in the brain a lateral network of blood vessels develops, forming a characteristic angiographic image.Case Report. In the paper a case is presented of a child who in the course of a month has suffered two strokes in two cerebral hemispheres. The damage in the central nervous system led to paresis in four limbs, speech impairment (later: lack of speech), problems with swallowing, and limited visual and audial contact.Discussion. The main aim of the therapy was to improve feeding, drinking, and chewing and an attempt to introduce alternative communication. Elements of sensory integration were employed, and regulatory therapy of Castillo Morales was used to allow swallowing, shutting the mouth fully, and controlling the mandible while eating and drinking. Furthermore, the child’s agility was being simultaneously enhanced the motor skills rehabilitation, the child would also benefit from a Room of World Experiences. Contrary to the initial assumptions, it has not been possible to reach all the aims of the therapy. Epileptic seizures have led to the loss of the acquired skills.Conclusions. Successfulness of therapy is dependent on a number of factors, which are often independent of the therapist. What is crucial is to adjust the level of the difficulty of the sessions and their duration to the child’s state of feeling on a particular day. After the conclusion of the programme improved eyesight was noticed. However, in the case of a child with such vast damage to the central nervous system the aim of the therapy is to retain the acquired skills and to carry out further attempts to develop new skills through their frequent repetition. (JNNN 2018;7(2):75–79)Wstęp. Moyamoya to rzadka choroba o nieznanej etiologii, prowadząca do udarów niedokrwiennych, na skutek niedrożności tętnic wewnątrzczaszkowych. Wskutek zamknięcia tętnic w mózgu rozwija się poboczna sieć naczyń krwionośnych, które składają się na charakterystyczny obraz angiograficzny.Opis przypadku. W pracy przedstawiono przypadek dziecka, które w przeciągu miesiąca przeszło dwa udary w obu półkulach mózgu. Uszkodzenia ośrodkowego układu nerwowego doprowadziły do niedowładu czterech kończyn, zaburzeń mowy (później jej braku), problemów z połykaniem, ograniczenia kontaktu wzrokowo-słuchowego.Dyskusja. Głównym celem terapii było usprawnienie karmienia, picia i żucia oraz próba wprowadzenia komunikacji alternatywnej. Zastosowano elementy integracji sensorycznej, wykorzystano terapię regulacyjną Castillo Moralesa w celu uzyskania połykania, domykania buzi, kontroli żuchwy w trakcie karmienia i picia. Dodatkowo dziecko było równolegle usprawniane rehabilitacją ruchową, korzystało z Sali Doświadczeń Świata. Wbrew początkowym założeniom nie udało się osiągnąć wszystkich celów terapii. Napady padaczkowe spowodowały utratę osiągniętych umiejętności.Wnioski. Sukces w prowadzeniu terapii jest zależny od wielu czynników, często niezależnych od terapeuty. Ważne jest dostosowanie poziomu trudności zajęć, ich długości do możliwości i samopoczucia dziecka w danym dniu. Po zakończeniu programu stwierdzono poprawę kontaktu wzrokowego. Jednak w przypadku dziecka z tak bardzo uszkodzonym centralnym układem nerwowym celem terapii jest już utrzymanie uzyskanych umiejętności i dalsze próby wypracowania kolejnych, poprzez ich wielokrotne powtarzanie. (PNN 2018;7(2):75–79

CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells

The transcription factor MYC is a proto-oncogene with a well-documented essential role in the pathogenesis and maintenance of several types of cancer. MYC binds to specific E-box sequences in the genome to regulate gene expression in a cell-type- and developmental-stage-specific manner. To date, a combined analysis of essential MYC-bound E-boxes and their downstream target genes important for growth of different types of cancer is missing. In this study, we designed a CRISPR/Cas9 library to destroy E-box sequences in a genome-wide fashion. In parallel, we used the Brunello library to knock out protein-coding genes. We performed high-throughput screens with these libraries in four MYC-dependent cancer cell lines - K562, ST486, HepG2 and MCF7 - which revealed several essential E-boxes and genes. Among them we pinpointed crucial common and cell-type-specific MYC-regulated genes involved in pathways associated with cancer development. Extensive validation of our approach confirmed that E-box disruption affects MYC binding, target-gene expression and cell proliferation in vitro as well as tumor growth in vivo. Our unique, well-validated tool opens new possibilities to gain novel insights into MYC-dependent vulnerabilities in cancer cells.</p

CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells

The transcription factor MYC is a proto-oncogene with a well-documented essential role in the pathogenesis and maintenance of several types of cancer. MYC binds to specific E-box sequences in the genome to regulate gene expression in a cell-type- and developmental-stage-specific manner. To date, a combined analysis of essential MYC-bound E-boxes and their downstream target genes important for growth of different types of cancer is missing. In this study, we designed a CRISPR/Cas9 library to destroy E-box sequences in a genome-wide fashion. In parallel, we used the Brunello library to knock out protein-coding genes. We performed high-throughput screens with these libraries in four MYC-dependent cancer cell lines - K562, ST486, HepG2 and MCF7 - which revealed several essential E-boxes and genes. Among them we pinpointed crucial common and cell-type-specific MYC-regulated genes involved in pathways associated with cancer development. Extensive validation of our approach confirmed that E-box disruption affects MYC binding, target-gene expression and cell proliferation in vitro as well as tumor growth in vivo. Our unique, well-validated tool opens new possibilities to gain novel insights into MYC-dependent vulnerabilities in cancer cells.</p

CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells

The transcription factor MYC is a proto-oncogene with a well-documented essential role in the pathogenesis and maintenance of several types of cancer. MYC binds to specific E-box sequences in the genome to regulate gene expression in a cell-type- and developmental-stage-specific manner. To date, a combined analysis of essential MYC-bound E-boxes and their downstream target genes important for growth of different types of cancer is missing. In this study, we designed a CRISPR/Cas9 library to destroy E-box sequences in a genome-wide fashion. In parallel, we used the Brunello library to knock out protein-coding genes. We performed high-throughput screens with these libraries in four MYC-dependent cancer cell lines - K562, ST486, HepG2 and MCF7 - which revealed several essential E-boxes and genes. Among them we pinpointed crucial common and cell-type-specific MYC-regulated genes involved in pathways associated with cancer development. Extensive validation of our approach confirmed that E-box disruption affects MYC binding, target-gene expression and cell proliferation in vitro as well as tumor growth in vivo. Our unique, well-validated tool opens new possibilities to gain novel insights into MYC-dependent vulnerabilities in cancer cells.</p

CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells

The transcription factor MYC is a proto-oncogene with a well-documented essential role in the pathogenesis and maintenance of several types of cancer. MYC binds to specific E-box sequences in the genome to regulate gene expression in a cell-type- and developmental-stage-specific manner. To date, a combined analysis of essential MYC-bound E-boxes and their downstream target genes important for growth of different types of cancer is missing. In this study, we designed a CRISPR/Cas9 library to destroy E-box sequences in a genome-wide fashion. In parallel, we used the Brunello library to knock out protein-coding genes. We performed high-throughput screens with these libraries in four MYC-dependent cancer cell lines - K562, ST486, HepG2 and MCF7 - which revealed several essential E-boxes and genes. Among them we pinpointed crucial common and cell-type-specific MYC-regulated genes involved in pathways associated with cancer development. Extensive validation of our approach confirmed that E-box disruption affects MYC binding, target-gene expression and cell proliferation in vitro as well as tumor growth in vivo. Our unique, well-validated tool opens new possibilities to gain novel insights into MYC-dependent vulnerabilities in cancer cells.</p

CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells

The transcription factor MYC is a proto-oncogene with a well-documented essential role in the pathogenesis and maintenance of several types of cancer. MYC binds to specific E-box sequences in the genome to regulate gene expression in a cell-type- and developmental-stage-specific manner. To date, a combined analysis of essential MYC-bound E-boxes and their downstream target genes important for growth of different types of cancer is missing. In this study, we designed a CRISPR/Cas9 library to destroy E-box sequences in a genome-wide fashion. In parallel, we used the Brunello library to knock out protein-coding genes. We performed high-throughput screens with these libraries in four MYC-dependent cancer cell lines - K562, ST486, HepG2 and MCF7 - which revealed several essential E-boxes and genes. Among them we pinpointed crucial common and cell-type-specific MYC-regulated genes involved in pathways associated with cancer development. Extensive validation of our approach confirmed that E-box disruption affects MYC binding, target-gene expression and cell proliferation in vitro as well as tumor growth in vivo. Our unique, well-validated tool opens new possibilities to gain novel insights into MYC-dependent vulnerabilities in cancer cells.</p

CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells

The transcription factor MYC is a proto-oncogene with a well-documented essential role in the pathogenesis and maintenance of several types of cancer. MYC binds to specific E-box sequences in the genome to regulate gene expression in a cell-type- and developmental-stage-specific manner. To date, a combined analysis of essential MYC-bound E-boxes and their downstream target genes important for growth of different types of cancer is missing. In this study, we designed a CRISPR/Cas9 library to destroy E-box sequences in a genome-wide fashion. In parallel, we used the Brunello library to knock out protein-coding genes. We performed high-throughput screens with these libraries in four MYC-dependent cancer cell lines - K562, ST486, HepG2 and MCF7 - which revealed several essential E-boxes and genes. Among them we pinpointed crucial common and cell-type-specific MYC-regulated genes involved in pathways associated with cancer development. Extensive validation of our approach confirmed that E-box disruption affects MYC binding, target-gene expression and cell proliferation in vitro as well as tumor growth in vivo. Our unique, well-validated tool opens new possibilities to gain novel insights into MYC-dependent vulnerabilities in cancer cells.</p

Nadekspresja miR-652-5p u chorych z nowo rozpoznaną cukrzycą typu 1

Wstęp. MicroRNA (miRNA) to krótkie, niekodujące RNA, które regulują ekspresję genów na poziomie potransktypcyjnym. Cząsteczki miRNA odgrywają istotną rolę w regulacji centralnej i obwodowej tolerancji immunologicznej, dlatego analiza niekodujących RNA w cukrzycy typu 1 (T1D) jest istotnym problemem badawczym. Celem badania była analiza ekspresji miR-652-5p w nowo zdiagnozowanych przypadkach cukrzycy typu 1 oraz ocena miejsc wiązania miR-652-5p w potencjalnych genach docelowych ADAR i MARCH5. Metody. Analiza ekspresji miR-652-5p została przeprowadzona w komórkach jednojądrzastych krwi obwodowej dzieci z nowo rozpoznaną cukrzycą typu 1 (n = 28) oraz w dobranej pod względem wieku grupie kontrolnej (n = 28) na podstawie metody PCR w czasie rzeczywistym. Miejsca wiązania miR-652-5p w genach docelowych zostały ocenione z wykorzystaniem układu reporterowego lucyferazy. Wyniki. Analiza ekspresji wykazała podwyższony poziom miR-652-5p u pacjentów z T1D w porównaniu z grupą zdrowych dawców (p &lt; 0,05). Ocena miejsc wiązania w układzie reporterowym lucyferazy nie wskazała genu ADAR i MARCH5 jako potencjalnych genów docelowych miR-652-5p. Wnioski. Przeprowadzone badania wskazały miR-652-5p jako potencjalny biomarker cukrzycy typu 1

The miR-26b-5p/KPNA2 Axis Is an Important Regulator of Burkitt Lymphoma Cell Growth

The expression of several microRNAs (miRNAs) is known to be changed in Burkitt lymphoma (BL), compared to its normal counterparts. Although for some miRNAs, a role in BL was demonstrated, for most of them, their function is unclear. In this study, we aimed to identify miRNAs that control BL cell growth. Two BL cell lines were infected with lentiviral pools containing either 58 miRNA inhibitors or 44 miRNA overexpression constructs. Eighteen constructs showed significant changes in abundance over time, indicating that they affected BL growth. The screening results were validated by individual green fluorescent protein (GFP) growth competition assays for fifteen of the eighteen constructs. For functional follow-up studies, we focused on miR-26b-5p, whose overexpression inhibited BL cell growth. Argonaute 2 RNA immunoprecipitation (Ago2-IP) in two BL cell lines revealed 47 potential target genes of miR-26b-5p. Overlapping the list of putative targets with genes showing a growth repression phenotype in a genome-wide CRISPR/Cas9 knockout screen, revealed eight genes. The top-5 candidates included EZH2, COPS2, KPNA2, MRPL15, and NOL12. EZH2 is a known target of miR-26b-5p, with oncogenic properties in BL. The relevance of the latter four targets was confirmed using sgRNAs targeting these genes in individual GFP growth competition assays. Luciferase reporter assay confirmed binding of miR-26b-5p to the predicted target site for KPNA2, but not to the other genes. In summary, we identified 18 miRNAs that affected BL cell growth in a loss- or gain-of-function screening. A tumor suppressor role was confirmed for miR-26b-5p, and this effect could at least in part be attributed to KPNA2, a known regulator of OCT4, c-jun, and MYC

Effect of the Addition of Buckwheat Sprouts Modified with the Addition of Saccharomyces cerevisiae var. boulardii to an Atherogenic Diet on the Metabolism of Sterols, Stanols and Fatty Acids in Rats

The aim of the study was to evaluate the effect of the addition of Fagopyrum esculentum Moench buckwheat sprouts modified with the addition of Saccharomyces cerevisiae var. boulardii to an atherogenic diet on the metabolism of sterols and fatty acids in rats. It was noticed in the study that the group fed with modified sprouts (HFDPRS) had a greater amount of sterols by 75.2%, compared to the group fed on an atherogenic diet (HFD). The content of cholesterol in the liver and feces was lower in the HFDPRS group than the HFD group. In the serum of the HFDPRS group, a more significant amount of the following acids was observed: C18:2 (increase by 13.5%), C20:4 (increase by 15.1%), and C22:6 (increase by 13.1%), compared to the HFDCS group. Regarding the biochemical parameters, it was noted that the group fed the diet with the addition of probiotic-rich sprouts diet had lower non-HDL, LDL-C and CRP ratios compared to the group fed the high-fat diet. The obtained results indicate that adding modified buckwheat sprouts to the diet by adding the probiotic strain of the yeast may have a significant impact on the metabolism of the indicated components in the organism