Результаты поиска

Selected Abstracts from the 13th Annual Meeting of the Clinical Immunology Society: 2022 Annual Meeting: Immune Deficiency and Dysregulation North American Conference

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Совпадение в полном тексте источника
… RelA haploinsufficiency has clinical feature of recurrent fever, chronic mucocutaneous ulceration and inflammatory bowel disease with variable penetrance and expressivity. Here we present a patient with a pathogenic variant in RELA with a phenotype of autoimmunity and immune dysregulation. … This is the second described patient with an acute presentation of lymphoproliferation and autoimmune cytopenia due to RelA haploinsufficiency. …

Cytogenetic Abnormalities in Myelodysplastic Syndromes: An Overview.

Karyotype is one of the main constituents of the International Prognostic Scoring System (IPSS) and revised-IPSS that are the cornerstones for the prognostication of patients with myelodysplastic syndromes (MDS). Del(5q), -7/del(7q), +8 and -Y are among the most extensively studied cytogenetic abnormalities in MDS. The same applies for normal karyotype. There are hundreds of other rare cytogenetic abnormalities that have been reported in MDS, included but not limited to -X, 3q abnormalities, +13/del(13q), i(17q), +21/-21. However, due to a very low number of patients, their impact on the progn

Совпадение в полном тексте источника
… Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood. 2011;117(9):2567–76. doi: 10.1182/blood-2010-07-295238. 19. Barlow JL, Drynan LF, Hewett DR, et al. … CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia. Blood. 2013;121(6):975–83. doi: 10.1182/blood-2012-04-426965. 29. Papaemmanuil E, Gerstung M, Malcovati L, et al. …

Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.

Lymphedema is a chronic inflammatory disease without an effective treatment method, and it results in a high disease burden and psychological distress in patients. Although there have been significant advances in targeted therapies, there are still no effective options to treat this refractory disease. In recent years, new advances and breakthroughs have been made in signaling pathways, including RAS/MAPK, PI3K/AKT, VEGF-C/VEGFR-3, HGF/MET, and TGF-β1, which are important for understanding the pathogenesis and disease progression of lymphedema. Mutations in genes encoding cell junctions affect

Совпадение в полном тексте источника
… Sotos syndrome is a childhood overgrowth syndrome caused by haploinsufficiency of the NSD1 gene ( Kurotaki et al., 2002 ). McClelland J reported the presence of primary lymphedema in female patients with Sotos syndrome caused by NSD1 internal mutations ( McClelland et al., 2016 ). … Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Nat. Genet. 37 (10), 1072–1081. 10.1038/ng1642 Herrada A. A., Olate-Briones A., Lazo-Amador R., Liu C., Hernández-Rojas B., Riadi G., et al. (2022). …

Role of Proteasomes in Inflammation.

The ubiquitin-proteasome system (UPS) is involved in multiple cellular functions including the regulation of protein homeostasis, major histocompatibility (MHC) class I antigen processing, cell cycle proliferation and signaling. In humans, proteasome loss-of-function mutations result in autoinflammation dominated by a prominent type I interferon (IFN) gene signature. These genomic alterations typically cause the development of proteasome-associated autoinflammatory syndromes (PRAAS) by impairing proteasome activity and perturbing protein homeostasis. However, an abnormal increased proteasomal

Совпадение в полном тексте источника
… Heterozygous loss-of-function mutations in the gene TNFAIP3 encoding A20 result in a Behçet-like disease named A20 haploinsufficiency [ 104 , 105 ]. … Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease Nat. Genet. 2016 48 67 73 10.1038/ng.3459 26642243 PMC4777523 105. Takagi M. Ogata S. Ueno H. Yoshida K. Yeh T. Hoshino A. Piao J. Yamashita M. Nanya M. Okano T. …

Targeted treatment of autoimmune cytopenias in primary immunodeficiencies.

Primary Immunodeficiencies (PID) are a group of rare congenital disorders of the immune system. Autoimmune cytopenia (AIC) represents the most common autoimmune manifestation in PID patients. Treatment of AIC in PID patients can be really challenging, since they are often chronic, relapsing and refractory to first line therapies, thus requiring a broad variety of alternative therapeutic options. Moreover, immunosuppression should be fine balanced considering the increased susceptibility to infections in these patients. Specific therapeutic guidelines for AIC in PID patients are lacking. Treatm

Совпадение в полном тексте источника
… CTLA4 haploinsufficiency is characterized by recurrent sinopulmonary infections, autoimmune manifestations and lymphoproliferation. AIC has been reported in 59% of these patients ( 56 ). … Thus, Abatacept represents a valid therapeutic option for treating AIC in CTLA4 haploinsufficiency with a high response rate ( 56 , 57 ). LRBA is an intracytoplasmic protein that rescues CTLA4 from degradation allowing its recycling on the cell surface. …

Hypoxia-induced CREB cooperates MMSET to modify chromatin and promote DKK1 expression in multiple myeloma.

Myeloma cells produce excessive levels of dickkopf-1 (DKK1), which mediates the inhibition of Wnt signaling in osteoblasts, leading to multiple myeloma (MM) bone disease. Nevertheless, the precise mechanisms underlying DKK1 overexpression in myeloma remain incompletely understood. Herein, we provide evidence that hypoxia promotes DKK1 expression in myeloma cells. Under hypoxic conditions, p38 kinase phosphorylated cAMP-responsive element-binding protein (CREB) and drove its nuclear import to activate DKK1 transcription. In addition, high levels of DKK1 were associated with the presence of foca

Совпадение в полном тексте источника
… Transgenic mice overexpressing Dkk1 develop osteopenia, whereas mice haploinsufficient for Dkk1 exhibit high bone mass [ 9 ]. … Intini G Nyman JS Dkk1 haploinsufficiency requires expression of Bmp2 for bone anabolic activity Bone 2015 75 151 60 10.1016/j.bone.2015.01.008 25603465 PMC4387090 10. Abe M [Wnt signaling in myeloma.] Clin Calcium 2019 29 349 55 30814381 10.20837/4201903349 11. …

Effects of Tcte1 knockout on energy chain transportation and spermatogenesis: implications for male infertility.

STUDY QUESTION: Is the Tcte1 mutation causative for male infertility? SUMMARY ANSWER: Our collected data underline the complex and devastat … eratozoospermia, while heterozygous animals were fertile but manifested oligozoospermia, suggesting haploinsufficiency. RNA-sequencing of the testicular tissue showed the influence of Tcte1 mutations on the expression pattern of 21 genes responsible for mitochondrial ATP processing or linked with apoptosis or spermatogenesis. In Tcte1-/- males, the protein was revea …

Коэффициенты транскрипции заболеваний экзокринной и эндокринной поджелудочной железы: эффекты, механизмы и клинические последствия.

Белки BTB и CNC (BACH) BACH1 и BACH2 являются высоко сберегаемыми транскрипционными репрессорами, которые оказывают свое воздействие, образуя гетеродимеры с маленькими мускулопоневрологическими фибросаркома (MAF). BACH1 повсеместно выражается и выполняет функции, конкурируя с эритроидом ядерного фактора 2-like 2 (NRF2) для привязки к MAF. Ограничивая транскрипцию гема кислородазы 1 (В тыс.HO-1/HMOX1), BACH1 препятствует выражению генов, участвующих в реакции клеточного окислительного стресса. Выражение BACH2 в основном ограничивается иммунными клетками как в врожденных, так и в адаптивных отсе

Совпадение в полном тексте источника
… Furthermore, BACH2 haploinsufficiency may result in a syndrome characterized by immunodeficiency and autoimmune disorders ( 4 ). Diseases of the endocrine and exocrine pancreas are among the most common diseases worldwide. …

Severe Relapsing Hailey-Hailey Disease Displaying a Durable Complete Response to Hydroxyurea.

Familial benign chronic pemphigus, also known as Hailey-Hailey disease, was first described by the Hailey brothers in 1939 (1). It represent … t any further evidence of skin lesions. The hallmark of Hailey-Hailey disease is believed to be the haploinsufficiency of the enzyme ATP2C1 (2). The ATP2C1 gene is located on chromosome 3 and encodes a Ca2+ ATPase protein. A mutation in one copy of the gene causes only half of this necessary protein to be synthesized. Consequently, impaired keratinocyte adhesion ens …

" Nucleolus in Human Beasons: Ribosome Biogenesis " , " Nucleolar Survey " и " Terrapeutic Opportunities " .

Nucleolus превратился в динамичную и многофункциональную субядерную органилию, интегрирующую рибосомный биогенез с клеточным ростом и сигнализацией стресса. Регулирование нуклеолярной функции все чаще признается в качестве главного движителя человеческих заболеваний, связывающего изменённое рибосомное производство и нуклеолярное наблюдение с раком, рибосомопатиями, синдромами преждевременного старения, нейродегенерацией и иммунными расстройствами. В этом обзоре мы интегрируем структурные, молекулярные и болезнетворные перспективы нуклеолярной биологии для определения того, как рипосомный биоге

Совпадение в полном тексте источника
… Extra-ribosomal functions of RPs may further contribute to oncogenesis; for example, loss of RPs that repress c-Myc expression, such as RPS14, RPL5, and RPL11, may promote malignant transformation, as demonstrated in lymphoma models with Rpl11 haploinsufficiency [ 215 , 216 , 250 , 251 , 252 ]. 6.1.4 … Diamond–Blackfan Anaemia Syndrome (DBAS), a ribosomopathy first described almost a century ago, is predominantly caused by RP haploinsufficiency, most commonly in RPS19 (~25% of cases), with biallelic variants in HEATR3 recently identified as an additional causative lesion [ 33 , 258 , 259 ]. …

Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells.

Hematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environmental stressors, such as infection, trigger active cycling of HSCs. These inflammatory signals can also directly induce HSCs to release cytokines into the bone marrow environment, promoting myeloid differentiation. After stress myelopoiesis is triggered, HSCs require intracellular signaling programs to

Совпадение в полном тексте источника
… By genetically inactivating S100A8 expression they rescued the erythroid differentiation defect in Rps14 haploinsufficient HSCs ( 66 ). This suggests that secretion of S100A8 and S100A9 by activated immune effector cells could promote hematopoietic dysplasia via TLR signaling. … Nat Med ( 2007 ) 13 : 1042 – 9 . 10.1038/nm1638 17767165 66 Schneider RK Schenone M Ferreira MV Kramann R Joyce CE Hartigan C Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9 . …

Ход работы сессии 31st Европейский педиатрический конгресс по педиатрии: часть 1.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Совпадение в полном тексте источника
… Patient Consent Yes, I received consent Disclosure of Interest None Declared New diseases OR06 Haploinsufficiency of PTPN2 and early systemic autoimmunity: from Evans syndrome to systemic lupus Marie Jean-Pierre 1 , Jade Cognard 2 , Maud Tusseau 2 , Quentin Riller 1 , Linh-Chi Bui 3 , Jeremy Berthelet … Haploinsufficiency of PTPN2 may constitute a new subset of autoimmune diseases, with clinical expression potentially influenced by other modifying or epigenetic factors, many of which are yet to be discovered. …

Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.

Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lympho

Совпадение в полном тексте источника
… In leukemia, conditional knockout of DNMT1 inhibited leukemia development, and DNMT1 haploinsufficiency delayed the progression of leukemogenesis and impaired LSC self-renewal without altering normal hematopoiesis. 59 In AML, Wang et al. discovered that the expression level of DNMT1 in AML patients was … The haploinsufficiency of DNMT3A could transform FLT3 -ITD myeloproliferative neoplasm (MPN) into AML, 152 and cooperate with oncogenic KRAS to promote the development of T-ALL. 153 The haploinsufficient tumor suppressor effect of DNMT3A was also reported in CLL, 154 CD8 + PTCL, 155 , and AITL. 156 – …

Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia.

Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylation is mediated by DNA methyltransferases (DNMTs) consisting of DNMT1, DNMT3A, and DNMT3B. DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML. The clinical response predictive roles of DNMTs in clinical trials utilising hy

Совпадение в полном тексте источника
… background) with Flt3-ITD and inducible deletion of Dnmt3a developed a rapidly lethal, penetrant, and transplantable AML. 57 The authors reported that single-cell assays identified clonogenic subpopulations expressing genes sensitive to methylation and responsive to Dnmt3a levels, and concluded that Dnmt3a haploinsufficiency … DNMT3A haploinsufficiency transforms FLT3ITD myeloproliferative disease into a rapid, spontaneous, and fully penetrant acute myeloid leukemia. Cancer Discov. 2016;6:501–515. 58. Sun QY, Ding LW, Tan KT, et al. …

Bortezomib-based regimens improve the prognosis of newly diagnosed MM patients with chromosomal aberrations except for del(17q13): A retrospective study from a single center.

AbstractChromosomal aberrations are generally considered to have a remarkable impact on the outcome of multiple myeloma. Bortezomib helps to achieve complete responses and leads to longer life expectancy in many multiple myeloma patients. This study was designed to clarify whether bortezomib can improve the poor prognosis resulting from del(17q13), del(13q14), amp(1q21), t(4,14), t(14,16) in patients with multiple myeloma. A total of 255 MM patients treated with bortezomib-based regimens were included in this study. All chromosomal aberrations were detected by interphase fluorescence in situ h

Совпадение в полном тексте источника
… [8] Teoh PJ, Chung TH, Sebastian S, et al. p53 haploinsufficiency and functional abnormalities in multiple myeloma. Leukemia 2014;28:2066–74. [9] Chng WJ, Dispenzieri A, Chim CS, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia 2014;28:269–77. …

Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer.

The most serious aspect of neoplastic disease is the spread of cancer cells to secondary sites. Skeletal metastases can escape detection long after treatment of the primary tumour and follow-up. Bone tissue is a breeding ground for many types of cancer cells, especially those derived from the breast, prostate, and lung. Despite advances in diagnosis and therapeutic strategies, bone metastases still have a profound impact on quality of life and survival and are often responsible for the fatal outcome of the disease. Bone and the bone marrow environment contain a wide variety of cells. No longer

Совпадение в полном тексте источника
… Sam68 haploinsufficiency delays onset of mammary tumorigenesis and metastasis Oncogene 2008 27 548 556 10.1038/sj.onc.1210652 17621265 89. Derry J.J. Richard S. Valderrama Carvajal H. Ye X. Vasioukhin V. Cochrane A.W. Chen T. Tyner A.L. … Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities PLoS ONE 2009 4 e4968 10.1371/annotation/14cb7d7e-a921-4ae6-a405-99c60656579f 19319191 PMC2656613 126. Lukong K.E. Richard S. …

Emerging mechanism and therapeutic potential of neurofibromatosis type 1-related nerve system tumor: Advancing insights into tumor development.

Neurofibromatosis Type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 gene, which increases susceptibility to various nervous system tumors, including plexiform neurofibromas, malignant peripheral nerve sheath tumors, and optic pathway gliomas. Recent research has shown that these tumors are intricately connected to the complex, dynamic interactions within neurons, culminating in neuronal signaling that fosters tumor growth. These interactions offer crucial insights into the molecular mechanisms underpinning tumor development, as well as broader implications for therapeutic

Совпадение в полном тексте источника
… Sensory neurons from Nf1 haploinsufficient mice exhibit increased excitability . J Neurophysiol. 2005 ; 94 ( 6 ): 3670 – 3676 . 16093333 10.1152/jn.00489.2005 133. … Nf1 haploinsufficiency augments angiogenesis . Oncogene. 2006 ; 25 ( 16 ): 2297 – 2303 . 16288202 10.1038/sj.onc.1209264 138. Zahalka AH , Arnal-Estapé A , Maryanovich M , et al Adrenergic nerves activate an angio-metabolic switch in prostate cancer . …

Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening.

Molecular targeted therapy has revolutionized the landscape of cancer treatment due to better therapeutic responses and less systemic toxicity. However, therapeutic resistance is a major challenge in clinical settings that hinders continuous clinical benefits for cancer patients. In this regard, unraveling the mechanisms of drug resistance may identify new druggable genetic alterations for molecularly targeted therapies, thus contributing to improved therapeutic efficacies. The recent rapid development of novel methodologies including CRISPR-Cas9 screening technology and patient-derived models

Совпадение в полном тексте источника
… In BRAF V600 mutant cancer cells, the haploinsufficiency of histone deacetylase Sirtuinb 6 (SIRT6) allowed BRAF V600 -mutant melanoma cell persistence in the presence of MAPK inhibitors due to upregulating insulin like growth factor binding protein 2 (IGFBP2) expression via increasing chromatin accessibility … Therefore, resistance to BRAF inhibitors in SIRT6-haploinsufficient melanoma cells can be relieved by combinatory application of a clinically available IGF-1R inhibitor. …

Расширенный полиглутамин в ATAXIN1 приводит к потере функции, которая усугубляет остроту множественного склероза в модели мыши EAE.

Ataxin-1 (ATXN1) — белок, в котором расширение его полиглутаминового тракта вызывает нервно-дегенеративное расстройство спинномозговой системы 1 (SCA1) в результате повышения функциональности. Недавно было продемонстрировано, что АТXN1 дикая порода играет защитную роль в регулировании жесткости экспериментального аутоиммунного энцефаломиелита (EAE) — хорошо зарекомендовавшей себя модели мыши для мультиклероза (MS). В этом исследовании дополнительно изучается роль ATXN1 с расширенным полиглутаминым трактом в контексте MS с использованием модели мыши EAE.МЕТОДЫ: Гемизиговые атксны1 (Atxn1 2Q/-)

Совпадение в полном тексте источника
… In the present study, using two different genetic modifications of Atxn1 in mice, we demonstrated that haploinsufficiency of Atxn1 and expansion of the CAG repeat exacerbate clinical EAE symptoms as well as underlying pathology, including axonal degeneration, oligodendrocyte loss and demyelination …

Abstracts of the 12th European Cytogenomics Conference 2019 : Salzburg, Austria. 6-9 July 2019

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.