Результаты поиска

Integrated transcriptomics of multiple sclerosis peripheral blood mononuclear cells explored potential biomarkers for the disease.

BACKGROUND: Despite their importance, blood RNAs have not been comprehensively studied as potential diagnostic markers for multiple sclerosis (MS). Herein, by the integration of GSE21942 and GSE203241 microarray profiles of peripheral blood mononuclear cells, this study explored potential biomarkers for the disease. METHODS: After identification of differentially expressed genes (DEGs), functional enrichment analyses were performed, and PPI and miRNA-mRNA regulatory networks were constructed. After implementing weighted gene co-expression network analysis (WGCNA) and discovering MS-specific m

m6A reader hnRNPA2B1 drives multiple myeloma osteolytic bone disease.

Rationale: Bone destruction is a hallmark of multiple myeloma (MM) and affects more than 80% of patients. Although previous works revealed the roles of N6-methyladenosine (m6A) reader hnRNPA2B1 in the development of tumors, whether hnRNPA2B1 regulates bone destruction in MM is still unknown. Methods: Alizarin red S staining, TRAP staining, ELISA and quantitative real-time PCR assays were used to evaluate osteogenesis and osteoclastogenesis in vitro. X ray and bone histomorphometric analysis were preformed to identify bone resorption and bone formation in vivo. Exosome isolation and characteriz

Non-canonical NFκB mutations reinforce pro-survival TNF response in multiple myeloma through an autoregulatory RelB:p50 NFκB pathway.

Environmental drug resistance constitutes a serious impediment for therapeutic intervention in multiple myeloma. Tumor-promoting cytokines, such as tumor necrosis factor (TNF), induce nuclear factor-κB (NFκB)- driven expression of pro-survival factors, which confer resistance in myeloma cells to apoptotic insults from TNF-related apoptosis-inducing ligand (TRAIL) and other chemotherapeutic drugs. It is thought that RelA:p50 dimer, activated from IκBα-inhibited complex in response to TNF-induced canonical NFκB signal, mediates the pro-survival NFκB function in cancerous cells. Myeloma cells add

Совпадение в полном тексте источника
… Tumor-associated CpG demethylation augments hypoxia-induced effects by positive autoregulation of HIF-1alpha . Oncogene 2011 ; 30 : 876 –882. 21042279 10.1038/onc.2010.481 Sanda T, Lawton LN, Barrasa MI, Fan ZP, Kohlhammer H, Gutierrez A et al. …

Comprehensive view on chemotherapy-free management of acute myeloid leukemia by using venetoclax in combination with targeted and/or immune therapies.

A hallmark of cancer biology is resistance to apoptosis. BCL-2 is an anti-apoptotic molecule that is being overexpressed in several myeloid diseases, such as acute myeloid leukemia and myelodysplastic syndromes, but also in several lymphoid cancers, such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphomas and multiple myeloma. Venetoclax (VEN) is a BCL-2 small molecule inhibitor. Data about its structure, biochemical characteristics and in vitro efficacy against several blood cancer cell lines were first reported in 2013. Shortly after, the first clinical trial

Совпадение в полном тексте источника
… During cell division, the analogs act as demethylating agents, replacing wild-type cytosine, thus the methyl group cannot be incorporated into DNA, leading to global demethylation. …

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

Фармакомикробиомика: От взаимодействия хост-микробиома-наркотики к клиническому переводу в докторскую медицину.

Заметная межиндивидуальная изменчивость реакции на наркотики по-прежнему является серьезной проблемой в области клинической фармакологии и не может быть в полной мере объяснена только генетикой принимающей страны. Растущие данные свидетельствуют о том, что кишечная микробиота является дополнительным фактором, определяющим эффективность и токсичность наркотиков посредством двустороннего взаимодействия с фармакологической терапией. Это признание привело к появлению фармакомикробиомики - области, которая изучает, как микробные сообщества влияют на утилизацию наркотиков и реагирование на них, и ка

Совпадение в полном тексте источника
… The gut microbiota is also capable of carrying out a wide range of further metabolic reactions, including acetylation, deacetylation, decarboxylation, dehydroxylation, demethylation, and dehalogenation. …

Intestinal Microbes and Hematological Malignancies.

Hematological malignancies are diverse, with high malignancy characteristics, poor prognoses, and high mortality rates. The development of hematological malignancies is driven by genetic factors, tumor microenvironment factors, or metabolic factors; however, even when considering all of these factors, one still cannot fully estimate the risk of hematological malignancies. Several recent studies have demonstrated an intimate connection between intestinal microbes and the progression of hematological malignancies, and gut microbes play a primary role in the initiation and progression of hematolo

Совпадение в полном тексте источника
… It plays a crucial role in DNA demethylation as an enzyme, which is essential for maintaining stem cell pluripotency [ 22 ]. …

Randomized phase II study of valproic acid in combination with bevacizumab and oxaliplatin/fluoropyrimidine regimens in patients with RAS-mutated metastatic colorectal cancer: the REVOLUTION study protocol.

BackgroundDespite effective treatments, metastatic colorectal cancer (mCRC) prognosis is still poor, mostly in RAS-mutated tumors, thus suggesting the need for novel combinatorial therapies. Epigenetic alterations play an important role in initiation and progression of cancers, including CRC. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with chemotherapy in the treatment of solid tumors. Owing to its HDACi activity and its safe use for epileptic disorders, valproic acid (VPA) is a good candidate for anticancer therapy that we have largely explored preclinically tra

Osteoporosis: Current and Emerging Therapies Targeted to Immunological Checkpoints.

Osteoporosis is a skeletal pathology characterized by compromised bone strength leading to increased risk of fracture, mainly the spine and hip fractures. Osteoporosis affects more than 200 million people worldwide and because of the skeletal fractures it causes, represents a major cause of morbidity, disability and mortality in older people. Recently, the new discoveries of osteoimmunology have clarified many of the pathogenetic mechanisms of osteoporosis, helping to identify new immunological targets for its treatment opening the way for new and effective therapies with biological drugs. Cur

Совпадение в полном тексте источника
… Synergistic efficacy of the demethylation agent decitabine in combination with the protease inhibitor bortezomib for treating multiple myeloma through the Wnt/βcatenin pathway. Oncol. Res. 2019;27(6):729–737. doi: 10.3727/096504018X15443011011637. 71. …

Sexual dimorphism in cancer: molecular mechanisms and precision oncology perspectives.

Sex differences play a crucial role in determining tumor incidence, treatment sensitivity, and prognosis among men and women. However, current clinical cancer treatment strategies fail to account for these differences. Furthermore, the underlying mechanisms of tumor disparities between sexes remain elusive. Sex differences in sex chromosomes, hormone levels, metabolism, and immunity synergistically contribute to tumor-related disparities. As the demand for precision medicine escalates, there is an urgent need to conduct further exploration and research to address the tumor differences between

Совпадение в полном тексте источника
… In addition to methylation-dependent regulation, sex differences in histone demethylation represent another key epigenetic mechanism contributing to sexual dimorphism in cancer. … The X-linked KDM6A (a histone demethylase) is expressed at higher levels in females, inhibiting tumor growth via H3K27me3 demethylation [ 51 ]. …

CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers.

CHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1's molecular functions, regulatory mechanisms, and effects in different pathological contexts. Specifically, the study objectives are to elucidate the biochemical pathways involving CHAC1, explore its regulatory network, and discuss its implications in disease progression and potential therapeutic strategies. As a γ-glutamyl cyclotrans

Совпадение в полном тексте источника
… Post-transcriptional and epigenetic regulation also plays a significant role, where ALKBH5-mediated m6A demethylation reduces ChaC1 mRNA stability, and the histone demethylase UTX suppresses ATF4, indirectly regulating ChaC1 expression. … In gastric cancer, ALKBH5-mediated m6A demethylation regulates the stability of target mRNAs, including CHAC1. By removing m 6 A marks from CHAC1 mRNA, ALKBH5 decreases its stability, leading to reduced CHAC1 expression. …

Revolutionizing ovarian cancer therapy by drug repositioning for accelerated and cost-effective treatments.

Drug repositioning, the practice of identifying novel applications for existing drugs beyond their originally intended medical indications, stands as a transformative strategy revolutionizing pharmaceutical productivity. In contrast to conventional drug development approaches, this innovative method has proven to be exceptionally effective. This is particularly relevant for cancer therapy, where the demand for groundbreaking treatments continues to grow. This review focuses on drug repositioning for ovarian cancer treatment, showcasing a comprehensive exploration grounded in thorough in vitro

Совпадение в полном тексте источника
… It is primarily used as a demethylating agent in the treatment of certain hematological malignancies, particularly myelodysplastic syndromes, where it can help to restore normal hematopoiesis by reversing aberrant DNA methylation patterns ( 268 – 270 ). … In mouse xenograft models, 5-azacytidine treatment suppressed tumor growth and increased the occurrence of metastatic nodules, indicating an enhanced metastatic potential due to DNA demethylation ( 271 ). …

Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Unders

Совпадение в полном тексте источника
… SAM, a universal methyl donor, leads to histone and DNA hypermethylation, and its demethylation produces S-adenosyl-homocysteine (SAH). SAH is hydrolysed into homocysteine, which can be recycled back into Met or enter the transculturation pathway. … Clinical trials in AML have analysed vitamin C levels ( NCT03526666 ) as well as the effect of oral vitamin C supplementation in improving the response to DNA methyltransferase inhibitors via increasing DNA demethylation (NCT0287727). 4.7. …

Длинная и извилистая дорога: гомеостатические и беспорядочные микроэкологические ниши: обзор описательной части.

Микроэкологические ниши Haematopoiet были охарактеризованы как "приемники" крови и иммунной системы. Эти ниши меняются во время онтгении, при этом костный мозг становится доминирующим местом гематопоисиса в послеродовой жизни в стабильных условиях. Для определения структуры и функции различных микроэкологических ниш гематопоиета необходимо четко определить конкретные подмножества гематопоиетических стеблей и потомковых клеток во время офгении и понять их временной внешний вид и анатомическое позиционирование. Различные гематопоиетические и негематопоиетические клетки способствуют появлению гем

Совпадение в полном тексте источника
… differentiate. 257 Epigenetic regulators of MSCs are also reported to include ten-eleven translocation 2 (TET2), additional sex combs-like 1 (ASXL1) and DNA methyltransferase 3. 247 , 252 The DNA dioxygenase TET2 catalyses 5-methylcytosine conversion to 5-hydroxymethylcytosine eventually leading to DNA demethylation …

Using ncRNAs as Tools in Cancer Diagnosis and Treatment-The Way towards Personalized Medicine to Improve Patients' Health.

Although the first discovery of a non-coding RNA (ncRNA) dates back to 1958, only in recent years has the complexity of the transcriptome started to be elucidated. However, its components are still under investigation and their identification is one of the challenges that scientists are presently facing. In addition, their function is still far from being fully understood. The non-coding portion of the genome is indeed the largest, both quantitatively and qualitatively. A large fraction of these ncRNAs have a regulatory role either in coding mRNAs or in other ncRNAs, creating an intracellular

Совпадение в полном тексте источника
… action on miR-1260b is exerted also in prostate cancer [ 130 ], where genistein also downregulates miR-151 [ 131 ], miR-221, miR-222 [ 132 ], and miR-223 [ 133 ] but upregulates miR-34a, miR-574-3p, and miR-1296 [ 134 , 135 , 136 ] and enhances the expression of miR-200c and miR-141 by promoting the demethylation … Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells Br. J. Cancer 2014 110 1645 1654 10.1038/bjc.2014.48 24504368 PMC3960620 131. Chiyomaru T. Yamamura S. Zaman M.S. Majid S. Deng G. Shahryari V. Saini S. …

DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.

Resistance to chemo- and radiotherapy is a common event among cancer patients and a reason why new cancer therapies and therapeutic strategies need to be in continuous investigation and development. DNA damage response (DDR) comprises several pathways that eliminate DNA damage to maintain genomic stability and integrity, but different types of cancers are associated with DDR machinery defects. Many improvements have been made in recent years, providing several drugs and therapeutic strategies for cancer patients, including those targeting the DDR pathways. Currently, poly (ADP-ribose) polymera

Совпадение в полном тексте источника
… In addition, restoration of the wild-type BRCA protein may occur via a secondary mutation that reverses the inherited mutation or by the demethylation of the BRCA1 promoter; both these events may lead to restoration of the wild-type BRCA protein [ 160 , 271 ]. …

Healthy Effects of Plant Polyphenols: Molecular Mechanisms.

The increasing extension in life expectancy of human beings in developed countries is accompanied by a progressively greater rate of degenerative diseases associated with lifestyle and aging, most of which are still waiting for effective, not merely symptomatic, therapies. Accordingly, at present, the recommendations aimed at reducing the prevalence of these conditions in the population are limited to a safer lifestyle including physical/mental exercise, a reduced caloric intake, and a proper diet in a convivial environment. The claimed health benefits of the Mediterranean and Asian diets have

Понимание и решение проблемы сопротивления иммуномодуляционным соединениям IMID в множестве миеломы.

Лекарственные средства иммуномодулирования (ИМИД), включая линалидомид и помалидомид в сочетании с протеаозными ингибиторами, дексаметазоном и антиCD38 моноклональными антителами, играют центральную роль в лечении множественной миеломы (ММ) на новых диагностированных и рецидивированных этапах. Эти методы лечения значительно улучшили результаты лечения пациентов во всем мире, в результате чего IMID стали одной из опор MM-терапии. В настоящее время разрабатывается новое поколение более мощных соединений, называемых лигами-модуляторами цереблиона Е3 (CELMODs), которые могут заменить старые IMID.

Совпадение в полном тексте источника
… Around 25% of MM‐specific differentially methylated genes lie within the 1q21.1 locus, including FAM72 , which promotes myeloma cell proliferation via FOXM1 activation following promoter demethylation [ 59 ]. …

Acute myeloid leukemia with plasmacytoid dendritic cell proliferation: A case report and literature review.

The present study describes a rare case of plasmacytoid dendritic cell-associated acute myeloid leukemia (pDC-AML). A 70-year-old male patient was diagnosed with pDC-AML and underwent induction chemotherapy using the venetoclax + azacitidine (VA) regimen. After 3 weeks of treatment, bone marrow examination indicated a morphologic leukemia-free state (MLFS); however, the patient experienced persistent cytopenia, which was further complicated by severe pneumonia and gastrointestinal bleeding, both of which improved following treatment. After 3 weeks in MLFS, bone marrow morphology and minimal re

Identified Medications Causing Medication-Related Osteonecrosis of the Jaw: A Literature Review.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse event that occurs in patients treated with certain medications, leading to a major side effect that can result in substantial morbidity. MRONJ is known to be associated with antiresorptive (AR) and antiangiogenic (AA) medicines, but recent evidence suggests that other medications may also be involved. Recognizing a broad range of drug-induced risk factors is important, notably in light of the increasing number of drugs associated with MRONJ. The primary objective of this review is to update and synthesize findings from th