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Effects of hsa-miR-28-5p on Adriamycin Sensitivity in Diffuse Large B-Cell Lymphoma.

BackgroundAdriamycin (doxorubicin) is an important traditional drug that exhibits cytotoxicity in Diffuse Large B-cell Lymphoma (DLBCL). Doxorubicin affects the DLBCL cells at all stages of their cell cycle. Combined with our previous results, this study discovered that the overexpression of hsa-miR-28-5p inhibited the proliferation, promoted apoptosis, and triggered cell cycle arrest at the S-phase in DLBCL cells. However, the effect of (Homo sapiens, hsa)-microRNA (miR)-28-5p on doxorubicin sensitivity in DLBCL has not been investigated. This study aims to reveal the effects of hsa-miR-28-5p

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… Epigenomics . 2019;11(1):35–51. doi: 10.2217/epi-2018-0123. 25. Leivonen S. K., Icay K., Jäntti K., et al. MicroRNAs regulate key cell survival pathways and mediate chemosensitivity during progression of diffuse large B-cell lymphoma. …

Chidamide increases the sensitivity of Non-small Cell Lung Cancer to Crizotinib by decreasing c-MET mRNA methylation.

Introduction: Crizotinib is a kinase inhibitor targeting c-MET/ALK/ROS1 used as the first-line chemical for the treatment of non-small cell lung cancer (NSCLC) with ALK mutations. Although c-MET is frequently overexpressed in 35-72% of NSCLC, most NSCLCs are primarily resistant to crizotinib treatment. Method: A set of NSCLC cell lines were used to test the effect of chidamide on the primary crizotinib resistance in vitro and in vivo. Relationships between the synergistic effect of chidamide and c-MET expression and RNA methylation were systemically studied with a battery of molecular biologic

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… Guttman M Jaffrey SR m(6)A RNA methylation promotes XIST-mediated transcriptional repression Nature 2016 537 7620 369 373 27602518 10.1038/nature19342 PMC5509218 47 Xiang MY Liu WS Tian W You AB Deng DJ RNA N-6-methyladenosine enzymes and resistance of cancer cells to chemotherapy and radiotherapy Epigenomics …

Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4.

Pluripotent and tissue-specific stem cells, such as blood-forming stem cells, are maintained through a balance of quiescence, self-renewal, and differentiation. Self-renewal is a specialized cell division that generates daughter cells with the same features as the parental stem cell. Although many factors are involved in the regulation of self-renewal, perhaps the most well-known factors are members of the Krüppel-like factor (KLF) family, especially KLF4, because of the landmark discovery that this protein is required to reprogram somatic cells into induced pluripotent stem cells. Because KLF

MicroRNA-mRNA Pairs Associated with Outcome in AML: From In Vitro Cell-Based Studies to AML Patients.

Cytarabine is the primary chemotherapeutic agent used for treatment of acute myeloid leukemia (AML). Disease relapse after initial remission remains one of the most pressing therapeutic challenges in the treatment of AML. Relapsed disease is often resistant to cytarabine and subsequent salvage therapy is ineffective. Recent studies have shown that some microRNAs (miRNAs) are associated with prognosis, but have not yet explored the role of miRNAs in cellular response to cytarabine. We identified 20 miRNAs that associate with the in vitro cytarabine chemo-sensitivity or apoptotic response of eig

KSHV and cancer: understanding the oncogenic machinery for next-generation diagnostic tools and therapies.

Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8), is an oncogenic virus responsible for Kaposi's sarcoma (KS) and lymphoproliferative disorders like primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). This review explores KSHV's oncogenic mechanisms, focusing on its ability to manipulate host cell signaling, evade immune detection, and promote tumorigenesis through latent and lytic viral proteins. Key oncoproteins, such as LANA, vCyc, vFLIP, and vGPCR, activate cancer hallmarks, as sustained proliferation, immune evasion, angiogenesis, and re

Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches.

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the

Epimutational profile of hematologic malignancies as attractive target for new epigenetic therapies.

In recent years, recurrent somatic mutations in epigenetic regulators have been identified in patients with hematological malignancies. Furthermore, chromosomal translocations in which the fusion protein partners are themselves epigenetic regulators or where epigenetic regulators are recruited/targeted by oncogenic fusion proteins have also been described. Evidence has accumulated showing that "epigenetic drugs" are likely to provide clinical benefits in several hematological malignancies, granting their approval for the treatment of myelodysplastic syndromes and cutaneous T-cell lymphomas. A

Протеиновая пальмитиоляция в гематологическое облучение: механистические связи с липидным метаболическим перепрограммированием и резистентностью к терапии.

Протеиновая пальмитиолация стала центральным постпереходным механизмом, регулирующим локализацию белков, стабильность и трансдукцию сигналов. В гематологических галактиках эта динамическая модификация находится на пересечении липидного метаболического перепрограммирования, взаимодействия между опухолью и иммуном и терапевтического сопротивления. Здесь мы рассматриваем вопрос о том, как дисрегулированные пальмитоилпереносазы и депальмитолазы изменяют метаболические ферменты, липидные переносчики, липидно-дрофтовые белки, онкогенные сигнальные компоненты и молекулы иммунного регулирования, созда

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… Epigenomics . ( 2023 ) 15 : 1195–203 . doi: 10.2217/epi-2023-0373 38059314 …

Shilajit mitigates chemotherapeutic drug-induced testicular toxicity: Study on testicular germ cell dynamics, steroidogenesis modulation, and Nrf-2/Keap-1 signaling.

BACKGROUND: Medications, including chemotherapeutic drugs, contribute to male infertility as external factors by inducing oxidative stress in testicular cells. Shilajit is a naturally occurring bioactive antioxidant used in Ayurvedic medicine to treat a variety of ailments. OBJECTIVE: This study examines the potential of Shilajit to counteract the negative effects of the chemotherapeutic drug cyclophosphamide (CPA) on testicular germ cell dynamics. MATERIAL AND METHODS: Male Parkes mice received single intraperitoneal CPA injection (200 mg/kg BW) on day one, followed by daily supplementation

GBA1 as a risk gene for osteoporosis in the specific populations and its role in the development of Gaucher disease.

BACKGROUND: Osteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations. METHODS: We selected 8115 patients with osteoporosis (T-score ≤ - 2.5) and 55,942 healthy individuals (T-score > - 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic

Вирус Эпштейн-Барр, витамин D и иммунная реакция: связи с последствиями множественного склероза.

Множественный склероз (MS) — аутоиммунное заболевание центральной нервной системы (CNS) без какого-либо окончательного запуска. Однако эпидемиологические исследования показывают, что важными факторами риска являются такие экологические факторы, как инфекция вируса Эпштейн-Барр (ЭБВ) и низкий уровень витамина D (вид D) у генетически предрасположенных лиц. Одно из ведущих предложений заключается в том, что EBV приводит в действие MS с помощью таких механизмов, как молекулярная имитация, где активированные автоматически реактивные B и T лимфоциты ошибочно нацелены на самоантигены. В соответствии

Patient-Derived Organoids as a Promising Tool for Multimodal Management of Sarcomas.

The management of sarcomas, a diverse group of cancers arising from connective tissues, presents significant challenges due to their heterogeneity and limited treatment options. Patient-derived sarcoma organoids (PDSOs) have emerged as a promising tool in the multimodal management of sarcomas, offering unprecedented opportunities for personalized medicine and improved treatment strategies. This review aims to explore the potential of PDSOs as a promising tool for multimodal management of sarcomas. We discuss the establishment and characterization of PDSOs, which realistically recapitulate the

Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders.

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, m

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… The Epigenomics of Cancer. Cell. 2007;128:683–692. doi: 10.1016/j.cell.2007.01.029. 32. Chauthe S.K., Mahajan S., Rachamalla M., Tikoo K., Singh I.P. Synthesis and Evaluation of Linear Furanocoumarinsas Potential Anti-Breast and Anti-Prostate Cancer Agents. Med. Chem. …

Resveratrol and Curcumin for Chagas Disease Treatment-A Systematic Review.

Chagas disease (CD) is a neglected protozoan infection caused by Trypanosoma cruzi, which affects about 7 million people worldwide. There are two available drugs in therapeutics, however, they lack effectiveness for the chronic stage-characterized mainly by cardiac (i.e., cardiomyopathy) and digestive manifestations (i.e., megaesophagus, megacolon). Due to the involvement of the immuno-inflammatory pathways in the disease's progress, compounds exhibiting antioxidant and anti-inflammatory activity seem to be effective for controlling some clinical manifestations, mainly in the chronic phase. Re

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… Epigenetics/Epigenomics and Prevention by Curcumin of Early Stages of Inflammatory-Driven Colon Cancer. Mol. Carci. 2019;59:227–236. doi: 10.1002/mc.23146. 79. Balasubramanyam K., Varier R.A., Altaf M., Swaminathan V., Siddappa N.B., Ranga U., Kundu T.K. …

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome.

The recent outbreak of Covid19 has required urgent treatments for numerous patients. No suitable vaccines or antivirals are available for Covid19. The efficiency against Covid19 of WHO therapies of choice, that are two antivirals developed for other pathologies, is controversial. Therefore, alternative approaches are required. Intravenous (IV) Vitamin C (Vit-C) has emerged as one of the other alternatives for this purpose. Here we review the effects of IV Vit-C on the immune system response, the antiviral properties of IV Vit-C, and finally the antioxidant properties of IV Vit-C to specificall

No patient left behind: The promise of immune priming with epigenetic agents.

Checkpoint inhibitors, monoclonal antibodies that inhibit PD-1 or CTLA-4, have revolutionized the treatment of multiple cancers. Despite the enthusiasm for the clinical successes of checkpoint inhibitors, and immunotherapy, in general, only a minority of patients with specific tumor types actually benefit from treatment. Emerging evidence implicates epigenetic alterations as a mechanism of clinical resistance to immunotherapy. This review presents evidence for that association, summarizes the epi-based mechanisms by which tumors evade immunogenic cell death, discusses epigenetic modulation as

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… Epigenomics 2009; 1:239-59; PMID:20495664; https://doi.org/ 10.2217/epi.09.33 22. Sigalotti L, Covre A, Fratta E, Parisi G, Colizzi F, Rizzo A, Danielli R, Nicolay HJ, Coral S, Maio M. Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies. …

Valproic acid potentiates the anticancer activity of capecitabine in vitro and in vivo in breast cancer models via induction of thymidine phosphorylase expression.

The prognosis of patients with metastatic breast cancer remains poor, and thus novel therapeutic approaches are needed. Capecitabine, which is commonly used for metastatic breast cancer in different settings, is an inactive prodrug that takes advantage of elevated levels of thymidine phosphorylase (TP), a key enzyme that is required for its conversion to 5-fluororacil, in tumors. We demonstrated that histone deacetylase inhibitors (HDACi), including low anticonvulsant dosage of VPA, induced the dose- and time-dependent up-regulation of TP transcript and protein expression in breast cancer cell

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… Clin Cancer Res 2015 10.1158/1078-0432.CCR-14-3119 25802282 13 Panobinostat approved for multiple myeloma Cancer discovery 2015 5 OF4 10.1158/2159-8290.CD-NB2015-040 25802326 14 Raha P Thomas S Munster PN Epigenetic modulation: a novel therapeutic target for overcoming hormonal therapy resistance Epigenomics …

Snail and Slug collaborate on EMT and tumor metastasis through miR-101-mediated EZH2 axis in oral tongue squamous cell carcinoma.

Lung diseases, including COVID-19 and lung cancers, is a huge threat to human health. However, for the treatment and diagnosis of various lung diseases, such as pneumonia, asthma, cancer, and pulmonary tuberculosis, are becoming increasingly challenging. Currently, several types of treatments and/or diagnostic methods are used to treat lung diseases; however, the occurrence of adverse reactions to chemotherapy, drug-resistant bacteria, side effects that can be significantly toxic, and poor drug delivery necessitates the development of more promising treatments. Nanotechnology, as an emerging t

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… Epigenomics. 2016;8:1079–1085. doi: 10.2217/epi-2016-0035. [101] Kao S C, Fulham M, Wong K, Cooper W, Brahmbhatt H, MacDiarmid J, Pattison S, Sagong J O, Huynh Y, Leslie F, et al. …

Application and Challenges of Chimeric Antigen Receptor T Cell Therapy in Systemic Rheumatic Diseases and Autoimmune Disorders.

Chimeric antigen receptor T (CAR-T) cell therapy, originally developed for hematologic malignancies, has emerged as a transformative candidate for systemic rheumatic diseases and autoimmune disorders (AIDs). Its unique efficacy in refractory AIDs relies on depleting autoreactive B cells and driving antigen-naïve immune reconstitution, achieving durable drug-free remission in early-phase trials. Despite promising clinical and serological responses lasting 2-5 years without long-term immunosuppression, the field faces unmet needs: complex manufacturing, limited tissue penetration, antigen escape

Epigenetic regulation in gynecological cancers: a paradigm shift in immunotherapy strategies.

Recent advances in immunotherapy have transformed the therapeutic landscape of gynecological cancers; however, durable responses remain limited by tumor heterogeneity and immune evasion mechanisms. Emerging evidence highlights epigenetic modifications comprising of DNA methylation, histone modifications, and RNA methylation as pivotal regulators of the tumor immune microenvironment and immunotherapy efficacy. This review comprehensively explores how these epigenetic alterations modulate immune cell infiltration, antigen presentation, immune checkpoint expression, and tumor immunogenicity acros