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Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to

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… Histone Acetylation Histone acetylation is a post-translational modification (PTM) that involves the addition of acetyl groups to lysine residues in histone tails, a reaction catalyzed by histone acetyltransferases (HATs), while histone deacetylases (HDACs) remove these acetyl groups [ 61 ]. … Enzymes such as histone deacetylases (HDACs) and histone acetyltransferases (HATs) orchestrate these changes, influencing not only the differentiation of osteoblasts and osteoclasts, but also their responsiveness to tumor-derived signals in the bone microenvironment [ 134 ]. …

Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then,

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

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… Histone modifications can result from the activity of various enzymes, including histone acetyltransferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and histone demethylases (HDMs). …

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties

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… The enzymes that catalyze histone acetylation are called histone acetyltransferases (HATs) and the ones that catalyze the removal of an acetyl group from a histone are called histone deacetylases (HDACs), both playing a crucial role in the remodeling of chromatin [ 41 ]. …

High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges.

Vitamin C, also known as ascorbic acid, has sparked controversy since it first emerged as a potential anti-cancer agent. However, an increasing number of preclinical studies have demonstrated that high-dose vitamin C exhibits selective anti-tumor effects, including "pro-oxidative cytotoxicity", "anti-cancer epigenetic regulation", and "immune modulation". Consequently, vitamin C has reemerged as a promising anti-cancer therapy in the form of high-dose administration. Advancements in pharmacokinetic research have facilitated the development of clinical trials. Early clinical studies across vari

Curcumin in Autoimmune and Rheumatic Diseases.

Over recent decades, many clinical trials on curcumin supplementation have been conducted on various autoimmune diseases including osteoarthritis, type 2 diabetes, and ulcerative colitis patients. This review attempts to summarize the highlights from these clinical trials. The efficacy of curcumin either alone or in conjunction with existing treatment was evaluated. Sixteen clinical trials have been conducted in osteoarthritis, 14 of which yielded significant improvements in multiple disease parameters. Eight trials have been conducted in type 2 diabetes, all yielding significant improvement i

Relationship between circulating syndecan-1 levels (CD138s) and serum free light chains in monoclonal gammopathies.

BackgroundMonoclonal gammopathies encompass a wide range of diseases characterized by the monoclonal expansion of a B-cell clone. Despite emerging therapeutic strategies, chances of survival of patients who are affected are still scarce, which implies that new tools are necessary not only for the diagnosis but also for the follow-up of patients affected by such diseases. In this context, the use of free light chains (FLCs) has been incorporated into many guidelines. Likewise, tumor microenvironment is consistently gaining importance as role player in tumor pathogenesis. Specifically, Syndecan-

Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.

Recent studies highlight the multifaceted roles of neurotransmitters in tumor immunomodulation, offering novel avenues for increasing therapeutic efficacy. These signaling molecules are classified into cholinergic agents, monoamines, amino acids, and peptides and regulate tumorigenesis, metastasis, and immune evasion via autocrine/paracrine pathways and receptor-mediated interactions. Notably, neurotransmitters influence tumor cell proliferation, apoptosis, and immune cell activity by modulating intracellular signaling cascades through posttranslational modifications (serotonylation and dopami

Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential.

Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic

Ebastine exerts antitumor activity and induces autophagy by activating AMPK/ULK1 signaling in an IPMK-dependent manner in osteosarcoma.

Numerous studies have confirmed that in addition to interfering with the tumor inflammatory environment, anti-inflammatory agents can directly increase apoptosis and sensitivity to conventional therapies and decrease invasion and metastasis, making them useful candidates for cancer therapy. Here, we first used high-throughput screening and had screened one compound candidate, ebastine (a H1-histamine receptor antagonist), for osteosarcoma therapy. Cell viability assays, colony formation assays, wound healing assays, and Transwell assays demonstrated that ebastine elicited antitumor effects in

Association of p-phenylenediamine exposure with alterations of pulmonary function, pruritus and health-related quality of life in hair dye factory workers: a cross-sectional study.

P-Phenylenediamine (PPD) is a common component of hair dye, which can cause skin contact allergy and asthma with impaired pulmonary function. However, the adverse effects of occupational exposure to different dose PPD was rarely mentioned. We recruited 124 workers from a hair dye factory to explore the association of occupational PPD exposure on pulmonary function, pruritus and health related quality of life (HRQL). We categorized exposure to PPD into 3 levels: lower exposure group (< 0.00001 mg/m3); middle exposure group (0.00001-0.00033 mg/m3); higher exposure group (0.00033-0.047 mg/m3). Th

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… Permanent hair dyes and bladder cancer: Risk modification by cytochrome P4501A2 and N-acetyltransferases 1 and 2. Carcinogenesis. 2003;24:483–489. doi: 10.1093/carcin/24.3.483. 13. Sangrajrang S, et al. Personal use of hair dyes–increased risk of non-Hodgkin's lymphoma in Thailand. Asian Pac. J. …

Integrating Single-Cell Transcriptome and Network Analysis to Characterize the Therapeutic Response of Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by a unique BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) were developed to target the BCR-ABL oncoprotein, inhibiting its abnormal kinase activity. TKI treatments have significantly improved CML patient outcomes. However, the patients can develop drug resistance and relapse after therapy discontinues largely due to intratumor heterogeneity. It is critical to understand the differences in therapeutic responses among subpopulations of cells. Single-cell RNA sequencing measures the transcriptome of individual c

Ginsenoside Rg3 inhibits melanoma cell proliferation through down-regulation of histone deacetylase 3 (HDAC3) and increase of p53 acetylation.

Malignant melanoma is an aggressive and deadly form of skin cancer, and despite recent advances in available therapies, is still lacking in completely effective treatments. Rg3, a monomer extracted from ginseng roots, has been attempted for the treatment of many cancers. It is reported that the expressions of histone deacetylase 3 (HDAC3) and p53 acetylation correlate with tumor cell growth. However, the antitumor effect of Rg3 on melanoma and the mechanism by which it regulates HDAC3 expression and p53 acetylation remain unknown. We found high expression of HDAC3 in human melanoma tissues to

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… Histone acetylation catalyzed by histone acetyltransferases (HATs) is typically associated with inducing gene transcription, while histone deacetylation controlled by histone deacetylases (HDACs) is mainly related to gene silence [6] . …

Modulating the JAK/STAT pathway with natural products: potential and challenges in cancer therapy.

The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is a critical signaling network governing cellular functions such as immune responses, proliferation, and apoptosis. Dysregulation of this pathway is strongly implicated in cancer progression. This review explores the therapeutic potential of natural products, including Curcumin, Resveratrol, Apigenin, and Epigallocatechin Gallate (EGCG), as modulators of the JAK/STAT pathway. These phytochemicals exhibit anticancer activity by inhibiting JAK/STAT phosphorylation, blocking STAT dimerization, and interfering wi

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

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… In addition, histone lysine acetyltransferases Kat6a (Moz), Kat6b (Morf) and Kat8 (Mof) regulate target gene expression by depositing H3K9 ac , H3K23 ac /H3K14 ac and H4K16 ac , respectively, on the regulatory regions of target genes. … Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice. Blood. 2017;129:48–59. doi: 10.1182/blood-2016-05-714568. 180. Yu VWC, et al. Epigenetic memory underlies cell-autonomous heterogeneous behavior of hematopoietic stem cells. …

A Novel Hydroxamic Acid-Based Curcumin Derivative as Potent Histone Deacetylase Inhibitor for the Treatment of Glioblastoma.

Glioblastoma (GBM) is one of the most common primary and deadliest malignant brain tumor with chemoresistance and poor prognosis. There is a lack of effective chemotherapeutic drug for the treatment of GBM. In this work, we reported the preparation of a histone deacetylase (HDAC) inhibitor, DMC-HA, from the structural modification of natural product curcumin. DMC-HAs were tested in an HDAC inhibition assay and an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cytotoxicity. It showed potent inhibition of HDAC1-2 and HDAC6 with IC50 values in the submicromolar conce

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… Histone deacetylases (HDACs) and histone acetyltransferases (HATs) determine the acetylation status of histones, regulating the transcription activation ( 6 ). …

Caspase-Dependent HMGB1 Release from Macrophages Participates in Peripheral Neuropathy Caused by Bortezomib, a Proteasome-Inhibiting Chemotherapeutic Agent, in Mice.

Given the role of macrophage-derived high mobility group box 1 (HMGB1) in chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel, we analyzed the role of HMGB1 and macrophages in the CIPN caused by bortezomib, a proteasome-inhibiting chemotherapeutic agent used for the treatment of multiple myeloma. Repeated administration of bortezomib caused CIPN accompanied by early-stage macrophage accumulation in the dorsal root ganglion. This CIPN was prevented by an anti-HMGB1-neutralizing antibody, thrombomodulin alfa capable of accelerating thrombin-dependent degradation of HMGB1, anta

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… In macrophages, paclitaxel causes cytoplasmic translocation and extracellular release of nuclear HMGB1 following the upregulation of histone acetyltransferases (HATs) through reactive oxygen species (ROS) accumulation and the activation of p38 MAP kinase (p38MAPK) and NF-κB signals, but independently …

Mechanisms and Clinical Applications of Genome Instability in Multiple Myeloma.

Ongoing genomic instability represents a hallmark of multiple myeloma (MM) cells, which manifests largely as whole chromosome- or translocation-based aneuploidy. Importantly, although it supports tumorigenesis, progression and, response to treatment in MM patients, it remains one of the least understood components of malignant transformation in terms of molecular basis. Therefore these aspects make the comprehension of genomic instability a pioneering strategy for novel therapeutic and clinical speculations to use in the management of MM patients. Here we will review mechanisms mediating genom

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… Among such events, CpG islands methylation achieved by DNA methyltransferases (Dnmts), and histone modifications resulting from histone acetyltransferases (HATs) or histone deacetylases (HDACs), are frequently observed in MM cells [ 52 , 53 ]. …

A Novel Approach to Prognostic Factors and Risk Stratification in Pediatric AML: Case Report and Literature Review.

Acute myeloid leukemia (AML), the second most common type of leukemia in children, is a heterogeneous disease known to be caused by genetic, epigenetic, and transcriptional changes, predominantly somatic and germline abnormalities. Despite significant improvement of overall survival rates, the prognosis of pediatric AML remains unfavorable in comparison with acute lymphoblastic leukemia (ALL), especially in relapsed or refractory settings. The current status and future directions are focused on establishing an accurate diagnosis and treatment strategies based on the genomic background. Next-ge

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… It is stabilized by histone deacetylases (HDACs) and histone acetyltransferases (HATs), adjusting gene expression. By suppressing HDACs, HDACis contribute to maintaining open chromatin conformation [ 182 , 183 ]. … Lymphocyte Infusion BCL-2 B-Cell Leukemia/Lymphoma-2 JM Juxtamembrane MCL-1 Myeloid Cell Leukemia 1 BH3 BCL-2 homology 3 MOMP Mitochondrial Outer Membrane Permeabilization HMA Hypomethylating Agent HDAC Histone Deacetylase HDACi Histone Deacetylases inhibitor AZA Azacitidine DEC Decytabine HATs Histone Acetyltransferases …

Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review.

Upon the induction of DNA damage, the chromatin structure unwinds to allow access to enzymes to catalyse the repair. The regulation of the winding and unwinding of chromatin occurs via epigenetic modifications, which can alter gene expression without changing the DNA sequence. Epigenetic mechanisms such as histone acetylation and DNA methylation are known to be reversible and have been indicated to play different roles in the repair of DNA. More importantly, the inhibition of such mechanisms has been reported to play a role in the repair of double strand breaks, the most detrimental type of DN