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Recent advances in CAR-MSCs: the new engine of cellular immunotherapy evolution.

In recent years, the development of chimeric antigen receptor (CAR) technology has greatly promoted the progress of cellular immunotherapy. Among them, CAR-T cell therapy has shown remarkable clinical effects in the treatment of hematological malignancies. However, this therapy still faces a series of challenges, including immunogenicity, toxic side effects, and insufficient maintenance of long-term efficacy. The latest research progress has extended CAR technology to mesenchymal stem cells (MSCs), and the resulting CAR-MSCs combine the precise targeting ability of CAR molecules with the inher

Multiple myeloma, a quintessential malignant disease of aging: a geroscience perspective on pathogenesis and treatment.

Multiple myeloma (MM) is an incurable plasma cell malignancy, which is predominantly a disease of older adults (the median age at diagnosis is 70 years). The slow progression from asymptomatic stages and the late-onset of MM suggest fundamental differences compared to many other hematopoietic system-related malignancies. The concept discussed in this review is that age-related changes at the level of terminally differentiated plasma cells act as the main risk factors for the development of MM. Epigenetic and genetic changes that characterize both MM development and normal aging are highlighted

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… In senescent cells, global hypomethylation is accompanied by hypermethylation of the senescent-associated heterochromatin foci (SAHFs). The SAHFs are at the loci of proliferative genes such as E2F target genes, responsible for initiating the G1 phase of the cell cycle. …

JCMM Annual Review on Advances in Biotechnology for the Treatment of Haematological Malignancies: A Review of the Latest In-Patient Developments 2024-2025.

Advances in biotechnology are set to revolutionise the treatment of haematological malignancies. Current treatments have limited efficacy due to their high toxicity and poor long-term outcomes, particularly in acute myeloid leukaemia (AML). In 2024-2025, emerging targeted therapies promise improved results with reduced adverse effects. This review is the first of an annual series exploring the latest in-patient developments in several key areas, focusing on mechanisms. We present advances in the use and action of several therapies including epigenetic modulators, protein degraders, apoptotic i

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… The other protein, MYC‐EC‐E2, includes a ZF DNA‐binding domain targeting a MYC enhancer fused to a Krüppel‐associated box (KRAB) domain, which deposes H3K9me3 marks resulting in the formation of heterochromatin [ 25 ]. …

Emerging Role of Epigenetic Modifiers in Breast Cancer Pathogenesis and Therapeutic Response.

Breast cancer pathogenesis, treatment, and patient outcomes are shaped by tumor-intrinsic genomic alterations that divide breast tumors into molecular subtypes. These molecular subtypes often dictate viable therapeutic interventions and, ultimately, patient outcomes. However, heterogeneity in therapeutic response may be a result of underlying epigenetic features that may further stratify breast cancer patient outcomes. In this review, we examine non-genetic mechanisms that drive functional changes to chromatin in breast cancer to contribute to cell and tumor fitness and highlight how epigeneti

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… The introduction of tamoxifen reverses estrogen-induced H3 and H4 acetylation, leading to global H3 hypoacetylation and an increase in heterochromatin, as well as a reduction in RNA pol II occupancy at PS2 and c-MYC genes [ 121 ]. …

Drugs and Epigenetic Molecular Functions. A Pharmacological Data Scientometric Analysis.

Interactions of drugs with the classical epigenetic mechanism of DNA methylation or histone modification are increasingly being elucidated mechanistically and used to develop novel classes of epigenetic therapeutics. A data science approach is used to synthesize current knowledge on the pharmacological implications of epigenetic regulation of gene expression. Computer-aided knowledge discovery for epigenetic implications of current approved or investigational drugs was performed by querying information from multiple publicly available gold-standard sources to (i) identify enzymes involved in c

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… Cocaine dynamically regulates heterochromatin and repeti-tive element unsilencing in nucleus accumbens. Proc. Natl. Acad. Sci. USA. 2011;108:3035–3040. doi: 10.1073/pnas.1015483108. 64. …

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

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… For example, methylation on H3K4, H3K36, and H3K79 is more often related to active euchromatin status, while methylation on H3K9, H3K27, and H4K20 usually causes repressive heterochromatin. 386 Moreover, H3K9me1 is commonly seen in actively transcribed genes, while H3K9me3 is frequently discovered in …

Recent Advances in the Applications of Small Molecules in the Treatment of Multiple Myeloma.

Therapy for multiple myeloma (MM), a hematologic neoplasm of plasma cells, has undergone remarkable changes over the past 25 years. Small molecules (molecular weight of less than one kDa), together with newer immunotherapies that include monoclonal antibodies, antibody-drug conjugates, and most recently, chimeric antigen receptor (CAR) T-cells, have combined to double the disease's five-year survival rate to over 50% during the past few decades. Despite these advances, the disease is still considered incurable, and its treatment continues to pose substantial challenges, since therapeutic refra

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… Tight winding (heterochromatin) tends to favor gene silencing, while gene expression is associated with more open conformations (euchromatin). …

PIWI-interacting RNAs (PiRNAs) as emerging biomarkers and therapeutic targets in biliary tract cancers: A comprehensive review.

Cancers affecting the biliary tract, such as gallbladder cancer and cholangiocarcinoma, make up a small percentage of adult gastrointestinal malignancies, but their incidence is on the rise. Due to the lack of dependable molecular biomarkers for diagnosis and prognosis, these cancers are often not detected until later stages and have limited treatment options. Piwi-interacting RNAs (piRNAs) are a type of small noncoding RNA that interacts with Piwi proteins and has been linked to various diseases, especially cancer. Manipulation of piRNA expression has the potential to serve as an important bi

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… This interaction leads to the suppression of gene expression through various mechanisms, such as promoting RNA instability, inhibiting translation, cleaving the transcripts, or inducing heterochromatinization [ 58 , 59 ]. PiRNAs, miRNAs, and siRNAs have several notable distinctions. …

Transcription and Translation Inhibitors in Cancer Treatment.

Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targ

DNA Methylation Cancer Biomarkers: Translation to the Clinic.

Carcinogenesis is accompanied by widespread DNA methylation changes within the cell. These changes are characterized by a globally hypomethylated genome with focal hypermethylation of numerous 5'-cytosine-phosphate-guanine-3' (CpG) islands, often spanning gene promoters and first exons. Many of these epigenetic changes occur early in tumorigenesis and are highly pervasive across a tumor type. This allows DNA methylation cancer biomarkers to be suitable for early detection and also to have utility across a range of areas relevant to cancer detection and treatment. Such tests are also simple in

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… Histone modifications can lead to either tightly packed and inactive conformations or open and accessible DNA (termed heterochromatin and euchromatin respectively). …

Abstracts from the 53rd European Society of Human Genetics (ESHG) Conference: e-Posters.

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… They include varying sizes of heterochromatin blocks, satellite or repeat sequence regions and inversions. However, previous studies have reported that heterochromatin polymorphisms are more frequent in infertile men. This may be associated with infertility and unsuccessful pregnancy. … After the analysis, in the male partner was detected heterochromatin polymorphism, karyotype- 46, XY, 9qh+. After genetic counseling, PGD-A was used. …

Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies.

The pathophysiological mechanisms of cardiovascular disease and microvascular complications in diabetes have been extensively studied, but effective methods of prevention and treatment are still lacking. In recent years, DNA methylation, histone modifications, and non-coding RNAs have arisen as possible mechanisms involved in the development, maintenance, and progression of micro- and macro-vascular complications of diabetes. Epigenetic changes have the characteristic of being heritable or deletable. For this reason, they are now being studied as a therapeutic target for the treatment of diabe

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… Chromatin remodelling is responsible for the dynamic component of the fixed genotype and, from a functional and structural point of view, chromatin occurs in two higher-order structures: euchromatin and heterochromatin. …

Epigenetic Therapies for Acute Myeloid Leukemia and Their Immune-Related Effects.

Over the past decades, our molecular understanding of acute myeloid leukemia (AML) pathogenesis dramatically increased, thanks also to the advent of next-generation sequencing (NGS) technologies. Many of these findings, however, have not yet translated into new prognostic markers or rationales for treatments. We now know that AML is a highly heterogeneous disease characterized by a very low mutational burden. Interestingly, the few mutations identified mainly reside in epigenetic regulators, which shape and define leukemic cell identity. In the light of these discoveries and given the increasi

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… Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer. Nat. Cell Biol. 13 292–302. 10.1038/ncb2170 Dillon M. B., Bachovchin D. A., Brown S. J., Finn M. G., Rosen H., Cravatt B. F., et al. (2012). …

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms.

The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by reg

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… In the binary switch hypothesis, also known as the binary methylation-phosphorylation switch, Aurora B and SUV39H1 have been identified to maintain the kinetic equilibrium of heterochromatin [ 188 ]. …

Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.

G-quadruplex (G4) structures represent noncanonical secondary formations found in DNA and RNA. Recent research reveals that G4s are abnormally enriched in various cancers, with closely linked to malignancy, metastatic potential, and prognosis. These structures have emerged as promising biomarkers for cancer with notable clinical relevance. Concurrently, investigations into compounds that selectively recognize DNA or RNA G4s as potential anticancer agents offer new avenues for early cancer diagnosis and therapeutic strategies. This review systematically analyzes the chemical structural characte

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… (A) Telomeric G4s in chromosome maintenance: TERRA R-loops/rG4s promote ALT, with LSD1 modulating this process; POT1b mitigates DNA damage; BRCA2 loss disrupts homeostasis via R-loops, while TERRA rG4 recruits PRC2 for heterochromatinization. …

Epigenetic Regulation of Autophagy in Bone Metabolism.

The skeletal system is crucial for supporting bodily functions, protecting vital organs, facilitating hematopoiesis, and storing essential minerals. Skeletal homeostasis, which includes aspects such as bone density, structural integrity, and regenerative processes, is essential for normal skeletal function. Autophagy, an intricate intracellular mechanism for degrading and recycling cellular components, plays a multifaceted role in bone metabolism. It involves sequestering cellular waste, damaged proteins, and organelles within autophagosomes, which are then degraded and recycled. Autophagy's i

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… In contrast, reduced acetylation levels and heightened methylation at H3K9, H3K27, and H4K20 indicate a more condensed, transcriptionally inactive heterochromatin structure. 23 , 40 Histone modification is the most intricate mode of regulation among the three epigenetic modifications. 41 Currently, the …

A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy.

The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy. Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies. Human epidermal growth factor receptor, hormone receptors, and angiogenesis factors are among the established therapies in tumor reduction and managing side effects. Novel targeted therapies like KRAS G12C, Claudin-18 isoform 2 (CLDN18.2), Trophoblast cell-surface antigen 2 (TROP2), and epigenetic r

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… To access transcriptional events, acetylation is an important step in unwinding closely coiled heterochromatin, which plays a major role in increasing the inner pore space between histones and chromatin. …

Metabolic reprogramming in cancer and senescence.

The rising trend in global cancer incidence has caused widespread concern, one of the main reasons being the aging of the global population. Statistical data show that cancer incidence and mortality rates show a clear upward trend with age. Although there is a commonality between dysregulated nutrient sensing, which is one of the main features of aging, and metabolic reprogramming of tumor cells, the specific regulatory relationship is not clear. This manuscript intends to comprehensively analyze the relationship between senescence and tumor metabolic reprogramming; as well as reveal the impac

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… Downregulation of LaminB1 leads to heterochromatin decondensation and the production of cytoplasmic chromatin fragments, which cause DNA damage. 75 , 81 The downregulation of LaminB1 mRNA in transcriptomic studies is a widespread hallmark of cellular senescence. …

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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… Conversely, HDACs remove these acetyl groups, restoring the positive charge and resulting in chromatin condensation (heterochromatin), thereby suppressing transcription [ 63 ]. Proper balance between HAT and HDAC activity is essential for maintaining normal cellular function. …

Immunotherapies for Aging and Age-Related Diseases: Advances, Pitfalls, and Prospects.

Aging is characterized by a gradual decline in the functionality of all the organs and tissues, leading to various diseases. As the global population ages, the urgency to develop effective anti-aging strategies becomes increasingly critical due to the growing severity of associated health problems. Immunotherapy offers novel and promising approaches to combat aging by utilizing approaches including vaccines, antibodies, and cytokines to target specific aging-related molecules and pathways. In this review, we summarize the recent advancements of immunotherapies to eliminate senescence cells and

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… Physical and chemical damage, telomere shortening, and oncogene activation lead to DNA damage, triggering the DNA damage response (DDR) and senescence-associated heterochromatin foci (SAHF). …