The continuing challenges facing gene‐targeted therapies DOI Open Access
Nina F. Schor

Developmental Medicine & Child Neurology, Journal Year: 2023, Volume and Issue: 65(8), P. 998 - 998

Published: April 27, 2023

Years ago, the biomedical community convinced itself that, once we knew sequence of human genome, would hold keys to curable universe. Clearly, this is far from case. Unlocking genome made us realize genetics more complex than ever imagined. To be fair, gene-targeted therapies have already yielded enormous triumphs and promise for conquest developmental disorders nervous system. But they also many challenges demanded different solutions.1 Every cell in body has same complement DNA at least during some phase its lifetime. a pars compacta neuron not reticular formation astrocyte. This partly because represents whole repertoire proteins that could produced by cell, but which ones are particular cell. Histone methylation, histone acetylation, transcription factor activation binding, presence enhancers suppressors all play roles gating production mRNA. In addition, modification status individual networks genes changes over time.2 For reason, understanding impact errors or modifications requires an anatomical temporo-physiological map each these biochemical processes. The ability do single-cell transcriptomics, methylomic acetylomic analyses, cryo-electron microscopy should aid basic science enterprise translation genetic metabolic disease organ organ, system system.3 Antisense been implemented with varying degrees success several neurological diseases. Challenges include need cost lifelong therapy, off-target delivery, adverse effects both construct delivery vehicle chemical modification. Furthermore, variability severity course makes it difficult decide whom risks therapy outweigh disease.4 It critical develop standardized metrics progression and, them, robust natural history deep phenotypic subtypes diverse cohorts patients. We must use prodigious tools understand relationship between antisense sequences organs target, therapeutically adversely. Gene most often delivered viral vehicles. From study investigator investigator, viruses vary widely. date, there no road virus targets tissue type causes what effects. Virally-mediated gene known cause acute hepatic failure microangiopathic thrombocytopenia renal failure. immune reactions mean if first successful correcting disorder, patient likely cannot safely effectively receive another.1 codify best specific type. effective, non-toxic methods building tolerance given virus. explore non-viral systems, such as nanoparticles, avoid presented currently available strategies. Because answer begets another question fuller reveals unimaginable complexity biological much work yet done effect cures. Only through innovative, collaborative efforts will achieve goal children families neurogenetic disorders.5 Not required

Language: Английский

Brief guide to RNA sequencing analysis for nonexperts in bioinformatics DOI Open Access
Gee‐Yoon Lee, Seokjin Ham, Seung‐Jae Lee

et al.

Molecules and Cells, Journal Year: 2024, Volume and Issue: 47(5), P. 100060 - 100060

Published: April 16, 2024

Transcriptome analysis is widely used for current biological research, but remains challenging many experimental scientists. Here, we present a brief broad guideline transcriptome analysis, focusing on RNA sequencing, by providing the list of publicly available datasets, tools, and R packages practical analysis. This work will be useful biologists to perform key transcriptomic with minimum expertise in bioinformatics.

Language: Английский

Citations

12

Antitumor Effect and Gut Microbiota Modulation by Quercetin, Luteolin, and Xanthohumol in a Rat Model for Colorectal Cancer Prevention DOI Open Access
Álvaro Pérez‐Valero, Patricia Magadán‐Corpas, Suhui Ye

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(8), P. 1161 - 1161

Published: April 13, 2024

Colorectal cancer stands as the third most prevalent form of worldwide, with a notable increase in incidence Western countries, mainly attributable to unhealthy dietary habits and other factors, such smoking or reduced physical activity. Greater consumption vegetables fruits has been associated lower colorectal cancer, which is attributed their high content fiber bioactive compounds, flavonoids. In this study, we have tested flavonoids quercetin, luteolin, xanthohumol potential antitumor agents an animal model induced by azoxymethane dodecyl sodium sulphate. Forty rats were divided into four cohorts: Cohort 1 (control cohort), 2 (quercetin 3 (luteolin 4 (xanthohumol cohort). These administered intraperitoneally evaluate pharmaceutical agents. At end experiment, after euthanasia, different parameters intestinal microbiota populations analyzed. Luteolin was effective significantly reducing number tumors compared control cohort. Furthermore, main significant differences at level observed between cohort treated experienced reduction abundance genera disease inflammatory conditions, Clostridia UCG-014 Turicibacter. On hand, healthy state, Muribaculum, showed luteolin results underline anti-colorectal manifested through modulation tumors.

Language: Английский

Citations

11

Overview of the epigenetic/cytotoxic dual-target inhibitors for cancer therapy DOI

Hailiu Liang,

Shuqing Li, Xiaopeng Peng

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 285, P. 117235 - 117235

Published: Jan. 5, 2025

Language: Английский

Citations

1

A review of the role of epigenetic studies for intramuscular fat deposition in beef cattle DOI
Belete Kuraz Abebe, Jianfang Wang, Juntao Guo

et al.

Gene, Journal Year: 2024, Volume and Issue: 908, P. 148295 - 148295

Published: Feb. 21, 2024

Language: Английский

Citations

7

Histone H3 lysine 9 tri-methylation is associated with pterygium DOI Creative Commons
Dahee Choi,

Ann-Yae Na,

Seok-Won Jeoung

et al.

BMC Ophthalmology, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 3, 2025

Pterygium, abnormal growths of conjunctival tissue onto the cornea, are common ocular surface conditions with a high risk recurrence after surgery and potential ophthalmic complications. The exact cause pterygium remains unclear, triggers still unknown. This study aims to investigate relationship between epigenetics uncover identify biomarkers for its diagnosis. We performed ChIP-seq assay compare genome-wide histone modification levels normal conjunctiva stage 3 samples. In this study, we epigenetic profiles patients pterygium, focusing on H3 lysine 4 (H3K4) 9 (H3K9) trimethylation (me3). While H3K4me3 showed no significant change, they were significantly altered in genes related development diseases. Conversely, H3K9me3 markedly elevated genome-wide, particularly at promoters 82 involved developmental pathways. Furthermore, six genes, ANK2, AOAH, CBLN2, CDH8, CNTNAP4, DPP6, decreased gene expression correlated substantially increased H3K9me3, suggesting their as pterygium. represents first report linking progression, providing valuable insights into therapeutic strategies drug targets.

Language: Английский

Citations

0

Nutrient starvation-induced Hda1C rewiring: coordinated regulation of transcription and translation DOI Creative Commons
Min Kyung Lee, Byunghee Kang, Min Kyung Shin

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(7)

Published: March 23, 2025

In yeast, Hda1 histone deacetylase complex (Hda1C) plays an important role in transcriptional regulation by modulating acetylation. We here explored the changes Hda1C binding nutrient-rich and -starved conditions. Chromatin immunoprecipitation sequencing revealed that starvation alters RNA Pol II to coding genes a highly correlated manner. Interestingly, we discovered transcription-independent recruitment of intergenic regions, particularly upstream regulatory sequences (URS) ribosomal protein (RP) genes, which are enriched with Rap1 sites. Under nutrient starvation, contributes these URS where deacetylates histones, thereby fine-tuning basal gene expression delaying RP reactivation. Furthermore, is also required for I transcription RNAs (rRNAs) III transfer (tRNA) especially nutrient-limited Significantly, mutants sensitive translation inhibitors display altered ribosome profiles. Thus, may coordinate within nucleus control cytoplasm could be key regulator responses stress.

Language: Английский

Citations

0

Epigenetics of Skeletal Muscle Atrophy DOI Open Access

Jiacheng Du,

Qian Wu, Eun Ju Bae

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8362 - 8362

Published: July 31, 2024

Skeletal muscle atrophy, characterized by diminished strength and mass, arises from various causes, including malnutrition, aging, nerve damage, disease-related secondary atrophy. Aging markedly escalates the prevalence of sarcopenia. Concurrently, incidence atrophy significantly rises among patients with chronic ailments such as heart failure, diabetes, obstructive pulmonary disease (COPD). Epigenetics plays a pivotal role in skeletal elevates methylation levels promoter regions specific genes within tissues. This aberrant is similarly observed conditions like neurological disorders, cardiovascular diseases. study aims to explore relationship between epigenetics thereby enhancing understanding its pathogenesis uncovering novel therapeutic strategies.

Language: Английский

Citations

3

In vivo pulse-chase in C. elegans reveals intestinal histone turnover changes upon starvation DOI Creative Commons
Christopher Borchers,

Kara Osburn,

Hyun Cheol Roh

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 110299 - 110299

Published: May 1, 2025

Language: Английский

Citations

0

Exploring the potential of histone demethylase inhibition in multi-therapeutic approaches for cancer treatment DOI
Deping Li,

Hailiu Liang,

Yifei Wei

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 264, P. 115999 - 115999

Published: Nov. 29, 2023

Language: Английский

Citations

6

Meta-analysis of the transcriptome identifies aberrant RNA processing as common feature of aging in multiple species DOI Open Access
Gee‐Yoon Lee, Seokjin Ham, Jooyeon Sohn

et al.

Molecules and Cells, Journal Year: 2024, Volume and Issue: 47(4), P. 100047 - 100047

Published: March 18, 2024

Aging is accompanied by the gradual deregulation of transcriptome. However, whether age-dependent changes in transcriptome are evolutionarily conserved or diverged remains largely unexplored. Here, we performed a meta-analysis examining using publicly available datasets eleven representative metazoans, ranging from Caenorhabditis elegans to human. To identify transcriptomic associated with aging, analyzed various aspects transcriptome, including genome composition, RNA processing, and functional consequences. The use introns novel splice sites tended increase age, particularly brain. In addition, our analysis suggests that accumulation premature termination codon-containing transcripts common feature aging across multiple animal species. Using C. as test model, showed several splicing factors age-dependently downregulated were required maintain normal lifespan. Thus, aberrant processing appears be short lifespan

Language: Английский

Citations

2