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Cell Death Discovery Apr 2024Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and... (Review)
Review
Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and therapeutic tools are limited. Thus, identifying new targets for the diagnosis and treatment of corneal diseases has gained great interest. Methylation, a type of epigenetic modification, modulates various cellular processes at both nucleic acid and protein levels. Growing evidence shows that methylation is a key regulator in the pathogenesis of corneal diseases, including inflammation, fibrosis, and neovascularization, making it an attractive potential therapeutic target. In this review, we discuss the major alterations of methylation and demethylation at the DNA, RNA, and protein levels in corneal diseases and how these dynamics contribute to the pathogenesis of corneal diseases. Also, we provide insights into identifying potential biomarkers of methylation that may improve the diagnosis and treatment of corneal diseases.
PubMed: 38589350
DOI: 10.1038/s41420-024-01935-2 -
Medicinal Research Reviews Mar 2024Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3... (Review)
Review
Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1-targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.
Topics: Humans; Lysine; Histone Demethylases; Monoamine Oxidase Inhibitors; Histones; Neoplasms; Drug Discovery; Enzyme Inhibitors
PubMed: 38014919
DOI: 10.1002/med.22000 -
Hematology (Amsterdam, Netherlands) Dec 2023Arsenic trioxide (ATO) might be effective for myelodysplastic syndrome (MDS) by apoptosis induction and demethylation. But ATO has not been widely recommended for small... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Arsenic trioxide (ATO) might be effective for myelodysplastic syndrome (MDS) by apoptosis induction and demethylation. But ATO has not been widely recommended for small sample and conflicting conclusion of existing trials. This review aimed to systematically evaluate the efficacy of regimens containing ATO for the MDS and explore optimal combination.
METHOD
Randomized clinical trials (RCTs) about ATO regimens were retrieved from China National Knowledge Infrastructure, Embase and PubMed. With odds ratio (OR) as the effect size, network meta-analysis (NMA) and component network meta-analysis (CNMA) were conducted by R and 'netmeta' package, after study selection, quality assessment and data extraction.
RESULT
Thirty-night RCTs were included with a total of 2125 patients, including 1235 treated by ATO containing regimen. With support therapy alone as reference, no inconsistency and heterogeneity were observed. Although NMA did not demonstrate better efficacy of ATO alone, the result of CNMA indicated that ATO was effective in the improvement of overall remission (ORR) [OR = 2.09(1.61, 2.71)] and complete remission (CR) [OR = 1.66(1.25, 2.21)]. Five ATO-containing regimens reported could effectively improve ORR, some of them benefit in CR or hematological improvement (HI) as well. ATO + Traditional Chinese Medicine (TCM), ATO + Thalidomide (T)+TCM, ATO + Chemotherapy (Chem)+T + TCM were regarded as the optimal combination, which improved both ORR, CR and HI in theory. ATO did not increase the risk of common adverse events compared to supportive therapy [(OR = 0.90(0.67, 1.21)].
CONCLUSION
ATO may be an effective and well-tolerant option for patients with myelodysplastic syndrome.
Topics: Humans; Arsenic Trioxide; Network Meta-Analysis; Arsenicals; Oxides; Myelodysplastic Syndromes; Treatment Outcome
PubMed: 37908176
DOI: 10.1080/16078454.2023.2274149 -
European Review For Medical and... Mar 2024The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia.
MATERIALS AND METHODS
A comprehensive literature search identified related studies from PubMed, Medline, Embase, Scopus, and Cochrane Library. Overall complete remission (CR) and overall response rate (ORR) were applied to evaluate the efficacy of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia, and incidence of grade 3-4 adverse events were used to evaluate the safety.
RESULTS
10 studies, including a total of 930 patients, were identified in our study and analyzed using the random-effects model. Meta-analysis showed the pooled overall CR rate of 70% (95% CI: 63-77%), the pooled ORR rate of 53% (95% CI: 39-67%), and the median overall survival ranged from 7.7 to 16.9 months. A total of 6 studies reported related adverse events, mainly including thrombocytopenia, febrile neutropenia, neutropenia, leukopenia, anemia, and pneumonia. The pooled incidence of overall adverse events was 30% (95% CI: 22-38%), and all adverse events were tolerable and resolved with treatment.
CONCLUSIONS
The combination of venetoclax and demethylating drugs has a good therapeutic effect on elderly patients with acute myeloid leukemia, but it also induces some adverse events. Although this therapy has a small impact on the quality of life, further attention is still needed to reduce the occurrence of such adverse events.
Topics: Aged; Humans; Quality of Life; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Leukemia, Myeloid, Acute; Pathologic Complete Response; Thrombocytopenia
PubMed: 38497866
DOI: 10.26355/eurrev_202403_35597 -
The Science of the Total Environment Jan 2024Biological methane, a major source of global methane budget, is traditionally thought to be produced in anaerobic environments. However, the recent reports about methane... (Review)
Review
Biological methane, a major source of global methane budget, is traditionally thought to be produced in anaerobic environments. However, the recent reports about methane supersaturation occurring in oxygenated water layer, termed as "methane paradox", have challenged this prevailing paradigm. Significantly, growing evidence has indicated that phytoplankton including prokaryotic cyanobacteria and eukaryotic algae are capable of generating methane under aerobic conditions. In this regard, a systematic review of aerobic methane production by phytoplankton is expected to arouse the public attention, contributing to the understanding of methane paradox. Here, we comprehensively summarize the widespread phenomena of methane supersaturation in oxic layers. The remarkable correlation relationships between methane concentration and several key indicators (depth, chlorophyll a level and organic sulfide concentration) indicate the significance of phytoplankton in in-situ methane accumulation. Subsequently, four mechanisms of aerobic methane production by phytoplankton are illustrated in detail, including photosynthesis-driven metabolism, reactive oxygen species (ROS)-driven demethylation of methyl donors, methanogenesis catalyzed by nitrogenase and demethylation of phosphonates catalyzed by CP lyase. The first two pathways occur in various phytoplankton, while the latter two have been specially discovered in cyanobacteria. Additionally, the effects of four crucial factors on aerobic methane production by phytoplankton are also discussed, including phytoplankton species, light, temperature and crucial nutrients. Finally, the measures to control global methane emissions from phytoplankton, the precise intracellular mechanisms of methane production and a more complete global methane budget model are definitely required in the future research on methane production by phytoplankton. This review would provide guidance for future studies of aerobic methane production by phytoplankton and emphasize the potential contribution of aquatic ecosystems to global methane budget.
Topics: Phytoplankton; Ecosystem; Chlorophyll A; Methane; Cyanobacteria
PubMed: 37866611
DOI: 10.1016/j.scitotenv.2023.167864