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Frontiers in Endocrinology 2024We present the case of a 36-year-old female who was diagnosed at birth with CHI that caused severe hypoglycaemia unresponsive to Diazoxide. Subtotal pancreatectomy was...
We present the case of a 36-year-old female who was diagnosed at birth with CHI that caused severe hypoglycaemia unresponsive to Diazoxide. Subtotal pancreatectomy was performed at the age of three weeks. Later, histological analysis of her pancreas in a research setting revealed a focal form of CHI. Genetic testing was not available at that time. The patient developed pancreatic exocrine deficiency and insulin-dependent diabetes at the age of 9 years. In 2016, a genetic test revealed a missense heterozygous variant in the ABCC8 gene inherited from her father and classified as having a recessive inheritance. The geneticist concluded that the risk of CHI for her offspring would be low (1/600), making pregnancy favourable. As there was no consanguinity in the family, testing the future father was deemed unnecessary (carrier frequency 1/150 in the general population). The pregnancy occurred spontaneously in 2020 and at a gestational age of 28 weeks, the mother went into premature labour. An emergency C-section was performed in April 2021 resulting in the birth of bichorial bi-amniotic male twins. Following birth, both newborns experienced persistent severe hypoglycaemia which required glucagon treatment and intravenous glucose infusion initially, followed by Diazoxide from day 51 after birth, without satisfactory response. Continuous intravenous Octreotide treatment was introduced on day 72. Due to the recurrence of hypoglycaemia episodes despite reaching maximum doses of Octreotide, from day 92 the treatment was switched to Pasireotide. Genetic tests revealed the same genotypes for both infants: the exon 39 missense variant (c.4716C>A; p.Ser1572Arg) inherited from their mother and a truncating variant in exon 28 (c.3550del; p.Val1184*), inherited from their asymptomatic father. As a result of inheriting two recessive variants of the ABCC8 gene, the children were diagnosed with a diffuse form of CHI, consistent with the diazoxide-unresponsive presentation. This situation is very rare outside consanguinity. This case emphasises the significance of genetic counselling for individuals with a history of rare diseases outside the context of consanguinity, as there is a potential risk of recurrence. Prenatal diagnosis can lead to better outcomes for affected neonates, as well as help families make informed decisions about future pregnancies.
Topics: Humans; Female; Congenital Hyperinsulinism; Pregnancy; Adult; Infant, Newborn; Sulfonylurea Receptors; Male; Twins, Dizygotic
PubMed: 38952388
DOI: 10.3389/fendo.2024.1408003 -
Journal of Korean Medical Science Jul 2024A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with...
A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant (CRKP) harboring carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of variants.
Topics: Humans; Ceftazidime; Klebsiella pneumoniae; Male; Azabicyclo Compounds; Drug Combinations; Adult; Anti-Bacterial Agents; beta-Lactamases; Klebsiella Infections; Bacteremia; Microbial Sensitivity Tests; Carbapenems; Whole Genome Sequencing; Bacterial Proteins; Meropenem; Drug Resistance, Multiple, Bacterial
PubMed: 38952349
DOI: 10.3346/jkms.2024.39.e208 -
Physiologia Plantarum 2024Under changing climatic conditions, plants are simultaneously facing conflicting stresses in nature. Plants can sense different stresses, induce systematic ROS signals,...
Under changing climatic conditions, plants are simultaneously facing conflicting stresses in nature. Plants can sense different stresses, induce systematic ROS signals, and regulate transcriptomic, hormonal, and stomatal responses. We performed transcriptome analysis to reveal the integrative stress response regulatory mechanism underlying heavy metal stress alone or in combination with heat and drought conditions in pitaya (dragon fruit). A total of 70 genes were identified from 31,130 transcripts with conserved differential expression. Furthermore, weighted gene co-expression network analysis (WGCNA) identified trait-associated modules. By integrating information from three modules and protein-protein interaction (PPI) networks, we identified 10 interconnected genes associated with the multifaceted defense mechanism employed by pitaya against co-occurring stresses. To further confirm the reliability of the results, we performed a comparative analysis of 350 genes identified by three trait modules and 70 conserved genes exhibiting their dynamic expression under all treatments. Differential expression pattern of genes and comparative analysis, have proven instrumental in identifying ten putative structural genes. These ten genes were annotated as PLAT/LH2, CAT, MLP, HSP, PB1, PLA, NAC, HMA, and CER1 transcription factors involved in antioxidant activity, defense response, MAPK signaling, detoxification of metals and regulating the crosstalk between the complex pathways. Predictive analysis of putative candidate genes, potentially governing single, double, and multifactorial stress response, by several signaling systems and molecular patterns. These findings represent a valuable resource for pitaya breeding programs, offering the potential to develop resilient "super pitaya" plants.
Topics: Gene Expression Regulation, Plant; Gene Regulatory Networks; Fruit; Vanadium; Stress, Physiological; Caragana; Plant Proteins; Protein Interaction Maps; Gene Expression Profiling; Droughts; Transcriptome; Cactaceae
PubMed: 38952344
DOI: 10.1111/ppl.14416 -
ACS Nano Jul 2024Traditional external field-assisted therapies, e.g., microwave (MW) therapy and phototherapy, cannot effectively and minimally damage eliminate deep-seated infection,...
Traditional external field-assisted therapies, e.g., microwave (MW) therapy and phototherapy, cannot effectively and minimally damage eliminate deep-seated infection, owing to the poor penetrability of light and low reactive oxygen species (ROS) stimulation capability of MW. Herein, an implantable and wireless-powered therapeutic platform (CNT-FeTHQ-TS), in which external MW can be converted into internal light via MW wireless-powered light-emitting chips, is designed to eradicate deep-seated tissue infections by MW-induced deep-seated photodynamic therapy. In application, CNT-FeTHQ-TS is implanted at internal lesions, and the chip emits light under external MW irradiation. Subsequently, CNT-FeTHQ coating in the platform can respond to both MW and light simultaneously to generate ROS and MW-hyperthermia for rapid and precise sterilization at focus. Importantly, MW also improves the photodynamic performance of CNT-FeTHQ by introducing vacancies in FeTHQ to facilitate the photoexcitation process and changing the spin state of electrons to inhibit the complexation of photogenerated electron-hole pairs, which were confirmed by simulation calculations and in situ MW-irradiated photoluminescence experiments. In vivo, CNT-FeTHQ-TS can effectively cure mice with infection in dorsal subcutaneous tissue. This work overcomes the key clinical limitations of safe energy transmission and conversion for treating deep-seated infections.
Topics: Photochemotherapy; Microwaves; Animals; Mice; Reactive Oxygen Species; Wireless Technology; Photosensitizing Agents; Light; Staphylococcus aureus; Staphylococcal Infections; Mice, Inbred BALB C; Anti-Bacterial Agents
PubMed: 38952327
DOI: 10.1021/acsnano.4c03654 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Jun 2024To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal...
OBJECTIVE
To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal mucosal injury induced by infection, and to examine the effect of oxymatrine (OMT) on in mice.
METHODS
Forty SPF 4-week-old BALB/c mice were randomly divided into four groups, including the control group, infection group, glycyrrhizin (GA) group and OMT group. Each mouse was orally administered with 1 × 10 oocysts one week in the infection, GA and OMT groups following dexamethasone-induced immunosuppression to model intestinal infections in mice. Upon successful modeling, mice in the GA group were intraperitoneally injected with GA at a daily dose of 25.9 mL/kg for successive two weeks, and animals in the OMT group were orally administered OMT at a daily dose of 50 mg/kg for successive two weeks, while mice in the control group were given normal food and water. All mice were sacrificed two weeks post-treatment, and proximal jejunal tissues were sampled. The pathological changes of mouse intestinal mucosal specimens were observed using hematoxylin-eosin (HE) staining, and the mouse intestinal villous height, intestinal crypt depth and the ratio of intestinal villous height to intestinal crypt depth were measured. The occludin and zonula occludens protein 1 (ZO1) expression was determined in mouse intestinal epithelial cells using immunohistochemistry, and the relative expression of , , , myeloid differentiation primary response gene 88 () and was quantified in mouse jejunal tissues using quantitative real-time PCR (qPCR) assay.
RESULTS
HE staining showed that the mouse intestinal villi were obviously atrophic, shortened, and detached, and the submucosal layer of the mouse intestine was edematous in the infection group as compared with the control group, while the mouse intestinal villi tended to be structurally intact and neatly arranged in the GA and OMT groups. There were significant differences among the four groups in terms of the mouse intestinal villous height ( = 6.207, = 0.000 5), intestinal crypt depth ( = 6.903, = 0.000 3) and the ratio of intestinal villous height to intestinal crypt depth ( = 37.190, < 0.000 1). The mouse intestinal villous height was lower in the infection group than in the control group [(321.9 ± 41.1) μm vs. (399.5 ± 30.9) μm; = 4.178, < 0.01] and the GA group [(321.9 ± 41.1) μm vs. (383.7 ± 42.7) μm; = 3.130, < 0.01], and the mouse intestinal crypt depth was greater in the infection group [(185.0 ± 35.9) μm] than in the control group [(128.4 ± 23.6) μm] ( = 3.877, < 0.01) and GA group [(143.3 ± 24.7) μm] ( = 2.710, < 0.05). The mouse intestinal villous height was greater in the OMT group [(375.3 ± 22.9) μm] than in the infection group ( = 3.888, < 0.01), and there was no significant difference in mouse intestinal villous height between the OMT group and the control group ( = 1.989, > 0.05). The mouse intestinal crypt depth was significantly lower in the OMT group [(121.5 ± 27.3) μm] than in the infection group ( = 4.133, < 0.01), and there was no significant difference in mouse intestinal crypt depth between the OMT group and the control group ( = 0.575, > 0.05). The ratio of the mouse intestinal villous height to intestinal crypt depth was significantly lower in the infection group (1.8 ± 0.2) than in the control group (3.1 ± 0.3) ( = 10.540, < 0.01) and the GA group (2.7 ± 0.3) ( = 7.370, < 0.01), and the ratio of the mouse intestinal villous height to intestinal crypt depth was significantly higher in the OMT group (3.1 ± 0.2) than in the infection group ( = 15.020, < 0.01); however, there was no significant difference in the ratio of the mouse intestinal villous height to intestinal crypt depth between the OMT group and the control group ( = 0.404, > 0.05). Immunohistochemical staining showed significant differences among the four groups in terms of occludin ( = 28.031, < 0.000 1) and ZO1 expression ( = 14.122, < 0.000 1) in mouse intestinal epithelial cells. The proportion of positive occluding expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.3 ± 4.5)% vs. (28.3 ± 0.5)%; = 3.810, < 0.01], and the proportions of positive occluding expression were significantly higher in mouse intestinal epithelial cells in the GA group [(30.3 ± 1.3)%] and OMT group [(25.8 ± 1.5)%] than in the infection group ( = 7.620 and 5.391, both values < 0.01); however, there was no significant differences in the proportion of positive occluding expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group ( = 1.791 and 2.033, both values > 0.05). The proportion of positive ZO1 expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.4 ± 1.8)% vs. (24.2 ± 2.8)%; = 4.485, < 0.01], and the proportions of positive ZO1 expression were significantly higher in mouse intestinal epithelial cells in the GA group [(24.1 ± 2.3)%] ( = 5.159, < 0.01) and OMT group than in the infection group [(22.5 ± 1.9)%] ( = 4.441, < 0.05); however, there were no significant differences in the proportion of positive ZO1 expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group ( = 0.037 and 0.742, both values > 0.05). qPCR assay showed significant differences among the four groups in terms of ( = 21.980, < 0.000 1), ( = 20.630, < 0.000 1), ( = 17.000, = 0.000 6), ( = 8.907, = 0.000 5) and expression in mouse jejunal tissues ( = 8.889, = 0.000 7). The relative expression of [(5.97 ± 1.07) vs. (1.05 ± 0.07); = 6.482, < 0.05] 、 [(5.92 ± 1.29) vs. (1.10 ± 0.14); = 5.272, < 0.05] 、 [(5.96 ± 1.50) vs. (1.02 ± 0.03); = 4.644, < 0.05] 、 [(3.00 ± 1.26) vs. (1.02 ± 0.05); = 2.734, < 0.05] and [(2.33 ± 0.72) vs. (1.04 ± 0.06); = 2.665, < 0.05] was all significantly higher in mouse jejunal tissues in the infection group than in the control group. A significant reduction was detected in the relative expression of (0.63 ± 0.01), (0.42 ± 0.10), (0.35 ± 0.07), (0.70 ± 0.11) and (0.75 ± 0.01) in mouse jejunal tissues in the GA group relative to the control group ( = 8.629, 5.830, 11.500, 4.729 and 6.898, all values < 0.05), and the relative expression of , , , and significantly reduced in mouse jejunal tissues in the GA group as compared to the infection group ( = 7.052, 6.035, 4.084, 3.165 and 3.274, all values < 0.05). In addition, the relative expression of (1.14 ± 0.60), (1.00 ± 0.24), (1.14 ± 0.07), (0.96 ± 0.25) and N (1.12 ± 0.17) was significantly lower in mouse jejunal tissues in the OMT group than in the infection group ( = 7.059, 5.320, 3.510, 3.466 and 3.273, all values < 0.05); however, there were no significant differences between the OMT and control groups in terms of relative expression of , , , or in mouse jejunal tissues ( = 0.239, 0.518, 1.887, 0.427 and 0.641, all values > 0.05).
CONCLUSIONS
infection causes intestinal inflammatory responses and destruction of intestinal mucosal barrier through up-regulating of the HMGB1-TLR2/TLR4-NF-κB pathway. OMT may suppress the intestinal inflammation and repair the intestinal mucosal barrier through inhibiting the activity of the HMGB1-TLR2/TLR4-NF-κB pathway.
Topics: Animals; Cryptosporidiosis; Quinolizines; Mice, Inbred BALB C; Cryptosporidium parvum; Toll-Like Receptor 4; Mice; Toll-Like Receptor 2; NF-kappa B; Alkaloids; HMGB1 Protein; Signal Transduction; Male; Intestinal Mucosa; Matrines
PubMed: 38952315
DOI: 10.16250/j.32.1374.2024019 -
Renal Failure Dec 2024Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study...
AIMS
Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis.
METHODS
This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing and models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein.
RESULTS
studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1.
CONCLUSION
CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.
Topics: STAT3 Transcription Factor; Receptor, Notch1; Diabetic Nephropathies; Animals; Signal Transduction; Fibrosis; Chlorogenic Acid; Humans; Mice; Male; Kidney; Lipid Metabolism; Molecular Docking Simulation; Mice, Inbred C57BL; Diabetes Mellitus, Experimental; Cell Line
PubMed: 38952291
DOI: 10.1080/0886022X.2024.2371988 -
Veterinary Medicine and Science Jul 2024Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of...
BACKGROUND
Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a non-steroidal anti-inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties.
OBJECTIVES
The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid were investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 ± 0.5°C.
METHODS
The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography-ultraviolet (UV) and pharmacokinetic parameters were assessed using non-compartmental analysis.
RESULTS
The elimination half-life (t) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 µg/mL, and 78.45% and 21.48%, respectively. The mean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent.
CONCLUSIONS
While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.
Topics: Animals; Oncorhynchus mykiss; ortho-Aminobenzoates; Biological Availability; Anti-Inflammatory Agents, Non-Steroidal; Administration, Oral; Blood Proteins; Injections, Intramuscular; Protein Binding; Injections, Intravenous; Half-Life
PubMed: 38952278
DOI: 10.1002/vms3.1533 -
Analytical Chemistry Jul 2024Carboxylesterase (CE), an enzyme widely present in organisms, is involved in various physiological and pathological processes. Changes in the levels of CEs in the liver...
Carboxylesterase (CE), an enzyme widely present in organisms, is involved in various physiological and pathological processes. Changes in the levels of CEs in the liver may predict the presence of type 2 diabetes mellitus (T2DM). Here, a novel dicyanoisophorone (DCI)-based proximity-labeled far-red fluorescent probe DCI2F-Ac with endoplasmic reticulum targeting was proposed for real-time monitoring and imaging of the CEs activity. DCI2F-Ac featured very low cytotoxicity and biotoxicity and was highly selective and sensitive for CEs. Compared with traditional CEs probes, DCI2F-Ac was covalently anchored directly to CEs, thus effectively reducing the loss of fluorescent signals due to diffusion. Through the "on-off" fluorescence signal readout, DCI2F-Ac was able to distinguish cell lines and screen for CEs inhibitors. In terms of endoplasmic reticulum (ER) stress, it was found that thapsigargin (Tg) induced upregulation of CEs levels but not tunicamycin (Tm), which was related to the calcium homeostasis of the ER. DCI2F-Ac could efficiently detect downregulated CEs in the livers of T2DM, and the therapeutic efficacy of metformin, acarbose, and a combination of these two drugs was assessed by tracking the fluctuation of CEs levels. The results showed that combining metformin and acarbose could restore CEs levels to near-normal levels with the best antidiabetic effect. Thus, the DCI2F-Ac probe provides a great opportunity to explore the untapped potential of CEs in liver metabolic disorders and drug efficacy assessment.
Topics: Fluorescent Dyes; Diabetes Mellitus, Type 2; Humans; Carboxylesterase; Endoplasmic Reticulum; Animals; Mice; Optical Imaging; Hep G2 Cells; Endoplasmic Reticulum Stress
PubMed: 38952276
DOI: 10.1021/acs.analchem.4c01721 -
Clinical and Translational Science Jul 2024The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination... (Randomized Controlled Trial)
Randomized Controlled Trial
The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination therapy in carbapenem-resistant Gram-negative infections. The aim of this reverse translational study was to integrate all individual preclinical and clinical pharmacokinetic-pharmacodynamic (PKPD) data from the AIDA trial in a pharmacometric framework to explore whether individualized predictions of bacterial burden were associated with the trial outcomes. The compiled dataset included for each of the 207 patients was (i) information on the infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, and fitness in a murine model), (ii) colistin plasma concentrations and colistin and meropenem dosing history, and (iii) disease scores and demographics. The individual information was integrated into PKPD models, and the predicted change in bacterial count at 24 h for each patient, as well as patient characteristics, was correlated with clinical outcomes using logistic regression. The in vivo fitness was the most important factor for change in bacterial count. A model-predicted growth at 24 h of ≥2-log (164/207) correlated positively with clinical failure (adjusted odds ratio, aOR = 2.01). The aOR for one unit increase of other significant predictors were 1.24 for SOFA score, 1.19 for Charlson comorbidity index, and 1.01 for age. This study exemplifies how preclinical and clinical anti-infective PKPD data can be integrated through pharmacodynamic modeling and identify patient- and pathogen-specific factors related to clinical outcomes - an approach that may improve understanding of study outcomes.
Topics: Humans; Acinetobacter baumannii; Meropenem; Middle Aged; Microbial Sensitivity Tests; Female; Male; Anti-Bacterial Agents; Colistin; Adult; Aged; Animals; Treatment Outcome; Mice; Acinetobacter Infections; Translational Research, Biomedical; Drug Therapy, Combination; Models, Biological
PubMed: 38952168
DOI: 10.1111/cts.13870 -
Current Cancer Drug Targets Jun 2024Epigenetic mechanisms have been shown to play a critical role in the development and progression of gastrointestinal [GI] cancers. These mechanisms involve modifications...
Epigenetic mechanisms have been shown to play a critical role in the development and progression of gastrointestinal [GI] cancers. These mechanisms involve modifications to DNA and histones that can alter gene expression patterns and may contribute to the initiation and progression of cancers. In recent years, epigenetic therapies have emerged as a promising approach to treating GI cancers. These therapies target specific epigenetic modifications, such as DNA methylation and histone acetylation, to restore normal gene expression patterns and inhibit cancer cell growth. Several epigenetic drugs have been approved for the treatment of GI cancers. Moreover, the use of epigenetic therapies in combination with other treatments, such as chemotherapeutic agents, is being studied to improve treatment outcomes. We have provided an overview of the role of epigenetic mechanisms in GI cancer treatment aimed to focus on recent evidence of the use of epigenetic agents in clinical and preclinical GI cancer studies, including gastric, esophageal, hepatic, pancreatic, and colorectal cancers. Overall, the role of epigenetic mechanisms in GI cancer treatments is an active area of research with the potential to improve patients' treatment outcomes and advance cancer treatment strategies.
PubMed: 38952157
DOI: 10.2174/0115680096306639240520053736