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1.
Cell Mol Bioeng ; 17(4): 263-277, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39372551

ABSTRACT

Objectives: This review explores the potential applications of large language models (LLMs) such as ChatGPT, GPT-3.5, and GPT-4 in the medical field, aiming to encourage their prudent use, provide professional support, and develop accessible medical AI tools that adhere to healthcare standards. Methods: This paper examines the impact of technologies such as OpenAI's Generative Pre-trained Transformers (GPT) series, including GPT-3.5 and GPT-4, and other large language models (LLMs) in medical education, scientific research, clinical practice, and nursing. Specifically, it includes supporting curriculum design, acting as personalized learning assistants, creating standardized simulated patient scenarios in education; assisting with writing papers, data analysis, and optimizing experimental designs in scientific research; aiding in medical imaging analysis, decision-making, patient education, and communication in clinical practice; and reducing repetitive tasks, promoting personalized care and self-care, providing psychological support, and enhancing management efficiency in nursing. Results: LLMs, including ChatGPT, have demonstrated significant potential and effectiveness in the aforementioned areas, yet their deployment in healthcare settings is fraught with ethical complexities, potential lack of empathy, and risks of biased responses. Conclusion: Despite these challenges, significant medical advancements can be expected through the proper use of LLMs and appropriate policy guidance. Future research should focus on overcoming these barriers to ensure the effective and ethical application of LLMs in the medical field.

2.
J Nanobiotechnology ; 22(1): 537, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39227963

ABSTRACT

Preserving pulp viability and promoting pulp regeneration in pulpitis have attracted widespread attention. Restricted by the oxidative stress microenvironment of dental pulpitis, excessive reactive oxygen and nitrogen species (RONS) trigger uncontrolled inflammation and exacerbate pulp tissue destruction. However, modulating redox homeostasis in inflamed pulp tissue to promote pulp regeneration remains a great challenge. Herein, this work proposes an effective antioxidative system (C-NZ/GelMA) consisting of carbon dot nanozymes (C-NZ) with gelatin methacryloyl (GelMA) to modulate the pulpitis microenvironment for dental pulp regeneration by utilizing the antioxidant properties of C-NZ and the mechanical support of an injectable GelMA hydrogel. This system effectively scavenges RONS to normalize intracellular redox homeostasis, relieving oxidative stress damage. Impressively, it can dramatically enhance the polarization of regenerative M2 macrophages. This study revealed that the C-NZ/GelMA hydrogel promoted pulp regeneration and dentin repair through its outstanding antioxidant, antiapoptotic, and anti-inflammatory effects, suggesting that the C-NZ/GelMA hydrogel is highly valuable for pulpitis treatment.


Subject(s)
Antioxidants , Carbon , Dental Pulp , Gelatin , Hydrogels , Oxidative Stress , Pulpitis , Regeneration , Oxidative Stress/drug effects , Dental Pulp/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Carbon/chemistry , Carbon/pharmacology , Pulpitis/drug therapy , Regeneration/drug effects , Mice , Antioxidants/pharmacology , Antioxidants/chemistry , Gelatin/chemistry , Gelatin/pharmacology , Reactive Oxygen Species/metabolism , Humans , Male , Rats , RAW 264.7 Cells , Macrophages/drug effects , Macrophages/metabolism , Methacrylates
3.
Int Immunopharmacol ; 142(Pt A): 113078, 2024 Dec 05.
Article in English | MEDLINE | ID: mdl-39236461

ABSTRACT

The clinical use of doxorubicin has been severely limited by doxorubicin-induced cardiotoxicity (DIC). Its mechanism is extremely complex and involves reactive oxygen species overgeneration, DNA damage, and aberrant inflammatory activity, which also involves multi-regulatory cell death mechanisms, including apoptosis, autophagy, and pyroptosis. These mechanisms overlap and crosstalk, resulting in the poor intervention of DIC injury. Astragaloside IV (Ast) has polybioactivity and mitigates DIC damage; however, the underlying mechanisms remain unknown. This study aimed to investigate whether Ast pretreatment (Ast-pre) could protect the myocardium against DIC damage and the underlying mechanisms. In particular, the relationship between Ast-pre, AMPKα2 activity, autophagy, apoptosis, and pyroptosis was explored. Firstly, DIC injury models were established using neonatal rat cardiomyocytes (NRCMs) and mice. And then the effects of adaptive autophagy, anti-pyroptosis and anti-apoptosis of Ast-pre were detected using multi-relevant indexes in NRCMs. Further, how does Ast-pre in AMPKα2 phosphorylation was explored. Finally, these results were validated by DIC injury in mice. Ast-pre, similar to disulfiram (pyroptosis inhibitor), effectively alleviated the inflammatory response, inhibited oxidative and energy stress, prevented mitochondrial dysfunction, and protected the myocardium resisting DIC damage, as demonstrated using multi-indexes. The protection of Ast-pre to DIC damage was almostly canceled by paclitaxel (pyroptosis inducer), 3-methyladenine (autophagy inhibitor), and pAD/AMPKα2-shRNA or compound C (AMPK inhibitor) to varying degrees. In conclusion, Ast-pre could upregulate and activate AMPKα2, enhance adaptive autophagy, and improve energy metabolism and mitochondrial function, thereby alleviate DIC-induced pyroptosis and apoptosis in NRCMs and mice.


Subject(s)
AMP-Activated Protein Kinases , Autophagy , Cardiotoxicity , Doxorubicin , Myocytes, Cardiac , Saponins , Signal Transduction , Triterpenes , Animals , AMP-Activated Protein Kinases/metabolism , Cardiotoxicity/drug therapy , Triterpenes/pharmacology , Triterpenes/therapeutic use , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Myocytes, Cardiac/metabolism , Rats , Saponins/pharmacology , Saponins/therapeutic use , Mice , Autophagy/drug effects , Male , Signal Transduction/drug effects , Mice, Inbred C57BL , Apoptosis/drug effects , Pyroptosis/drug effects , Rats, Sprague-Dawley , Cells, Cultured
4.
Iran J Basic Med Sci ; 27(10): 1331-1339, 2024.
Article in English | MEDLINE | ID: mdl-39229571

ABSTRACT

Objectives: Chronic alcohol abuse causes cognitive deficits. Huangqi Gegen Decoction (HGD), a traditional Chinese herbal formula comprising Huangqi and Gegen, has been documented for its therapeutic efficacy in the treatment of alcoholic liver injury. However, its potential neuroprotective effects against alcohol-induced brain injury remain unexplored. This study aims to evaluate the neuroprotection of HGD on alcohol-induced cognitive dysfunction and the associated mechanism. Materials and Methods: Wistar rats were orally administered 50% ethanol for 10 weeks, followed by treatment with HGD at doses of 16, 32, or 64 mg/kg/day for an additional 6 weeks. The spatial learning and memory abilities of rats were assessed through the Morris Water Maze experiment. The pathological condition in the hippocampus was assessed using H&E and Nissl staining. Tight junction proteins, oxidative stress, and inflammation cytokines were measured by IF, ELISA, PCR, and western blot. The mRNA and protein expression of Keap1, Nrf-2, HO-1, and NQO-1 were tested by PCR and western blot. Results: Results showed that HGD effectively mitigated cognitive dysfunction and pathological changes in alcohol-induced rats while enhancing the expression of ZO-1, Occludin, and Claudin-5. Furthermore, HGD effectively mitigated oxidative stress by reducing levels of ROS and MDA, while elevating levels of SOD, CAT, and GSH-PX in brain tissue. Moreover, HGD significantly suppressed microglial activation and down-regulated expressions of IL-1ß, IL-6, and TNF-α. Mechanistically, HGD remarkably up-regulated the expression of Nrf-2, HO-1, and NQO-1 while down-regulating Keap1 expression. Conclusion: These findings suggest that HGD may be a promising therapeutic agent for alleviating alcohol-induced cognitive dysfunction.

5.
Front Vet Sci ; 11: 1468981, 2024.
Article in English | MEDLINE | ID: mdl-39205805

ABSTRACT

The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly significant infectious disease that poses a substantial threat to the global pig industry. In recent years, the NADC30-like strain has gradually emerged as prevalent in China, causing a profound impact on the country's pig farming industry. Therefore, it is important to conduct an in-depth study on the characteristics and gene functions of the NADC30-like strain. An infectious cDNA clone is an indispensable tool for investigating the functions of viral genes. In this current study, we successfully isolated a NADC30-like strain and constructed its full-length infectious cDNA clone. The utilization of this clone will facilitate our investigation into the viral replication, pathogenesis, and immune response associated with the PRRSV NADC30-like strain.

6.
Int J Biol Macromol ; 279(Pt 4): 134970, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39181347

ABSTRACT

It's currently a challenge to design a drug delivery system for chemotherapy with high drug contents and minimal side effects. Herein, we constructed a novel one-dimensional binary-drug delivery system for cancer treatment. In this drug delivery system, drugs (doxorubicin (DOX) and resveratrol (RES)) self-assemble on bacterial cellulose nano-whiskers (BCW) and are subsequently encapsulated by polydopamine (PDA) with high encapsulation efficiencies (DOX: 81.53 %, RES: 70.32 %) and high drug loading efficiencies (DOX: 51.54 %, RES: 36.93 %). The cumulative release efficiencies can reach 89.27 % for DOX and 80.05 % for RES in acidic medium within 96 h. The BCW/(DOX + RES)/PDA can enter tumor cells easily through endocytosis and presents significant anti-cancer effects. Furthermore, the released-RES plays a protective role in normal cells through up-regulation of antioxidant enzymes activities and scavenging of reactive oxygen species. Taken together, the one-dimensional BCW/(DOX + RES)/PDA binary-drug delivery system can be used for the anticancer treatment along with slight side effects.

8.
Heliyon ; 10(13): e33902, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39071555

ABSTRACT

Photodynamic therapy (PDT) is attracting great attention for cancer treatments, while its therapeutic efficacy is limited by unsatisfactory photosensitizers and hypoxic tumor microenvironment (TME). To address these problems, we have developed catalase-loaded manganese-porphyrin frameworks (CAT@MnPFs) for catalytically-assisted PDT of cancer cells. CAT@MnPFs were constructed by the assembly of Mn2+ ions and PpIX into MnPFs and the subsequent loading of catalase. Under 650 nm light irradiation, the porphyrin (Protoporphyrin IX) within the structure of CAT@MnPFs can convert oxygen (O2) into singlet oxygen (1O2), showing the photodynamic effect. Importantly, the loaded catalase can decompose hydrogen peroxide (H2O2) into O2 with a huge elevation of O2 level (13.22 mg L-1) in 600 s, thus promoting 1O2 generation via PDT. As a result, CAT@MnPFs combined with 650 nm light can effectively ablate cancer cells due to the catalase-assisted oxygen-evolving PDT, showing a high therapeutic efficacy. Meanwhile, after the incubation with CAT@MnPFs, unobvious damage can be found in normal and red blood cells. Thus, the obtained CAT@MnPFs integrate the advantage of photosensitizers and catalase for oxygen-evolving PDT, which can provide some insight for treating hypoxic cells.

9.
Heliyon ; 10(11): e32270, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38961981

ABSTRACT

DLAT has been recognized as a cuproptosis-related gene that is crucial for cuproptosis in earlier research. The study is to look at how DLAT affects individuals with low-grade glioma's prognosis and immune infiltration. The Genotype-Tissue Expression (GTEx) database and the TCGA database were used in this work to download RNAseq data in TPM format. DLAT was found to be overexpressed in LGG by comparing DLAT expression levels between LGG and normal brain tissue, and the expression of DLAT was verified by immunohistochemistry and semi-quantitative analysis. Then, the functional enrichment analysis revealed that the biological functional pathways and possible signal transduction pathways involved were primarily focused on extracellular matrix organization, transmembrane transporter complex, ion channel complex, channel activity, neuroactive ligand-receptor interaction, complement and coagulation cascades, and channel activity. The level of immune cell infiltration by plasmacytoid dendritic cells and CD8 T cells was subsequently evaluated using single-sample gene set enrichment analysis, which showed that high DLAT expression was inversely connected with that level of infiltration. The link between the methylation and mRNA transcription of DLAT was then further investigated via the MethSurv database, and the results showed that DLAT's hypomethylation status was linked to a poor outcome. Finally, by evaluating the prognostic value of DLAT using the Cox regression analysis and Kaplan-Meier technique, a column line graph was created to forecast the overall survival (OS) rate at 1, 3, and 5 years after LGG identification. The aforementioned results demonstrated that high DLAT expression significantly decreased OS and DSS, and that overexpression of DLAT in LGG was significantly linked with WHO grade, IDH status, primary therapy outcome, overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) events. DLAT was discovered as a separate predictive sign of OS in the end. DLAT might thus represent a brand-new predictive biomarker.

10.
Interv Neuroradiol ; : 15910199241263633, 2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39034153

ABSTRACT

Subdural hematoma (SDH) refers to the collection of blood between the dura matter and the arachnoid membrane. Advancements in imaging technology have enabled the categorization of SDH based on specific imaging characteristics, causative factors, and the onset of symptoms. Given that the prognosis of SDHs varies significantly and is contingent upon the size and chronicity of the hemorrhage, a comprehensive understanding of its subtypes may carry crucial treatment implications. For example, an acute SDH classically results from severe traumatic brain injury and appears as a homogenous, crescent-shaped hyperdense extra-axial collection. If not treated, over the course of 1-3 weeks, this hematoma will evolve into a sub-acute phenotype as a consequence of subdural effusion and demonstrate mixed-density hemorrhage on imaging. Chronic SDH (cSDH) becomes the end result of an untreated SDH, with neo-membranization and neo-angiogenesis from branches of the middle meningeal artery driving a mass-like growth pattern. This review article aims to elucidate the complex anatomical features of the end-stage cSDH, with a particular focus on reconceptualization of this entity based on its mass-like growth patterns, and how this is driving a shift towards endovascular treatment.

11.
Exp Hematol ; 137: 104255, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38876252

ABSTRACT

The genetic lesions that drive acute megakaryoblastic leukemia (AMKL) have not been fully elucidated. To search for genetic alterations in AMKL, we performed targeted deep sequencing in 34 AMKL patient samples and 8 AMKL cell lines and detected frequent genetic mutations in the NOTCH pathway in addition to previously reported alterations in GATA-1 and the JAK-STAT pathway. Pharmacological and genetic NOTCH activation, but not inhibition, significantly suppressed AMKL cell proliferation in both in vitro and in vivo assays employing a patient-derived xenograft model. These results suggest that NOTCH inactivation underlies AMKL leukemogenesis. and NOTCH activation holds the potential for therapeutic application in AMKL.


Subject(s)
Cell Proliferation , Leukemia, Megakaryoblastic, Acute , Receptors, Notch , Signal Transduction , Leukemia, Megakaryoblastic, Acute/genetics , Leukemia, Megakaryoblastic, Acute/pathology , Leukemia, Megakaryoblastic, Acute/metabolism , Humans , Animals , Receptors, Notch/metabolism , Receptors, Notch/genetics , Mice , Cell Survival , Cell Line, Tumor , Mutation , Female , Male
12.
Cytotherapy ; 26(10): 1252-1263, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38904585

ABSTRACT

Despite the potential of mesenchymal stromal cells (MSCs) in osteoarthritis (OA) treatment, the challenge lies in addressing their therapeutic inconsistency. Clinical trials revealed significantly varied therapeutic outcomes among patients receiving the same allogenic MSCs but different treatment regimens. Therefore, optimizing personalized treatment strategies is crucial to fully unlock MSCs' potential and enhance therapeutic consistency. We employed the XGBoost algorithm to train a self-collected database comprising 37 published clinical reports to create a model capable of predicting the probability of effective pain relief and Western Ontario and McMaster Universities (WOMAC) index improvement in OA patients undergoing MSC therapy. Leveraging this model, extensive in silico simulations were conducted to identify optimal personalized treatment strategies and ideal patient profiles. Our in silico trials predicted that the individually optimized MSC treatment strategies would substantially increase patients' chances of recovery compared to the strategies used in reported clinical trials, thereby potentially benefiting 78.1%, 47.8%, 94.4% and 36.4% of the patients with ineffective short-term pain relief, short-term WOMAC index improvement, long-term pain relief and long-term WOMAC index improvement, respectively. We further recommended guidelines on MSC number, concentration, and the patients' appropriate physical (body mass index, age, etc.) and disease states (Kellgren-Lawrence grade, etc.) for OA treatment. Additionally, we revealed the superior efficacy of MSC in providing short-term pain relief compared to platelet-rich plasma therapy for most OA patients. This study represents the pioneering effort to enhance the efficacy and consistency of MSC therapy through machine learning applied to clinical data. The in silico trial approach holds immense potential for diverse clinical applications.


Subject(s)
Computer Simulation , Machine Learning , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Osteoarthritis , Humans , Osteoarthritis/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Clinical Trials as Topic , Male , Treatment Outcome , Algorithms , Female
13.
Front Vet Sci ; 11: 1430113, 2024.
Article in English | MEDLINE | ID: mdl-38872801

ABSTRACT

N-glycosylation is a highly conserved glycan modification that plays crucial roles in various physiological processes, including protein folding, trafficking, and signal transduction. Porcine deltacoronavirus (PDCoV) poses a newly emerging threat to the global porcine industry. The spike protein of PDCoV exhibits a high level of N-glycosylation; however, its role in viral infection remains poorly understood. In this study, we applied a lentivirus-based entry reporter system to investigate the role of N-glycosylation on the viral spike protein during PDCoV entry stage. Our findings demonstrate that N-glycosylation at positions 652 and 661 of the viral spike protein significantly reduces the infectivity of PDCoV pseudotyped virus. Overall, our results unveil a novel function of N-glycosylation in PDCoV infection, highlighting its potential for facilitating the development of antiviral strategies.

14.
Glob Chang Biol ; 30(5): e17304, 2024 May.
Article in English | MEDLINE | ID: mdl-38711381

ABSTRACT

Subtropical forests, recognized for their intricate vertical canopy stratification, exhibit high resistance to extreme drought. However, the response of leaf phenology to drought in the species-rich understory remains poorly understood. In this study, we constructed a digital camera system, amassing over 360,000 images through a 70% throughfall exclusion experiment, to explore the drought response of understory leaf phenology. The results revealed a significant advancement in understory leaf senescence phenology under drought, with 11.75 and 15.76 days for the start and end of the leaf-falling event, respectively. Pre-season temperature primarily regulated leaf development phenology, whereas soil water dominated the variability in leaf senescence phenology. Under drought conditions, temperature sensitivities for the end of leaf emergence decreased from -13.72 to -11.06 days °C-1, with insignificance observed for the start of leaf emergence. Consequently, drought treatment shortened both the length of the growing season (15.69 days) and the peak growth season (9.80 days) for understory plants. Moreover, this study identified diverse responses among intraspecies and interspecies to drought, particularly during the leaf development phase. These findings underscore the pivotal role of water availability in shaping understory phenology patterns, especially in subtropical forests.


Subject(s)
Droughts , Plant Leaves , Seasons , Plant Leaves/growth & development , Plant Leaves/physiology , Temperature , Forests , Water/metabolism , Trees/growth & development , Trees/physiology , Soil , Tropical Climate , China
15.
Environ Sci Pollut Res Int ; 31(24): 35206-35218, 2024 May.
Article in English | MEDLINE | ID: mdl-38720129

ABSTRACT

As alternative substances of PBDEs, organophosphate esters (OPEs), an emerging organic pollutant, were increasingly produced and used in many kinds of industries and consumer products. However, OPEs also have various adverse toxic effects. Information on the pollution levels and exposure to OPEs in related industries is still limited. This study presented data on OPE contamination in the soil, leaf, and river water samples from seven typical industrial parks in Southwest China. Total concentration of seven OPEs (Σ7OPE) including tri-n-butyl phosphate (TnBP), tris-(2-ethylhexyl) phosphate (TEHP), tris-(2-butoxyethyl) phosphate (TBEP), tris-(2-carboxyethyl) phosphine (TCEP), triphenyl phosphate (TPhP), tris-(1,3-dichloro-2-propyl) ester (TDCPP), and tris-(chlorisopropyl) phosphate (TCPP) in the soil samples (36.2 ~ 219.7 ng/g) and the surrounding river water samples (118.9 ~ 287.7 ng/L) were mostly lower than those in other studies, while the Σ7OPE level in the leaves (2053.3 ~ 8152.7 ng/g) was relatively high. There were significant differences in the concentration and distribution of OPEs in the surrounding environment of different industrial parks. TDCPP, TnBP, and TCPP could be used as the characteristic compound in soil samples from auto industrial park, river samples from shoe making industrial park, and leaf samples from logistics park, respectively. The parameter m (the content ratio of chlorinated OPEs to alkyl OPEs) was suggested to distinguish the types of industrial park preliminary. When m ≥ 1, it mainly refers to heavy industries sources such as automobiles, electronics, and machinery, etc. When m<1, it mainly for the light industrial sources such as textile industry, transportation services, and resources processing, etc. For logistics park, furniture park and Wuhou comprehensive industrial park, the volatilization of materials was the main sources of OPEs in the surrounding environment, while more effort was required to strengthen the pollution control and management of the waste water and soil in the pharmacy industrial park, shoe making industrial park and auto industrial park. Risk assessment showed that there was a negligible non-cancer and carcinogenic risk in the soil, while high attention should be paid to the non-cancer risk for children.


Subject(s)
Environmental Monitoring , Esters , Organophosphates , China , Risk Assessment , Organophosphates/analysis , Esters/analysis , Soil/chemistry , Water Pollutants, Chemical/analysis
16.
J Neurointerv Surg ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637150

ABSTRACT

Advancements in technology and technical expertise increasingly enable neurointerventionalists to deliver safer and more effective endovascular treatments to cancers of the brain, spine, head, and neck. In addition to established neuro-oncological interventions such as pre-surgical tumor embolization and percutaneous ablation, newer modalities focused on direct arterial infusion of chemotherapy, radioisotopes, and radiosensitizers continue to gain traction as complementary treatment options, while stem cell-mediated delivery of theranostic nanoparticles and oncolytic virus are being explored for even greater specificity in targeting cancers across the blood-brain barrier. This article aims to provide an overview of the current state of the art and future directions for the field of interventional neuro-oncology, as well as opportunities and challenges presented by this emerging treatment modality.

17.
Opt Express ; 32(7): 11665-11672, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571008

ABSTRACT

We demonstrated a 978 nm laser diode (LD) side-pumped YSGG/Er:YSGG/YSGG composite crystal with a size of Ф 3 mm × 65 mm and continuous-wave (CW) mode. By optimizing resonator length and output mirror transmittance, a maximum output power of 28.02 W is generated, corresponding to slope efficiency of 17.55% and optical-optical efficiency of 12.29%, respectively. The thermal focal lengths are obtained by resonator stability condition. The laser wavelength is centered near 2.8 µm. Moreover, the beam quality factors M x2/M y2 are fitted to be 8.14 and 7.35, respectively. The above results indicate that a high-performance 2.8 µm CW laser can be achieved by LD side-pumped YSGG/Er:YSGG/YSGG composite crystal with excellent heat dissipation ability, which promotes effectively the development and applications of the mid-infrared solid-state lasers.

18.
Clin Cancer Res ; 30(10): 2170-2180, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38437679

ABSTRACT

PURPOSE: DNA methylation alterations are widespread in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), some of which appear to have evolved independently of somatic mutations in epigenetic regulators. Although the presence of somatic mutations in peripheral blood can predict the risk of development of AML and MDS, its accuracy remains unsatisfactory. EXPERIMENTAL DESIGN: We performed global DNA methylation profiling in a case control study nested within the Singapore Chinese Health Study to evaluate whether DNA methylation alterations were associated with AML/MDS development. Targeted deep sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-seq) were performed on peripheral blood collected a median of 9.9 years before diagnosis of AML or MDS, together with age-matched still-healthy individuals as controls. RESULTS: Sixty-six individuals who developed AML or MDS displayed significant DNA methylation changes in the peripheral blood compared with 167 age- and gender-matched controls who did not develop AML/MDS during the follow-up period. Alterations in methylation in the differentially methylation regions were associated with increased odds of developing AML/MDS. CONCLUSIONS: The epigenetic changes may be acquired independently and before somatic mutations that are relevant for AML/MDS development. The association between methylation changes and the risk of pre-AML/MDS in these individuals was considerably stronger than somatic mutations, suggesting that methylation changes could be used as biomarkers for pre-AML/MDS screening.


Subject(s)
DNA Methylation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , Male , Female , Middle Aged , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/diagnosis , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/diagnosis , Case-Control Studies , Aged , Adult , Epigenesis, Genetic , Singapore/epidemiology , Mutation , Genetic Predisposition to Disease , Risk Factors
19.
Phytomedicine ; 128: 155365, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38552436

ABSTRACT

BACKGROUND: Ferroptosis, a form of regulated cell death (RCD) that relies on excessive reactive oxygen species (ROS) generation, Fe2+accumulation, abnormal lipid metabolism and is involved in various organ ischemia/reperfusion (I/R) injury, expecially in myocardium. Mitochondria are the powerhouses of eukaryotic cells and essential in regulating multiple RCD. However, the links between mitochondria and ferroptosis are still poorly understood. Salidroside (Sal), a natural phenylpropanoid glycoside isolated from Rhodiola rosea, has mult-bioactivities. However, the effects and mechanism in alleviating ferroptosis caused by myocardial I/R injury remains unclear. PURPOSE: This study aimed to investigate whether pretreated with Sal could protect the myocardium against I/R damage and the underlying mechanisms. In particular, the relationship between Sal pretreatment, AMPKα2 activity, mitochondria and ROS generation was explored. STUDY DESIGN AND METHODS: Firstly, A/R or I/R injury models were employed in H9c2 cells and Sprague-Dawley rats. And then the anti-ferroptotic effects and mechanism of Sal pretreatment was detected using multi-relevant indexes in H9c2 cells. Further, how does Sal pretreatment in AMPKα2 phosphorylation was explored. Finally, these results were validated by I/R injury in rats. RESULTS: Similar to Ferrostatin-1 (a ferroptosis inhibitor) and MitoTEMPO, a mitochondrial free radical scavenger, Sal pretreatment effectively alleviated Fe2+ accumulation, redox disequilibrium and maintained mitochondrial energy production and function in I/R-induced myocardial injury, as demonstrated using multifunctional, enzymatic, and morphological indices. However, these effects were abolished by downregulation of AMPKα2 using an adenovirus, both in vivo and in vitro. Moreover, the results also provided a non-canonical mechanism that, under mild mitochondrial ROS generation, Sal pretreatment upregulated and phosphorylated AMPKα2, which enhanced mitochondrial complex I activity to activate innate adaptive responses and increase cellular tolerance to A/R injury. CONCLUSION: Overall, our work highlighted mitochondria are of great impotance in myocardial I/R-induced ferroptosis and demonstrated that Sal pretreatment activated AMPKα2 against I/R injury, indicating that Sal could become a candidate phytochemical for the treatment of myocardial I/R injury.


Subject(s)
AMP-Activated Protein Kinases , Ferroptosis , Glucosides , Myocardial Reperfusion Injury , Phenols , Rats, Sprague-Dawley , Reactive Oxygen Species , Rhodiola , Ferroptosis/drug effects , Phenols/pharmacology , Animals , Glucosides/pharmacology , Myocardial Reperfusion Injury/drug therapy , Rats , Male , Rhodiola/chemistry , AMP-Activated Protein Kinases/metabolism , Reactive Oxygen Species/metabolism , Cell Line , Mitochondria/drug effects , Mitochondria/metabolism , Myocytes, Cardiac/drug effects
20.
Interv Neuroradiol ; : 15910199241236820, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38477583

ABSTRACT

INTRODUCTION: Dynamic catheter-directed cerebral digital subtraction angiography (dcDSA) is the gold standard for diagnosing dynamic vascular occlusion syndromes such as bowhunter syndrome (BHS). Nonetheless, concerns about its safety exist and no standardized protocols have been published to date. METHODS: We describe our methodology and insights regarding the use of dcDSA in patients with BHS. We also perform a systematic literature review to identify cases of typical and atypical presentations of BHS wherein dcDSA was utilized and report on any procedural complications related to dcDSA. RESULTS: Our study included 104 cases wherein dcDSA was used for the diagnosis of BHS. There were 0 reported complications of dcDSA. DcDSA successfully established diagnosis in 102 of these cases. Thirty-eight cases were deemed atypical presentations of BHS. Fourteen patients endorsed symptoms during neck flexion/extension. In eight cases, there was dynamic occlusion of bilateral vertebral arteries during a single maneuver. Three patients had multiple areas of occlusion along a single vertebral artery (VA). An anomalous entry of the VA above the C6 transverse foramen was observed in four patients. One patient had VA occlusion with neutral head position and recanalization upon contralateral lateral head tilt. CONCLUSION: Our study highlights the safety and diagnostic benefits of dcDSA in characterizing the broad spectrum of BHS pathology encountered in clinical practice. This technique offers a powerful means to evaluate changes in cerebral blood flow and cervical arterial morphology in real time, overcoming the constraints of static imaging methods. Our findings pave the way for further studies on dcDSA to enhance cross-sectional imaging methods for the characterization of BHS and other dynamic vascular occlusion syndromes.

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