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1.
J Adv Res ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657902

RESUMO

BACKGROUND: Myocardial infarction (MI) is a heart injury caused by ischemia and low oxygen conditions. The occurrence of MI lead to the activation of a large number of neutrophils and macrophages, inducing severe inflammatory injury. Meanwhile, the inflammatory response produces much more free radicals, further exacerbating the inflammatory response and tissue damage. Efforts are being dedicated to developing antioxidants and enzymes, as well as small molecule drugs, for treating myocardial ischemia. However, poor pharmacokinetics and potential side effects limit the clinical application of these drugs. Recent advances in nanotechnology have paved new pathways in biomedical and healthcare environments. Nanozymes exhibit the advantages of biological enzymes and nanomaterials, including with higher catalytic activity and stability than natural enzymes. Thus, nanozymes provide new possibilities for the diagnosis and treatment of oxidative stress and inflammation-related diseases. AIM OF REVIEW: We describe the application of nanozymes in the diagnosis and therapy of MI, aiming to bridge the gap between the diagnostic and therapeutic needs of MI. KEY SCIENTIFIC CONCEPTS OF REVIEW: We describe the application of nanozymes in the diagnosis and therapy of MI, and discuss the new strategies for improving the diagnosis and treatment of MI. We review in detail the applications of nanozymes to achieve highly sensitive detection of biomarkers of MI. Due to their unique enzyme catalytic capabilities, nanozymes have the ability to sensitively detect biomolecules through colorimetric, fluorescent, and electrochemical assays. In addition, nanozymes exhibit excellent antioxidase-mimicking activity to treat MI by modulating reduction/oxidation (REDOX) homeostasis. Nanozymes can also passively or actively target MI tissue sites, thereby protecting ischemic myocardial tissue and reducing the infarct area. These innovative applications of nanozymes in the field of biomedicine have shown promising results in the diagnosis and treatment of MI, offering a novel therapeutic strategy.

2.
iScience ; 27(4): 109502, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38591009

RESUMO

Constitutive explorations indicate a correlation between circular RNAs (circRNAs) and cardiovascular diseases. However, the involvement of circRNAs in endothelial recuperation and in-stent restenosis (ISR) remains underexplored. CircTMEM165 has first been reported to be highly expressed in hypoxic human umbilical vein endothelial cells (HUVECs). Here, we identified that circTMEM165 was downregulated in ISR patients, inversely correlating with ISR severity. Functionally, circTMEM165 was found to be abundant in endothelial cells, inhibiting inflammation, and adhesion. Particularly, we first observed that circTMEM165 could alleviate HUVECs apoptosis and mitochondrial fission induced by lipopolysaccharide (LPS). Mechanistically, circTMEM165, as a miR-192-3p sponge, enhancing SCP2 expression, which serves as a critical regulator of HUVECs biological functions. Moreover, in vivo, circTMEM165 attenuated intimal hyperplasia and facilitated repair following classic rat carotid artery balloon injury model. These findings investigated the circTMEM165-miR-192-3p-SCP2 axis as a critical determinant of endothelial health and a potential biomarker and therapeutic target for vascular disorders.

3.
Cell Biosci ; 14(1): 34, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493171

RESUMO

With the advancement of sequencing technologies and bioinformatics, over than 170 different RNA modifications have been identified. However, only a few of these modifications can lead to base pair changes, which are called RNA editing. RNA editing is a ubiquitous modification in mammalian transcriptomes and is an important co/posttranscriptional modification that plays a crucial role in various cellular processes. There are two main types of RNA editing events: adenosine to inosine (A-to-I) editing, catalyzed by ADARs on double-stranded RNA or ADATs on tRNA, and cytosine to uridine (C-to-U) editing catalyzed by APOBECs. This article provides an overview of the structure, function, and applications of RNA editing enzymes. We discuss the structural characteristics of three RNA editing enzyme families and their catalytic mechanisms in RNA editing. We also explain the biological role of RNA editing, particularly in innate immunity, cancer biogenesis, and antiviral activity. Additionally, this article describes RNA editing tools for manipulating RNA to correct disease-causing mutations, as well as the potential applications of RNA editing enzymes in the field of biotechnology and therapy.

4.
Crit Rev Oncol Hematol ; 197: 104330, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38556071

RESUMO

Sialic acid (SA), as the ultimate epitope of polysaccharides, can act as a cap at the end of polysaccharide chains to prevent their overextension. Sialylation is the enzymatic process of transferring SA residues onto polysaccharides and is catalyzed by a group of enzymes known as sialyltransferases (SiaTs). It is noteworthy that the sialylation level of glycoproteins is significantly altered when digestive cancer occurs. And this alteration exhibits a close correlation with the progression of these cancers. In this review, from the perspective of altered SiaTs expression levels and changed glycoprotein sialylation patterns, we summarize the pathogenesis of gastric cancer (GC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC). Furthermore, we propose potential early diagnostic biomarkers and prognostic indicators for different digestive cancers. Finally, we summarize the therapeutic value of sialylation in digestive system cancers.

5.
Front Immunol ; 15: 1335519, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515760

RESUMO

Cardiovascular diseases (CVDs) are multifactorial chronic diseases and have the highest rates of morbidity and mortality worldwide. The ubiquitin-proteasome system (UPS) plays a crucial role in posttranslational modification and quality control of proteins, maintaining intracellular homeostasis via degradation of misfolded, short-lived, or nonfunctional regulatory proteins. Noncoding RNAs (ncRNAs, such as microRNAs, long noncoding RNAs, circular RNAs and small interfering RNAs) serve as epigenetic factors and directly or indirectly participate in various physiological and pathological processes. NcRNAs that regulate ubiquitination or are regulated by the UPS are involved in the execution of target protein stability. The cross-linked relationship between the UPS, ncRNAs and CVDs has drawn researchers' attention. Herein, we provide an update on recent developments and perspectives on how the crosstalk of the UPS and ncRNAs affects the pathological mechanisms of CVDs, particularly myocardial ischemia/reperfusion injury, myocardial infarction, cardiomyopathy, heart failure, atherosclerosis, hypertension, and ischemic stroke. In addition, we further envision that RNA interference or ncRNA mimics or inhibitors targeting the UPS can potentially be used as therapeutic tools and strategies.


Assuntos
Doenças Cardiovasculares , MicroRNAs , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Ubiquitina , Ligases , RNA não Traduzido/genética , MicroRNAs/genética , Complexo de Endopeptidases do Proteassoma
6.
Front Immunol ; 15: 1352484, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444855

RESUMO

Notch signaling pathway is a highly conserved system of cell-to-cell communication that participates in various biological processes, such as stem cell maintenance, cell fate decision, cell proliferation and death during homeostasis and development. Dysregulation of Notch signaling has been associated with many aspects of cancer biology, such as maintenance of cancer stem-like cells (CSCs), cancer cell metabolism, angiogenesis and tumor immunity. Particularly, Notch signaling can regulate antitumor or pro-tumor immune cells within the tumor microenvironment (TME). Currently, Notch signaling has drawn significant attention in the therapeutic development of cancer treatment. In this review, we focus on the role of Notch signaling pathway in remodeling tumor immune microenvironment. We describe the impact of Notch signaling on the efficacy of cancer immunotherapies. Furthermore, we summarize the results of relevant preclinical and clinical trials of Notch-targeted therapeutics and discuss the challenges in their clinical application in cancer therapy. An improved understanding of the involvement of Notch signaling in tumor immunity will open the door to new options in cancer immunotherapy treatment.


Assuntos
Imunoterapia , Neoplasias , Transdução de Sinais , Comunicação Celular , Diferenciação Celular , Células-Tronco Neoplásicas , Neoplasias/terapia
7.
Pathol Res Pract ; 256: 155255, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492360

RESUMO

OBJECTIVE: Long non-coding RNA (lncRNA), especially RNA associated with lymph node metastasis, plays an important role in the development of cancer. Identifying metastasis related lncRNAs and exploring their clinical significance can guide the treatment and prognosis of thyroid cancer patients. METHODS: RNA expression and clinical data of thyroid cancer was derived from The Cancer Genome Atlas (TCGA) database, while the survival data was obtained from the ULCAN database. R language and SPSS software were used to analyze the correlation between lncRNA and lymph node metastasis of thyroid cancer and the lncRNAs associated with lymph node metastasis were screened. RESULT: 10 lncRNAs showed significant differential expression in thyroid cancer with and without lymph node metastasis. Four lncRNAs (LRRC52-AS1, AP002358.1, AC004847.1, and AC254633.1) were overexpressed in metastatic thyroid cancer, while six lncRNAs (SLC26A4-AS1, LINC01886, LINC01789, AF131216.3, AC062015.1, and AL031710.1) were underexpressed. The expression levels of these lncRNAs were associated with the clinical staging of tumors. Cox regression analysis further showed that elevated expression levels of AP002358.1 and LRRC52-AS1 were associated with poor prognosis in patients with thyroid cancer. In addition, analysis of the UALCAN database indicated that these two lncRNAs were significantly overexpressed in thyroid cancer compared to other cancers, and the expression levels of AF131216.3 and AL031710.1 were associated with progression-free survival in thyroid cancer patients. CONCLUSION: These lncRNAs may play crucial roles in the development and progression of thyroid cancer and could serve as potential markers for predicting tumor metastasis, clinical stage, and patient prognosis.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias da Glândula Tireoide , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Metástase Linfática/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , MicroRNAs/genética , Prognóstico , Regulação Neoplásica da Expressão Gênica/genética
8.
Front Pharmacol ; 15: 1293980, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482052

RESUMO

Autophagy is a conserved, cellular self-degradation system that is essential for maintaining intracellular homeostasis. Increasing evidence suggests that autophagy plays an important dual regulatory role in the development of many human diseases, such as cancer. Recent studies have shown that the autophagy process in tumor cells can be regulated by various stimuli from both intracellular and extracellular environments, including the effects of anesthesia. Anesthetics have been shown to not only have clinical anesthetic and sedative effects but also play important roles in the progression of tumors. The effects of different types of anesthetics on tumors differ. In this review, we summarize the basic information on autophagy, the regulatory function of autophagy in cancer, currently used autophagy-targeted tumor therapy, and the effects of different types of anesthetics on tumor progression. We focus on the molecular mechanisms by which anesthetics exert tumor-inhibiting effects by activating or inhibiting autophagy. Herein, we also explore the potential application of the anesthetic/autophagy system in clinical tumor treatment. These findings provide a theoretical basis for the use of anesthetics during the perioperative period to suppress tumor development and provide insights for autophagy-targeted cancer treatment and drug development.

9.
Mol Pharm ; 21(3): 1027-1037, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38315004

RESUMO

Circular RNAs (circRNAs) have been identified as important regulators in different developmental processes and disease pathogenesis. The loop structure of circRNAs makes them very stable in different conditions and microenvironments. circRNAs can affect microRNA (miRNA) and RNA binding protein (RBP) activity, encode functional proteins and regulate gene transcription. Recently, two circNFIX variants derived from the same gene, the Nuclear Factor I X (NFIX) gene, were determined as participants in the pathological processes of various diseases such as heart diseases and cancers. Both circNFIX variants are exonic circular RNAs and mainly function by sponging miRNAs. In this review, we summarize the current knowledge on circRNAs, elucidate the origins and properties of two circNFIX variants, explore the roles of two circNFIX variants in different diseases, and present clinical perspectives.


Assuntos
MicroRNAs , Neoplasias , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Fatores de Transcrição NFI , MicroRNAs/genética , Neoplasias/genética , Microambiente Tumoral
10.
Int J Biol Macromol ; 262(Pt 1): 130005, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331061

RESUMO

Nucleosomes play a crucial role in regulating gene expression through their composition and post-translational modifications. When cells die, intracellular endonucleases are activated and cleave chromatin into oligo- and mono-nucleosomes, which are then released into the body fluids. Studies have shown that the levels of nucleosomes are increased in serum and plasma in various cancer types, suggesting that analysis of circulating nucleosomes can provide an initial assessment of carcinogenesis. However, it should be noted that elevated serum nucleosome levels may not accurately diagnose certain tumor types, as increased cell death may occur in different pathological conditions. Nevertheless, detection of circulating nucleosomes and their histone modifications, along with specific tumor markers, can help diagnose certain types of cancer. Furthermore, monitoring changes in circulating nucleosome levels during chemotherapy or radiotherapy in patients with malignancies can provide valuable insights into clinical outcomes and therapeutic efficacy. The utilization of circulating nucleosomes as biomarkers is an exciting and emerging area of research, with the potential for early detection of various diseases and monitoring of treatment response. Integrating nucleosome-based biomarkers with existing ones may improve the specificity and sensitivity of current assays, offering the possibility of personalized precision medical treatment for patients.


Assuntos
Neoplasias , Nucleossomos , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Biomarcadores Tumorais , Cromatina
11.
Small ; : e2306257, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377302

RESUMO

Due to the disadvantages of poor targeting, slow action, and low effectiveness of current commonly used cancer treatments, including surgery, chemotherapy, and radiotherapy, researchers have turned to DNA as a biomaterial for constructing drug delivery nanocarriers. DNA is favored for its biocompatibility and programmability. In order to overcome the limitations associated with traditional drug delivery systems (DDSs), researchers have developed smart-responsive DNA DDSs that can control drug release in response to specific physical or chemical stimuli at targeted sites. In this review, a summary of multiple targeted ligand structures is provided, various shapes of stable DNA nanomaterials, and different stimuli-responsive drug release strategies in DNA DDSs. Specifically, targeted cell recognition, in vivo stable transport, and controlled drug release of smart DDSs are focused. Finally, the further development prospects and challenges of clinical application of DNA nanomaterials in the field of smart drug delivery are discussed. The objective of this review is to enhance researchers' comprehension regarding the potential application of DNA nanomaterials in precision drug delivery, with the aim of expediting the clinical implementation of intelligent DDSs.

12.
ACS Appl Mater Interfaces ; 16(7): 9078-9087, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38326938

RESUMO

Piezoelectric ceramics, as essential components of actuators and transducers, have captured significant attention in both industrial and scientific research. The "entropy engineering" approach has been demonstrated to achieve excellent performance in lead-based materials. In this study, the "entropy engineering" approach was employed to introduce the morphotropic phase boundary (MPB) into the bismuth ferrite (BF)-based lead-free system. By employing this strategy, a serial of novel "medium to high entropy" lead-free piezoelectric ceramics were successfully synthesized, namely (1-x)BiFeO3-x(Ba0.2Sr0.2Ca0.2Bi0.2Na0.2)TiO3 (BF-xBSCBNT, x = 0.15-0.5). Our investigation systematically examined the phase structure, domain configuration, and ferroelectric/piezoelectric properties as a function of conformational entropy. Remarkable performances with a largest strain of 0.50% at 100 kV/cm, remanent polarization ∼40.07 µC/cm2, coercive field ∼74.72 kV/cm, piezoelectric coefficient ∼80 pC/N, and d33* ∼500 pm/V were achieved in BF-0.4BSCBNT ceramics. This exceptional performance can be attributed to the presence of MPB, coexisting rhombohedral and cubic phases, along with localized nanodomains. The concept of high-entropy lead-free piezoelectric ceramics in this study provides a promising strategy for the exploration and development of the next generation of lead-free piezoelectric materials.

13.
Mar Pollut Bull ; 200: 116095, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325205

RESUMO

An integrated observation of NOx that included coastal cities and oceanic cruises covering the Qingdao coastal waters sites (QDCW) and the Yellow Sea and East China Sea sites (YECS) was conducted in spring. The average concentrations of the coastal cities, the QDCW, and the YECS were 5.4 ± 4.1, 4.2 ± 3.5, and 2.9 ± 6.8 ppb for NO while 18.5 ± 7.2, 9.4 ± 5.2, and 4.9 ± 6.4 ppb for NO2, depicting lowest levels in the open seas. Atmospheric NO and NO2 showed similar spatial variations over the seas, the stations where the air masses originated from land or nearshore regions showed higher levels, but the decisive influencing factors were not the same in the different study areas. The calculated NOx flux value in the YECS (-8.7 × 10-17 mol N cm-2) indicated that the sea surface was a net sink of atmospheric NOx.


Assuntos
Poluentes Atmosféricos , Água do Mar , Poluentes Atmosféricos/análise , Dióxido de Nitrogênio , Monitoramento Ambiental , Oceanos e Mares , Óxidos de Nitrogênio , China
14.
Chem Biol Drug Des ; 103(1): e14440, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38230784

RESUMO

Naoxintong capsule (NXT) is a clinical drug for the treatment of cardiovascular diseases, but its pharmacological mechanism against hypertension remains unclear. Data concerning the compounds and targets of NXT were obtained from the TCMSP and DrugBank, whereas data concerning hypertension-related genes were obtained from DisGeNET. The network was analyzed and established by STRING and Cytoscape, and function enrichment was analyzed by GO and KEGG analysis. Molecular docking was performed to analyze the interaction between ingredients and targets, cellular activity was evaluated by MTT assay, and RT-qPCR and western blot were used to evaluate the expressions of related genes. The results showed that 146 active therapeutic components can target hypertension-related genes, and we found that core genes were mainly involved in the metabolism of lipids, lipopolysaccharides, the inflammatory signaling pathway, and the oxidative stress pathway. In addition, there was high affinity between the components of NXT and targets of hypertension, where the former can increase cell viability and reduce the expressions of NOX4, MCP-1, BAX, TNF-α and IL-1ß. Moreover, NXT inhibited the expressions of IL-6 and Fis1, as well as increased the expression of MCL-1. These results revealed the active compounds, hypertension targets, signaling pathways, and molecular mechanisms of NXT for treating hypertension, offering references for the clinical application of NXT and the treatment of hypertension.


Assuntos
Doenças Cardiovasculares , Medicamentos de Ervas Chinesas , Hipertensão , Humanos , Simulação de Acoplamento Molecular , Hipertensão/tratamento farmacológico , Fator de Necrose Tumoral alfa , Medicamentos de Ervas Chinesas/farmacologia
15.
Int J Oncol ; 64(2)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38186313

RESUMO

Circular RNAs (circRNAs) represent a class of RNA molecules characterized by their covalently closed structures. There are three types of circRNAs, namely exonic circRNAs, exon­intron circRNAs and circular intronic RNAs. To date, four distinct mechanisms have been unveiled through which circRNAs exert their functional influence, including serving as microRNA (miRNA) sponges, interacting with RNA binding proteins (RBPs), modulating parental gene transcription and acting as templates for translation. Of note, among these mechanisms, the miRNA/RBP sponge function has been the most investigated one. Recent research has uncovered the presence of various proteins or peptides encoded by circRNA. CircRNAs are translated independent of the 5' cap and 3' polyA tail, which are typical elements for linear RNA translation. Some unique elements, such as internal ribosome entry sites and N­methyladenosine modifications, facilitate the initiation of translation. These circRNA­encoded proteins or peptides participate in diverse signalling pathways and act as important regulators in carcinogenesis by influencing cell proliferation, migration, apoptosis and other key processes. Consequently, circRNA­encoded proteins or peptides have great potential as therapeutic targets for anticancer drugs. The present comprehensive review aimed to systematically summarize the current understanding of circRNA­encoded proteins or peptides and to unveil their roles in carcinogenesis.


Assuntos
MicroRNAs , Neoplasias , Humanos , RNA Circular/genética , Peptídeos/genética , Neoplasias/genética , Carcinogênese
16.
Int J Biol Macromol ; 259(Pt 1): 129150, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171441

RESUMO

It is generally believed that the regulation of gene expression involves protein translation occurring before RNA transcription. Therefore, it is crucial to investigate protein translation and its regulation. Recent advancements in biological sciences, particularly in the field of omics, have revolutionized protein translation research. These studies not only help characterize changes in protein translation during specific biological or pathological processes but also have significant implications in disease prevention and treatment. In this review, we summarize the latest methods in ribosome-based translation omics. We specifically focus on the application of fluorescence imaging technology and omics technology in studying overall protein translation. Additionally, we analyze the advantages, disadvantages, and application of these experimental methods, aiming to provide valuable insights and references to researchers studying translation.


Assuntos
Biossíntese de Proteínas , Ribossomos , RNA Mensageiro/genética , Ribossomos/genética , Ribossomos/metabolismo
17.
Int J Biol Sci ; 20(1): 347-366, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164177

RESUMO

Mesenchymal stem cells (MSCs) are a type of stromal cells characterized by their properties of self-renewal and multi-lineage differentiation, which make them prominent in regenerative medicine. MSCs have shown significant potential for the treatment of various diseases, primarily through the paracrine effects mediated by soluble factors, specifically extracellular vesicles (EVs). MSC-EVs play a crucial role in intercellular communication by transferring various bioactive substances, including proteins, RNA, DNA, and lipids, highlighting the contribution of MSC-EVs in regulating cancer development and progression. Remarkably, increasing evidence indicates the association between MSC-EVs and resistance to various types of cancer treatments, including radiotherapy, chemotherapy, targeted therapy, immunotherapy, and endocrinotherapy. In this review, we provide an overview of the recent advancements in the biogenesis, isolation, and characterization of MSC-EVs, with an emphasis on their functions in cancer therapy resistance. The clinical applications and future prospects of MSC-EVs for mitigating cancer therapy resistance and enhancing drug delivery are also discussed. Elucidating the role and mechanism of MSC-EVs in the development of treatment resistance in cancer, as well as evaluating the clinical significance of MSC-EVs, is crucial for advancing our understanding of tumor biology. Meanwhile, inform the development of effective treatment strategies for cancer patients in the future.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Neoplasias , Humanos , Vesículas Extracelulares/metabolismo , Diferenciação Celular/fisiologia , Medicina Regenerativa , Células-Tronco Mesenquimais/metabolismo , Biologia , Neoplasias/terapia , Neoplasias/metabolismo
18.
Cytotherapy ; 26(1): 11-24, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37930294

RESUMO

Mitochondrial DNA (mtDNA) is a critical genome contained within the mitochondria of eukaryotic cells, with many copies present in each mitochondrion. Mutations in mtDNA often are inherited and can lead to severe health problems, including various inherited diseases and premature aging. The lack of efficient repair mechanisms and the susceptibility of mtDNA to damage exacerbate the threat to human health. Heteroplasmy, the presence of different mtDNA genotypes within a single cell, increases the complexity of these diseases and requires an effective editing method for correction. Recently, gene-editing techniques, including programmable nucleases such as restriction endonuclease, zinc finger nuclease, transcription activator-like effector nuclease, clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated 9 and base editors, have provided new tools for editing mtDNA in mammalian cells. Base editors are particularly promising because of their high efficiency and precision in correcting mtDNA mutations. In this review, we discuss the application of these techniques in mitochondrial gene editing and their limitations. We also explore the potential of base editors for mtDNA modification and discuss the opportunities and challenges associated with their application in mitochondrial gene editing. In conclusion, this review highlights the advancements, limitations and opportunities in current mitochondrial gene-editing technologies and approaches. Our insights aim to stimulate the development of new editing strategies that can ultimately alleviate the adverse effects of mitochondrial hereditary diseases.


Assuntos
Edição de Genes , Genes Mitocondriais , Animais , Humanos , Edição de Genes/métodos , Mitocôndrias/genética , DNA Mitocondrial/genética , Mutação , Mamíferos/genética
19.
Ann Diagn Pathol ; 69: 152243, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38128440

RESUMO

BACKGROUND: Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis; however, 5 %-15 % develop radioactive iodine-refractory (RAIR) DTC (RAIR-DTC), which has a poor prognosis and limited treatment options. The aim of the present study was to investigate the clinicopathological characteristics of RAIR-DTC in order to provide clinical evidence for timely prediction of the effects of iodine therapy. METHODS: Clinicopathological data for 44 patients with RAIR-DTC and 50 patients with radioiodine-avid DTC (RAIA-DTC) were retrospectively analyzed. The risk factors for RAIR-DTC were evaluated and a RAIR-DTC prediction model was established. RESULTS: RAIR-DTC showed unique clinicopathological features that differed from those of RAIA-DTC; these included age >55 years, a high-risk histological subtype, a large tumor size, a late TNM stage, calcification, distant metastasis, and more than six metastatic lymph nodes. Patients with RAIR-DTC also developed earlier tumor progression. Binary logistic regression analysis showed that distant metastasis, a high-risk histological subtype, and a maximum tumor diameter of ≥12.5 mm were independent risk factors for RAIR-DTC, and the specificity and sensitivity of a combination of these three parameters for the prediction of RAIR-DTC were 98.0 % and 56.8 %, respectively. Decision curve analysis and the calibration curve revealed that the combined prediction of these three parameters had good repeatability and accuracy. CONCLUSION: The clinicopathological features of DTC can effectively predict the effects of iodine therapy. A combination of distant metastasis, a high-risk histological subtype, and a maximum tumor diameter of ≥12.5 mm showed significantly higher prediction accuracy.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/patologia , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Adenocarcinoma/tratamento farmacológico , Prognóstico
20.
Exp Eye Res ; 239: 109759, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142763

RESUMO

Early diagnosis is important for improving the outcomes of keratoconus (KC). Stable expression and a closed-loop structure of circular RNAs (circRNAs) make them ideal for the diagnosis and treatment of diseases. However, the expression pattern and potential function of circRNAs in KC is not studied yet. Hence, this study explored the circRNA expression profile of KC corneas through transcriptome sequencing and circRNA expression profile analysis. The diagnostic potential of blood circRNAs for KC was explored by analysing the circRNAs' expression levels of fifty paired blood samples from patients with KC and normal controls. The results showed that 107 significantly upregulated and 145 significantly downregulated circRNAs (|fold change| ≥ 2.0, p-value <0.05) were identified in KC tissues. Eight top differently expressed circRNAs were further validated in more cornea samples. Among them, five circRNAs expressed in peripheral blood, and four circRNAs (circ_0006156, circ_0006117, circ_0000284 and circ_0001801) showed significant downregulation in KC patients' peripheral blood too. The blood circ_0000284 expression levels of early, moderate, and advanced KC patients both were significantly lower than the controls. The blood circ_0006117 expression levels present a positive correlation with corrected distance visual acuity values, and a negative correlation with back elevation values of KC eyes. Notably, the expression levels of these circRNAs distinguished KC patients from their healthy counterparts, with the area under the curve (AUC) of circ_0000284, circ_0001801, and circ_0006117 being 0.7306, 0.6871 and 0.6701, respectively. Further, the AUC value for five circRNAs under the logistic regression model was 0.8203, indicating that they can function as effective biomarkers for the KC diagnostics. In conclusion, the expression of circRNAs showed a relationship with KC, with four significantly differentially expressed circRNAs demonstrating potential as biomarkers for the disease.


Assuntos
Ceratocone , RNA Circular , Humanos , RNA Circular/genética , Ceratocone/diagnóstico , Ceratocone/genética , Biomarcadores/metabolismo , Regulação para Baixo , Área Sob a Curva , RNA/genética , RNA/metabolismo
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