Surface coating technology is broadly demanded across various fields, including marine and biomedical materials; therefore, a facile and versatile approach is desired. This study proposed an attractive surface coating strategy using photo-crosslinkable benzophenone (BP) moiety for biomaterials application. BP-containing "bioglue" polymer can effectively crosslink with all kinds of surfaces and biomolecules. Upon exposure to ultraviolet (UV) light, free radical reaction from the BP glue facilitates the immobilization of diverse molecules onto different substrates in a straightforward and user-friendly manner. Through either one-step, mixing the bioglue with targeted biomolecules, or two-step methods, pre-coating the bioglue and then adding targeted biomolecules, polyacrylic acid (PAA), cyclic RGD-containing peptides, and proteins (gelatin, collagen, and fibronectin) were successfully immobilized on substrates. After drying the bioglue, targeted biomolecules can still be immobilized on the surfaces preserving their bioactivity. Cell culture on biomolecule-immobilized surfaces using NIH 3T3 fibroblasts and human bone marrow stem cells (hBMSCs) showed significant improvement of cell adhesion and activity compared to the unmodified control in serum-free media after 24 hours. Furthermore, hBMSCs on the fibronectin-immobilized surface showed an increased calcium deposition after 21 days of osteogenic differentiation, suggesting that the immobilized fibronectin is highly bioactive. Given the straightforward protocol and substrate-independent bioglue, the proposed coating strategy is promising in broad-range fields.
Introduction: Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism's pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets. Methods: Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed. Results: MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol's binding to IRF3, indicating a stable interaction. Conclusion: This study comprehensively elucidates inflammation, immune response, and metabolism's intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo's etiology, informing future research and drug development endeavors.
BACKGROUND: Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch-to-batch variations, lack of the native microenvironment and clinical applicability. MAIN BODY: The concept of organoids has derived patient-derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, 'tumour assembloids' inspired by cell-coculture technology have attracted attention to complement the current PDTO technology. High-quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour-infiltrating lymphocyte, T cell receptor-engineered T cell and chimeric antigen receptor-T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank. CONCLUSION: Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre-clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. KEY POINTS: The current PDTO models have not yet constructed key cellular and non-cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.
Immunotherapy , Neoplasms , Organoids , Humans , Organoids/drug effects , Immunotherapy/methods , Neoplasms/therapy , Neoplasms/drug therapy , Neoplasms/immunology , Precision Medicine/methods , Avatar
STUDY OBJECTIVES: Previous studies have highlighted the importance of sleep patterns for human health. This study aimed to investigate the association of sleep timing with all-cause and cardiovascular disease mortality. METHODS: Participants were screened from two cohort studies: the Sleep Heart Health Study (SHHS; n = 4,824) and the Osteoporotic Fractures in Men Study (n = 2,658). Sleep timing, including bedtime and wake-up time, was obtained from sleep habit questionnaires at baseline. The sleep midpoint was defined as the halfway point between the bedtime and wake-up time. Restricted cubic splines and Cox proportional hazards regression analyses were used to examine the association between sleep timing and mortality. RESULTS: We observed a U-shaped association between bedtime and all-cause mortality in both the SHHS and Osteoporotic Fractures in Men Study groups. Specifically, bedtime at 11:00 pm and waking up at 7:00 am was the nadir for all-cause and cardiovascular disease mortality risks. Individuals with late bedtime (> 12:00 am) had an increased risk of all-cause mortality in SHHS (hazard ratio 1.53, 95% confidence interval 1.28-1.84) and Osteoporotic Fractures in Men Study (hazard ratio 1.27, 95% confidence interval 1.01-1.58). In the SHHS, late wake-up time (> 8:00 am) was associated with increased all-cause mortality (hazard ratio 1.39, 95% confidence interval 1.13-1.72). No significant association was found between wake-up time and cardiovascular disease mortality. Delaying sleep midpoint (> 4:00 am) was also significantly associated with all-cause mortality in the SHHS and Osteoporotic Fractures in Men Study. CONCLUSIONS: Sleep timing is associated with all-cause and cardiovascular disease mortality. Our findings highlight the importance of appropriate sleep timing in reducing mortality risk. CITATION: Ma M, Fan Y, Peng Y, et al. Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study. J Clin Sleep Med. 2024;20(4):545-553.
Cardiovascular Diseases , Osteoporotic Fractures , Male , Humans , Cardiovascular Diseases/complications , Sleep , Polysomnography , Cohort Studies
Fibromyalgia is a chronic, widespread pain disorder that is strongly represented across the affective and cognitive dimensions of pain, given that the underlying pathophysiology of the disorder is yet to be identified. These affective and cognitive deficits are crucial to understanding and treating the fibromyalgia pain experience as a whole but replicating this multidimensionality on a preclinical level is challenging. To understand the underlying mechanisms, animal models are used. In this scoping review, we evaluate the current primary animal models of fibromyalgia regarding their translational relevance within the affective and cognitive pain realms, as well as summarize treatments that have been identified preclinically for attenuating these deficits.
INTRODUCTION: Helicobacter pylori (H. pylori) infection has been associated with gastric carcinogenesis. However, the precise involvement of LRP8, the low-density lipoprotein receptor-related protein 8, in H. pylori pathogenesis and gastric cancer (GC) remains poorly understood. OBJECTIVES: To investigate the potential role of LRP8 in H. pylori infection and gastric carcinogenesis. METHODS: Three-dimensional human-derived gastric organoids (hGO) and gastric cancer organoids (hGCO) were synthesized from the tissues obtained from human donors. In this work, multi-omics combined with in vivo and in vitro studies were conducted to investigate the potential involvement of LRP8 in H. pylori-induced GC. RESULTS: We found that H. pylori infection significantly upregulated the expression of LRP8 in human GC tissues, cells, organoids, and mouse gastric mucous. In particular, LRP8 exhibited a distinct enrichment in cancer stem cells (CSC). Functionally, silencing of LRP8 affected the formation and proliferation of tumor spheroids, while increased expression of LRP8 was associated with increased proliferation and stemness of GC cells and organoids. Mechanistically, LRP8 promotes the binding of E-cadherin to ß-catenin, thereby promoting nuclear translocation and transcriptional activity of ß-catenin. Furthermore, LRP8 interacts with the cytotoxin-associated gene A (CagA) to form the CagA/LRP8/ß-catenin complex. This complex further amplifies H. pylori-induced ß-catenin nuclear translocation, leading to increased transcription of inflammatory factors and CSC markers. Clinical analysis demonstrated that abnormal overexpression of LRP8 is correlated with a poor prognosis and resistance to 5-Fluorouracil in patients with GC. CONCLUSION: Our findings provide valuable information on the molecular intricacies of H. pylori-induced gastric carcinogenesis, offering potential therapeutic targets and prognostic markers for GC.
Background: In addition to abnormal liver inflammation, the main symptoms of non-alcoholic steatohepatitis (NASH) are often accompanied by gastrointestinal digestive dysfunction, consistent with the concept of spleen deficiency (SD) in traditional Chinese medicine. As an important metabolic sensor, whether peroxisome proliferator-activated receptor alpha (PPARα) participates in regulating the occurrence and development of NASH with SD (NASH-SD) remains to be explored. Methods: Clinical liver samples were collected for RNA-seq analysis. C57BL/6J mice induced by folium sennae (SE) were used as an SD model. qPCR analysis was conducted to evaluate the inflammation and metabolic levels of mice. PPARα knockout mice (PPARαko) were subjected to SE and methionine-choline-deficient (MCD) diet to establish the NASH-SD model. The phenotype of NASH and the inflammatory indicators were measured using histopathologic analysis and qPCR as well. Results: The abnormal expression of PPARα signaling, coupled with metabolism and inflammation, was found in the results of RNA-seq analysis from clinical samples. SD mice showed a more severe inflammatory response in the liver evidenced by the increases in macrophage biomarkers, inflammatory factors, and fibrotic indicators in the liver. qPCR results also showed differences in PPARα between SD mice and control mice. In PPARαko mice, further evidence was found that the lack of PPARα exacerbated the inflammatory response phenotype as well as the lipid metabolism disorder in NASH-SD mice. Conclusion: The abnormal NR signaling accelerated the vicious cycle between lipotoxicity and inflammatory response in NAFLD with SD. Our results provide new evidence for nuclear receptors as potential therapeutic targets for NAFLD with spleen deficiency.
Non-alcoholic Fatty Liver Disease , PPAR alpha , Animals , Mice , Inflammation , Mice, Inbred C57BL , Mice, Knockout , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , PPAR alpha/metabolism , Spleen/metabolism , Spleen/pathology
The successful reprogramming of impaired wound healing presents ongoing challenges due to the impaired tissue microenvironment caused by severe bacterial infection, excessive oxidative stress, as well as the inappropriate dosage timing during different stages of the healing process. Herein, a dual-layer hydrogel with sodium alginate (SA)-loaded zinc oxide (ZnO) nanoparticles and poly(N-isopropylacrylamide) (PNIPAM)-loaded Cu5.4O ultrasmall nanozymes (named programmed time-released multifunctional hydrogel, PTMH) was designed to dynamically regulate the wound inflammatory microenvironment based on different phases of wound repairing. PTMH combated bacteria at the early phase of infection by generating reactive oxygen species through ZnO under visible-light irradiation with gradual degradation of the lower layer. Subsequently, when the upper layer was in direct contact with the wound tissue, Cu5.4O ultrasmall nanozymes were released to scavenge excessive reactive oxygen species. This neutralized a range of inflammatory factors and facilitated the transition from the inflammatory phase to the proliferative phase. Furthermore, the utilization of Cu5.4O ultrasmall nanozymes enhanced angiogenesis, thereby facilitating the delivery of oxygen and nutrients to the impaired tissue. Our experimental findings indicate that PTMHs promote the healing process of diabetic wounds with bacterial infection in mice, exhibiting notable antibacterial and anti-inflammatory properties over a specific period of time.
Bacterial Infections , Zinc Oxide , Animals , Mice , Hydrogels/pharmacology , Reactive Oxygen Species , Zinc Oxide/pharmacology , Anti-Inflammatory Agents , Anti-Bacterial Agents/pharmacology
The development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.
Atherosclerosis , Emodin , Iridoids , Plaque, Atherosclerotic , Humans , Plaque, Atherosclerotic/drug therapy , Liposomes/therapeutic use , Reactive Oxygen Species/metabolism , Emodin/pharmacology , Emodin/therapeutic use , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Cholesterol
Dead-corner areas in space station that untouched by the clean-up campaign often experience microorganisms outbreaks, but the microbiome of these areas has never been studied. In this study, the microbiome in a ground-based analog ``Tianhe'' core module of China Space Station was first investigated during a 50-day three-crew occupation. Dead-corner areas were receiving attention by adopting a new sampling method. Results indicate that the astronauts occupation did not affect the dominant bacteria community, but affected a small proportion. Due to the frequent activity of astronauts in the work and sleep areas, the biomarkers in these two areas are common human skin surface and gut microorganisms, respectively. For areas that astronaut rarely visits, the biomarkers in which are common environmental microbial groups. Fluorescence counting showed that 70.12-84.78% of bacteria were alive, with a quantity of 104-105 cells/100 cm2. With the occupation time extension, the number of microorganisms increased. At the same sampling time, there was no significant bioburden difference in various locations. The cultivable bioburden ranged from 101 to 104 colony forming unit (CFU)/100 cm2, which are the following eight genera Penicillium, Microsphaeropsis, Stachybotrys, Humicola, Cladosporium, Bacillus, Planomicrobium, and Acinetobacter. Chryseomicrobium genus may be a key focus for future microbial prevention and control work.
OBJECTIVE: Natural killer cells (NK) acts a central player of the immune system in liver cirrhosis. The aim of this study was to examine the expression of activating intra-hepatic NK cell group 2D (NKG2D) in patients with chronic hepatitis B (CHB) and analyzed the correlation between NKG2D expression and prognosis of liver cirrhosis in these patients. METHODS: This was a cross-section study. Subjects with liver biopsy or sponge hemangioma surgery were included. The primary outcome was the NKG2D expression on intra-hepatic NK cells and their subtype cells in patients with CHB-related liver cirrhosis. Subsequently, the correlation of expression of NKG2D and clinical characteristic indicators were assayed RESULTS: Among 38 subjects, 11 (28.95%) normal liver sections adjacent the sponge hemangioma (healthy group) were collected during surgery, and 27 (71.05%) CHB-cirrhosis tissues (Cirrhosis group) were preserved after liver biopsy. Compared with healthy group, sections from cirrhosis group revealed more severe inflammation and collagen deposition and lower NKG2D expression in hepatic NK cells. The proportion of hepatic NK cells and the mean fluorescence intensity (MFI) of NKG2D on hepatic NK cells showed a positive correlation with serum albumin (Alb) level, platelet (Plt) count. Moreover, they had a significantly negative correlation with patient prothrombin time (PT), international standardized ratio (INR), the sirius red positive stained area and fibrosis stages. CONCLUSIONS: Lower NKG2D expression in intra-hepatic NK cells may be predictive of poorer prognosis of CHB patients with cirrhosis.
Background: Conjunctival melanoma (CM) is a rare, invasive tumor in the eye that readily metastasizes and spreads. Based on some significant clinicopathological information, we aimed to develop a prognostic model to predict the overall survival (OS) of CM patients. Methods: Data of patients diagnosed with CM from 2000 to 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were extracted and integrated based on competing risk regression to build a nomogram. Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration plots were used to evaluate the performance of the nomogram. Results: The study included 272 patients with CM, with a median age of 63 years. A nomogram was developed using age and tumor-node-metastasis (TNM) stage as variables. The model's C-index was 0.755, and the area under the curve (AUC) was 0.774, 0.812, and 0.815 at 5, 8, and 10 years, respectively. The calibration plot used to predict CM demonstrated good consistency between the predicted OS probability and the actual OS probability. Conclusions: We have developed a nomogram model to predict the OS of patients with CM, which can predict the survival of these patients. The model's prognostic value is higher than that of the American Joint Committee on Cancer (AJCC) staging system alone. This tool can help evaluate the tumor-specific prognosis, identify patients at high risk of cancer-specific death, and guide clinical decision-making.
Spherical nucleic acids (SNAs) have been used to construct various nanobiosensors with gold nanoparticles (AuNPs) as nuclei. The SNAs play a critical role in biosensing due to their various physical and chemical properties, programmability, and specificity recognition ability. In this study, CRISPR-responsive self-assembled spherical nucleic acid (CRISPR-rsSNA) detection probes were constructed by conjugating fluorescein-labeled probes to the surface of AuNPs to improve the sensing performance. Also, the mechanism of ssDNA and the role of different fluorescent groups in the self-assembly process of CRISPR-rsSNA were explored. Then, CRISPR-rsSNA and reverse transcription-recombinase polymerase amplification (RT-RPA) were combined to develop an ultrasensitive fluorescence-detection strategy for norovirus. In the presence of the virus, the target RNA sequence of the virus was transformed and amplified by RT-RPA. The resulting dsDNA activated the trans-cleavage activity of CRISPR cas12a, resulting in disintegrating the outer nucleic acid structure of the CRISPR-rsSNA at a diffusible rate, which released reporter molecules. Norovirus was quantitated by fluorescence detection. This strategy facilitated the detection of the norovirus at the attomolar level. An RT-RPA kit for norovirus detected would be developed based on this method. The proposed method would be used for the detection of different viruses just by changing the target RNA and crRNA of the CRISPR cas12a system which provided a foundation for high-throughput detection of various substances.
Metal Nanoparticles , Norovirus , Nucleic Acids , Norovirus/genetics , Gold , Cell Nucleus , Nucleic Acid Amplification Techniques , CRISPR-Cas Systems
Naringin is a natural flavonoid with therapeutic properties found in citrus fruits and an active natural product from herbal plants. Naringin has become a focus of attention in recent years because of its ability to actively participate in the body's immune response and maintain the integrity of the immune barrier. This review aims to elucidate the mechanism of action and therapeutic efficacy of naringin in various inflammatory diseases and to provide a valuable reference for further research in this field. The review provided the chemical structure, bioavailability, pharmacological properties, and pharmacokinetics of naringin and found that naringin has good therapeutic potential for inflammatory diseases, exerting anti-inflammatory, anti-apoptotic, anti-oxidative stress, anti-ulcerative and detoxifying effects in the disease. Moreover, we found that the great advantage of naringin treatment is that it is safe and can even alleviate the toxic side effects associated with some of the other drugs, which may become a highlight of naringin research. Naringin, an active natural product, plays a significant role in systemic diseases' anti-inflammatory and antioxidant regulation through various signaling pathways and molecular mechanisms.
BACKGROUND: To gain insight into the real-life care of patients in the healthcare system, data from hospital information systems and insurance systems are required. Consequently, linking clinical data with claims data is necessary. To ensure their syntactic and semantic interoperability, the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) from the Observational Health Data Sciences and Informatics (OHDSI) community was chosen. However, there is no detailed guide that would allow researchers to follow a generic process for data harmonization, i.e. the transformation of local source data into the standardized OMOP CDM format. Thus, the aim of this paper is to conceptualize a generic data harmonization process for OMOP CDM. METHODS: For this purpose, we conducted a literature review focusing on publications that address the harmonization of clinical or claims data in OMOP CDM. Subsequently, the process steps used and their chronological order as well as applied OHDSI tools were extracted for each included publication. The results were then compared to derive a generic sequence of the process steps. RESULTS: From 23 publications included, a generic data harmonization process for OMOP CDM was conceptualized, consisting of nine process steps: dataset specification, data profiling, vocabulary identification, coverage analysis of vocabularies, semantic mapping, structural mapping, extract-transform-load-process, qualitative and quantitative data quality analysis. Furthermore, we identified seven OHDSI tools which supported five of the process steps. CONCLUSIONS: The generic data harmonization process can be used as a step-by-step guide to assist other researchers in harmonizing source data in OMOP CDM.
Medical Informatics , Vocabulary , Humans , Databases, Factual , Data Science , Semantics , Electronic Health Records
The tumor microenvironment (TME) is critical for tumor growth and metastasis. The TME contains cancer-associated cells, tumor matrix, and tumor secretory factors. The fabrication of artificial tumors, so-called tumoroids, is of great significance for the understanding of tumorigenesis and clinical cancer therapy. The assembly of multiple tumor cells and matrix components through interdisciplinary techniques is necessary for the preparation of various tumoroids. This article discusses current methods for constructing tumoroids (tumor tissue slices and tumor cell co-culture) for pre-clinical use. This article focuses on the artificial matrix materials (natural and synthetic materials) and biofabrication techniques (cell assembly, bioengineered tools, bioprinting, and microfluidic devices) used in tumoroids. This article also points out the shortcomings of current tumoroids and potential solutions. This article aims to promotes the next-generation tumoroids and the potential of them in basic research and clinical application.
Neoplasms , Humans , Neoplasms/therapy , Coculture Techniques , Tumor Microenvironment
BACKGROUND: Multisite clinical studies are increasingly using real-world data to gain real-world evidence. However, due to the heterogeneity of source data, it is difficult to analyze such data in a unified way across clinics. Therefore, the implementation of Extract-Transform-Load (ETL) or Extract-Load-Transform (ELT) processes for harmonizing local health data is necessary, in order to guarantee the data quality for research. However, the development of such processes is time-consuming and unsustainable. A promising way to ease this is the generalization of ETL/ELT processes. OBJECTIVE: In this work, we investigate existing possibilities for the development of generic ETL/ELT processes. Particularly, we focus on approaches with low development complexity by using descriptive metadata and structural metadata. METHODS: We conducted a literature review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We used 4 publication databases (ie, PubMed, IEEE Explore, Web of Science, and Biomed Center) to search for relevant publications from 2012 to 2022. The PRISMA flow was then visualized using an R-based tool (Evidence Synthesis Hackathon). All relevant contents of the publications were extracted into a spreadsheet for further analysis and visualization. RESULTS: Regarding the PRISMA guidelines, we included 33 publications in this literature review. All included publications were categorized into 7 different focus groups (ie, medicine, data warehouse, big data, industry, geoinformatics, archaeology, and military). Based on the extracted data, ontology-based and rule-based approaches were the 2 most used approaches in different thematic categories. Different approaches and tools were chosen to achieve different purposes within the use cases. CONCLUSIONS: Our literature review shows that using metadata-driven (MDD) approaches to develop an ETL/ELT process can serve different purposes in different thematic categories. The results show that it is promising to implement an ETL/ELT process by applying MDD approach to automate the data transformation from Fast Healthcare Interoperability Resources to Observational Medical Outcomes Partnership Common Data Model. However, the determining of an appropriate MDD approach and tool to implement such an ETL/ELT process remains a challenge. This is due to the lack of comprehensive insight into the characterizations of the MDD approaches presented in this study. Therefore, our next step is to evaluate the MDD approaches presented in this study and to determine the most appropriate MDD approaches and the way to integrate them into the ETL/ELT process. This could verify the ability of using MDD approaches to generalize the ETL process for harmonizing medical data.
Acute kidney injury (AKI) is a prevalent and serious condition in the intensive care unit (ICU), associated with significant morbidity and mortality. Septic acute kidney injury (SAKI) contributes substantially to AKI cases in the ICU. However, current diagnostic methods have limitations, necessitating the exploration of novel biomarkers. In this study, we investigated the potential of plasma and urine CCL2 levels as diagnostic markers for AKI and SAKI in 216 ICU patients. Our findings revealed significant differences in plasma (p < 0.01) and urine CCL2 (p < 0.0001) levels between AKI and non-AKI patients in the ICU. Notably, urine CCL2 demonstrated promising predictive value for AKI, exhibiting high specificity and sensitivity (AUC = 0.8976; p < 0.0001). Furthermore, we observed higher urine CCL2 levels in SAKI compared to non-septic AKI (p < 0.001) and urine CCL2 could also differentiate SAKI from non-septic AKI (AUC = 0.7597; p < 0.0001). These results suggest that urine CCL2 levels hold promise as early biomarkers for AKI and SAKI, offering valuable insights for timely intervention and improved management of ICU patients.
Acute Kidney Injury , Sepsis , Humans , Sepsis/diagnosis , Sepsis/complications , Biomarkers , Critical Care , Intensive Care Units , Chemokine CCL2
N6-methyladenosine (m6A) methylation is the most prevalent internal epigenetic posttranscriptional mechanism for regulating mammalian RNA. Despite recent advances in determining the biological functions of m6A methylation, its association with the pathology of ovarian endometriosis remains uncertain. Herein, we performed m6A transcriptome-wide profiling to identify key lncRNAs with m6A modification involved in ovarian endometriosis development by bioinformatics analysis. We found the total m6A level was lower in ovarian endometriosis than in normal endometrium samples, with 9663 m6A peaks associated with 8989 lncRNAs detected in ovarian endometriosis and 9902 m6A peaks associated with 9210 lncRNAs detected in normal endometrium samples. These m6A peaks were primarily enriched within AAACU motifs. Functional enrichment analysis indicated that pathways involving the regulation of adhesion and development were significantly enriched in these differentially methylated lncRNAs. The regulatory relationships among lncRNAs, microRNAs (miRNAs), and mRNAs were identified by competing endogenous RNA (ceRNA) analysis and determination of the network regulating lncRNA-mRNA expression. Several specific lncRNA, including LINC00665, LINC00937, FZD10-AS1, DIO3OS and GATA2-AS1 which were differently expressed and modified by m6A, were validated using qRT-PCR and its interaction with infiltrating immune cells was explored. Furthermore, we found LncRNA DIO3OS promotes the invasion and migration of Human endometrial stromal cells (THESCs) and ALKBH5 regulates the expression of the lncRNA DIO3OS through m6A modification in vitro. Our study firstly revealed the transcriptome-wide map of m6A modification in lncRNAs of ovarian endometriosis. These findings may enable the determination of the underlying mechanism governing the pathogenesis of ovarian endometriosis and provide theoretical basis for further deeper research on the role of m6A in the development of ovarian endometriosis.
Endometriosis , RNA, Long Noncoding , Female , Humans , Animals , RNA, Long Noncoding/genetics , Transcriptome , Endometriosis/genetics , Adenosine , Methylation , Mammals
