Biological functions and affected signaling pathways by Long Non-Coding RNAs in the immune system.

Recently, the various regulative functions of long non-coding RNAs (LncRNAs) have been well determined. Recently, the vital role of LncRNAs as gene regulators has been identified in the immune system, especially in the inflammatory response. All cells of the immune system are governed by a complex and ever-changing gene expression program that is regulated through both transcriptional and post-transcriptional processes. LncRNAs regulate gene expression within the cell nucleus by influencing transcription or through post-transcriptional processes that affect the splicing, stability, or translation of messenger RNAs (mRNAs). Recent studies in immunology have revealed substantial alterations in the expression of lncRNAs during the activation of the innate immune system as well as the development, differentiation, and activation of T cells. These lncRNAs regulate key aspects of immune function, including the manufacturing of inflammatory molecules, cellular distinction, and cell movement. They do this by modulating protein-protein interactions or through base pairing with RNA and DNA. Here we review the current understanding of the mechanism of action of lncRNAs as novel immune-related regulators and their impact on physiological and pathological processes related to the immune system, including autoimmune diseases. We also highlight the emerging pattern of gene expression control in important research areas at the intersection between immunology and lncRNA biology.

Emerging roles of non-coding RNAs in modulating the PI3K/Akt pathway in cancer.

Cancer progression results from the dysregulation of molecular pathways, each with unique features that can either promote or inhibit tumor growth. The complexity of carcinogenesis makes it challenging for researchers to target all pathways in cancer therapy, emphasizing the importance of focusing on specific pathways for targeted treatment. One such pathway is the PI3K/Akt pathway, which is often overexpressed in cancer. As tumor cells progress, the expression of PI3K/Akt increases, further driving cancer advancement. This study aims to explore how ncRNAs regulate the expression of PI3K/Akt. NcRNAs are found in both the cytoplasm and nucleus, and their functions vary depending on their location. They can bind to the promoters of PI3K or Akt, either reducing or increasing their expression, thus influencing tumorigenesis. The ncRNA/PI3K/Akt axis plays a crucial role in determining cell proliferation, metastasis, epithelial-mesenchymal transition (EMT), and even chemoresistance and radioresistance in human cancers. Anti-tumor compounds can target ncRNAs to modulate the PI3K/Akt axis. Moreover, ncRNAs can regulate the PI3K/Akt pathway both directly and indirectly.

Circular RNAs in laryngeal cancer.

Laryngeal cancer remains a significant global health concern, with poor prognosis for advanced-stage disease highlighting the need for novel diagnostic, prognostic, and therapeutic approaches. Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs, have emerged as important regulators of gene expression and cellular processes in various cancers, including laryngeal cancer. This review summarizes the current understanding of circRNAs in laryngeal cancer, covering their biogenesis, regulatory mechanisms, and potential clinical applications. We explore the diverse functions of circRNAs, including their roles as miRNA sponges, protein interactors, and direct mRNA regulators, and their influence on key cellular processes such as proliferation, invasion, and metastasis. The review highlights promising circRNAs as diagnostic and prognostic biomarkers, as well as potential therapeutic targets. We also outline current strategies for circRNA modulation, including suppression techniques like RNA interference and CRISPR/Cas systems, and overexpression methods using vectors and synthetic circRNAs.

Overexpression of Long Non-coding RNAs MCM3AP-AS1 and LINC00092 Predict Poor Prognosis in Patients with Gastric Adenocarcinoma.

Background: LINC00092 and MCM3AP-AS1 long non-coding RNAs (LncRNAs) play significant roles in the development and pathogenesis of many cancers. However, their expression levels and prognostic values were not evaluated in human gastric adenocarcinoma (GAC). Therefore, the present study aimed to investigate the clinico-pathological correlations of LINC00092 and MCM3AP-AS1, LncRNAs expression in GAC, and evaluate their prognostic values. Materials and Methods: The expression of LINC00092 and MCM3AP-AS1 was detected in 89 GAC tissues by quantitative real-time reverse-transcription PCR (qRT-PCR). Results: Our results showed that LINC00092 and MCM3AP-AS1 are overexpressed in GAC patients and positively correlated with GAC invasion and vascular, peritoneal, and lymph node metastasis (P < 0.05). Furthermore, the results indicated that MCM3AP-AS1 (P = 0.0225) and LINC00092 (P < 0.001) have positive correlations with GAC patients' overall survival. Conclusion: Altogether, the present results indicated that LINC00092 and MCM3AP-AS1 overexpression is associated with clinico-pathological characteristic of GAC patients. In addition, both of these LncRNAs may have prognostic value for estimation of patients' overall survival.

Uncovering the functions and mechanisms of regulatory elements-associated non-coding RNAs.

Over the past decade, regulatory non-coding RNAs (ncRNAs) produced by RNA Pol II have been revealed as meaningful players in various essential cellular functions. In particular, thousands of ncRNAs are produced at transcriptional regulatory elements such as enhancers and promoters, where they may exert multiple functions to regulate proper development, cellular programming, transcription or genomic stability. Here, we review the mechanisms involving these regulatory element-associated ncRNAs, and particularly enhancer RNAs (eRNAs) and PROMoter uPstream Transcripts (PROMPTs). We contextualize the mechanisms described to the processing and degradation of these short lived RNAs. We summarize recent findings explaining how ncRNAs operate locally at promoters and enhancers, or further away, either shortly after their production by RNA Pol II, or through post-transcriptional stabilization. Such discoveries lead to a converging model accounting for how ncRNAs influence cellular fate, by acting on transcription and chromatin structure, which may further involve factors participating to 3D nuclear organization.

Who is at-risk for severe anaphylaxis in France?

Background: The understanding of risk factors related to severe anaphylaxis is key to implementing prevention strategies. We present the first French population-based nine-year anaphylaxis hospitalization study evaluating specific trends and factors related to severe anaphylaxis (SA), to support identification of phenotypes at-risk. Methods: This study used descriptive data from the French hospitalization database for the years 2012-2021, and included all patients hospitalized with anaphylaxis using International Classification of Diseases (ICD)-10 codes listed as a primary diagnosis. SA were cases that either required a hospitalization in intensive care units or resulted in death. Potential risk factors were identified according to corresponding ICD codes, available as secondary data during the patient's hospitalization. Results: The average hospitalization rate of all cases of anaphylaxis (SA and non-SA) was 1.34/100,000/year, and rate of admissions for SA was 0.08/100,000/year. Among the 5463 SA, 37.7% had unspecified coding label, when trigger was not identified. For SA cases in which trigger was identified, most were related to drugs (45.6%), followed by food (9.3%) and insect sting (7.2%). Overall, admissions due to anaphylaxis (SA and non-SA) were more frequent in males (57%). However, when the trigger was drugs, the proportion was significantly higher in females. For children aged 5-9 years, the most common trigger for SA was food. Patients for which SA was triggered by insect stings were identified exclusively in the 10-14 years age group. Chronic spontaneous urticaria was associated with insect sting-induced anaphylaxis, regardless of the severity. Angioedema was associated with all causes of SA. Cases of anaphylaxis presenting with urticaria and angioedema included cases with identified and unidentified triggers. Asthma and a personal history of allergy were associated with drug- and food-induced anaphylaxis. Conclusion: This is the first study to provide data on severe phenotypes of anaphylaxis in France. Data presented is key to the implementation of public health actions and preventive strategies to improve quality care.

Long journey on the role of long non-coding RNA (lncRNA) in acute kidney injury (AKI).

Acute kidney injury (AKI) has a high rate of morbidity, death, and medical expenses, making it a worldwide public health problem. There are still few viable treatment plans for AKI despite medical advancements. A subclass of non-coding RNAs with over 200 nucleotides in length, long non-coding RNAs (lncRNAs) have a wide range of biological roles. Lately, lncRNAs have become important mediators of AKI and prospective biomarkers. However, current studies show that, via constructing the lncRNA/microRNA/target gene regulatory axis, abnormal expression of lncRNAs has been connected to significant pathogenic processes associated with AKI, such as the inflammatory response, cell proliferation, and apoptosis. In order to compete with mRNAs for binding to the same miRNAs and affect the expression of transcripts targeted by miRNAs, lncRNAs may function as competing endogenous RNAs (ceRNAs). The most widely used approach for researching the biological roles of lncRNAs is the construction of ceRNA regulation networks. Our goal in this article is to deliver an updated review of lncRNAs in AKI and to provide more knowledge on their possible applications as therapeutic targets and AKI biomarkers.

Coding and coverage for cardiac CT in the era of algorithm-based healthcare procedures and services.

In order for patients to gain the benefit of innovation in cardiac CT, it is necessary for coding, coverage, and payment to adapt to the novelty of algorithm-based healthcare procedures and services (ABHS). Appendix S to the CPT Code Set, the "AI Taxonomy", enables creation of discrete and differentiable codes for reimbursement of ABHS which has been clinically validated and FDA-labeled. Payment policy in OPPS and PFS is evolving to take account of the unique opportunities and issues arising from the clinical adoption of ABHS.

Integrating Deep Learning and Synthetic Biology: A Co-Design Approach for Enhancing Gene Expression via N-Terminal Coding Sequences.

N-terminal coding sequence (NCS) influences gene expression by impacting the translation initiation rate. The NCS optimization problem is to find an NCS that maximizes gene expression. The problem is important in genetic engineering. However, current methods for NCS optimization such as rational design and statistics-guided approaches are labor-intensive yield only relatively small improvements. This paper introduces a deep learning/synthetic biology codesigned few-shot training workflow for NCS optimization. Our method utilizes k-nearest encoding followed by word2vec to encode the NCS, then performs feature extraction using attention mechanisms, before constructing a time-series network for predicting gene expression intensity, and finally a direct search algorithm identifies the optimal NCS with limited training data. We took green fluorescent protein (GFP) expressed by Bacillus subtilis as a reporting protein of NCSs, and employed the fluorescence enhancement factor as the metric of NCS optimization. Within just six iterative experiments, our model generated an NCS (MLD62) that increased average GFP expression by 5.41-fold, outperforming the state-of-the-art NCS designs. Extending our findings beyond GFP, we showed that our engineered NCS (MLD62) can effectively boost the production of N-acetylneuraminic acid by enhancing the expression of the crucial rate-limiting GNA1 gene, demonstrating its practical utility. We have open-sourced our NCS expression database and experimental procedures for public use.

Decoding the Epigenetics of Infertility: Mechanisms, Environmental Influences, and Therapeutic Strategies.

Infertility is a complex condition caused by a combination of genetic, environmental, and lifestyle factors. Recent advances in epigenetics have highlighted the importance of epigenetic changes in fertility regulation. This review aims to provide a comprehensive overview of the epigenetic mechanisms involved in infertility, with a focus on DNA methylation, histone modification, and non-coding RNAs. We investigate the specific epigenetic events that occur during gametogenesis, with a focus on spermatogenesis and oogenesis as distinct processes. Furthermore, we investigate how environmental factors such as diet, stress, and toxin exposure can influence these epigenetic changes, potentially leading to infertility. The second part of the review explores epigenetic changes as therapeutic targets for infertility. Emerging therapies that modulate epigenetic marks present promising opportunities for fertility restoration, particularly in spermatogenesis. By summarizing current research findings, this review emphasizes the importance of understanding epigenetic contributions to infertility. Our discussion aims to lay the groundwork for future research directions and clinical applications in reproductive health.

Two-plus-two fringe projection profilometry based on phase-shifted coding.

In fringe projection profilometry based on temporal phase unwrapping, determining a fringe order map commonly requires a large number of fringes. To reduce the fringe number, this paper proposes a concise absolute phase retrieval algorithm just by projecting four fringes. The first two orthogonal fringes with relatively large frequency can collect reliable height information. The second two fringes are designed the same as the first two, but the only difference is that each 2π-phase of them is shifted by a unique amount, which can robustly label a large number of fringe orders. For decoding the fringes, we develop an average intensity one-time extraction algorithm, which allows for the rapid acquisition of the two pairs of alternating current components. From this, the wrapped phase containing height information and the stair-coded phase providing fringe orders can be directly extracted by arctangent operation in a point-to-point manner. Furthermore, we also develop a universal fringe order correction algorithm that can simultaneously correct the common errors and the misalignment between the wrapped phase and fringe orders. Experiment results demonstrate that this method achieves comparable accuracy and adaptability to the phase-coding method, while utilizing two fewer fringes.

[Retracted] Long non­coding RNA SNHG3 promotes the development of non­small cell lung cancer via the miR­1343­3p/NFIX pathway.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell cell migration and invasion assay data shown in Fig. 3B were strikingly similar to data appearing in different form in a pair of other articles written by different authors at different research institutes, one of which had already been published elsewhere prior to the submission of this paper to International Journal of Molecular Medicine, and one of which was under consideration for publication at around the same time. In view of the fact that the abovementioned data had already apparently been published previously, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 48: 147, 2021; DOI: 10.3892/ijmm.2021.4980].

Can GPT-3.5 generate and code discharge summaries?

OBJECTIVES: The aim of this study was to investigate GPT-3.5 in generating and coding medical documents with International Classification of Diseases (ICD)-10 codes for data augmentation on low-resource labels. MATERIALS AND METHODS: Employing GPT-3.5 we generated and coded 9606 discharge summaries based on lists of ICD-10 code descriptions of patients with infrequent (or generation) codes within the MIMIC-IV dataset. Combined with the baseline training set, this formed an augmented training set. Neural coding models were trained on baseline and augmented data and evaluated on an MIMIC-IV test set. We report micro- and macro-F1 scores on the full codeset, generation codes, and their families. Weak Hierarchical Confusion Matrices determined within-family and outside-of-family coding errors in the latter codesets. The coding performance of GPT-3.5 was evaluated on prompt-guided self-generated data and real MIMIC-IV data. Clinicians evaluated the clinical acceptability of the generated documents. RESULTS: Data augmentation results in slightly lower overall model performance but improves performance for the generation candidate codes and their families, including 1 absent from the baseline training data. Augmented models display lower out-of-family error rates. GPT-3.5 identifies ICD-10 codes by their prompted descriptions but underperforms on real data. Evaluators highlight the correctness of generated concepts while suffering in variety, supporting information, and narrative. DISCUSSION AND CONCLUSION: While GPT-3.5 alone given our prompt setting is unsuitable for ICD-10 coding, it supports data augmentation for training neural models. Augmentation positively affects generation code families but mainly benefits codes with existing examples. Augmentation reduces out-of-family errors. Documents generated by GPT-3.5 state prompted concepts correctly but lack variety, and authenticity in narratives.

Suppression by RNA Polymerase I Inhibitors Varies Greatly Between Distinct RNA Polymerase I Transcribed Genes in Malaria Parasites.

Transcription of ribosomal RNA (rRNA) by RNA Polymerase I (Pol I) is the rate-limiting step in ribosome biogenesis and a major determinant of cellular growth rates. Unlike virtually every other eukaryote, which express identical rRNA from large tandem arrays of dozens to hundreds of identical rRNA genes in every cell, the genome of the human malaria parasite Plasmodium falciparum contains only a handful single-copy 47S rRNA loci that differ substantially from one another in length, sequence and expression in different cell-types. We found that growth of malaria parasite was acutely sensitive to the Pol I inhibitors 9-hydroxyellipticine and BMH-21 and demonstrate that they greatly reduce the transcription of 47S rRNAs as well as transcription of other non-coding RNA genes. Surprisingly, we found that the various types of Pol I-transcribed genes differed by more than two orders of magnitude in their susceptibility to these inhibitors and explore the implications of these findings for regulation of rRNA in P. falciparum.

Targeting non-coding RNAs as a promising biomarker in peritoneal metastasis: Background, mechanism, and therapeutic approach.

Peritoneal metastasis (PM) pathophysiology is complex and not fully understood. PM, originating from gastrointestinal (GI) cancer, is a condition that significantly worsens patient prognosis due to its complex nature and limited treatment options. The non-coding RNAs (ncRNAs) have been shown to play pivotal roles in cancer biology, influencing tumorigenesis, progression, metastasis, and therapeutic resistance. Increasing evidence has demonstrated the regulatory functions of different classes of ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in PM. Identifying biomarkers for early detection of PM is a crucial step towards improving patient outcomes, and how ncRNA profiles correlate with survival rates, response to therapy, and recurrence risks have raised much attention in recent years. Additionally, exploring innovative therapeutic approaches utilizing ncRNAs, such as targeted therapy and gene silencing, may offer new horizons in treating this dire condition. Recent advances in systemic treatments and the development of novel loco-regional therapies have opened doors to multimodal treatment approaches. Radical surgeries combined with hyperthermic intraperitoneal chemotherapy (HIPEC) have shown promising results, leading to extended patient survival. Current research is focused on the molecular characterization of PM, which is crucial for early detection and developing future therapeutic strategies. By summarizing the latest findings, this study underscores the transformative potential of ncRNAs in enhancing the diagnosis, prognosis, and treatment of PM in GI cancer, paving the way for more personalized and effective clinical strategies.

Identification and validation of a five-necroptosis-related lncRNAs signature for prognostic prediction in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is among the most prevalent digestive system malignancies and is associated with a poor prognosis. Necroptosis, a form of regulated death mediated by death receptors, exhibits characteristics of both necrosis and apoptosis. Long non-coding RNAs (lncRNAs) have been identified as crucial regulators in tumor necroptosis. This study aims to identify the necroptosis-related lncRNAs (np-lncRNA) in HCC and investigate their relationships with prognosis. Method: The RNA-sequencing data, along with clinicopathological and survival information of HCC patients were sourced from The Cancer Genome Atlas (TCGA) database. The np-lncRNAs were analyzed to assess their potential in predicting HCC prognosis. Prognostic signatures related to necroptosis were constructed using stepwise multivariate Cox regression analysis. The prognosis of patients was compared using Kaplan-Meier (KM) analysis. The accuracy of the prognostic signature was evaluated using Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Quantitative real-time polymerase chain reaction(qPCR) was employed to validate the lncRNAs expression levels of lncRNAs among samples from an independent cohort. Results: The np-lncRNAs ZFPM2-AS1, AC099850.3, BACE1-AS, KDM4A-AS1 and MKLN1-AS were identified as potential prognostic biomarkers. The prognostic signature constructed from these np-lncRNAs achieved an Area Under the Curve (AUC) of 0.773. Based on the risk score derived from the signature, patients were divided into two groups, with the high-risk group exhibiting poorer overall survival. Gene Set Enrichment Analysis (GSEA) revealed significantly different between the low risk and high risk groups in tumor-related pathways (such as mTOR, MAPK and p53 signaling pathways) and immune-related functions (like T cell receptor signaling pathway and natural killer cell mediated cytotoxicity). The increased expression of np-lncRNAs was confirmed in another independent HCC cohort. Conclusions: This signature offers a dependable method for forecasting the prognosis of HCC patients. Our findings indicate a subset of np-lncRNA biomarkers that could be utilized for prognosis prediction and personalized treatment strategies of HCC patients.

Exosomal non-coding RNAs (ncRNAs) as potential biomarkers in tumor early diagnosis.

Exosomes, extracellular vesicles carrying a cargo rich in various non-coding RNAs (ncRNAs), have emerged as crucial mediators of intercellular communication. Their stability, abundance, and specificity make exosomal ncRNAs promising candidates for biomarker discovery. The discovery of exosomal ncRNAs has unveiled a novel avenue for the exploration of biomarkers in tumor early diagnosis. This review consolidates current knowledge on the role of exosomal ncRNAs as potential biomarkers in the early detection of various tumors. We provide an overview of recent studies demonstrating the diagnostic potential of exosomal ncRNAs across multiple cancer types, highlighting their sensitivity, specificity, and feasibility for early detection. This review underscores the potential of exosomal ncRNAs as non-invasive biomarkers for early tumor diagnosis, paving the way for improved clinical outcomes through timely intervention and personalized management strategies.

Polyphenol-Mediated Modulation of Non-Coding RNAs: A New Therapeutic Approach for Hypertension - A Review.

Hypertension (HTN) is a leading risk factor for cardiovascular diseases (CVDs) and a major contributor to global morbidity and mortality. Conventional pharmacological treatments have been effective but are often accompanied by side effects and do not address all pathological aspects of the disease. Recent advances in molecular biology have identified non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), as key regulators in the pathogenesis of hypertension. These ncRNAs influence various cellular processes, such as gene expression, vascular tone, and inflammation, making them promising targets for therapeutic intervention. This review explores the potential of polyphenols, a diverse group of phytochemicals with potent antioxidant and anti-inflammatory properties, in modulating ncRNA expression and function. We discuss how polyphenols, such as epigallocatechin-3-gallate (EGCG), resveratrol, curcumin, and quercetin impact the regulation of ncRNAs, particularly focusing on their roles in reducing oxidative stress, improving endothelial function, and ameliorating vascular remodeling associated with hypertension. The review synthesizes current evidence from both in vitro and in vivo studies, highlighting significant findings and the mechanisms by which polyphenols exert their effects on ncRNA-mediated pathways. Moreover, we address the challenges of translating these findings into clinical applications, including issues related to bioavailability, dosing, and the complex interactions of polyphenols with other cellular components. Future directions for research are suggested, with an emphasis on the need for comprehensive clinical trials to establish the efficacy of polyphenol-based therapies targeting ncRNAs in hypertension management. By targeting ncRNAs, polyphenols offer a novel therapeutic strategy that could enhance the treatment landscape for hypertension and potentially other cardiovascular conditions.

Complete coding sequence of Tembusu virus isolate 2211-5 isolated in Taiwan.

We reported the complete coding sequence of a Tembusu virus from sick geese in Taiwan in 2022. The nucleotide sequence of the 2211-5 isolate was most closely related to the strain CTLN isolated from chicken in China and classified into Cluster 3 of Tembusu virus.

Biomarkers and diagnostic significance of non-coding RNAs in extracellular vesicles of pathologic pregnancy.

Intercellular communication is an important mechanism for the development and maintenance of normal biological processes in all organs, including the female reproductive system. Extracellular vesicles, as important carriers of intercellular communication, contain a variety of biologically active molecules, such as mRNAs, miRNAs, lncRNAs, and circRNAs, which are involved in cell-to-cell exchanges as well as in many physiological and pathological processes in the body. Compared with biomarkers found in tissues or body fluids, extracellular vesicles show better stability due to the presence of their envelope membrane which prevents the degradation of the RNA message in their vesicles. Therefore, the genomic and proteomic information contained in extracellular vesicles can serve as important markers and potential therapeutic targets for female reproductive system-related diseases or placental function. Moreover, changes in the expression of non-coding RNAs (mainly miRNAs, lncRNAs, and circRNAs) in maternal extracellular vesicles can accurately and promptly reflect the progress of female reproductive system diseases. The aim of this review is to collect information on different types of non-coding RNAs with key molecular carriers in female pathologic pregnancies (preeclampsia and recurrent spontaneous abortion), so as to explore the relevant molecular mechanisms in female pathologic pregnancies and provide a theoretical basis for clinical research on the pathogenesis and therapeutic approaches of reproductive system diseases. The current state of the art of exosome isolation and extraction is also summarized.