Research progress on prediction of RNA-protein binding sites in the past five years.

Accurately predicting RNA-protein binding sites is essential to gain a deeper comprehension of the protein-RNA interactions and their regulatory mechanisms, which are fundamental in gene expression and regulation. However, conventional biological approaches to detect these sites are often costly and time-consuming. In contrast, computational methods for predicting RNA protein binding sites are both cost-effective and expeditious. This review synthesizes already existing computational methods, summarizing commonly used databases for predicting RNA protein binding sites. In addition, applications and innovations of computational methods using traditional machine learning and deep learning for RNA protein binding site prediction during 2018-2023 are presented. These methods cover a wide range of aspects such as effective database utilization, feature selection and encoding, innovative classification algorithms, and evaluation strategies. Exploring the limitations of existing computational methods, this paper delves into the potential directions for future development. DeepRKE, RDense, and DeepDW all employ convolutional neural networks and long and short-term memory networks to construct prediction models, yet their algorithm design and feature encoding differ, resulting in diverse prediction performances.

Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation.

Background: Klotho deficiency is a common feature of premature aging and chronic kidney disease (CKD). As such, restoring Klotho expression could be a logic strategy for protecting against various nephropathies. In this study, we demonstrate that KP1, a Klotho-derived peptide, inhibits cellular senescence by restoring endogenous Klotho expression. Methods: The effects of KP1 on cellular senescence and Klotho expression were assessed in mouse models of CKD. RNA-sequencing was employed to identify the microRNA involved in regulating Klotho by KP1. Gain- or loss-of-function approaches were used to assess the role of miR-223-3p and IncRNA-TUG1 in regulating Klotho and cellular senescence. Results: KP1 inhibited senescence markers p21, p16 and γ-H2AX in tubular epithelial cells of diseased kidneys, which was associated with its restoration of Klotho expression at the posttranscriptional level. Profiling of kidney microRNAs by RNA sequencing identified miR-223-3p that bound to Klotho mRNA and inhibited its protein expression. Overexpression of miR-223-3p inhibited Klotho and induced p21, p16 and γ-H2AX, which were negated by KP1. Conversely, inhibition of miR-223-3p restored Klotho expression, inhibited cellular senescence. Furthermore, miR-223-3p interacted with lncRNA-TUG1 and inhibited its expression. Knockdown of lncRNA-TUG1 increased miR-223-3p, aggravated Klotho loss and worsened cellular senescence, whereas KP1 mitigated all these changes. Conclusion: These studies demonstrate that KP1 inhibits cellular senescence and induces Klotho expression via posttranscriptional regulation mediated by miR-223-3p and lncRNA-TUG1. By restoring endogenous Klotho, KP1 elicits a broad spectrum of protective actions and could serve as a promising therapeutic agent for fibrotic kidney disorders.

FDG PET/CT in a Case of Primary Lymphoma of the Ureter.

ABSTRACT: Primary lymphoma of the ureter is extremely rare. We describe the contrast-enhanced CT and FDG PET/CT findings in a case of diffuse large B-cell lymphoma transformed from mucosa-associated lymphoid tissue lymphoma limited to the left ureter. Contrast-enhanced CT showed 2 short-segment circumferential thickening and enhancement of the left pelvic and intramural ureteral wall. The thickened ureteral wall showed significantly increased FDG uptake mimicking urothelial carcinoma.

Neisseria mucosa - A rare cause of peritoneal dialysis-related peritonitis: A case report.

BACKGROUND: Neisseria mucosa is a gram negative diplococcus belonging to the genus Neisseria found commonly in the upper respiratory tract. It is typically a commensal organism when it is parasitic on oral and nasal mucosa. To our knowledge, it does not cause disease in healthy individuals with normal immunity, but can be pathogenic in those with impaired immune function or change in bacterial colonization site. Neisseria mucosa has been reported to cause bacterial meningitis, conjunctivitis, pneumonia, endocarditis, peritonitis and urethritis. However, peritoneal dialysis-related peritonitis caused by Neisseria mucosa is extremely rare in clinical practice, which has not previously been reported in China. CASE SUMMARY: A 55-year-old female presented to the nephrology clinic with upper abdominal pain without apparent cause, accompanied by nausea, vomiting and diarrhea for two days. The patient had a history of Stage 5 chronic kidney disease for five years, combined with renal hypertension and renal anemia, and was treated with peritoneal dialysis for renal replacement therapy. The patient was subsequently diagnosed with peritoneal dialysis-related peritonitis. Routine examination of peritoneal dialysis fluid showed abdominal infection, and the results of microbial culture of the peritoneal dialysis fluid confirmed Neisseria mucosa. Imi-penem/ cilastatin 1.0 g q12h was added to peritoneal dialysis fluid for anti-infection treatment. After 24 d, the patient underwent upper extremity arteriovenous fistulation. One month later, the patient was discharged home in a clinically stable state. CONCLUSION: Peritonitis caused by Neisseria mucosa is rare. Patients with home-based self-dialysis cannot guarantee good medical and health conditions, and require education on self-protection.

Mesoporous Polydopamine Loaded Pirfenidone Target to Fibroblast Activation Protein for Pulmonary Fibrosis Therapy.

Recently, fibroblast activation protein (FAP), an overexpressed transmembrane protein of activated fibroblast in pulmonary fibrosis, has been considered as the new target for diagnosing and treating pulmonary fibrosis. In this work, mesoporous polydopamine (MPDA), which is facile prepared and easily modified, is developed as a carrier to load antifibrosis drug pirfenidone (PFD) and linking FAP inhibitor (FAPI) to realize lesion-targeted drug delivery for pulmonary fibrosis therapy. We have found that PFD@MPDA-FAPI is well biocompatible and with good properties of antifibrosis, when ICG labels MPDA-FAPI, the accumulation of the nanodrug at the fibrosis lung in vivo can be observed by NIR imaging, and the antifibrosis properties of PFD@MPDA-FAPI in vivo were also better than those of pure PFD and PFD@MPDA; therefore, the easily produced and biocompatible nanodrug PFD@MPDA-FAPI developed in this study is promising for further clinical translations in pulmonary fibrosis antifibrosis therapy.

Echinacoside alleviates acetaminophen-induced liver injury by attenuating oxidative stress and inflammatory cytokines in mice.

This study evaluates the protective effect of Echinacoside on acute liver toxicity induced by acetaminophen in mice and the mechanism behind it. Echinacoside and N-Acetyl Cysteine were intragastrically administrated for 7 days, and acetaminophen was intraperitoneally injected into mice 1 h after the last treatment on day 7. At the end of the experimental period, histological examination, parameters for the level of oxidative damage, hepatic malondialdehyde, serum pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1ß), UDP-glucuronosyltransferases, and sulfotransferases changes were examined using enzyme-linked immunosorbent assay and standard biochemical procedures. The expression of cytochrome P450 2E1 protein was assessed by western blot, followed by in silico molecular docking. Acetaminophen treatment obviously increased the levels of ALT and AST, changed hepatic histopathology, promoted oxidative stress, decreased antioxidant enzyme activities, and elevated the pro-inflammatory cytokines. Echinacoside significantly attenuated Acetaminophen-induced liver damage in a dose-dependent manner, with the most effective dose at 100 mg/kg. The pretreatments of Echinacoside in different concentrations altered the Acetaminophen-induced hepatotoxicity levels by decreasing the level of liver enzymes, reducing the liver necrosis with vacuolization, decreasing the hepatic malondialdehyde formation, increasing hepatic antioxidants activities, suppressing the pro-inflammatory cytokines (Tumor Necrosis Factor, Interleukin-6 and Interleukin-1beta), inhibiting Nitric Oxide production, enhancing sulfotransferases and UDP-glucuronosyltransferases activities. Notably, the expression of cytochrome P450 2E1 was inhibited by Echinacoside in a dose-dependent manner and the binding energy was -214.3 MeV. Echinacoside showed a significant protective effect against Acetaminophen-induced hepatotoxicity through the inhibition of oxidative stress, the expression of pro-inflammatory cytokines and cytochrome P450 2E1 protein expression.

Radiomics analysis of [18F]FDG PET/CT for microvascular invasion and prognosis prediction in very-early- and early-stage hepatocellular carcinoma.

As a reliable preoperative predictor for microvascular invasion (MVI) and disease-free survival (DFS) is lacking, we developed a radiomics nomogram of [18F]FDG PET/CT to predict MVI status and DFS in patients with very-early- and early-stage (BCLC 0, BCLC A) hepatocellular carcinoma (HCC). METHODS: Patients (N = 80) with BCLC0-A HCC who underwent [18F]FDG PET/CT before surgery were enrolled in this retrospective study and were randomized to a training cohort and a validation cohort. Texture features from patients obtained using Lifex software in the training cohort were subjected to LASSO regression to select the most useful predictive features of MVI and DFS. Then, the radiomics nomogram was constructed using the radiomics signature and clinical features and further validated. RESULTS: To predict MVI, the [18F]FDG PET/CT radiomics signature consisted of five texture features from the PET and six texture features from CT. The signature was significantly associated with MVI status in the training cohort (P = 0.001). None of the clinical features was independent predictors for MVI status (P > 0.05). The area under the curve value of the M-PET/CT model was 0.891 (95% CI: 0.799-0.984) in the training cohort and showed good discrimination and calibration. To predict DFS, the [18F]FDG PET/CT radiomics nomogram (D-PET/CT model) and a clinicopathologic nomogram were built in the training cohort. The D-PET/CT model, which integrated the D-PET/CT radiomics signature with INR and TB, provided better predictive performance (C-index: 0.831, 95% CI: 0.761-0.900) and larger net benefits than the simple clinical model, as determined by decision curve analyses. CONCLUSION: The newly developed [18F]FDG PET/CT radiomics signature was an independent biomarker for the estimation of MVI and DFS in patients with very-early- and early-stage HCC. Moreover, PET/CT nomogram, which incorporated the radiomics signature of [18F]FDG PET/CT and clinical risk factors in patients with very-early- and early-stage HCC, performed better for individualized DFS estimation, which might enable a step forward in precise medicine.

Role of miRNA-671-5p in Mediating Wnt/ß-Catenin-Triggered Podocyte Injury.

Podocyte injury and proteinuria are the most common features of glomerular disease, which is the leading cause of end-stage renal failure. Hyperactivated Wnt/ß-catenin signaling is closely associated with podocyte injury, but the underlying mechanisms are incompletely understood. Here we show that miRNA-671-5p (miR-671-5p) plays a crucial role in mediating ß-catenin-triggered podocyte injury by targeting Wilms tumor 1 (WT1). Microarray-based expression profiling revealed that miR-671-5p was the most upregulated miRNA in podocytes after ß-catenin activation. MiR-671-5p was colocalized with ß-catenin in the glomeruli of proteinuric CKD in vivo. Bioinformatics analyses and luciferase reporter assays confirmed that miR-671-5p targeted WT1 mRNA. Overexpression of miR-671-5p mimics inhibited WT1 and impaired podocyte integrity, whereas miR-671-5p antagomir preserved the expression of WT1 and other podocyte-specific proteins under basal conditions or after ß-catenin activation. In mouse remnant kidney model, overexpression of miR-671-5p aggravated podocyte injury, worsened kidney dysfunction and exacerbated renal fibrosis after 5/6 nephrectomy. In contrast, miR-671-5p antagomir alleviated podocyte injury and attenuated proteinuria and renal fibrotic lesions after glomerular injury in vivo. These studies underscore a pivotal role of miR-671-5p in mediating WT1 depletion and podocyte injury induced by ß-catenin. Targeting miR-671-5p may serve as a new approach to prevent podocyte injury and proteinuria in proteinuric CKD.

Astragaloside IV Alleviates the Myocardial Damage Induced by Lipopolysaccharide via the Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB)/Proliferator-Activated Receptor α (PPARα) Signaling Pathway.

BACKGROUND We previously reported that astragaloside IV (As-IV) can alleviate myocardial damage induced by lipopolysaccharide (LPS). However, the anti-inflammatory effects of As-IV following LPS stimulation in mice and H9C2 cardiomyocytes remain unclear. The present study was designed to explore the mechanism of action of As-IV. MATERIAL AND METHODS In vivo, C57BL/6J mice were randomly divided into 5 groups: the control group, the LPS group (10 mg/kg), and 3 LPS groups receiving different doses of As-IV (20, 40, and 80 mg/kg). The protective effect of As-IV on LPS-stimulated H9C2 cardiomyocytes was evaluated in vitro. Cardiac function was detected by echocardiography, and H&E staining was used to evaluate morphologic changes. Cardiomyocyte viability was detected by MTT assay. ELISA was used to detect free fatty acid (FFA), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor alpha (TNF-alpha) levels in mouse serum and in cell supernatant. Adenosine triphosphate (ATP) and adenosine monophosphate (AMP) contents in myocardial tissues and cells were detected by high-performance liquid chromatography. ATP5D and TLR4/NF-kappaB/PPARalpha signaling pathway proteins (TLR4, NF-kappaB, p65, and PPARalpha) were detected by Western blotting. RESULTS As-IV significantly improved cardiac function, myocardial cell viability, and pathological changes and reduced FFA, IL-1ß, IL-6, and TNF-alpha levels. The ATP/AMP ratio in the cardiac tissues of mice and in H9C2 cardiomyocytes was increased compared to that in the LPS group. In addition, As-IV enhanced ATP synthase and PPARalpha protein expression. In H9C2 cardiomyocytes, the p65-specific inhibitor BAY11-7082 exerted similar effects as As-IV. CONCLUSIONS As-IV alleviates LPS-induced myocardial damage by modulating TLR4/NF-kappaB/PPARalpha signaling-mediated energy biosynthesis.