1.tRF Prospect: tRNA-derived Fragment Target Prediction Based on Neural Network Learning
Dai-Xi REN ; Jian-Yong YI ; Yong-Zhen MO ; Mei YANG ; Wei XIONG ; Zhao-Yang ZENG ; Lei SHI
Progress in Biochemistry and Biophysics 2025;52(9):2428-2438
ObjectiveTransfer RNA-derived fragments (tRFs) are a recently characterized and rapidly expanding class of small non-coding RNAs, typically ranging from 13 to 50 nucleotides in length. They are derived from mature or precursor tRNA molecules through specific cleavage events and have been implicated in a wide range of cellular processes. Increasing evidence indicates that tRFs play important regulatory roles in gene expression, primarily by interacting with target messenger RNAs (mRNAs) to induce transcript degradation, in a manner partially analogous to microRNAs (miRNAs). However, despite their emerging biological relevance and potential roles in disease mechanisms, there remains a significant lack of computational tools capable of systematically predicting the interaction landscape between tRFs and their target mRNAs. Existing databases often rely on limited interaction features and lack the flexibility to accommodate novel or user-defined tRF sequences. The primary goal of this study was to develop a machine learning based prediction algorithm that enables high-throughput, accurate identification of tRF:mRNA binding events, thereby facilitating the functional analysis of tRF regulatory networks. MethodsWe began by assembling a manually curated dataset of 38 687 experimentally verified tRF:mRNA interaction pairs and extracting seven biologically informed features for each pair: (1) AU content of the binding site, (2) site pairing status, (3) binding region location, (4) number of binding sites per mRNA, (5) length of the longest consecutive complementary stretch, (6) total binding region length, and (7) seed sequence complementarity. Using this dataset and feature set, we trained 4 distinct machine learning classifiers—logistic regression, random forest, decision tree, and a multilayer perceptron (MLP)—to compare their ability to discriminate true interactions from non-interactions. Each model’s performance was evaluated using overall accuracy, receiver operating characteristic (ROC) curves, and the corresponding area under the ROC curve (AUC). The MLP consistently achieved the highest AUC among the four, and was therefore selected as the backbone of our prediction framework, which we named tRF Prospect. For biological validation, we retrieved 3 high-throughput RNA-seq datasets from the gene expression omnibus (GEO) in which individual tRFs were overexpressed: AS-tDR-007333 (GSE184690), tRF-3004b (GSE197091), and tRF-20-S998LO9D (GSE208381). Differential expression analysis of each dataset identified genes downregulated upon tRF overexpression, which we designated as putative targets. We then compared the predictions generated by tRF Prospect against those from three established tools—tRFTar, tRForest, and tRFTarget—by quantifying the number of predicted targets for each tRF and assessing concordance with the experimentally derived gene sets. ResultsThe proposed algorithm achieved high predictive accuracy, with an AUC of 0.934. Functional validation was conducted using transcriptome-wide RNA-seq datasets from cells overexpressing specific tRFs, confirming the model’s ability to accurately predict biologically relevant downregulation of mRNA targets. When benchmarked against established tools such as tRFTar, tRForest, and tRFTarget, tRF Prospect consistently demonstrated superior performance, both in terms of predictive precision and sensitivity, as well as in identifying a higher number of true-positive interactions. Moreover, unlike static databases that are limited to precomputed results, tRF Prospect supports real-time prediction for any user-defined tRF sequence, enhancing its applicability in exploratory and hypothesis-driven research. ConclusionThis study introduces tRF Prospect as a powerful and flexible computational tool for investigating tRF:mRNA interactions. By leveraging the predictive strength of deep learning and incorporating a broad spectrum of interaction-relevant features, it addresses key limitations of existing platforms. Specifically, tRF Prospect: (1) expands the range of detectable tRF and target types; (2) improves prediction accuracy through multilayer perceptron model; and (3) allows for dynamic, user-driven analysis beyond database constraints. Although the current version emphasizes miRNA-like repression mechanisms and faces challenges in accurately capturing 5'UTR-associated binding events, it nonetheless provides a critical foundation for future studies aiming to unravel the complex roles of tRFs in gene regulation, cellular function, and disease pathogenesis.
2.Data Mining of Medication Rules for the Treatment of Atopic Dermatitis the Children by Chinese Medical Master XUAN Guo-Wei
Jin-Dian DONG ; Cheng-Cheng GE ; Yue PEI ; Shu-Qing XIONG ; Jia-Fen LIANG ; Qin LIU ; Xiu-Mei MO ; Hong-Yi LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):752-758
Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency>100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.
3.Circular RNAs Involved in The Development of Nasopharyngeal Carcinoma
Si-Cheng ZUO ; Dan WANG ; Yong-Zhen MO ; Yu-Hang LIU ; Jiao-Di CAI ; Can GUO ; Fang XIONG ; Guo-Qun CHEN
Progress in Biochemistry and Biophysics 2024;51(4):809-821
Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.
4.The Effects of Wenfei Huaxian Decoction (温肺化纤汤) on Pulmonary Fibrosis and Endoplasmic Reticulum Stress in Systemic Sclerosis-Associated Interstitial Lung Disease Model Mice
Mingliang QIU ; Jiali XIONG ; Chenxiao XIAO ; Xinzhu ZHOU ; Lisha MO ; Shiwen KE ; Guoshuang ZHU ; Liangji LIU
Journal of Traditional Chinese Medicine 2024;65(13):1383-1391
ObjectiveTo investigate the possible mechanism of Wenfei Huaxian Decoction (温肺化纤汤) in treatment of pulmonary fibrosis in systemic sclerosis-associated interstitial lung disease (SSc-ILD). MethodsSixty C3H/He female rats were randomly divided into a control group, a model group, a pirfenidone group, and low-, medium-, and high-dose Wenfei Huaxian Decoction groups. The SSc-ILD model mice was established by subcutaneous injection of bleomycin solution 0.04 mg/d into the back of mice for 28 days in all groups but the control group. After successful modelling, the pirfenidone group was given pirfenidone capsule 300 mg/(kg·d) by gavage, the low-, medium- and high-dose Wenfei Huaxian Decoction groups were given Wenfei Huaxian Decoction 7.81, 15.62, and 31.24 g/(kg·d) by gavage, respectively, and the control group as well as the model group were given normal saline 0.1 ml/10 g by gavage, for a total of 21 days. At the end of the intervention, HE staining and Masson staining were used to observe the pathological changes in the skin and lung tissues; the hydroxyproline content of the skin and lung tissues was detected; the protein expression levels of endoplasmic reticulum stress-related proteins glucose-regulated protein 78 (BIP) and C/EBP homologous protein (CHOP) as well as those of nuclear factor kappa B (NF-κB) pathway p65 were measured by western blot; ELISA was performed to determine the expression levels of interferon gamma (IFN-γ), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) in serum of rats. ResultsThe results of HE and Masson staining indicated that compared with the control group, the dermis significantly thickened, the number of collagen fibers significantly enlarged, and the number of inflammatory cells significantly increased in the model group; the lung tissue showed a marked inflammatory cellular response with massive collagen fibre proliferation with inflammatory cell infiltration. Compared with the model group, the skin tissue and lung tissue collagen fibre proliferation significantly reduced and inflammatory cell infiltration reduced in the pirfenidone group and all dose groups of Wenfei Huaxian Decoction, and the effects of pirfenidone group and Wenfei Huaxian Decoction medium- and high-dose groups were basically comparable. Compared with the model group, the content of hydroxyproline in skin and lung tissue, the serum level of IFN-γ, IL-6 and TNF-α, and the expression levels of BIP and CHOP protein in lung tissue increased in model group (P<0.05). Compared with model group, the content of hydroxyproline in skin tissue of pirfenidone group, low-and medium-dose Wenfei Huaxian Decoction groups decreased, and the content of hydroxyproline in lung tissue of medium-dose Wenfei Huaxian Decoction group decreased. The serum level of IFN-γ, IL-6, TNF-α and the expression levels of BIP, CHOP and p65 protein in lung tissue of rats in pirfenidone group and high-dose Wenfei Huaxian Decoction group decreased (P<0.05). The content of hydroxyproline in lung tissue of medium-dose Wenfei Huaxian Decoction group was significantly lower than that of low-dose and high-dose Wenfei Huaxian Decoction group, and the serum level of IFN-γ, IL-6, TNF-α in low- and medium-dose Wenfei Huaxian Decoction group were higher than those in high-dose Wenfei Huaxian Decoction group. The expression level of BIP protein in high-dose group was significantly lower than that in low- and medium-dose Wenfei Huaxian Decoction groups (P<0.05). ConclusionWenfei Huaxian Decoction can improve the skin and lung fibrosis of SSc-ILD rats, which may act through anti-inflammation, inhibition of NF-κB pathway, and then inhibition of endoplasmic reticulum stress, which ultimately blocked the fibrotic process.
5.Review on signal detection and processing of human crawling
Jieyi MO ; Yuan LIU ; Jinliang WAN ; Ying CHEN ; Qiliang XIONG
Chinese Journal of Medical Physics 2024;41(6):754-760
Crawling is a significant sign of gross motor development in infants,and also an important means of rehabilitation training for patients with motor disorders.The accurate measurement of the motion state during human crawling is essential for evaluating the gross motor developmental process in infants and the rehabilitation outcome of patients with motor disorders.In recent years,many studies have attempted to quantitatively evaluate the motion state by detecting physiological signals during human crawling,but there is a lack of overview on human crawling motion signal acquisition and processing.Herein the detection and processing methods for motion signals during human crawling and relevant researches are reviewed.The mainstream methods for detecting motion signals during human crawling are introduced from the perspectives of inertial sensors,pressure sensors,and surface electromyography.Then,the signal processing and analysis such as periodic segmentation,kinematic analysis,and dynamic analysis in human crawling are summarized.Based on the theory of motion coordination,the research advances in joint synergy and muscle synergy during human crawling are elaborated.Finally,the current problems and future development directions of motion analysis for human crawling are discussed.
6.Effect of TET2 inhibitor itaconate on proliferation and migration of breast cancer cells
Junjie ZENG ; Zhongxun XIONG ; Shaojiang MO ; Hui ZHANG
Chongqing Medicine 2024;53(17):2566-2570
Objective To investigate the effects and mechanism of TET2 inhibitor itaconate in prolifer-ation and migration of breast cancer cell line MDA-MB-231.Methods The MDA-MB-231 cells were treated for 24 h with dimethyl sulfoxide(DMSO)and 1,5 μmol/L itaconate respectively.The cellular apoptosis was determined by flow cytometry to determine the available itaconic acid concentration.The immunofluorescence was performed to determine the inhibiting effect of itaconate on hydroxymethylcytosine(5hmC)expression level.The cell counting and MTS were performed to determine the effect of itaconate on cell proliferation and activity.The Transwell experiment was performed to determine the effect of itaconate on cell transfer ability.The methylation-specific real-time fluorescence quantitative PCR(qPCR)was used to detect the effects of ita-conic acid treatment on the methylation of promoter regions of genes related to cell proliferation and migra-tion.qPCR was used to detect the effects of itaconate on the cellular proliferation,migration related genes ex-pression.Results 5 μmol/L itaconate treating the cells had no significant effect on the cellular apoptosis,mo-reover could inhibit 5hmC expression level.The cell count and MTS results showed that itaconate could pro-mote the cell proliferation(increase by about 58%,P<0.05)and increase the cell activity(increase by 42%,P<0.05).The Transwell experiment results showed that itaconate increased the cell migration(increase by 55%,P<0.05).The methylation-specific qPCR showed that the itaconate treatment significantly promoted the methyaltion of the promoters p21 and PTEN.The qPCR results showed that itaconate significantly inhibi-ted the expression levels of p21 and PTEN(P<0.05).Conclusion Itaconate promotes the proliferation and migration of MDA-MB-231 cells through inhibiting 5hmC level of p21 and PTEN and decrease its expression.
7.Research of the therapeutic effect of Zhuangjin Yangxue decoction on osteochondral lesion of the talus
Yanghua TANG ; Liping SHI ; Zhuosong MU ; Yafeng MO ; Zhenfei XIONG
China Modern Doctor 2024;62(22):92-95
Objective To investigate the clinical efficacy of Zhuangjin Yangxue decoction on Hepple stage Ⅰ and Ⅱ of osteochondral lesion of the talus(OLT).Methods From February 2021 to December 2022,a total of 62 cases of OLT were seleted from the Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine.According to random number table method,the patients were divided into observation group and control group,with 31 cases in each group.The control group was treated with Western medicine,and the observation group received an additional treatment of Zhuangjin Yangxue decoction alongside with Western medicine.Serum matrix metalloproteinase 13(MMP-13),tumor necrosis factor-α(TNF-α),ankle visual analogue scale(VAS)score,American Orthopedic Foot and Ankle Society(AOFAS)ankle-hind foot function score,TCM syndrome score and magnetic resonance observation of cartilage repair tissue(MOCART)score before and after treatment were compared between two groups.Results After 5 weeks and 3 months of treatment,MMP-13,TNF-α,VAS score and TCM syndrome score in two groups were significantly lower than before treatment,and AOFAS ankle-hind foot function score and MOCART score were significantly higher than before treatment(P<0.05).MMP-13,TNF-α and TCM syndrome scores in observation group were significantly lower than those in control group,and MOCART score was significantly higher than that in control group(P<0.05).After 5 weeks of treatment,VAS score of observation group was significantly lower than that of control group,and AOFAS ankle-hind foot function score was significantly higher than that of control group(P<0.05).Conclusion Zhuangjin Yangxue decoction shows a good short-term efficacy in treating Hepple stage Ⅰ and Ⅱ of OLT,with anti-inflammatory and analgesic effects,improved joint function,and promotion of cartilage repair.
8.Construction and Evaluation of Animal Model with Spleen Deficiency and Dampness Stagnation Syndrome Combining Atopic Dermatitis
Tingjing ZHONG ; Qin LIU ; Xiong LI ; Junfeng LIU ; Xiumei MO ; Dacan CHEN ; Fenggen YAN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):862-869
Objective To establish a mouse model of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis(AD)and explore the feasibility of modeling by comparing 2,4-dinitrochlorobenzene(DNCB)-induced atopic dermatitis model of mouse,"external dampness+improper diet+irrigation of senna"-induced spleen deficiency and dampness stagnation syndrome model of mouse,as well as both in combination of model mouse.Methods The construction of a mouse(Balb/c)with spleen deficiency and dampness stagnation syndrome was explored by using the method of"external dampness+improper diet+irrigation of senna",and then DNCB was applied to induce the AD-like lesions in Balb/c mice to establish a mouse model of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis.The general condition and body weight of mice in each group were observed,and the symptoms of spleen deficiency and dampness were scored.The severity of AD was evaluated by comparing the skin lesion degree,EASI score,transcutaneous water loss value(TEWL),spleen index and thymus index.The levels of creatinine,glucose,total cholesterol,triglyceride,gastrin,and amylase were measured.Results(1)During the modeling period of spleen deficiency and dampness stagnation syndrome,compared with the normal group,spleen deficiency and dampness stagnation syndrome group,spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group showed obesity,listlessness,filthy and greasy hair,diarrhea,and poor cleanliness around the anal.After combining with the application of the atopic dermatitis model,the body weight of the mice in atopic dermatitis group(P<0.001),spleen deficiency and dampness stagnation syndrome group(P<0.05)and spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group(P<0.001)decreased sharply compared with the normal group.(2)Compared with the atopic dermatitis group,the degree of skin lesions,EASI score(P<0.05)and TEWL(P>0.05)were higher in the spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group.(3)Compared with the normal group,the spleen index of the atopic dermatitis group increased(P<0.001)and the thymus index decreased(P<0.001).Compared with the atopic dermatitis group,the spleen index(P>0.05)and thymus index(P<0.05)of the spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group decreased.(4)The results of serum biochemical indexes showed that compared with the normal group,the levels of creatinine(P<0.01),glucose(P<0.001),total cholesterol(P>0.05),triglyceride(P>0.05)and gastrin(P<0.001)in the spleen deficiency and dampness stagnation syndrome group were increased,and the level of amylase was decreased(P<0.01).Compared with the atopic dermatitis group,the levels of creatinine(P>0.05),glucose(P<0.05),total cholesterol(P>0.05),triglyceride(P>0.05),gastrin(P<0.001)increased and the level of amylase decreased(P>0.05).Conclusion A mouse model of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis,which was induced by the combination of DNCB and"external dampness+improper diet+irrigation of senna",can not only show obvious TCM indications of spleen deficiency and dampness syndrome,but also show the characteristics of AD.This model can be used as a reliable animal model of combination of disease and syndrome.It provides reference for further study on pathological mechanism,pharmacodynamic evaluation and pharmacological mechanism of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis.
9.Chrysin attenuates hepatic steatosis and blood lipid dysregulation in a mouse model of nonalcoholic steatohepatitis
Xingxing WANG ; Mo LI ; Chuanyue GAO ; Bocheng XIONG ; Xiufen ZHANG ; Xiaomei LI ; Xifei YANG
Chinese Journal of Pathophysiology 2024;40(5):899-907
AIM:To investigate the therapeutic effects of chrysin on nonalcoholic steatohepatitis(NASH).METHODS:Eight-week-old male C57BL/6 mice were randomly divided into control group,model group,and chrysin group.The mice in control group were fed with normal diet,and those in model and chrysin groups were fed with methio-nine-and choline-deficient(MCD)diet.After 5 weeks of adaptation,the mice in chrysin group received chrysin treatment(20 mg/kg)by continuous lavage for 6 weeks,while those in control and model groups were given equal volume of saline.During the experiment,the health condition of the mice was monitored.Liver morphology was examined after the mice were sacrificed.Serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-den-sity lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured using a biochemical analyzer.Liver tissue TG and TC levels were measured using assay kits.Liver cell damage and inflammation were assessed by hematoxylin-eosin(HE)staining and F4/80 immunohistochemistry staining.The ex-tent of liver lipid deposition was explored by oil red O staining.Masson staining and Sirius red staining were performed to assess liver fibrosis.Immunohistochemistry was performed to analyze the expression of fibrosis-related molecules.RE-SULTS:Compared with control group,the mice in model group showed significant decrease in body weight,liver wet weight,and liver volume.Serum TG,LDL-C,ALT and AST levels,as well as liver TG and TC levels were significantly elevated,and HDL-C levels were decreased in model group.Pathological staining showed significant inflammatory cell in-filtration,lipid deposition,and liver fibrosis.After the treatment with chrysin,increased body weight and liver weight,a reddish appearance of the liver,relatively smooth surface,and sharp liver edges were observed.Serum TG,LDL-C,AST and ALT levels,and liver TG levels were significantly reduced by chrysin.Inflammatory cell infiltration,lipid deposition,and liver tissue fibrosis were also significantly attenuated by chrysin.CONCLUSION:Chrysin shows a potential as a can-didate drug for the treatment of NASH by inhibiting hepatic steatosis,inflammation,and liver fibrosis.
10.Research progress on the role of leonurine in inflammation-related diseases
Jia-Wei XIONG ; Rui-Qi MA ; Hua-Peng YU ; Lin MOU ; Xiao-Fen MO
Fudan University Journal of Medical Sciences 2024;51(4):614-619
Leonurine(SCM-198)was discovered as one of the active constituents of the Herba Leonuri(HL).Now it can be artificially synthesized.Several recent researches has proven that it exhibits anti-inflammatory effect in several systems in animal models and cell culture in vitro.The key mechanism involves downgrading the activity of nuclear transcription factor-κB(NF-κB),thereby inhibiting the phosphorylation of several signal pathways such as PI3K/Akt,MAPK,ERK,and JNK,or upregulating the activity of Nrf2 related pathways,resulting in downregulated expression of inflammatory cytokines such as tumor necrosis factor-α(TNF-α),IL-1β,IL-2,IL-6,IL-8,inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),chemokines,adhesion molecules,etc.Owing to the advantages of high safety and efficiency,the ease of administration,as well as its effectiveness in many organs and systems,leonurine has a widely prospect for future research and clinical applications.This article reviews the progress in the fundamental research of leonurine in multiple inflammation-related disease,and it could be expect to offer new possibilities for the treatment of these disease.

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