1.Molecular Mechanisms of RNA Modification Interactions and Their Roles in Cancer Diagnosis and Treatment
Jia-Wen FANG ; Chao ZHE ; Ling-Ting XU ; Lin-Hai LI ; Bin XIAO
Progress in Biochemistry and Biophysics 2025;52(9):2252-2266
RNA modifications constitute a crucial class of post-transcriptional chemical alterations that profoundly influence RNA stability and translational efficiency, thereby shaping cellular protein expression profiles. These diverse chemical marks are ubiquitously involved in key biological processes, including cell proliferation, differentiation, apoptosis, and metastatic potential, and they exert precise regulatory control over these functions. A major advance in the field is the recognition that RNA modifications do not act in isolation. Instead, they participate in complex, dynamic interactions—through synergistic enhancement, antagonism, competitive binding, and functional crosstalk—forming what is now termed the “RNA modification interactome” or “RNA modification interaction network.” The formation and functional operation of this interactome rely on a multilayered regulatory framework orchestrated by RNA-modifying enzymes—commonly referred to as “writers,” “erasers,” and “readers.” These enzymes exhibit hierarchical organization within signaling cascades, often functioning in upstream-downstream sequences and converging at critical regulatory nodes. Their integration is further mediated through shared regulatory elements or the assembly into multi-enzyme complexes. This intricate enzymatic network directly governs and shapes the interdependent relationships among various RNA modifications. This review systematically elucidates the molecular mechanisms underlying both direct and indirect interactions between RNA modifications. Building upon this foundation, we introduce novel quantitative assessment frameworks and predictive disease models designed to leverage these interaction patterns. Importantly, studies across multiple disease contexts have identified core downstream signaling axes driven by specific constellations of interacting RNA modifications. These findings not only deepen our understanding of how RNA modification crosstalk contributes to disease initiation and progression, but also highlight its translational potential. This potential is exemplified by the discovery of diagnostic biomarkers based on interaction signatures and the development of therapeutic strategies targeting pathogenic modification networks. Together, these insights provide a conceptual framework for understanding the dynamic and multidimensional regulatory roles of RNA modifications in cellular systems. In conclusion, the emerging concept of RNA modification crosstalk reveals the extraordinary complexity of post-transcriptional regulation and opens new research avenues. It offers critical insights into the central question of how RNA-modifying enzymes achieve substrate specificity—determining which nucleotides within specific RNA transcripts are selectively modified during defined developmental or pathological stages. Decoding these specificity determinants, shaped in large part by the modification interactome, is essential for fully understanding the biological and pathological significance of the epitranscriptome.
2.Rapid Screening of 34 Emerging Contaminants in Surface Water by UHPLC-Q-TOF-MS
Chen-Shan LÜ ; Yi-Xuan CAO ; Xiao-Xi MU ; Hai-Yan CUI ; Tao WANG ; Zhi-Wen WEI ; Ke-Ming YUN ; Meng HU
Journal of Forensic Medicine 2024;40(1):30-36
Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.
3.Effects of Astragaloside Ⅳ on High Glucose-Induced Pyroptosis and Invasive Migration of Human Chorionic Trophoblast Cells(HTR-8/SVneo)
Wen-Hui YE ; Hai-Xia XIAO ; Shuang-Ming CAI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):178-184
Objective To investigate the effect of astragaloside Ⅳ on high glucose-induced pyroptosis and invasive migration of human chorionic trophoblast cells(HTR-8/SVneo).Methods HTR-8/SVneo cells were divided into 4 groups:control group(untreated),high glucose group(high glucose stimulation)and astragaloside Ⅳ 50 and 100 μmol/L group(high glucose stimulation + astragaloside).Cell activity was detected by Cell Counting Kit 8(CCK-8),cell invasion and migration abilities were determined by Transwell assay and scratch assay,respectively,cell pyroptosis was assessed by Hoechst 33342/propidium iodide(PI)dual fluorescence staining.The protein expression levels of NOD-like receptor thermoprotein structural domain(NLRP3),cleaved-Caspase-1,GSDMD-NT,and IL-18 were detected by Western Blot.Results Compared with the control group,HTR-8/SVneo cell viability was significantly reduced in the high glucose group,the rate of cell migration was significantly reduced,the number of invasive cells was significantly reduced,the percentage of PI-positive cells was significantly increased,and the levels of NLRP3,cleaved-Caspase-1,GSDMD-NT and IL-18 protein expression levels were significantly increased(P<0.05 or P<0.01);compared with the high glucose group,cell viability was significantly higher in the astragaloside Ⅳ treated group,the rate of cell migration was significantly increased,the number of invasive cells was significantly increased,the percentage of PI-positive cells was significantly decreased,and the protein expressions of number of NLRP3,cleaved-Caspase-1,GSDMD-NT,IL-18 were significantly decreased(P<0.05 or P<0.01).Conclusion AstragalosideⅣcan inhibit high glucose-induced HTR-8/SVneo cell pyrolysis and improve cell invasion and migration ability.
4.Influence of Modified Shashen Maidong Decoction Combined with Camrelizumab Immunotherapy Plus Chemotherapy on the Efficacy,Survival Status,and Serum CYFRA21-1 and NSE Levels in Patients with Advanced Non-Small Cell Lung Cancer
Hai-Feng WANG ; Yi-Qun ZHAO ; Xiao-Li DU ; Lu LIU ; Bao-Song HOU ; Wen-Yan ZHAN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):606-611
Objective To investigate the influence of modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy on the efficacy,survival status and serum cytokeratin 19 fragment(CYFRA21-1)and neuron-specific enolase(NSE)levels in patients with advanced non-small cell lung cancer(NSCLC).Methods Forty patients with advanced NSCLC of lung-stomach yin deficiency with intense heat-toxin type were randomly divided into a control group and a study group,with 20 patients in each group.The patients in the control group were given Camrelizumab immunotherapy plus chemotherapy,and the patients in the study group were given modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy,with 21 days as a course of treatment and for a total of 4 courses of treatment.The changes of serum NSE and CYFRA21-1 levels in the two groups before and after treatment were observed,and the clinical efficacy,survival status and the incidence of toxic and side effects were compared between the two groups.Results(1)After 4 courses of treatment,the total effective rate of the study group was 70.00%(14/20),which was significantly higher than that of the control group(9/20,45.00%),but the intergroup comparison(tested by chi-square test)showed that the difference was not statistically significant(P>0.05).(2)After 2 years of follow-up,the overall survival(OS),time to progression(TTP),and progression-free survival(PFS)of the patients in the study group were significantly prolonged compared with those in the control group(P<0.01).(3)After treatment,the serum NSE and CYFRA21-1 levels of the patients in the two groups were decreased compared with those before treatment(P<0.05),and the decrease of serum NSE and CYFRA21-1 levels in the study group was significantly superior to that in the control group(P<0.01).(4)The incidence of toxic and side effects in the study group was 25.00%(5/20),which was significantly lower than that of 65.00%(13/20)in the control group,and the intergroup comparison showed that the difference was statistically significant(P<0.05).Conclusion Modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy has satisfactory therapeutic effect on patients with advanced NSCLC,which can reduce the toxic and side effects of chemotherapy,lower the level of serum tumor markers,and prolong the survival period and time to progression(TTP)of the patients.
5.Jianwei Xiaozhang Tablets Improves Precancerous Lesions of Gastric Cancer in Rats via Regulating PI3K-Akt-eNOS Pathway
Hai-Yang HUANG ; Shao-Wen ZHONG ; Yun AN ; Yu-Xin WANG ; Shu-Min ZHU ; Jie GAO ; Xiao-Min LU ; Ming-Guo DONG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):709-718
Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P<0.01),splenic coefficient and hepatic coefficient were significantly decreased(P<0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P<0.01),the serum GAS content was significantly increased(P<0.01),and the MTL,GC contents were significantly reduced(P<0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P<0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P<0.01),and the protein expression level of VEGFA was reduced(P<0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P<0.05 or P<0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.
6.Discussion of the methodology and implementation steps for assessing the causality of adverse event
Hong FANG ; Shuo-Peng JIA ; Hai-Xue WANG ; Xiao-Jing PEI ; Min LIU ; An-Qi YU ; Ling-Yun ZHOU ; Fang-Fang SHI ; Shu-Jie LU ; Shu-Hang WANG ; Yue YU ; Dan-Dan CUI ; Yu TANG ; Ning LI ; Ze-Huai WEN
The Chinese Journal of Clinical Pharmacology 2024;40(2):299-304
The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.
7.Cardamomine attenuates cardiotoxicity induced by anthracyclines in rats by regulating Notch/NF-κB signal pathway mediated pyroptosis
Xiao-Lei YU ; Wen-Xin LI ; Pan-Pan CHEN ; Yun-Fei LIANG ; Yan-Rong CUI ; Hai-Jing JIAO ; Fan XU
The Chinese Journal of Clinical Pharmacology 2024;40(9):1277-1281
Objective To investigate the protective effect of cardamomine(CAR)on anthracycline-induced cardiotoxicity in rats by regulating the pyroptosis mediated by Notch/nuclear factor-κB(NF-κB)signal pathway.Methods The rat model of cardiotoxicity was established by intraperitoneal injection of doxorubicin(DOX).The model rats were randomly divided into DOX group,CAR-L group,CAR-H group and Jagged1 group.Another 10 rats were taken as the control group.The control group and the DOX group were given the same amount of 0.9%NaCl.The CAR-L group and CAR-H group were given 40 and 80 mg·kg-1 CAR by gavage,respectively.The Jagged1 group was given 80 mg·kg-1 CAR+and 25 ng·kg-1 Jagged1 by gavage once a day for 4 weeks.Myocardial injury markers creatine kinase isoenzyme(CK-MB)and troponin Ⅰ(cTn Ⅰ)were detected by kit.The expression of pyroptosis protein Nod-like receptor protein 3(NLRP3)and desquamate D(GSDM-D)were observed by immunohistochemistry.The expression of Notch1 and phosphorylated NF-κB p65(p-NF-κB p65)protein in myocardial tissue was detected by Western blotting.Results The levels of CK-MB in control group,DOX group,CAR-L group,CAR-H group and Jagged1 group were(48.51±5.39),(175.93±13.27),(106.83±9.73),(83.71±8.39)and(126.08±9.74)U·L-1;the levels of cTn Ⅰ were(1.95±0.18),(12.46±1.83),(7.15±0.64),(4.13±0.38)and(8.01±0.78)ng·mL-1;the average optical density of NLRP3 protein were 0.19±0.07,0.36±0.05,0.25±0.05,0.21±0.03 and 0.31±0.06;the average optical density of GSDM-D were 0.18±0.04,0.43±0.06,0.24±0.03,0.19±0.04 and 0.32±0.05.There were significant differences in the above indexes between DOX group and control group(all P<0.05).There were significant differences in the above indexes between CAR-L group,CAR-H group and DOX group(all P<0.05),and there were significant differences between CAR-L group and CAR-H group(all P<0.05).The above indexes in Jagged1 group were significantly different from those in CAR-H group(all P<0.05).Conclusion CAR can improve myocardial injury in DOX cardiotoxic rats,reduce oxidative stress,inflammatory reaction and pyroptosis,and its mechanism may be related to the inhibition of Notch/NF-κB pathway.
8.Effect of hand hygiene intervention on healthcare-associated case infection incidence from 2014 to 2022
Jia-Yan DING ; Rui-Hong SHEN ; Wen-Qin ZHOU ; Ya-Yun YUAN ; Mei HUANG ; Ya YANG ; Bing-Chao CAI ; Hai-Qun BAN ; Xiao-Fang FU
Chinese Journal of Infection Control 2024;23(2):208-213
Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98%in 2014 to 85.01%in 2022(P<0.001),and HA case infection incidence decreased from 1.21%to 0.83%(P<0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P<0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P<0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.
9.Clinical Study on Therapy of Unblocking Bowels in the Treatment of Acute Pancreatitis of Pathogenic-Cold Accumulation and Retention Type
Jing-Jing XIAO ; Hai-Yi LI ; Pei-Shan WU ; Zheng ZHOU ; Guang-Wen HUANG ; Li-Qing YANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(9):2340-2346
Objective To observe the clinical efficacy of modified Dahuang Fuzi Decoction following the therapy of unblocking bowels for the treatment of acute pancreatitis of pathogenic-cold accumulation and retention type.Methods A total of 78 patients with acute pancreatitis of pathogenic-cold accumulation and retention type were randomly divided into a study group and a control group,39 cases in each group.The control group was treated with conventional western medicine,and the study group was treated with oral use or nasogastric feeding of Dahuang Fuzi Decoction on the basis of treatment for the control group.The course of treatment covered seven days.The two groups were observed in the changes of serum pancreatic enzyme indicators of serum amylase and lipase,inflammatory factors of C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6)and interleukin-8(IL-8),acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,and modified CT severity index(MCTSI)score before and after treatment.The time for abdominal pain relief,time for abdominal distension relief,and time for anal defecation were compared between the two groups.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,there was one patient falling off separately from the study group and the control group,and 38 patients in each group were eventually included in the efficacy statistics.(2)After seven days of treatment,the total effective rate of the study group was 86.84%(33/38),and that of the control group was 78.95%(30/38).The intergroup comparison(tested by rank sum test)showed that the efficacy of the study group was significantly superior to that of the control group(P<0.05).(3)After treatment,the serum levels of pancreatic enzyme indicators of amylase and lipase in the two groups were decreased compared with those before treatment(P<0.05),and the decrease of serum amylase and lipase levels in the study group was significantly superior to that in the control group(P<0.05).(4)After treatment,the serum levels of inflammatory factors of CRP,PCT,IL-6 and IL-8 in the two groups were decreased compared with those before treatment(P<0.05),and the decrease of serum CRP,PCT,IL-6 and IL-8 levels in the study group was significantly superior to that in the control group(P<0.05).(5)After treatment,the APACHE Ⅱ and MCTSI scores of the two groups were decreased compared with those before treatment(P<0.05),and the decrease of APACHE Ⅱ and MCTSI scores in the study group was significantly superior to that in the control group(P<0.05).(6)For the time of symptom relief,the time for abdominal pain relief,time for abdominal distension relief,and time for anal defecation in the study group were significantly shortened compared with those in the control group,and the differences were statistically significant(P<0.05).(7)No obvious adverse reactions occurred in the two groups during the treatment,indicating high safety.Conclusion On the basis of conventional treatment,the use of modified Dahuang Fuzi Decoction following the therapy of unblocking bowels exerts certain efficacy for the treatment of patients with acute pancreatitis of pathogenic-cold accumulation and retention type.The therapy is effective on relieving the symptoms and signs of patients,and decreasing the level of serum pancreatic enzyme indicators and inflammatory factors.
10.Effect of RNF113A on the malignant biological behavior of hepatocellular carcinoma cells
Hai-Jie DAI ; Xia HUANG ; Li-Jun DONG ; Ming-Xuan XING ; Teng-Yue ZOU ; Wen-Xiao LI
Chinese Journal of Current Advances in General Surgery 2024;27(4):275-281
Objective:To explore the effects of RNF113A on the proliferation,migration,in-vasion,apoptosis,and autophagy of hepatocellular carcinoma cells.Methods:Hep3B cells were divided into control group and RNF113A overexpression group(RNF113A-OE),HepG2 was divided into control group and RNF113A knockdown group(si-RNF113A),CCK-8 assay was used to detect changes in cell viability,clone formation assay was used to detect changes in cell proliferation abili-ty,Transwell assay was used to detect changes in cell invasion ability,wound healing assay was used to detect changes in cell migration ability,and flow cytometry was used to detect changes in cell apoptosis ability,Western blot experiments were used to detect changes in protein expression of autophagy related genes and AMPK signaling pathway related genes.Results:Compared with the control group,the proliferation,cloning,invasion,and migration abilities of Hep3B cells in the RNF113A-OE group were improved,while apoptosis and autophagy abilities were decreased,and the AMPK signaling pathway was inhibited;In the si-RNF113A group,the proliferation,cloning,in-vasion,and migration abilities of HepG2 cells were significantly reduced,while apoptosis and au-tophagy abilities were increased,and the activation of the AMPK signaling pathway was promoted.Conclusion:RNF113A promotes the proliferation,cloning,invasion,and migration of hepatocel-lular carcinoma cells,and inhibited apoptosis and autophagy by inhibiting the AMPK signaling path-way.

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