1.PDGF-C: an Emerging Target in The Treatment of Organ Fibrosis
Chao YANG ; Zi-Yi SONG ; Chang-Xin WANG ; Yuan-Yuan KUANG ; Yi-Jing CHENG ; Ke-Xin REN ; Xue LI ; Yan LIN
Progress in Biochemistry and Biophysics 2025;52(5):1059-1069
Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.
2.Effect of type of carrier material on the in vitro properties of solid dispersions of progesterone
Jing-nan QUAN ; Yi CHENG ; Jing-yu ZHOU ; Meng LI ; Zeng-ming WANG ; Nan LIU ; Zi-ming ZHAO ; Hui ZHANG ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2024;59(3):735-742
This study investigated the effect of different carrier materials on the
3.Analysis of recognition sites and application for commercial and homemade antibodies to aquaporin 9
Quan-Cheng CHENG ; Hui-Ru DING ; Zi-Yuan WANG ; Jin-Yu FANG ; Xiao-Li ZHANG ; Wei-Guang ZHANG
Acta Anatomica Sinica 2024;55(2):237-240
Objective To analyze the antigen recognition sites of commercial and homemade antibodies against aquaporin(AQP)9,and to identify the application effect.Methods Western blotting was used to compare the efficacy of three commercial antibodies and self-made antibody in identifying AQP9 genotypes.The antigen recognition sites of four antibodies and their specificities in practical applications were analyzed.Results Western blotting showed that protein bands of three commercial antibodies were detected in both WT and Aqp9-/-mice.The keyhole limpet hemocyanin(KLH)conjugated synthetic peptides corresponding to the three commercial antibodies were derived from rat,human and human,respectively.And The sequences of these three synthetic peptides were different from those of mice.AQP3/7 and AQP9 have similar molecular weight and were expressed in the liver with high homology.An obvious band of self-made antibody was observed at the 27 kD position in WT mice,but no band was observed at the corresponding position in Aqp9-/-mice.Conclusion Commercial antibodies 1 and 3 can be used to assist in the identification of genotypes in Aqp9-/-mice.Homemade antibodies can accurately identify genotypes at the protein level.
4.Study on the effect of different administration regimens of iprrazole enteric-coated tablets on inhibiting gastric acid secretion
Ting-Yuan PANG ; Zhi WANG ; Zi-Shu HU ; Zi-Han SHEN ; Yue-Qi WANG ; Ya-Qian CHEN ; Xue-Bing QIAN ; Jin-Ying LIANG ; Liang-Ying YI ; Jun-Long LI ; Zhi-Hui HAN ; Guo-Ping ZHONG ; Guo-Hua CHENG ; Hai-Tang HU
The Chinese Journal of Clinical Pharmacology 2024;40(1):92-96
Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH>3 after 20 mg qd and 10 mg bid were 82.64%and 61.92%,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.
5.Clinical trial of empagliflozin and linagliptin in the treatment of patients with type 2 diabetes mellitus with heart failure
Guang-Hui CHENG ; Xin-Jun LI ; Ying-Jie LI ; Hui WANG ; Dan-Dan CUI ; Hai-Yang ZHANG ; Zi-Jian WANG
The Chinese Journal of Clinical Pharmacology 2024;40(8):1131-1135
Objective To compare the efficacy and safety of empagliflozin and linagliptin in the treatment of patients with type 2 diabetes mellitus(T2DM)with heart failure(HF).Methods Patients with T2DM and HF were randomly into control group and treatment group.Both groups were treated with individualized anti-HF and metformin-based hypoglycemic therapy.On this basis,the control group was given linagliptin orally(5 mg each time,once a day),while the treatment group was given oral administration of empagliflozin 10 mg every day.Patients in both groups were treated continuously for 6 months.The clinical efficacy and blood glucose indicators[fasting blood glucose(FBG),2 h postprandial blood glucose(2 h PBG),hemoglobin A1c(HbA1c)],cardiac molecular markers[N-terminal pro-brain natriuretic peptide(NT-proBNP),fibroblast growth factor 23(FGF23),copeptin(CPP)]and caridac function indicators[left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),left ventricular remodeling index(LVRI)]before and after treatment were compared,and the adverse drug reactions were recorded.Results There were 40 cases in treatment group and 40 cases in control group.After treatment,the total effective rates in treatment group and control group were 97.50%(39 cases/40 cases)and 80.00%(32 cases/40 cases),with no significant difference(P<0.05).The FBG levels in treatment group and control group were(7.64±1.18)and(7.83±1.24)mmol·L-1;2 h PBG levels were(8.97±1.46)and(9.04±1.35)mmol·L-1;HbA1c levels were(7.58±1.27)%and(7.65±1.42)%,all with no significant difference(all P>0.05).The NT-proBNP levels in treatment group and control group were(612.53±204.62)and(1 045.24±316.75)pg·mL-1;FGF23 levels were(362.74±62.61)and(493.27±74.64)μg·L-1;CPP levels were(12.58±3.43)and(16.87±4.36)pmol·L-1;LVEDD values were(51.19±2.36)and(53.35±2.24)mm;LVEF values were(52.69±3.38)%and(50.28±3.75)%;LVRI values were(2.62±0.29)and(2.96±0.33)kg·L-1,all with significant difference(all P<0.05).The incidence rates of adverse reactions in treatment group and control group were 5.00%(2 cases/40 cases)and 10.00%(4 cases/40 cases),with no significant difference(P>0.05).Conclusion Both empagliflozin and linagliptin can effectively reduce the blood glucose in patients with T2DM complicated with HF.Empagliflozin can better promote the improvement of cardiac function in patients without significantly increase the incidence of adverse drug reactions.
6.Development and Application of Detection Methods for Capture and Transcription Elongation Rate of Bacterial Nascent RNA
Yuan-Yuan LI ; Yu-Ting WANG ; Zi-Chun WU ; Hao-Xuan LI ; Ming-Yue FEI ; Dong-Chang SUN ; O. Claudio GUALERZI ; Attilio FABBRETTI ; Anna Maria GIULIODORI ; Hong-Xia MA ; Cheng-Guang HE
Progress in Biochemistry and Biophysics 2024;51(9):2249-2260
ObjectiveDetection and quantification of RNA synthesis in cells is a widely used technique for monitoring cell viability, health, and metabolic rate.After exposure to environmental stimuli, both the internal reference gene and target gene would be degraded. As a result, it is imperative to consider the accurate capture of nascent RNA and the detection of transcriptional levels of RNA following environmental stimulation. This study aims to create a Click Chemistry method that utilizes its property to capture nascent RNA from total RNA that was stimulated by the environment. MethodsThe new RNA was labeled with 5-ethyluridine (5-EU) instead of uracil, and the azido-biotin medium ligand was connected to the magnetic sphere using a combination of “Click Chemistry” and magnetic bead screening. Then the new RNA was captured and the transcription rate of 16S rRNA was detected by fluorescence molecular beacon (M.B.) and quantitative reverse transcription PCR (qRT-PCR). ResultsThe bacterial nascent RNA captured by “Click Chemistry” screening can be used as a reverse transcription template to form cDNA. Combined with the fluorescent molecular beacon M.B.1, the synthesis rate of rRNA at 37℃ is 1.2 times higher than that at 15℃. The 16S rRNA gene and cspI gene can be detected by fluorescent quantitative PCR,it was found that the measured relative gene expression changes were significantly enhanced at 25℃ and 16℃ when analyzed with nascent RNA rather than total RNA, enabling accurate detection of RNA transcription rates. ConclusionCompared to other article reported experimental methods that utilize screening magnetic columns, the technical scheme employed in this study is more suitable for bacteria, and the operation steps are simple and easy to implement, making it an effective RNA capture method for researchers.
7.Improved YOLOv8 model-based object detection method for inspection robot
Bei-Chen YIN ; Zi-Jian WANG ; Zhi CHENG ; Xin-Xi XU
Chinese Medical Equipment Journal 2024;45(3):1-8
Objective To propose a object detection method based on an improved YOLOv8 model to solve the problems of the inspection robot in low accuracy for recognizing pointer-type or obscured meters.Methods Firstly,a YOLOv8 model was chosen as the foundation object detection model,based on which the coordinate attention(CA)mechanism was introduced to enhance the model's understanding of the spatial structure of the input data over long distances;secondly,the original complete IoU(CIoU)loss function was replaced by an efficient IoU(EIoU)loss function to accelerate the convergence of the model's detection frame;finally,the soft non-maximum suppression(Soft-NMS)function took the place of the traditional NMS method to suppress the redundant bounding box smoothly and further improve the detection accuracy.The improved YOLOv8 model(YOLOv8nxt model)was compared with the YOLOv8n model to verify its efficacy for object detection.Results The YOLOv8nxt model with a size of 6.2 M had the position loss decreased by 1.3%,mAP_0.5∶0.95 increased by 1.7%,detection accuracy raised by 0.87%and detection time prolonged by only 0.2 ms when comparted with the YOLOv8n model.Conclusion The improved YOLOv8 model-based object detection method enhances the accuracy and speed of the inspection robot's recognition of meters during movement,and can effectively solve the problems of the inspection robot in the object detection stage.[Chinese Medical Equipment Journal,2024,45(3):1-8]
8.Design,numerical simulation and experimental study of novel oxygenator
Ming-Hao YUE ; Shi-Yao ZHANG ; Ji-Nian LI ; Hui-Chao LIU ; Zi-Hua SU ; Ya-Wei WANG ; Zeng-Sheng CHEN ; Shi-Hang LIN ; Jin-Yu LI ; Ya-Ke CHENG ; Yong-Fei HU ; Cun-Ding JIA ; Ming-Zhou XU
Chinese Medical Equipment Journal 2024;45(3):23-28
Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]
9.Biomarkers Screening and Mechanisms Analysis of the Restraint Stress-Induced Myocardial Injury in Hyperlipidemia ApoE-/-Mice
Shang-Heng CHEN ; Sheng-Zhong DONG ; Zhi-Min WANG ; Guang-Hui HONG ; Xing YE ; Zi-Jie LIN ; Jun-Yi LIN ; Jie-Qing JIANG ; Shou-Yu WANG ; Han-Cheng LIN ; Yi-Wen SHEN
Journal of Forensic Medicine 2024;40(2):172-178
Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.
10.Research on the application of non-contact physiological and psychological detection in the analysis of long-term simulated weightlessness effects
Shuai DING ; Zi XU ; Qian RONG ; Shujuan LIU ; Zihao LIU ; Yuan WU ; Yao YU ; Zhili LI ; Cheng SONG ; Lina QU ; Hao WANG ; Yinghui LI
Space Medicine & Medical Engineering 2024;35(2):78-83,98
Objective Explore a non-contact physiological and psychological detection model based on facial video in simulations of weightlessness effects,research new methods for non-contact heart rate and negative mood state detection in long-term simulations of weightlessness effect analysis.Methods Construct a non-contact physiological and psychological data collection system for fusion analysis of visible light and thermal infrared videos.Collect physiological and psychological data of volunteers in the"Earth Star-Ⅱ"90-day head-down bed rest experiment.A non-contact heart rate detection model based on GCN facial multi-region feature fusion and a non-contact negative mood state detection model considering data reliability were constructed,and the effectiveness of the models were validated with finger clip heart rate and POMS-SF scale as labels.Results The experimental results show that the average difference in the Bland-Altman plot of the non-contact heart rate detection model is-1.26 bpm,and 96.3%of value error detection data falls within the 95%confidence interval,indicating a high consistency between the model detected heart rate and the finger clip heart rate.The non-contact negative mood state detection model achieves an accuracy of>0.85 for detecting tension,depression,anger,and fatigue.Features such as heart rate,AU06,eye gaze,and head pose were observed to be important to mood state detection.Conclusion Non-contact physiological and psychological detection methods not only can be utilized for long-term physiological analysis in simulations of weightlessness effects,but also provide a novel technical approach for on-orbit astronauts health assurance during long-term space flight in the future.

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