1.ATPR alleviates lipopolysaccharide-induced acute liver injury in mice by promoting autophagy
Chuanlin SHU ; Xiaorui SHI ; Rumeng ZHU ; Qing ZHOU ; Yuan WANG ; Yi WANG ; Huaqing ZHU
Acta Universitatis Medicinalis Anhui 2024;59(2):200-206
Objective To investigate the effect of4-amino-2-trifluoromethyl-phenyl retinate(ATPR)on acute liver injury induced by lipopolysaccharide(LPS)in C57BL/6 mice and its related mechanism.Methods Fifteen 6-week-old male C57BL/6 strain mice were randomly divided into normal group,model group and ATPR group,with 5 mice in each group.Mice in the ATPR group were intraperitoneally injected with ATPR(15 mg/kg·d),and normal group and model group were given solvent.After continuous administration for one week,model group and ATPR group were intraperitoneally injected with LPS(6 mg/kg),and all mice were sacrificed 6 hours later.The contents of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in serum of mice were detec-ted.The mRNA levels of Interleukin-6(IL-6)and Tumor necrosis factor-alpha(TNF-α)were detected by qPCR.Hematoxylin-eosin(H&E)staining was used to observe the histopathological changes of liver in mice.The ultra-structural changes of mouse hepatocytes were observed by Transmission electron microscope(TEM).The expres-sion levels of mitochondrial damage-related proteins FUNDC1 and OPA1 and autophagy related proteins LC3B,P62,Beclin1 and ATG5 were detected by Western blot.Results Compared with the normal group,the content of ALT and AST in serum and the mRNA levels of IL-6 and TNF-α in liver tissue increased in the model group,and the changes were reversed in the ATPR group.H&E staining showed that the hepatic lobule structure was normal in the normal group,the hepatic cords were arranged radially,there was no hyperemia and inflammatory cell infiltra-tion,and the hepatocyte boundary was clear.In the model group,the intercellular space of liver was enlarged,the arrangement of hepatic cords was disordered,and inflammatory cells infiltrated.In the ATPR group,the intercellu-lar space of liver and the structure of hepatic cords were restored,and the inflammatory cell infiltration was less.TEM showed that the damaged mitochondria and lipid droplet accumulation in the hepatocytes of mice in the model group were compared with that in the normal group,and the morphology and quantity of mitochondria and lipid droplet in the hepatocytes of mice in the ATPR group tended to be normal.Western blot showed that compared with the normal group,the expression of FUNDC1 protein in the liver tissues of mice in the model group increased,the expression of OPA1 protein decreased,the ratio of LC3B Ⅱ to LC3B Ⅰ decreased,the expression of P62 protein in-creased,the expression of Beclin1 and ATG5 protein decreased,and the above changes were reversed in the ATPR group.Conclusion ATPR alleviates acute liver injury induced by lipopolysaccharide in mice by promoting autoph-agy.
2.Gain deeper insights into traditional Chinese medicines using multidimensional chromatography combined with chemometric approaches.
Xinyue YANG ; Pingping ZENG ; Jin WEN ; Chuanlin WANG ; Liangyuan YAO ; Min HE
Chinese Herbal Medicines 2024;16(1):27-41
Traditional Chinese medicines (TCMs) possess a rich historical background, unique theoretical framework, remarkable therapeutic efficacy, and abundant resources. However, the modernization and internationalization of TCMs have faced significant obstacles due to their diverse ingredients and unknown mechanisms. To gain deeper insights into the phytochemicals and ensure the quality control of TCMs, there is an urgent need to enhance analytical techniques. Currently, two-dimensional (2D) chromatography, which incorporates two independent separation mechanisms, demonstrates superior separation capabilities compared to the traditional one-dimensional (1D) separation system when analyzing TCMs samples. Over the past decade, new techniques have been continuously developed to gain actionable insights from complex samples. This review presents the recent advancements in the application of multidimensional chromatography for the quality evaluation of TCMs, encompassing 2D-gas chromatography (GC), 2D-liquid chromatography (LC), as well as emerging three-dimensional (3D)-GC, 3D-LC, and their associated data-processing approaches. These studies highlight the promising potential of multidimensional chromatographic separation for future phytochemical analysis. Nevertheless, the increased separation capability has resulted in higher-order data sets and greater demands for data-processing tools. Considering that multidimensional chromatography is still a relatively nascent research field, further hardware enhancements and the implementation of chemometric methods are necessary to foster its robust development.
3.Changes in the total volume and contour density of oval cells in hepatic lobules of rats with carbon tetrachloride-induced hepatic fibrosis: A stereological study
Chuanlin WANG ; Quanming LIU ; Xia YANG ; Zhengwei YANG ; Xiaoping MEI ; Bin PENG
Journal of Clinical Hepatology 2024;40(1):70-75
ObjectiveTo quantitatively investigate the changes in the total volume and contour density of hepatic oval cells (HOC) in hepatic lobules of rats with carbon tetrachloride (CCl4)-induced hepatic fibrosis. MethodsA total of 11 healthy male Sprague-Dawley rats were randomly divided into control group with 5 rats and hepatic fibrosis group with 6 rats, and CCl4 and olive oil suspension were injected subcutaneously twice a week, 3 mL/kg each time. After five weeks of hepatic fibrosis modeling, five liver tissue blocks with a size of about 1 mm3 were randomly selected from the liver of each rat to prepare one Epon812 epoxy resin-embedded ultrathin section, and the stereological method and transmission electron microscopy were used for the quantitative analysis of the total volume and contour density of HOC in the hepatic lobules of rats. In addition, four liver tissue blocks with a thickness of 2 mm were randomly selected from the remaining liver of each rat to prepare two paraffin-embedded Masson staining sections, and the degree of liver fibrosis in each rat was qualitatively evaluated according to the Metavir staging criteria for liver fibrosis. The independent-samples t test was used for comparison of continuous data between groups. ResultsThe quantitative stereological analysis showed that the total volume of HOC in hepatic lobules was 15.40±7.63 mm3 in the control group and 146.80±114.00 mm3 in the liver fibrosis group, and compared with the control group, the total volume of HOC in hepatic lobules of rats in the liver fibrosis group was significantly increased by 8.53 times (t=-2.551, P=0.031); the contour density of HOC in hepatic lobules was 56.20±40.40 in the control group and 566.50±317.00 in the liver fibrosis group, and compared with the control group, the contour density of HOC in hepatic lobules of rats in the liver fibrosis group was significantly increased by 9.08 times (t=-3.539, P=0.006). Qualitative observation showed that liver fibrosis stage of rats reached stage Ⅱ-Ⅲ according to the Metavir scoring criteria, and massive proliferation of HOC was observed around the proliferation site of hepatic stellate cells in the perisinusoidal space of rats. ConclusionCCl4 induces significant proliferation of HOC in hepatic lobules of rats with liver fibrosis.
4.Interpretation of the key points of Regulation for Diagnosis and Treatment of Non-neonatal Tetanus (2024 Edition)
Si LIU ; Cheng LIU ; Jiayang LIU ; Qingjun CHEN ; Xin KANG ; Pin LAN ; Qiaosheng XUE ; Zhenggang ZHU ; Xinjun LYU ; Wenwu YIN ; Chuanlin WANG
Chinese Journal of Epidemiology 2024;45(11):1468-1476
Non-neonatal tetanus is an acute, specific, toxic disease in patients over 28 days of age, characterized by continuous rigidity and paroxysmal spasms of the skeletal muscles throughout the body caused by the intrusion of Clostridium tetani through skin or mucosal membrane into the body and reproducing in anaerobic environments to produce exotoxins. The mortality rate of severe patients is close to 100% without medical intervention. Even with aggressive comprehensive treatment, the global mortality rate remains at 30%-50%, making it a potentially fatal disease. In order to standardize the diagnosis, treatment and prevention of non-neonatal tetanus, based on "Regulation for Diagnosis and Treatment of Non-neonatal Tetanus (2019 Edition)", experts have revised this regulation according to clinical practice and recent research progress in this field to guide medical institutions in the prevention and control of non-neonatal tetanus. This article interprets the key points and basis for updating the 2024 edition regulation to guide clinical implementation and application.
5.The prospect of eliminating human rabies in China
Chinese Journal of Experimental and Clinical Virology 2024;38(4):369-372
Since 2007, the annual incidence of human rabies in China has been continuously decreasing, and China has entered the critical stage of eliminating human rabies. China will prioritize the control of rabies among dogs as the primary task for human rabies prevention and control, and implement surveillance and containment strategies, while also focusing on improving the standardization of post-exposure prophylaxis (PEP) for rabies. The sufficient production capacity of rabies immune preparations in China provides good biological product guarantee conditions for rabies prevention and control. However, dog management issues are prominent in China, not only affecting canine immunization, but also leading to a high number of canine injuries, resulting in huge costs for human rabies PEP. China lags behind in developing cheaper and more efficient rabies vaccines, which can help more rabies-exposed individuals obtain PEP. There are no insurmountable technical barriers in rabies prevention and control in China, and the prospect of achieving the elimination of human rabies by 2030 in China is promising.
6.Relationship between GTSE1 and Cell Cycle and Potential Regulatory Mechanisms in Lung Cancer Cells
WANG CHUANLIN ; XU JIALI ; LIU MINGZHU ; LIU JIAYU ; HUANG YUNCHAO ; ZHOU LAN
Chinese Journal of Lung Cancer 2024;27(6):451-458
The regulation of the cell cycle is essential for maintaining normal cellular function,especially in the development of diseases such as lung cancer.The cell cycle consists of four major phases(G1,S,G2 and M phases),which are characterized by a series of precise molecular events to ensure proper cell proliferation and division.In lung cancer cells,cell cycle dysregulation can lead to disordered proliferation and increased invasiveness of cancer cells.G2 and S-phase expressed 1(GTSE1)is a regulatory protein found in the cytoplasm of the cell,which plays a key role in the cell cycle distribution of a wide range of cancer cells and is involved in life processes such as cell proliferation and apoptosis.GTSE1 affects cell cycle progres-sion by interacting with cyclin-dependent kinase inhibitor 1A(p21)and maintaining the stability of p21,which in turn inhibits the activity of cyclin-dependent kinase 1/2(CDK1/2).In addition,GTSE1 is also involved in the regulation of tumor protein 53(p53)signaling pathway.With the assistance of mouse double minute 2 homolog(MDM2),GTSE1 is able to transport p53 from the nucleus to the cytoplasm and promote its ubiquitination and degradation,thus affecting cell cycle and cell death-related signaling pathways.This paper reviews the expression of GTSE1 in lung cancer cells and its effects on lung cancer,as well as its potential mechanisms involved in cell cycle regulation.
7.Preparation and performance evaluation on chitosan/gelatin hydrogel hemostatic material containing Panax notoginseng
Haining ZHI ; Rongjiang SHAO ; Wei GUO ; Chuanlin WANG ; Ming LI
International Journal of Biomedical Engineering 2023;46(1):48-54
Objective:To prepare chitosan/gelatin hydrogel composite hemostatic materials loaded with Panax notoginseng (PN/CMC/GMs) and evaluate their performance. Methods:PN/CMC/GMs hydrogel composite hemostatic material were prepared by the freeze-drying method, and their morphology was observed by scanning electron microscopy. Their rheological properties were observed by a rheometer. Their water absorption rate was tested by dissolution. Their biocompatibility was detected by a cytotoxicity assay. Their rapid hemostatic effect was tested using a SD rat liver hemorrhage model.Results:PN/CMC/GMs composite hemostatic materials were prepared in a lattice-like structure with certain porosity. With the increase in Panax notoginseng powder content, the modulus of PN/CMC/GMs increased accordingly, and the mechanical strength increased. PN/CMC/GMs have better water absorption and expansion functions, which can form compression hemostasis and concentrated blood to achieve rapid hemostasis, and have good biocompatibility. Hemostasis experiments showed that the hemostatic time and hemostatic effect of PN, CMC/GMs hemostatic materials on liver injury in rats were better than those of the blank control group. Conclusions:PN/CMC/GMs have good hemostatic effect and biocompatibility and have the potential for further research and clinical application.
8.Role of HSF1 in endogenous protective mechanism underlying mechanical ventilator-induced lung injury in mice: relationship with HMGB1
Xinggui XU ; Chuanlin MU ; Lili SUN ; Xia BI ; Lixin SUN ; Mingshan WANG ; Fuguo MA ; Wei HAN
Chinese Journal of Anesthesiology 2023;43(2):210-215
Objective:To evaluate the role of heat shock transcription factor 1 (HSF1) in the endogenous protective mechanism underlying mechanical ventilator-induced lung injury (VILI) in mice and the relationship with high mobility group box 1 (HMGB1).Methods:Forty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) by the random number table method: control group (group C), VILI group (group VILI), negative control siRNA + VILI group (group NV) and HSF1 siRNA + VILI group (group siRNA). At 48 h before mechanical ventilation, negative control siRNA 5 nmol and HSF1 siRNA 5 nmol were intratracheally injected in NV and siRNA groups respectively, and the solution was diluted to 50 μl with the sterile phosphate buffer in both groups. Group C kept spontaneous breathing for 4 h, and the rest animals were mechanically ventilated (tidal volume 35 ml/kg, respiratory rate 75 breaths/min, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 21%) for 4 h. Blood samples from the femoral artery were collected for arterial blood gas analysis immediately after endotracheal intubation and at 4 h of ventilation, and PaO 2 was recorded. Then the mice were sacrificed under deep anesthesia to collect lung tissues and bronchoalveolar lavage fluid (BALF). The concentrations of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and HMGB1 in BALF were determined by enzyme-linked immunosorbent assay. The pathological results were observed by hematoxylin-eosin staining, and lung injury was assessed and scored. The wet/dry (W/D) weight ratio of lung tissues was calculated. The expression of HMGB1 and HSF1 mRNA in lung tissues (by quantitative real-time polymerase chain reaction) and expression of HMGB1 and HSF1 protein in lung tissues (by Western blot) were determined. Results:Compared with group C, PaO 2 was significantly decreased at 4 h of ventilation, the concentrations of TNF-α, IL-1β and HMGB1 in BALF, W/D ratio and lung injury score were increased, and the expression of HMGB1 protein and mRNA in lung tissues was up-regulated in group VILI, group NV and group siRNA ( P<0.05 or 0.01). Compared with group VILI and group NV, PaO 2 was significantly decreased at 4 h of ventilation, the concentrations of TNF-α, IL-1β and HMGB1 in BALF, W/D ratio and lung injury score were increased, and the expression of HMGB1 protein and mRNA in lung tissues was up-regulated, and the expression of HSF1 protein and mRNA was down-regulated in group siRNA ( P<0.05 or 0.01). There was no significant difference in the parameters mentioned above between group VILI and group NV ( P>0.05). Conclusions:HSF1 is involved in the endogenous protective mechanism underlying VILI in mice, which may be related to the down-regulation of HMGB1 expression and attenuation of inflammatory responses in lung tissues.
9.ATRA alleviates lipopolysaccharide -induced acute myocardial injury in mice by inhibiting Ferroptosis
Zhangyong Dan ; Chuanlin Shu ; Xiaorui Shi ; Qing Zhou ; Yuan Wang ; Mengfei Ren ; Yi3 Wang ; Huaqing Zhu
Acta Universitatis Medicinalis Anhui 2023;58(3):373-378
Objective :
To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on lipopolysaccharide (LPS) -induced acute myocardial injury in C57BL/6 mice.
Methods :
Male mice of C57BL/6 strain were randomly divided into normal group,model group,ATRA group,and ferrostatin-1 group.Mice in the ATRA group were injected intraperitoneally with ATRA 15mg / (kg · d) ,ferrostatin-1 group received ferrostatin-1 2 mg / ( kg · d) ,the normal group and the model group were given solvent.After one week of continuous administration,the model group,ATRA group ,and ferrostatin-1 group were intraperitoneally injected with LPS 6 mg / kg. All mice were sacrificed after 6 hours.The contents of malondialdehyde ( MDA) and glutathione ( GSH) in serum of mice were detected. qPCR was used to detect mRNA levels of interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha (TNF-α) in heart tissue.Hematoxylin-eosin ( HE) staining was used to observe the changes of heart tissue in mice.Transmission electron microscopy (TEM) was used to observe the structure of mouse myocardial mitochondria.Western blot was used to detect the expression of ferroptosis markers glutathione peroxidase 4 ( GPX4) ,ferritin heavy chain 1 ( FTH1 ) ,Solute carrier family 7 member 11 ( SLC7A11 ) ,acyl-CoA synthetase long-chain family member 4 (ACSL4) and related regulatory proteins,Nuclear factor erythroid 2-related factor 2 ( NRF2 ) ,kelchlike ECH-associated protein 1 (KEAP1) .
Results:
Compared with the normal group,the MDA content in the serum of the model group increased and the GSH content decreased,the above changes were reversed in the ATRA group as well as in the ferrostatin-1 group.Compared with normal group,the mRNA levels of IL-6 and TNF-α in the heart tissue of model group increased steeply,the above changes were relieved in the ATRA group and the ferrostatin-1 group.There was no significant difference in HE staining of myocardial tissue among the groups of mice. Compared with the normal group,myocardial mitochondria in the model group showed the phenomenon of cristaereduction or disappearance under TEM,while myocardial mitochondrial injury was alleviated in the ATRA group and the ferrostatin-1 group.Western blot showed that GPX4,FTH1,SLC7A11,and NRF2 expression were reduced in the myocardial tissue of mice in the model group compared with the normal group,ACSL4 and KEAP1 expression increased.The above changes were reversed in the ATRA group as well as in the ferrostatin-1 group.
Conclusion
ATRA alleviates lipopolysaccharide-induced acute myocardial injury in mice by inhibiting ferroptosis.
10.Interpretation of the National Regulation for the Rabies Exposure Prophylaxis (2023 Edition)
Si LIU ; Cheng LIU ; Qingjun CHEN ; Zhenggang ZHU ; Xinjun LYU ; Chuanlin WANG ; Wenwu YIN
Chinese Journal of Epidemiology 2023;44(10):1497-1506
Rabies is one of the important zoonotic infectious diseases, with a mortality rate of almost 100%. Rabies is a vaccine preventable disease, and proper rabies exposure prophylaxis can effectively prevent the occurrence of human rabies. In recent years, there has been significant progress in clinical research on the rabies exposure prophylaxis both domestically and internationally. World Health Organization (WHO) released the Rabies Vaccine: WHO Position Paper-April 2018. In order to guide medical institutions of all levels in rabies exposure prophylaxis, the National Administration of Disease Prevention and Control, in conjunction with the National Health Commission of the People's Republic of China, organized the Rabies Vaccine Working Group of the National Immunization Program Technical Working Group and invited experts to revise and issue the National Regulation for the Rabies Exposure Prophylaxis (2023 Edition). This article compares the National Regulation for the Rabies Exposure Prophylaxis (2009 Edition) and interprets the updated key points and supporting basis of the new version of the guidelines to guide clinical application and implementation.


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