1.Overview of lipid metabolism in pulmonary fibrosis
Jing-Ying WANG ; Yong XU ; Wei-Chen XU ; Tong XIE ; Chen SHI ; Jin-Jun SHAN
Chinese Pharmacological Bulletin 2024;40(9):1612-1616
Pulmonary fibrosis is a diffuse interstitial lung disease with poor prognosis,and its pathogenesis has not been fully clar-ified.Lipid,as a key component of cell structure involved in signal transduction,plays an important role in maintaining lung function.More and more studies show that lipid changes are closely related to the progress of pulmonary fibrosis.This paper briefly reviews the pulmonary fibrosis disease,the research pro-gress of lipidomics in pulmonary fibrosis and the role of various lipids in pulmonary fibrosis.
2.Comparison of intracellular uptake and target protein binding characteristics of two BTK inhibitors with different selectivities
Teng ZHANG ; Ting-Fei TAN ; Ying-Li ZHAO ; Gong-Wei HAN ; Zi-Tong XIA ; Han-Bing SHI ; He-Ying LIU ; Jun-Ping WANG ; Quan XIA
Chinese Pharmacological Bulletin 2024;40(10):1899-1905
Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.
3.Carnosine attenuates OGD/R damage to BV2 cells by inhibiting ROS/NLRP3/GSDMD-mediated pyroptosis
Rui-Li RAN ; Yu-Tong WANG ; Jun-Qiu SONG ; Jiang BIAN ; De-Wei WANG ; Xiao-Han JIANG ; Fu-Lin YOU ; Jing YANG
Chinese Pharmacological Bulletin 2024;40(11):2150-2158
Aim To investigate the protective effect of carnosine on BV2 cell damage induced by oxygen-glu-cose deprivation/reperfusion(OGD/R)and its role in mediating pyrodeath through the ROS/NLRP3/GSDMD pathway.Methods BV2 cells were randomly divided into the control group(Con),model group(OGD/R),carnosine group(OGD/R+CAR),inhibitor group(OGD/R+MCC950),and carnosine+inhibitor group(OGD/R+CAR+MCC950).The cell survival rate was detected by MTT assay.The release rate of lactate dehydrogenase(LDH)in cell supernatant was detected by microenzyme labeling method.Cell damage was as-sessed using Hoechst 33342/SYTOX Green staining.ROS levels in cells were detected by DCFH-DA.The nucleation level of NF-κB p65 was observed by immu-nofluorescence.The protein expression levels of NLRP3,ASC,cleaved caspase-1,and GSDMD-N were detected by Western blot.The levels of IL-1 β and IL-18 in the supernatant were detected by ELISA.Results Com-pared with Con group,the survival rate of cells in the OGD/R group was significantly reduced,LDH release was significantly raised,cell morphology was damaged,and the positive rate of SYTOX Green was significantly elevated with ROS level in cells.The fluorescence in-tensity of NF-κB p65 in the nucleus increased,and the protein expression levels of NLRP3,ASC,cleaved caspase-1,GSDMD-N increased significantly,and the levels of IL-1 β and IL-18 in the cell superserum in-creased significantly.Compared with the OGD/R group,the survival rate of cells in other groups in-creased significantly,the LDH release rate significantly decreased,and the cell damage was improved to a cer-tain extent.The positive rate of SYTOX Green and ROS production in cells significantly decreased,and the fluorescence intensity of NF-κB p65 in nucleus markedly decreased.The expression levels of related proteins and the levels of IL-1 β and IL-18 in cell super-natant significantly decreased.Conclusion Carnosine can protect BV2 cells from OGD/R-induced damage by inhibiting oxidative stress and NF-κB activation,then inhibiting NLRP3/GSDMD signaling pathway.
4.Short-term clinical efficacy of unilateral biportal endoscopic technique in the treatment of adjacent segment disease after lumbar interbody fusion
Shao-Tong SUN ; Jun LIU ; Ting-Yu LIU ; Jun WU ; Wei-Jian REN
Journal of Regional Anatomy and Operative Surgery 2024;33(7):575-578
Objective To evaluate the short-term clinical efficacy of unilateral biportal endoscopic(UBE)technique in the treatment of adjacent segment disease after lumbar interbody fusion.Methods The clinical data of 21 patients with adjacent segment disease after lumbar interbody fusion who treated with UBE technique and followed up for more than 3 months in our hospital from March 2020 to January 2023 were retrospectively analyzed.The operation time,decrease value of hemoglobin 1 day before and after operation,drainage volume of the operation area,time of bed rest and complications were recorded.The Japanese Orthopaedic Association(JOA)score was used to evaluate lumbar function 1 day before operation,3 days and 3 months after operation to determine the improvement.The visual analogue scale(VAS)score was used to evaluate the pain 1 day before operation,3 days and 3 months after operation.Results The operation time was 60~175 minutes,with an average of(95.38±18.64)minutes;the decrease value of hemoglobin was 2~6 g/L,with an average of(1.42±0.18)g/L;the time of bed rest was 27~88 hours,with an average of(36.42±15.33)hours;the drainage volume of the operation area was 50~315 mL,with an average of(85.56±15.65)mL;and one case of dural tear occurred during the operation,who was converted to open surgery for repairing dural sac.There was statistically significant difference in VAS score before operation compared with that 3 days and 3 months after operation(P<0.05).There was statistically significant difference in the JOA score before operation compared with that 3 days and 3 months after surgery(P<0.05).Conclusion UBE technique is effective in the treatment of adjacent segment disease after lumbar interbody fusion,with the advantages of small trauma,little bleeding and short time of bed rest.However,patients with the serious adjacent segment degeneration and severe spinal stenosis may have dural tear during operation.Once it occurs,active repair should be performed to avoid cauda equina herniation and necrosis,or switch to open surgery,if necessary.
5.Exploration of the application of i-Scan endoscopy in nasopharyngeal lesions
Tong CHU ; Qiuli WANG ; Weihua XU ; Jun WEI
China Journal of Endoscopy 2024;30(5):63-68
Objective To compare the diagnostic value of white light endoscopy and intelligent scan(i-Scan)endoscopy for nasopharyngeal masses.Methods We collected 127 patients with nasopharyngeal masses from January 2019 to December 2021 and obtained biopsy pathological results.From January 2019 to December 2020,59 cases were treated with white light endoscopy,and from January 2021 to December 2021,68 cases were treated with i-Scan endoscopy.Compare the accuracy of diagnosis between the two groups based on pathological results as the gold standard;Evaluate the microvascular morphology and lesion boundaries of nasopharyngeal masses under i-Scan endoscopy,and conduct correlation analysis with pathological results.Results The specificity and accuracy of i-Scan endoscopy in the diagnosis of nasopharyngeal masses were higher than those of white light endoscopy(91.80%and 86.00%,91.17%and 86.44%),and the sensitivity was lower than that of white light endoscopy(85.71%and 88.89%),but there was no significant difference(P>0.05).The diagnostic consistency of i-Scan group was slightly higher than that of white light group(Kappa=0.619 and 0.588);The lesion site boundary score,microvascular score,and their total score in i-Scan group were positively correlated with the pathological score(r=0.429,r=0.421,r=0.460),the differences were statistically significant(P<0.05);Typical disordered and twisted submucosal vessels(SV)and branching vessels(BV)were observed in nasopharyngeal carcinoma,most benign lesions could observe dilated and regularly distributed SV and BV,regardless of pathological malignancy,no obvious intraepithelial papillary capillary loop(IPCL)was observed in the nasopharynx.Conclusion The diagnostic efficacy of i-Scan endoscopy for nasopharyngeal masses is higher than that of white light endoscopy.
6.Based on LC-MS technology explored the metabolomics of Agrimonia pilosa intervening in non-small cell lung cancer A549 cells
Ze-hua TONG ; Wen-jun GUO ; Han-rui ZOU ; Li-wei XU ; Ya-juan XU ; Wei-fang WANG
Acta Pharmaceutica Sinica 2024;59(3):704-712
The objective of this study was to analyze the effects on cell viability, apoptosis, and cell cycle of non-small cell lung cancer (NSCLC) A549 cells after intervention with
7.Expert consensus on cryoablation therapy of oral mucosal melanoma
Guoxin REN ; Moyi SUN ; Zhangui TANG ; Longjiang LI ; Jian MENG ; Zhijun SUN ; Shaoyan LIU ; Yue HE ; Wei SHANG ; Gang LI ; Jie ZHNAG ; Heming WU ; Yi LI ; Shaohui HUANG ; Shizhou ZHANG ; Zhongcheng GONG ; Jun WANG ; Anxun WANG ; Zhiyong LI ; Zhiquan HUNAG ; Tong SU ; Jichen LI ; Kai YANG ; Weizhong LI ; Weihong XIE ; Qing XI ; Ke ZHAO ; Yunze XUAN ; Li HUANG ; Chuanzheng SUN ; Bing HAN ; Yanping CHEN ; Wenge CHEN ; Yunteng WU ; Dongliang WEI ; Wei GUO
Journal of Practical Stomatology 2024;40(2):149-155
Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.
8.Experimental study on anti-fatigue effect of Polysaccharides of Panax notoginseng
Pan-Pan WEI ; Zi-Jun YAN ; Meng-Yue DENG ; Die XIA ; Yu-Zhen DING ; Lei ZHANG ; Tong CHEN
The Chinese Journal of Clinical Pharmacology 2024;40(1):87-91
Objective To explore the effect of Polysaccharides of Panax notoginseng(PPN)on anti-exercise fatigue in mice.Methods One hundred male KM mice were randomly divided into negative control group,positive control group and experimental-L,-M,-H groups,with 20 cases per group.Experimental-L,-M,-H groups was given 100,200,400 mg·kg-1 PPN,respectively;positive control group was given 200 mg·kg-1 vitamin C;negative control group was given 0.1 mL·10 g-1 0.9%NaCl.Five groups were gavaged once a day for 28 days.After the last administration,the loaded swimming time was measured;after 90 minutes of the unloaded swimming test,the mice were allowed to rest for 30 minutes,the levels of lactic acid(LD),blood urea nitrogen(BUN),glycogen,and malondialdehyde(MDA)were measured,the safety of PPN with organ indices and histopathology.Results LD levels in negative control group,positive control group and experimental-L,-M,-Hgroupswere(4.76±0.84),(2.86±0.34),(3.00±0.69),(2.35±0.65)and(1.39±0.48)mg·kg-1;BUN contents were(13.65±1.25),(12.55±0.91),(12.12±1.24),(11.06±1.30)and(9.85±1.05)mmol·L-1;liver glycogen contents were(3.24±0.56),(11.11±2.16),(5.61±1.41),(6.60±1.49)and(12.05±2.25)mg·g-1;MDA levels were(2.36±0.21),(1.23±0.41),(1.93±0.23),(1.73±0.21)and(1.04±0.18)mg prot·mL-1.Compared with negative control group,the differences of above indexes in the positive control group and experimental-L,-M,-H groups were statistically significant(P<0.05,P<0.01,P<0.001).Conclusion PPN can increase exercise endurance in mice and has an anti-fatigue effect.This study provides a theoretical basis for the application of PPN in the field of anti-fatigue research.
9.Antioxidant activity and organ protection of Panax notoginseng polysaccharide on oxidative damage and aging model mice
Meng-Yue DENG ; Pan-Pan WEI ; Ming LI ; Zi-Jun YAN ; Die XIA ; Yu-Zhen DING ; Lei ZHANG ; Tong CHEN
The Chinese Journal of Clinical Pharmacology 2024;40(6):889-893
Objective To study the antioxidant activity and organ protection of different components of Panax notoginseng polysaccharide(PNPS)in D-galactose-induced oxidative damage aging model mice.Methods KM mice were randomly divided into normal group,model group,vitamin C(VC)group(given 200 mg·kg-1 VC),crude polysaccharide from Panax notoginseng(CPPN)group,neutral polysaccharide from Panax notoginseng(NPPN)group and acidic polysaccharide from Panax notoginseng(APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ)group(given 400 mg·kg-1 CPPN,NPPN,APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ,respectively).Except for the normal group,oxidative injury aging mouse models were established by intraperitoneal injection of 1 g·kg-1 D-galactose.The mice were sacrificed after continuous administration for 42 days,and serum and liver homogenate were prepared.Malondialdehyde(MDA)was determined by thiobarbituric acid method;superoxide dismutase(SOD)was determined by tetrazole salt method;glutathione peroxidase(GSH-Px)was determined by double antibody sandwich method.Results Serum SOD in the normal group,model group,VC group,CPPN group,NPPN group and APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ groups were(15.07±0.69),(12.79±1.51),(15.56±1.01),(13.69±0.96),(14.27±0.64),(14.31±0.99),(14.18±0.79)and(15.85±0.89)U·mL-1;serum GSH-Px were(105.35±4.97),(90.36±4.31),(111.51±7.00),(113.03±8.06),(118.77±5.19),(123.60±8.08),(131.65±3.60)and(149.22±13.32)ng·L-1;serum MDA were(1.72±0.26),(4.16±0.92),(2.26±0.59),(2.82±0.47),(2.46±0.50),(1.98±0.41),(2.39±0.39)and(2.07±0.24)nmol·mL-1;the liver SOD were(234.22±3.84),(205.04±7.28),(234.63±6.37),(214.99±17.66),(234.13±3.63),(234.63±3.44),(233.87±5.63)and(235.42±2.33)U·mgprot-1;liver GSH-Px were(274.27±23.72),(207.00±15.22),(257.68±16.39),(249.79±18.78),(252.62±10.92),(256.25±21.83),(261.20±17.52)and(263.16±17.98)ng·L-1;liver MDA were(35.70±3.52),(49.65±6.32),(36.15±2.48),(39.17±4.29),(37.40±6.19),(35.34±4.06)and(35.90±5.36),(33.31±7.64)nmol·mgprot-1.Compared with the normal group,SOD,GSH-Px in serum and liver of mice in the model group were significantly reduced,and the content of MDA was significantly increased(all P<0.01).After treatment with different components of Panax notoginseng polysaccharide,the oxidative indicators in mice were significantly improved,among which APPN-Ⅲ have the best antioxidant activity,which could significantly increase the activities of SOD,GSH-Px in serum and liver,and reduce the content of MDA(all P<0.01).Conclusion Different components of Panax notoginseng polysaccharide have antioxidant activity and organ protection in vivo,among which APPN-Ⅲ has the best antioxidant activity and has a good organ protection effect.
10.Research status of traditional Chinese medicine in regulating the cGAS-STING signaling pathway in anti-tumor therapy
Ke-Ya WANG ; Jun-Wei QI ; Tong ZHANG ; Tian-Le FU ; Xiao LI
The Chinese Journal of Clinical Pharmacology 2024;40(18):2752-2756
With the aging and changes in living conditions,the incidence rate and mortality of tumors have been rising rapidly,which has become a hot topic in the medical field.At present,the treatment methods or tumors are also improving day by day,mainly relying on surgical resection.However,the characteristics of fast tumor metastasis and spread,as well as complex growth locations,make the surgical resection method limited.More and more people choose drug targeted therapy for tumors in order to reduce surgical side effects,among which cyclic guanosine monophosphate synthase interferon gene stimulatory factor(cGAS-STING signaling pathway)plays an important role in the occurrence,proliferation,and survival of tumor cells.At present,there are many types of drugs used to treat tumors,but most of them have limited control over tumor spread.In order to study the role of traditional Chinese medicine in tumor treatment and leverage its multi-component,multi target,and multi pathway characteristics,this article comprehensively analyzes and summarizes the treatment of tumors using traditional Chinese medicine based on the cGAS-STING signaling pathway in recent years,in order to further study the mechanism of action of traditional Chinese medicine and its active ingredients in the cGAS-STING signaling pathway,it also provides ideas for clinical research on new drugs.

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