1.The effects of Xinjia-Liangfu formula combined 5-Fu on survivin and caspase-3 expression of gastric cancer xenografts in nude mice
Yanping SONG ; Jing XU ; Lintao ZHAO ; Xiaoyong WU ; Jing WANG ; Li HOU
International Journal of Traditional Chinese Medicine 2014;(8):707-710
Objective To observe the effect of Xinjia-Liangfu(XJLF)formula on human gastric cancer(SGC-7901)tumor growth in nude mice and its impact on survivinand Caspase-3 expression in tumor tissue. Methods The animal model of SGC-7901 xenografted nude mice was established, and all the mice were randomly divided into 6 groups, namely model control group, 5-Fu group, XJLF formula high-dose group, XJLF formula medium-dose group , XJLF formula low-dose group and drug combination group(XJLFformula medium-dose and 5-Fu). After 10 days of continuous treatment, tumor inhibition rate was calculated and the expression of Survivin and Caspase-3 was detected by immunohistochemistry techniques. Results The tumor inhibition rates of 5-Fu group, XJLF formula high-dose group, XJLF formula medium-dose group, XJLF formula low-dose group and drug combination group were 55.03%, 56.38%, 41.23%, 23.09%and 60.28%respectively, and the tumor inhibition rate of drug combination group was significantly increased compared to the model control group(P<0.05), 5-Fu group(P<0.05)and XJLF high-dose group(P<0.05) Meanwhile, the Caspase-3 expression was significantly up-regulated and the Survivin expression was significantly down-regulated in drug combination group(Caspase-3 was 77 539.74±50 912.5, Suvivin was 35 709.1±10404.4)compared to the model control group(Caspase-3 was 18 464.71±7 537.01,Suvivin was 63 449.4±50 498.8), P<0.05 or 0.01, 5-Fu groupCaspase-3 was (47 198.89±10 751.2), Suvivin was(37 016.8±6 024.4), P<0.05 or 0.01and XJLF formula high-dose groupCaspase-3was (44213.57±7041.6), Suvivin was (38811.1±7313.0)respectively. Conclusion The tumor inhibition rate of drug combination group was higher than XJLF formula high-dose group and 5-Fu group. Also combination group hadstronger effect compared to model control group in terms of down-regulation of Caspase-3 expression and up-regulation of Survivin expression, which indicates a benefit ofXJLF and 5-Fu combination treatment.
2.Design,synthesis and anti-NSCLC activity of hybrids of anilinopyrimidines and diazeniumdiolates
Chun HAN ; Lintao WU ; Xiaoqin HU ; Long SUN ; Zhangjian HUANG ; Yihua ZHANG
Journal of China Pharmaceutical University 2018;49(1):48-55
To search for potent drugs against non-small-cell lung cancer(NSCLC),a series of hybrids(9a-9e, 10a-10e and 11a-11e﹚ from anilinopyrimidines and diazeniumdiolates were designed and synthesized.The MTT assay was employed to evaluate their antiproliferative activity against H1975 cells harboring epithelial growth factor receptor(EGFR)L858R/T790M mutation.The results showed that compounds 9a-9e displayed remarkable inhibitory activity on H1975 cells.Among these compounds, the most potent was compound 9b(IC50=0.65 μmol/L),which was superior to the positive control gefitinib.Additionally,molecular docking study indicated that 9b could bind with EGFR T790M by forming hydrogen bond, electrostatic interactions, et al, suggesting that compound 9b may be a potential anti-NSCLC agent for further investigation.
3.Preparation and characterization of microbubbles loaded with hydrogen sulfide.
Gangbin CHEN ; Li YANG ; Xinzhong LI ; Lintao ZHONG ; Juefei WU ; Jianping BIN
Journal of Southern Medical University 2015;35(12):1672-1677
OBJECTIVETo prepare a phospholipid-coated microbubble loaded with hydrogen sulfide (HSMB) and evaluate its physicochemical and acoustic properties.
METHODSHydrogen sulfide and perfluoropropane were mixed at the ratios of 4:0, 3:1, 2:2, 1:3, and 0:4 to prepare hydrogen sulfide-loaded microbubbles (termed HSMB4:0, HSMB3:1, HSMB2:2, HSMB1:3, and HSMB0:4, respectively). The microbubble concentration and diameter were investigated and their stability were evaluated. The optimal ratio of hydrogen sulfide and perfluoropropane was determined according to the changes of microbubble concentration. The changes of dissolved hydrogen sulfide and concentration of the microbubbles were investigated after exposure to ultrasound, and their acoustic enhancement effects in the myocardium and kidney were observed after intravenous injection in rats.
RESULTSHSMBs were milky in color and spherical in shape without aggregations. The concentrations of HSMB4:0 and HSMB3:1 were lower than that of HSMB2:2 and decreased with time. HSMB2:2, HSMB1:3 and HSMB0:4 showed comparable concentrations and were stable within 72 h. After exposure to ultrasound, the concentration of HSMB2:2 decreased while the dissolved hydrogen sulfide increased significantly. Intravenous injection of HSMB2:2 produced a satisfactory contrast-enhancing effect in the myocardium and kidney of rats.
CONCLUSIONHSMB prepared with the hydrogen sulfide to perfluoropropane ratio of 2:2 has excellent contrast-enhancing effect and is capable of carrying and releasing hydrogen sulfide upon ultrasound exposure to potentially allow visual site-specific delivery of hydrogen sulfide.
Animals ; Contrast Media ; chemistry ; Fluorocarbons ; chemistry ; Heart ; Hydrogen Sulfide ; chemistry ; Kidney ; Microbubbles ; Phospholipids ; chemistry ; Rats ; Ultrasonics
4.Effects of hydroxy safflor yellow A on blood vessel and mRNA expression with VEGF and bFGF of transplantation tumor with gastric adenocarcinoma cell line BGC-823 in nude mice.
Shengyan XI ; Qian ZHANG ; Hua XIE ; Lintao LIU ; Chaoyang LIU ; Xuemin GAO ; Jianjun ZHANG ; Likun WU ; Lili QIAN ; Xiaoying DENG
China Journal of Chinese Materia Medica 2009;34(5):605-610
OBJECTIVETo investigate the effects of Hydroxy Safflor yellow A (HSYA) on the growth of blood vessel of transplantation tumor of gastric adenocarcinoma cell line BGC-823 in nude mice and its underlying mechanism of antagonizing tumor angiogenesis.
METHODThe BGC-823 cells was subcutaneouly injected into the right anterior armpit of BALB/C nu/nu nude mice and established the animal model of transplantation tumor. Then nude mice were divided into 4 groups at random: model group, control group, high or low dosage of HSYA group. The model group were treated with normal sodium by intraperitoneal injection, HSYA groups were treated with HSYA at concentration of 0.056 g x L(-1) and 0.028 g x L(-1) by intraperitoneal injection, and in these groups each mouse was injected 2 times everyday with 0.2 mL by 4-6 hours interval. The control group were injected in enterocoelia 1 times every 2 days starting from the third day with cytoxan at 2 g x L(-1). 20 days later, the volume and weight of nude mice were observed. The pathological change of tumor tissue was observed under optical microscope. The mRNA expression of VEGF and bFGF of transplantation tumor were detected by real time quantitative PCR.
RESULTThe volume (607.42 +/- 252.96) mm3, weight (0.88 +/- 0.14) g of transplantation tumor, the mRNA expression level of VEGF 0.49 +/- 0.13 and bFGF 0.60 +/- 0.48 are reduced significantly after treatment with HSYA at the concentration of 0.028 g x L(-1) compared with physiologic saline-treated group (P < 0.05 or P < 0.01). The tumor pathological angiogenesis of HSYA group is also less obvious than the normal sodium-treated group.
CONCLUSIONHSYA in given concentration can inhibit the growth of BGC-823 transplantation tumor, and decreasing the mRNA expression of VEGF and bFGF, which suggests that inhibiting tumor angiogenesis may be one of the mechanisms of HSYA antagonizing tumor.
Adenocarcinoma ; drug therapy ; genetics ; metabolism ; Angiogenesis Inhibitors ; administration & dosage ; Animals ; Blood Vessels ; drug effects ; Cell Line, Tumor ; Chalcone ; administration & dosage ; analogs & derivatives ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Fibroblast Growth Factors ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Quinones ; administration & dosage ; Random Allocation ; Stomach Neoplasms ; drug therapy ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism
5.Effect of nebulized hypertonic saline solution for bronchiolitis in infant
Shanpu YANG ; Hongyan LIU ; Yuechao WU ; Ailin LIN ; Hong DONG ; Aiping HUANG ; Lintao ZHANG ; Bin PAN ; Xiaobin WANG
Chinese Journal of Primary Medicine and Pharmacy 2017;24(21):3229-3232
Objective To assess the efficacy and safety of nebulized hypertonic saline solution in infant with bronchiolitis.Methods From January 2014 to January 2016,95 patients at 3-13 months old in our hospital who diagnosed as bronchiolitis were randomly divided into three groups.On the basis of conventional suit support treatment,the observation group A was given nebulized 3% hypertonic saline (n =32),the observation group B was given nebulized 3% hypertonic saline and salbutamol (n =32),and the control group C was given nebulized normal saline (0.9%) and salbutamol (n =31),this therapy was repeated every 6 hours until discharge.The Lowell score,clinical symptoms remission time,days of hospitalization and incidence rate of adverse reaction of the three groups were compared.Results After treatment,the symptoms and signs of the three groups were all improved.The Lowell scores were lower in the two observation groups compared to the control group C in 24,48,72 hours after treatment[(5.81 ±1.53) points and (5.85 ± 1.37) points vs.(6.61 ± 1.54) points,(4.75 ± 1.34) points and (4.72 ± 1.30) points vs.(5.52 ± 1.29) points,(3.19 ± 1.15) points and (3.22 ± 1.16) points vs.(3.90 ± 1.01) points,Z =-1.999,-2.241,-2.518 and-2.002,-2.335,-2.316,all P < 0.05).And the cough,wheezing remission time and pulmonary rales disappearance time,days of hospitalization in the two observation groups were also shorter,there were statistically significant differences [(6.63 ± 1.41) d and (6.56 ± 1.37) d vs.(7.35 ± 1.25) d,(5.19 ± 1.03) d and (5.25 ± 1.05)d vs.(5.87 ± 1.09)d,(5.75 ±1.34)d and (5.72 ± 1.51)d vs.(6.68 ± 1.60)d,(7.25 ± 1.37)d and (7.16±1.48)d vs.(8.10±l.47)d,Z=-2.498,-2.469,-2.359,-2.213 and-2.982,-2.405,-2.373,-2.222,P <0.05,or P <0.01)].There were no significant differences in the Lowell score,the length of time of cough,wheeze,lung rales disappears and the length of hospital stay between the observation group A and observation groupB[(5.81 ± 1.53) points vs.(5.85 ± 1.37) points,(4.75 ± 1.34) points vs.(4.72 ±1.30) points,(3.19± 1.15) points vs.(3.22 ± 1.16) points,(6.63 ± 1.41) d vs.(6.56 ± 1.37) d,(5.19 ±1.03)d vs.(5.25 ± 1.05)d,(5.75 ± 1.34) d vs.(5.72 ± 1.51) d,(7.25 ± 1.37) d vs.(7.16 ± 1.48) d,Z =-0.164,-0.021,-0.140,-0.295,-0.167,-0.374,-0.233,all P > 0.05].Children in three groups had no serious adverse events (all P > 0.05).Conclusion Nebulized hypertonic saline in the treatment of bronchiolitis can relieve symptoms and signs,shorten the hospitalization time,and has less adverse reaction,it is worthy of clinical use.
6.Clinical analysis of streptococcal toxic shock syndrome caused by Group A Streptococcus infection in children
Qing MENG ; Yuhui WU ; Yanlan YANG ; Yanxia HE ; Lintao ZHOU ; Huabao CHEN ; Hui XIE ; Liangliang KANG ; Nannan HE ; Lifang SUN
Chinese Journal of Applied Clinical Pediatrics 2022;37(21):1665-1668
Objective:To analyze the clinical characteristics of Group A Streptococcal(GAS) toxic shock syndrome (STSS) in children. Methods:The clinical data of 10 STSS children hospitalized in Shenzhen Children′s Hospital from January 2015 to March 2022 were downloaded from the electronic medical record system.The clinical manifestations were analyzed and treatment experience was summarized respectively.Results:There were 5 males and 5 females, with an average age of (5.29±2.87) years.All the patients were healthy in the past.The diagnoses were confirmed by blood culture in 2 cases, pus culture in 5 cases, and blood metagenomics next generation sequencing in 3 cases.The rapid detection of GAS antigen was positive in 7 cases.All cases had fever, and 9 cases of them developed fever after viral infection, including pneumonia in 7 cases, skin and soft tissue infections in 6 cases, necrotizing fasciitis in 3 cases, and purulent meningitis in 1 case.All cases also presented with shock.Six cases had liver function injury, and 4 cases suffered from acute kindey injury.Four cases had infection-related encephalopathy, and 7 cases were afflicted with disseminated intravascular coagulation.Two cases had respiratory failure, and 2 cases had rhabdomyolysis.There were 3 cases with a decreased white blood cell (WBC) count and 7 cases with an increased WBC count on admission.Seven cases were found to have thrombocytopenia, but their platelet levels were all elevated after recovery.C-reactive protein and procalcitonin and the proportion of neutrophils were markedly increased in all cases.All cases suffered from hypoalbuminemia, hyponatremia and hypocalcemia.All the 10 positive strains were sensitive to Penicillin, Ceftriaxone/Cefotaxime and Vancomycin.Eight cases were treated with combined antibiotics after admission.Eight patients received intravenous immunoglobulin.All cases were cured and discharged.Conclusions:The STSS progresses rapidly in children, so pediatricians should pay great attention to the disease.Early identification, diagnosis of infection sources, infusion of antibiotics and surgical treatment are the keys to disease management.
7.Effect of Xiangsha Liu Junzitang Combined with Phlegm-removing and Detoxifying Traditional Chinese Medicine on Immune Escape in Lewis Lung Cancer Mice
Qian YANG ; Shumei WANG ; Shihan FENG ; Xue ZHAN ; Lintao XIA ; Mingxing WU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):78-86
ObjectiveTo study the effect and mechanism of Xiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine on immune escape in Lewis lung cancer mice. MethodA total of 60 specific-pathogen-free (SPF)-grade C57BL/6J male mice were injected subcutaneously with 0.2 mL of Lewis cell suspension (containing 2×106 cells·mL-1) in the right mid-axillary line. After 7 days, the mice that had been successfully modeled were randomly divided into six groups: the model group, the cisplatin group, the Xiangsha Liu Junzitang low-, medium-, and high-dose groups, and the combined group, with 10 mice in each group. The Xiangsha Liu Junzitang low-, medium- and high-dose groups were gavaged with 17.88, 35.75, 71.50 g·kg-1 Xiangsha Liu Junzitang solution once a day, respectively, and the dosage of cisplatin intraperitoneally injected into the mice was converted to 5 mg·kg-1 twice a week, and the tumour volumes of each group were measured every two days. The intervention lasted for 14 consecutive days. At the end of treatment, the tumour mass of mice in each group was weighed and the tumour inhibition rate was calculated. The morphological characteristics of tumours in each group were observed by hematoxylin-eosin (HE) staining. Fluorescent quantitative real-time polymerase chain reaction (Real-time PCR) assay was used to detect messenger ribonucleic acid (mRNA) contents of the natural killer group 2 member D (NKG2D) receptor, ribonucleic acid export-1 (RAE-1), and γ interferon (IFN-γ) in the tumour tissues of each group. NKG2D, RAE-1, and IFN-γ mRNA in tumour tissues of each group. Immunohistochemistry (IHC) and Western blot were applied to detect the expressions of RAE-1, NKG2D, and IFN-γ in tumour tissues of each group, and Western blot was used to detect the expressions of interleukin-6 (IL-6), Janus kinase 2 (JAK2), p-JAK2, signal transducer and activator of transcription 3 (STAT3), and p-STAT3 in tumour tissues of each group, as well as the protein levels of NKG2D, and RAE-1 in spleen tissues of each group. ResultCompared with that in the model group, the tumour mass decreased in all dose groups of Xiangsha Liu Junzitang, with no statistically significant difference. The tumour volume was reduced (P<0.05, P <0.01). The pathological morphology was improved. The mRNA contents of NKG2D, RAE-1 and IFN-γ were increased in the medium-dose group (P<0.05, P<0.01), and the protein expressions of NKG2D, RAE-1, and IFN-γ in tumour tissues were elevated (P<0.05, P<0.01), and p-JAK2 and p-STAT3 protein expressions were decreased (P<0.05, P<0.01). In spleen tissues, the protein expressions of NKG2D and RAE-1 in all dose groups of Xiangsha Liu Junzitang were significantly elevated (P<0.01). Compared with those in the cisplatin group, NKG2D, RAE-1 and IFN-γ mRNA contents were elevated in the middle-dose group of Xiangsha Liu Junzitang, and the difference was not statistically significant. IHC showed that the protein expressions of NKG2D and IFN-γ in the combined group were significantly elevated (P<0.01), and Western blot results showed that the protein expressions of RAE-1, NKG2D and IFN-γ were elevated (P<0.05, P<0.01). p-JAK2 and p-STAT3 protein expressions were decreased in the combined group (P<0.05, P<0.01). NKG2D and RAE-1 protein expressions were significantly increased in spleen tissues of the medium-dose groups and the combined group (P<0.01). ConclusionXiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine can inhibit the growth of tumours in Lewis lung cancer mice by up-regulating the expressions of RAE-1/NKG2D, promoting the activation of NK cells, and inhibiting immune escape, the mechanism of which may be related to down-regulation of the JAK2/STAT3 pathway.