1.Effects and mechanism of polysaccharides from Hedyotis diffusa on isoniazid-induced liver injury
Xiuping ZHUANG ; Li LI ; Chao CHEN ; Liyuan WANG ; Guangshang CAO ; Peng ZHOU ; Xin WANG
China Pharmacy 2024;35(6):665-670
OBJECTIVE To investigate the effects and mechanism of polysaccharides from Hedyotis diffusa (HDP) on isoniazid (INH)-induced liver injury. METHODS Healthy transgenic zebrafish with liver-specific fluorescence were divided into normal group, model group (4 mmol/L INH), HDP low-concentration group (4 mmol/L INH+50 mg/mL HDP) and HDP high- concentration group (4 mmol/L INH+100 mg/mL HDP). After grouping treating, the liver fluorescence area, fluorescence intensity and pathological changes of liver tissue were observed. Human liver L02 cells were divided into normal group, model group (4 mmol/L INH), HDP low-concentration group (4 mmol/L INH+2 mg/mL HDP), and HDP high-concentration group (4 mmol/L INH + 4 mg/mL HDP). After grouping treating, the cell viability was detected, and the levels of alanine transaminase (ALT), aspartate transaminase (AST), and the content of glutathione (GSH) as well as the expression levels of silent information regulator 1 (Sirt1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) proteins were detected. RESULTS Compared with the model group, the HDP low- and high-concentration groups showed varying degrees of increase in the fluorescence area and fluorescence intensity (except for HDP low-concentration group) of zebrafish liver (P<0.05 or P<0.01), and the characteristics of liver injury and necrosis had been improved to varying degrees. Compared with model group, the survival rate of L02 cells, the content of GSH (except for HDP low-concentration group), the protein expression levels of Sirt1 (except for HDP low-concentration group), Nrf2, NQO1, HO-1 (except for HDP low-concentration group) were significantly increased in HDP low- and high-concentration groups (P<0.05 or P<0.01), and the levels of ALT and AST (except for HDP low-concentration group) were significantly decreased (P<0.05); the number of survival cells significantly increased, while the number of damaged or dead cells significantly decreased. CONCLUSIONS HDP has a potential protective effect against INH-induced liver injury, the mechanism of which may be associated with activating Sirt1/Nrf2 signaling pathway, improving mitochondrial function and enhancing antioxidant capacity.
2.Study on the correlation between immediate hypersensitivity induced by pegylated liposomal doxorubicin and the anti-polyethylene glycol antibody in patients with advanced breast cancer
Wei ZHUANG ; Xiuping LAI ; Suiwen YE ; Junyi CHEN ; Qingxiu MAI ; Siming LI ; Junyan WU ; Herui YAO
Adverse Drug Reactions Journal 2021;23(9):456-460
Objective:To explore the correlation between immediate hypersensitivity induced by pegylated liposomal doxorubicin (PLD) and the plasma anti-polyethylene glycol (anti-PEG) antibody in advanced breast cancer patients.Methods:The study was designed as a prospective and noninterventional study. The subjects were selected from advanced breast cancer patients in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, who received monotherapy with PLD (an IV infusion of PLD 50 mg/m 2 in 5% glucose solution 250 ml for 90 minutes without pretreatment with dexamethasone or other drugs). Anti-PEG antibody before administration were detected for all the patients and antibody level >2 ng/L was defined as positive. Blood in patients who had hypersensitivity within 30 minutes after the start of infusion was collected (finding the opportunity as soon as possible) and IgE, C3, and C4 levels in serum were detected. According to whether there was an immediate hypersensitivity reaction, the patients were divided into hypersensitivity group and non-hypersensitivity group and the clinical characteristics and plasma anti-PEG antibody carrying status in patients between the 2 groups were compared; according to anti-PEG antibody carrying status, the patients were divided into anti-PEG antibody positive group and negative group and the clinical characteristics and the incidence of hypersensitivity in patients between the 2 groups were compared. Results:A total of 12 patients were included in the study, aged from 37 to 68 years with a median age of 50 (37-68) years. Ten patients had previously used non-pegylated anthracyclines and the median cumulative dose was 329 (185, 418) mg/m 2 after a doxorubicin equivalent dose conversion. Seven patients developed hypersensitivity within 2-18 minutes after the start of infusion. Between the hypersensitivity group and the non-hypersensitivity group, differences in clinical characteristics such as age, height, weight, body surface area, previous application of anthracyclines, and the cumulative doses in patients were not significant (all P>0.05); the difference in positive rate of anti-PEG antibodies in patients was also not statistically significant (4/7 vs. 2/5, P=1.000). Among the 12 patients, 6 were positive for anti-PEG antibody and 6 were negative and the differences in the above-mentioned clinical characteristics or the incidence of hypersensitivity (3/6 vs. 4/6) in patients between the 2 groups (all P>0.05) were not significant. In the hypersensitivity group, IgE, C3, and C4 levels in serum were detected in 4 patients. Two patients with positive anti-PEG antibody had increased IgE levels (404 and 545 μg/L, respectively), 1 of which had also increased C4 level (486 mg/L); the other 2 patients with negative anti-PEG antibody had normal IgE, C3, and C4 levels. Conclusions:It has not been found that PLD-induced immediate hypersensitivity is related to the anti-PEG antibody, which may be due to the small sample size of the study. It cannot be ruled out that anti-PEG antibody may be involved in the induction of the IgE-mediated immediate hypersensitivity, which may also be mediated by complement in some patients.
3.Study on the correlation between immediate hypersensitivity induced by pegylated liposomal doxorubicin and the anti-polyethylene glycol antibody in patients with advanced breast cancer
Wei ZHUANG ; Xiuping LAI ; Suiwen YE ; Junyi CHEN ; Qingxiu MAI ; Siming LI ; Junyan WU ; Herui YAO
Adverse Drug Reactions Journal 2021;23(9):456-460
Objective:To explore the correlation between immediate hypersensitivity induced by pegylated liposomal doxorubicin (PLD) and the plasma anti-polyethylene glycol (anti-PEG) antibody in advanced breast cancer patients.Methods:The study was designed as a prospective and noninterventional study. The subjects were selected from advanced breast cancer patients in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, who received monotherapy with PLD (an IV infusion of PLD 50 mg/m 2 in 5% glucose solution 250 ml for 90 minutes without pretreatment with dexamethasone or other drugs). Anti-PEG antibody before administration were detected for all the patients and antibody level >2 ng/L was defined as positive. Blood in patients who had hypersensitivity within 30 minutes after the start of infusion was collected (finding the opportunity as soon as possible) and IgE, C3, and C4 levels in serum were detected. According to whether there was an immediate hypersensitivity reaction, the patients were divided into hypersensitivity group and non-hypersensitivity group and the clinical characteristics and plasma anti-PEG antibody carrying status in patients between the 2 groups were compared; according to anti-PEG antibody carrying status, the patients were divided into anti-PEG antibody positive group and negative group and the clinical characteristics and the incidence of hypersensitivity in patients between the 2 groups were compared. Results:A total of 12 patients were included in the study, aged from 37 to 68 years with a median age of 50 (37-68) years. Ten patients had previously used non-pegylated anthracyclines and the median cumulative dose was 329 (185, 418) mg/m 2 after a doxorubicin equivalent dose conversion. Seven patients developed hypersensitivity within 2-18 minutes after the start of infusion. Between the hypersensitivity group and the non-hypersensitivity group, differences in clinical characteristics such as age, height, weight, body surface area, previous application of anthracyclines, and the cumulative doses in patients were not significant (all P>0.05); the difference in positive rate of anti-PEG antibodies in patients was also not statistically significant (4/7 vs. 2/5, P=1.000). Among the 12 patients, 6 were positive for anti-PEG antibody and 6 were negative and the differences in the above-mentioned clinical characteristics or the incidence of hypersensitivity (3/6 vs. 4/6) in patients between the 2 groups (all P>0.05) were not significant. In the hypersensitivity group, IgE, C3, and C4 levels in serum were detected in 4 patients. Two patients with positive anti-PEG antibody had increased IgE levels (404 and 545 μg/L, respectively), 1 of which had also increased C4 level (486 mg/L); the other 2 patients with negative anti-PEG antibody had normal IgE, C3, and C4 levels. Conclusions:It has not been found that PLD-induced immediate hypersensitivity is related to the anti-PEG antibody, which may be due to the small sample size of the study. It cannot be ruled out that anti-PEG antibody may be involved in the induction of the IgE-mediated immediate hypersensitivity, which may also be mediated by complement in some patients.
4.Isolating culture of adipose mesenchymal stem cells in psoriasis vulgaris patients and differentiation into immune regulation function
Xiuping YIN ; Rongjia ZHU ; Chen ZHUANG ; Xiaofei CHENG ; Qin HAN ; Ping SONG ; Chunhua ZHAO
Basic & Clinical Medicine 2017;37(7):975-981
Objeetive To study the differences of the biological characteristics and immune regulation function of adipose mesenchymal stem cells (AMSCs)from psoriasis patients and healthy people.Methods AMSCs were isolated and cultured from human psoriatic and healthy adipose tissue,the phenotypes and cell cycle of AMSCs taken from three generation were detected by flow eytometry.Alkaline phosphate enzyme staining and oil red o staining were used respectively to identify their adipogenic and osteogenic capacity.Next,the levels of inflammation antimicrobial proinflammatory factor were detected by PCR and ELISA.Then gene expression profile of AMSCs were screen by gene expression profile chip,as so to bolting the the gene array related with immunology gene.Results There was no significant change in cell morphology,and cell surface markers were expressed high for CD29,CD44,CD73,while lower for CD31,CD45 and HLA-DR.AMSCs of psoriasis patients and healthy people both had the ability of adipogenic and osteogenic differentiation.But the cell cycle showed the third generation AMSCs proliferation rates were slower than that of normal control,as compared with healthy controls,adipogenic differentiation ability was stronger.What'more,the level of inflammatory cytokines in psoriasis group was lower than that in controls such asIL-10,IDO,TGF-β,on the contrary the levels of proinflammatory factor in psoriasis group were higher than that in controls,such as TNF-α,IFN-γ.In addition,gene chip results suggested that psoriasis group AMSCs had obvious expression differences on JAK-STAT pathway with healthy controls.Conclusions Compared with the control,there are significant differences in patients AMSCs proliferation and adipogenic differentiation ability,immune inflammation suppression control ability is weaken,this phenomenon may be associated with JAK-STAT immune pathways related to downgrade.
5.The research progress of traditional Chinese medicinepigments′pharmacological activity and its adverse reaction
Rongrong HAO ; Yidan ZHANG ; Xiuping QIN ; Pengwei ZHUANG ; Yanjun ZHANG
Chinese Pharmacological Bulletin 2017;33(6):744-748
We systematically analyse and summarize on the literature(1996-2016) by reading and analysing them.Active ingredients and pharmacological activity of traditional Chinese medicine pigment composition(Saffower Yellower Injection) is introduced and its response characteristics, factors and potential causes of ADR are revealed, which provides the reference for safe, rational clinical management of drugs.Also it reminds that clinicians should master the characteristics of adverse reactions of traditional Chinese medicine pigment and grasp the ADR potential causes and control measures, in order to reach the goal of rational drug use.

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