1.Effects of Salidroside on expression of substance P and neurokinin-1 receptor of bone marrow cells in bone marrow depressed anemia mice
Xinsheng ZHANG ; Hang CHENG ; Manman XU ; Bide ZHU
Chinese Journal of Immunology 2015;(9):1195-1199
Objective:To observe the effects of salidroside on the expression of substance P (SP)and neurokinin-1 receptor (NK-1R)of bone marrow cells(BMCs)in bone marrow(BM)depressed anemia mice,and to explore its roles for hematopoietic regulation.Methods:Automatic blood cell analysator was used to detected the changes of peripheral blood cells in each group ,immuno-histochemistry and reverse transcription-polymerase chain reaction ( RT-PCR) were used to analyze the expressions of SP and its receptor NK-1R of BMCs in each group respectively.Results: Peripheral blood testing results showed that the number of white blood cells (WBC),red blood cells(RBC)and hemoglobin(HB)of model group were significantly decreased when compared with control group.Compared with model group ,low-dose,middle-dose and high-dose salidroside obviously elevated the number of white blood cells ,and middle-dose salidroside obviously elevated the number of platelets.Immunohistochemistry studies showed that the expression of SP and its receptor NK-1R of BMCs was found in each group.Compared with control group , the expression of SP of BMCs was decreased obviously in model group(P<0.05),and the expression of NK-1R of BMCs was decreased slightly in model group (P>0.05),and the expression of SP and its receptor NK-1R of BMCs was increased significantly in low-dose,middle-dose and high-dose salidroside groups (P<0.05).RT-PCR data showed that the expression of SP mRNA of BMCs was increased obviously in model group ,low-dose,middle-dose and high-dose salidroside groups when compared with control group (P<0.05).The expression of NK-1R mRNA of BMCs was un-detected in control group and model group.The expression level of NK-1R mRNA of BMCs was elevated gradually with the increase of salidroside dosage in low-dose,middle-dose and high-dose salidroside groups.Conclusion: The mRNA and protein expressions of SP and its receptor NK-1R of BMCs were up-regulated significantly by salidroside in dose-dependent manner.These data suggest that salidroside could participate in the recovery of hematopoietic function of BM depressed anemia mice by increasing the expression of SP and its receptor NK-1R of BMCs.
2.Preparation and in vitro release of ivabradine hydrochloride elementary osmotic pump tablets
Qinqing SHI ; Jinghua WANG ; Manman CHENG ; Lifang YIN ; Chao QIN
Journal of China Pharmaceutical University 2021;52(3):311-317
In this study, ivabradine hydrochloride (IVB) was prepared as elementary osmotic pump tablets whose administration frequency was reduced to once daily. The dissolution method was developed, and effects on drug release profiles were evaluated by single factor analysis involving suspending agents, osmotic active agents and aging process. Orthogonal test was carried out at 3 levels on 3 factors including the amount of polyoxyethylene (PEO) in the core, polyethylene glycol (PEG) percentage and weight increase of controlled-release film coatings. The final formulation consisted of IVB (16.25 mg), PEO N80 (60 mg), hypromellose E5 (10 mg), lactose (111.75 mg), magnesium stearate (2 mg); and the film coatings consisted of PEG (15%), cellulose acetate (85%), with a weight increase of 7.5%. In vitro drug release behaviors were investigated. Prepared tablets exhibited similar release profiles in different pH dissolution media, with no risk of dose dumping in 40% ethanol solutions. The osmotic pressure differences inside and outside the membrane drove drug release. IVB osmotic pump tablets could reduce the frequency of administration and improve patients'' compliance, thus with better application values.
3.Role of mitochondrial autophagy and the curative effect of rehmannia glutinosa leaves total glycoside capsules on nucleos(t)ide drug-induced renal injury
Kai ZHONG ; Manman ZHANG ; Zixin ZHU ; Xin LIAO ; Baofang ZHANG ; Mingliang CHENG
Chinese Journal of Hepatology 2024;32(2):125-132
Objective:To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury.Methods:Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ2 test or t-test was used for statistical analysis. Results:Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference ( χ2 ?=?9.975 0, P ?=?0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference ( χ2 ?= 0.593 5, P ?=?0.441 1). Conclusion:Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.
4.Preparation and characterization of folic acid modified D ⁃α⁃tocopheryl polyethylene glycol 1000 succinate nanomaterials encapsulated with siRNA
Manman Zhu ; Yong Cheng ; Peng Rao ; Guiyang Zhang ; Hao Liu ; Lei Xiao ; Jiatao Liu
Acta Universitatis Medicinalis Anhui 2023;58(11):1859-1864
Objective :
To construct folate modified D ⁃α ⁃tocopheryl polyethylene glycol 1000 succinate ( TPGS) oparticles on the cytotoxicity and spliced X ⁃box binding protein 1 ( XBP1s) of mouse leukemia cells of monocyte macrophage (RAW264. 7) .
Methods :
Mixed FA⁃TPGS and rhodamine B (RhB) labeled XBP1 siRNA solution in a proportion of 5 ∶ 1 and obtained the nano⁃complex coated with XBP1 siRNA(FT@ XBP1) . FT@ XBP1 nanocarriers were characterized by transmission electron microscope , dynamic light scattering , ultraviolet visible spectrum analysis and/or fluorescence analysis. And the release of siRNA from FA⁃TPGS nano⁃carriers was calculated simultaneously. The cell cytotoxicity of FT@ XBP1 nanomaterials were detected by scanning electron microscopy (SEM) , CCK⁃8 and flow cytometry. And the inhibited effect of XBP1 s of RAW264. 7 cells was checked by Western blot.
Results
FA modified TPGS could effectively bind XBP1 siRNA. And the average particle size of FT@ XBP1 nanocarriers were(200 ± 20) nm. The relative release assays showed that acidic environments (pH 5. 0) was beneficial for siRNA to release from FT@ XBP1 . Both CCK⁃8 and apoptosis assay showed that the effects of FT@ XBP1 on the proliferation and apoptosis of RAW264. 7 cells were relatively small , and FT@ XBP1 could significantly inhibit the expression of XBP1 s protein in RAW264. 7(P < 0. 001) . Conclusion TPGS nanoparticles modified with folic acid can effectively encapsulate XBP1 siRNA and inhibit XBP1 s expression of RAW264. 7 cells with good cellular compatibility.
5.Preparation and characterization of folic acid modified D ⁃α⁃tocopheryl polyethylene glycol 1000 succinate nanomaterials encapsulated with siRNA
Manman Zhu ; Yong Cheng ; Peng Rao ; Guiyang Zhang ; Hao Liu ; Lei Xiao ; Jiatao Liu
Acta Universitatis Medicinalis Anhui 2023;58(11):1865-1871
Objective :
To construct folate modified D ⁃α ⁃tocopheryl polyethylene glycol 1000 succinate ( TPGS) nanomaterials (FA⁃TPGS) , which can stably load and effectively release siRNA , and to observe the effects of nanoparticles on the cytotoxicity and spliced X ⁃box binding protein 1 ( XBP1s) of mouse leukemia cells of monocyte macrophage (RAW264. 7) .
Methods :
Mixed FA⁃TPGS and rhodamine B (RhB) labeled XBP1 siRNA solution in a proportion of 5 ∶ 1 and obtained the nano⁃complex coated with XBP1 siRNA(FT@ XBP1) . FT@ XBP1 nanocarriers were characterized by transmission electron microscope , dynamic light scattering , ultraviolet visible spectrum analysis and/or fluorescence analysis. And the release of siRNA from FA⁃TPGS nano⁃carriers was calculated simultaneously. The cell cytotoxicity of FT@ XBP1 nanomaterials were detected by scanning electron microscopy (SEM) , CCK⁃8 and flow cytometry. And the inhibited effect of XBP1 s of RAW264. 7 cells was checked by Western blot.
Results :
FA modified TPGS could effectively bind XBP1 siRNA. And the average particle size of FT@ XBP1 nanocarriers were(200 ± 20) nm. The relative release assays showed that acidic environments (pH 5. 0) was beneficial for siRNA to release from FT@ XBP1 . Both CCK⁃8 and apoptosis assay showed that the effects of FT@ XBP1 on the proliferation and apoptosis of RAW264. 7 cells were relatively small , and FT@ XBP1 could significantly inhibit the expression of XBP1 s protein in RAW264. 7(P < 0. 001) .
Conclusion
TPGS nanoparticles modified with folic acid can effectively encapsulate XBP1 siRNA and inhibit XBP1 s expression of RAW264. 7 cells with good cellular compatibility.
6.Case-control study on relationship between diet quality and papillary thyroid carcinoma
Manman XIA ; Jiajie ZANG ; Haoran CHENG ; Jun SONG ; Zhengyuan WANG ; Hong ZHU ; Wenbin DING ; Chazhen LIU ; Fengsong SHENG ; Fan WU
Journal of Environmental and Occupational Medicine 2021;38(11):1179-1184
Background There are few studies on the diet quality of patients with thyroid cancer, and the relationship between diet quality and thyroid cancer remains uncertain. Objective This study aims to assess the diet quality with the Chinese Health Diet Index (CHDI) and to explore the relationship between diet quality and papillary thyroid carcinoma (PTC). Methods A 1∶1 gender- and age-matched hospital-based case-control study included newly diagnosed PTC patients and matched controls from Shanghai Cancer Hospital and Renji Hospital (East) in Shanghai, China. A structured questionnaire was applied to collect data on general characteristics, history of diseases, dietary intakes, and lifestyles. Food intakes in the past one year were assessed using a validated food frequency questionnaire, from which the CHDI score was calculated. The CHDI, according to the Dietary Guidelines for Chinese Residents, was employed to evaluate the diet quality of the two groups. A multiple conditional logistic regression model was conducted to explore the relationship between diet quality and PTC. Results A total of 350 pairs of cases and controls were recruited. The overall median CHDI score of the cases was lower than that of the controls (67.8 vs. 73.4, P<0.001). The cases had lower median scores of fruits (6.8 vs. 9.5), dairy products (3.6 vs. 5.6), and soybeans (4.6 vs. 5.5) than the controls (P<0.05); the cases had a higher median score of refined grains than the controls (5.0 vs. 4.9), and the percentage of the cases that met diet recommendations for refined grains was higher than the percentage of the controls (65.4% vs. 48.6%) (P<0.05); the cases showed lower median scores of whole grains/beans/tubers, total vegetables, dark vegetables, and fish/shrimps (0.9 vs. 1.4, 3.1 vs. 4.4, 3.6 vs. 5.0, and 3.3 vs. 4.0, respectively), and the percentages of the cases meeting their diet recommendations were lower than the percentages of the controls (6.3% vs. 8.6%, 32.6% vs. 42.0%, 38.6% vs. 50.6%, and 34.0% vs. 40.3%, respectively, P<0.05). The results of multiple conditional logistic regression analysis suggested that qualified and good diet quality were associated with a reduced the risk of PTC (qualified diet quality, OR=0.37, 95%CI: 0.23−0.62; good diet quality, OR=0.19, 95%CI: 0.10−0.36); the statistical significance remained after excluding patients who had a history of benign thyroid conditions (qualified diet quality, OR=0.28, 95%CI: 0.15−0.52; good diet quality, OR=0.20, 95%CI: 0.09−0.43). Conclusion Those with qualified or good diet quality have a lower risk of PTC. PTC patients have insufficient intakes of fruits, dairy, soybeans, whole grains/beans/tubers, vegetables, and fish/shrimps.
7.Case-control study on relationship between iodine-rich food intake and papillary thyroid carcinoma
Manman XIA ; Jiajie ZANG ; Haoran CHENG ; Jun SONG ; Zhengyuan WANG ; Hong ZHU ; Wenbin DING ; Chazhen LIU ; Fengsong SHENG ; Fan WU
Journal of Environmental and Occupational Medicine 2021;38(11):1185-1191
Background Thyroid carcinoma is a serious threat to human health in Shanghai and a focus of cancer prevention and treatment. Objective This study aims to assess the relationship between foods rich in iodine and papillary thyroid carcinoma (PTC).Methods In a hospital-based case-control study matched by gender and age (±3 years old), 402 pairs of cases (new incidences) and controls were included and studied. A validated questionnaire and food frequency questionnaire survey was conducted face to face to obtain demographic characteristics and dietary intake. A multiple conditional logistic regression model was applied to explore the relationship between foods rich in iodine (including seaweeds, kelp, and dried shrimps) and PTC. Results The mean age of the participants was (41.17±11.51) years in this study. Compared with the controls, more cases had a lower education and a manual occupation (P<0.05); more cases were overweight or obese, had a history of benign thyroid conditions, and had a family history of thyroid diseases (P<0.05); the two groups were different in the frequency of CT examination in the past ten years (P<0.05). The results of multiple conditional logistic regression analysis showed that consumption of iodine-rich foods was associated with a lower risk of PTC (for <1 time per week, OR=0.20, 95%CI: 0.12−0.35; for 1−2 times per week, OR=0.18, 95%CI: 0.10−0.33; for ≥3 times per week, OR=0.13, 95%CI: 0.04−0.44) (P<0.05). Specifically, those who consumed seaweeds (for <1 time per week, OR=0.18, 95%CI: 0.11−0.30; for 1−2 times per week, OR=0.11, 95%CI: 0.05−0.23; for ≥3 times per week, OR=0.15, 95%CI: 0.03−0.75), kelp (for <1 time per week, OR=0.28, 95%CI: 0.18−0.43; for ≤2 times per week, OR=0.24, 95%CI: 0.11−0.50), and dried shrimps (for <1 time per week, OR=0.44, 95%CI: 0.29−0.69; for ≤2 times per week: OR=0.34, 95%CI: 0.18−0.65) had a lower risk of PTC (P<0.05). After excluding patients who had a history of benign thyroid conditions, the favorable association remained significant among patients who had consumption of iodine-rich foods, seaweeds, shrimps, and kelp (P<0.05). Conclusion Less PTC patients consume iodine-rich foods than the controls.