1.Curcumin extraction and preparation and optimization of curcumin nanoparticles
Yuhang WANG ; Han ZHANG ; Chaojing ZHANG ; Xurong KOU ; Tongtong JING ; Rimei LIN ; Xinyu LIU ; Shilei LOU ; Hui YAN ; Cong SUN
Chinese Journal of Tissue Engineering Research 2026;30(2):362-374
BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57%,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10%.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5%,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61%.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)%,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.
2.Curcumin extraction and preparation and optimization of curcumin nanoparticles
Yuhang WANG ; Han ZHANG ; Chaojing ZHANG ; Xurong KOU ; Tongtong JING ; Rimei LIN ; Xinyu LIU ; Shilei LOU ; Hui YAN ; Cong SUN
Chinese Journal of Tissue Engineering Research 2026;30(2):362-374
BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57%,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10%.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5%,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61%.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)%,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.
3.Clinical features and prognosis of patients with primary sclerosing cholangitis:An analysis of 107 cases
Tongtong MENG ; Weijia DUAN ; Xinyu LI ; Junqi NIU ; Huiguo DING ; Ying HAN ; Wen XIE ; Lu ZHOU ; Bangmao WANG ; Liping GUO ; Jie LI ; Bei JIA ; Lingyi ZHANG ; Liang WANG ; Xiaoqian XU ; Yu WANG ; Xiaojuan OU ; Xinyan ZHAO ; Hong YOU ; Jidong JIA ; Yuanyuan KONG
Journal of Clinical Hepatology 2025;41(7):1337-1343
Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.
4.Clinical observation of 25G+minimally invasive vitrectomy in the treatment of retinal arterial macroaneurysm
Nan ZHAO ; Tongtong LIU ; Yige XIA ; Haohao LU ; Yanhui HAN
International Eye Science 2025;25(7):1191-1194
AIM:To observe the therapeutic efficacy of 25G+minimally invasive vitrectomy for retinal arterial macroaneurysm.METHODS:Totally 40 patients(40 eyes)who admitted to Jinan Mingshui Eye Hospital from January 2021 to May 2024 and with vitreous hemorrhage or dense premacular hemorrhage in the macular area caused by retinal arterial macroaneurysm, underwent 25G+minimally invasive vitrectomy. Preoperative and postoperative best-corrected visual acuity(BCVA), complications, and special cases were analyzed.RESULTS: The general patient data aligned with previous literature reports. The postoperative BCVA was significantly improved(t=9.72, P<0.01), and no significant serious surgical complications were observed. Notably, intraoperative findings revealed secondary macular holes in 3 eyes, resulting in poor visual prognosis.CONCLUSION: For vitreous hemorrhage or dense premacular hemorrhage caused by retinal arterial macroaneurysm, 25G+ minimally invasive vitrectomy is a safe and effective treatment. Visual prognosis was excluded for secondary macular holes.
5.Clinical features and prognosis of patients with primary sclerosing cholangitis:An analysis of 107 cases
Tongtong MENG ; Weijia DUAN ; Xinyu LI ; Junqi NIU ; Huiguo DING ; Ying HAN ; Wen XIE ; Lu ZHOU ; Bangmao WANG ; Liping GUO ; Jie LI ; Bei JIA ; Lingyi ZHANG ; Liang WANG ; Xiaoqian XU ; Yu WANG ; Xiaojuan OU ; Xinyan ZHAO ; Hong YOU ; Jidong JIA ; Yuanyuan KONG
Journal of Clinical Hepatology 2025;41(7):1337-1343
Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.
6.Risk factors for varying severities of epiphyseal injury caused by distal tibial fractures in adolescents
Tongtong FENG ; Xin JIANG ; Jining QU ; Yu WANG ; Yating YANG ; Shuaikun LIU ; Kaiyang HAN ; Haoruo JIA ; Qiang JIE
Chinese Journal of Orthopaedics 2024;44(24):1588-1593
Objective:To explore the risk factors for different severities of epiphyseal injury caused by distal tibial fractures in adolescents.Methods:A retrospective analysis was conducted on 195 children with distal tibial fractures accompanied by epiphyseal injuries who were admitted to the Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2018 to December 2023. Among them, there were 132 males and 63 females; the age was 11.7±2.1 years (range, 5-15 years). Among them, 91 cases were on the left side and 104 cases were on the right side. Salter-Harris classification of epiphyseal injuries: there were 42 cases of type I, 90 cases of type II, 34 cases of type III, 26 cases of type IV, and 3 cases of type V. Causes of injury: 37 cases were sports injuries, 29 cases were traffic accident injuries, 120 cases were fall injuries, and 9 cases were fall from height injuries. Dias-Tachdjian classification of injury mechanisms: there were 65 cases of supination-adduction type, 59 cases of supination-plantar flexion type, 35 cases of supination-external rotation type, and 36 cases of pronation-abduction-external rotation type. Among them, 72 cases were complicated with fibular fractures, and 56 cases were accompanied by periosteum incarceration. The age, gender, side of injury, body mass index, cause of injury, presence or absence of fibular fracture, and injury mechanism of children with each type of Salter-Harris injury were compared. The indicators with statistically significant differences were included in the multiple logistic regression analysis to determine the independent risk factors for each type of Salter-Harris injury.Results:The ages of patients with type I-IV were 10.70±2.77, 12.18±1.70, 11.32±2.08, 12.35±1.19, and 11.67±2.08 years old respectively, and the difference was statistically significant ( F=4.794, P=0.001). The body mass indexes were 11.90±3.84, 21.30±4.48, 21.41±4.08, 22.42±3.74, and 24.32±4.82 kg/m 2 respectively, and the difference was statistically significant ( F=1.914, P=0.009). The numbers of cases of sports injuries/traffic accident injuries/fall injuries/fall-from-height injuries were 6/7/23/6, 17/12/59/2, 6/5/22/1, 7/4/15/0, and 1/1/1/0 respectively, and the difference was statistically significant ( P=0.032). The numbers of cases of supination-adduction/pronation-abduction-external rotation/supination-plantar flexion/supination-external rotation were 21/6/9/6, 21/16/37/16, 19/6/8/1, 4/7/4/11, and 0/1/1/1 respectively, and the difference was statistically significant ( P=0.001). The numbers of cases of periosteum incarceration (none/yes) were 32/10, 54/36, 27/7, 25/1, and 1/2 respectively, and the difference was statistically significant (χ 2=17.156, P=0.002). There was no statistically significant difference in gender, side of injury, and presence or absence of fibular fracture among patients with each type of epiphyseal injury ( P>0.05). Age, body mass index, cause of injury, injury mechanism, and periosteum incarceration were included in the multiple logistic regression analysis. The results showed that age [ OR=1.337, 95% CI (1.097, 1.628), P=0.004], the supination varus type of the injury mechanism [ OR=0.257, 95% CI (0.075, 1.013), P=0.015] in the Salter-Harris type II, and the supination plantar flexion type of the injury mechanism [ OR=0.154, 95% CI (0.027, 0.872), P=0.034] in the Salter-Harris type IV were independent risk factors for the severity of epiphyseal injury caused by distal tibial fractures in adolescents. Conclusion:The severity of distal tibial fractures accompanied by epiphyseal injuries in adolescents is related to multiple factors such as age, body mass index, cause of injury, injury mechanism, and periosteum incarceration. For every one-year increase in age, the risk of epiphyseal injury in children with Salter-Harris type II is 1.337 times higher than that in those with type I. The type I epiphyseal injury caused by supination varus injury is 3.891 times that of type II injury, and the type I epiphyseal injury caused by supination plantar flexion injury is 6.493 times that of type IV injury.
7.Risk factors for varying severities of epiphyseal injury caused by distal tibial fractures in adolescents
Tongtong FENG ; Xin JIANG ; Jining QU ; Yu WANG ; Yating YANG ; Shuaikun LIU ; Kaiyang HAN ; Haoruo JIA ; Qiang JIE
Chinese Journal of Orthopaedics 2024;44(24):1588-1593
Objective:To explore the risk factors for different severities of epiphyseal injury caused by distal tibial fractures in adolescents.Methods:A retrospective analysis was conducted on 195 children with distal tibial fractures accompanied by epiphyseal injuries who were admitted to the Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2018 to December 2023. Among them, there were 132 males and 63 females; the age was 11.7±2.1 years (range, 5-15 years). Among them, 91 cases were on the left side and 104 cases were on the right side. Salter-Harris classification of epiphyseal injuries: there were 42 cases of type I, 90 cases of type II, 34 cases of type III, 26 cases of type IV, and 3 cases of type V. Causes of injury: 37 cases were sports injuries, 29 cases were traffic accident injuries, 120 cases were fall injuries, and 9 cases were fall from height injuries. Dias-Tachdjian classification of injury mechanisms: there were 65 cases of supination-adduction type, 59 cases of supination-plantar flexion type, 35 cases of supination-external rotation type, and 36 cases of pronation-abduction-external rotation type. Among them, 72 cases were complicated with fibular fractures, and 56 cases were accompanied by periosteum incarceration. The age, gender, side of injury, body mass index, cause of injury, presence or absence of fibular fracture, and injury mechanism of children with each type of Salter-Harris injury were compared. The indicators with statistically significant differences were included in the multiple logistic regression analysis to determine the independent risk factors for each type of Salter-Harris injury.Results:The ages of patients with type I-IV were 10.70±2.77, 12.18±1.70, 11.32±2.08, 12.35±1.19, and 11.67±2.08 years old respectively, and the difference was statistically significant ( F=4.794, P=0.001). The body mass indexes were 11.90±3.84, 21.30±4.48, 21.41±4.08, 22.42±3.74, and 24.32±4.82 kg/m 2 respectively, and the difference was statistically significant ( F=1.914, P=0.009). The numbers of cases of sports injuries/traffic accident injuries/fall injuries/fall-from-height injuries were 6/7/23/6, 17/12/59/2, 6/5/22/1, 7/4/15/0, and 1/1/1/0 respectively, and the difference was statistically significant ( P=0.032). The numbers of cases of supination-adduction/pronation-abduction-external rotation/supination-plantar flexion/supination-external rotation were 21/6/9/6, 21/16/37/16, 19/6/8/1, 4/7/4/11, and 0/1/1/1 respectively, and the difference was statistically significant ( P=0.001). The numbers of cases of periosteum incarceration (none/yes) were 32/10, 54/36, 27/7, 25/1, and 1/2 respectively, and the difference was statistically significant (χ 2=17.156, P=0.002). There was no statistically significant difference in gender, side of injury, and presence or absence of fibular fracture among patients with each type of epiphyseal injury ( P>0.05). Age, body mass index, cause of injury, injury mechanism, and periosteum incarceration were included in the multiple logistic regression analysis. The results showed that age [ OR=1.337, 95% CI (1.097, 1.628), P=0.004], the supination varus type of the injury mechanism [ OR=0.257, 95% CI (0.075, 1.013), P=0.015] in the Salter-Harris type II, and the supination plantar flexion type of the injury mechanism [ OR=0.154, 95% CI (0.027, 0.872), P=0.034] in the Salter-Harris type IV were independent risk factors for the severity of epiphyseal injury caused by distal tibial fractures in adolescents. Conclusion:The severity of distal tibial fractures accompanied by epiphyseal injuries in adolescents is related to multiple factors such as age, body mass index, cause of injury, injury mechanism, and periosteum incarceration. For every one-year increase in age, the risk of epiphyseal injury in children with Salter-Harris type II is 1.337 times higher than that in those with type I. The type I epiphyseal injury caused by supination varus injury is 3.891 times that of type II injury, and the type I epiphyseal injury caused by supination plantar flexion injury is 6.493 times that of type IV injury.
8.Analysis of Safe Storage Moisture Content of Mume Flos Decoction Pieces Based on Theory of Water Activity and Water Molecular Mobility
Tongtong HAN ; Xiaoyong RAO ; Fengmei QI ; Yan HE ; Guoping ZHAN ; Xiaojian LUO ; Ruilin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):151-156
ObjectiveThe hygroscopic properties of Mume Flos decoction pieces were studied from the perspectives of macroscopic[water activity(Aw)] and microscopic(water molecular mobility), which provided a theoretical basis for the determination of the safe storage moisture content. MethodAdsorption isotherm of Mume Flos decoction pieces was obtained by static weighing method, and seven common hygroscopic models were fitted and estimated. The best model was selected according to the principle that determination coefficient(R2) was closer to 1, residual sum of squares(RSS) was closer to 0 and Akaike information criterion(AIC) was smaller. According to the optimal model, the absolute and relative safe moisture contents of Mume Flos decoction pieces at 25, 35, 45 ℃ was calculated. Low-field nuclear magnetic resonance(LF-NMR) was used to measure the water molecular mobility in the hygroscopic process of Mume Flos decoction pieces. ResultThe best model to describe the adsorption isotherm of Mume Flos decoction pieces was the Peleg model. According to the model expression, the absolute safe moisture contents of Mume Flos decoction pieces at 25, 35, 45 ℃ were 9.59%, 7.96% and 7.68%, and the relative safe moisture contents were 13.05%, 11.99%, 11.77%, respectively. Mume Flos decoction pieces all contained two water states during the process of hygroscopic absorption at different temperatures, namely bound water T21 and free water T22. During the process of hygroscopic absorption, bound water had the largest increase in peak area. The sum of peak areas of the bound water and free water had a good linear relationship with the moisture contents, and the R2 were 0.959 9, 0.911 8 and 0.974 7 at 25, 35, 45 ℃, respectively. When Aw<0.57, T21 did not change, and the water molecular mobility remained unchanged. When Aw>0.57, T21 showed an increasing trend, and the water molecular mobility increased. The moisture contents of Mume Flos decoction pieces were 8.44%, 6.81% and 6.25% when the water molecular mobility increased at 25, 35, 45 ℃, respectively. ConclusionCombined with the theory of water activity and water molecular mobility, 6.25% is recommended as the safe storage moisture content of Mume Flos decoction pieces, this study can provide reference for determining the safe storage moisture content of other decoction pieces.
9.Escape from abluminal LRP1-mediated clearance for boosted nanoparticle brain delivery and brain metastasis treatment.
Naveed Ullah KHAN ; Jiang NI ; Xiufeng JU ; Tongtong MIAO ; Haiyan CHEN ; Liang HAN
Acta Pharmaceutica Sinica B 2021;11(5):1341-1354
Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.
10.Expression of lncRNA GTSE1-AS1 in prostate cancer tissues and its effect on proliferation and invasion of LNCaP cells
LU Shuaiqi ; LI Xiaohui ; HAO Tongtong, ; HAN Xingtao, ; ZHANG Han
Chinese Journal of Cancer Biotherapy 2021;28(1):17-22
[Abstract] Objective: To explore the expression of long non-coding RNA (lncRNA) GTSE1-AS1 in prostate cancer tissues and the mechanism that affects the proliferation and invasion of LNCaP cells. Methods: From November 2017 to December 2018, 68 pairs of prostate cancer tissue and para-cancerous tissue specimens were resected from prostate cancer patients at the Department of Urology of Luoyang Central Hospital Affiliated to Zhengzhou University; in addition, prostate cancer cell lines LNCaP, PC-3, C4-2B, 22Rv1, DU-145 and normal prostate follicular epithelial RWPE-1 cells were also chosen for this study. qPCR was used to detect the expression level of GTSE1-AS1 in cancer tissues and cell lines. The GTSE1-AS1 over-expression plasmid (experimental group) and negative control plasmid (control group) were respectively transfected into LNCap cells. MTT assay and Transwell chamber method were used to detect the effect of GTSE1-AS1 over-expression on the proliferation and invasion ability of LNCaP cells, respectively. The targeting relationship among GTSE1-AS1 and miR-324-3P as well as FBXW7 (F-frame/WD repeat domain protein 7) was verified by bioinformatics tools and dual-luciferin reporter gene assay. The effect of GTSE1-AS1 over-expression on downstream gene and protein expression was detected by qPCR and WB assay. Results: The expression level of GTSE1-AS1 in prostate cancer tissues was significantly lower than that in para-cancerous tissues (P<0.01), and the expression of GTSE1-AS1 in prostate cancer cell lines was significantly lower than that in RWPE-1 cells (P<0.05 or P<0.01). Over-expression of GTSE1-AS1 significantly inhibited the proliferation and invasion (P<0.05 or P<0.01) of LNCaP cells. Dual-luciferin reporter gene assay confirmed the complementary binding between GTSE1-AS1 and miR-324-3p as well as between miR-324-3p and FBXW7. Over-expression of GTSE1-AS1 significantly reduced the expression of miR-324-3p in LNCaP cells (P<0.01), and promoted the mRNA and protein expressions of FBXW7 (all P<0.01). Conclusion: GTSE1-AS1 is under-expressed in prostate cancer tissues and cell lines. Over-expression of GTSE1-AS1 can inhibit the proliferation and invasion of LNCaP cells, the mechanism of which may be related with the inhibition of miR-324-3p to further promote FBXW7 expression.

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