1.Ameliorative effect of patchouli alcohol on mice with lung-heat syndrome based on PI3K/Akt/NF-κB pathway
Linze LI ; Yi LI ; Haoyi QIAO ; Jiakang JIAO ; Qi ZHANG ; Xiaofang WU ; Xingyu ZHAO ; Yinming ZHAO ; Chun WANG ; Jianjun ZHANG ; Linyuan WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):459-470
Objective:
To investigate the therapeutic effect of patchouli alcohol on mice with lung-heat syndrome based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/nuclear factor-kappa B(NF-κB) signaling pathway.
Methods:
First, network pharmacology was used to predict the potential targets of patchouli alcohol in the treatment of lung-heat syndrome, and a "component-disease-key target" network was constructed for pathway analysis. Then, 40 BALB/c mice were assigned to the normal, lung-heat model, honeysuckle, and low-dose and high-dose patchouli alcohol groups. All groups, except the blank group, were intranasally infected with 50 μL (103 TCID50) of influenza virus solution. After two hours of infection, mice were treated once a day for seven consecutive days. The therapeutic mechanism of patchouli alcohol was explored by measuring pulmonary inflammatory factors, the PI3K/Akt/NF-κB pathway, hypothalamic fever markers (PGE2, cAMP, cGMP levels), rectal temperature, and tissue energy metabolism.
Results:
Network pharmacology identified 135 target genes related to patchouli alcohol and lung-heat syndrome, with the key targets being STAT3, H1F1A, and NF-κB1. In animal experiments, patchouli alcohol significantly alleviated influenza virus-induced lung inflammatory damage in mice with lung-heat syndrome, inhibited the expression of TNF-α and IL-6 in lung tissues(P<0.01), and suppressed the activation of the PI3K/Akt/NF-κB pathway. It also reduced hypothalamic levels of PGE2 and cAMP(P<0.01), suppressed the increase in rectal temperature, significantly decreased liver glycogen and pyruvate levels(P<0.01), and increased the activities of SDH, LDH, and Na+ -K+ -ATPase in the liver(P<0.01)
Conclusion
Patchouli alcohol improves the symptoms of lung-heat syndrome in mice by inhibiting the activation of the PI3K/Akt/NF-κB pathway, reducing proinflammatory cytokines and inflammatory damage, and regulating hypothalamic fever markers and energy metabolism.
2.Application progress of hemoglobin-based oxygen carriers (HBOCs) in tumor therapy
Shifan ZHENG ; Hong WANG ; Yingcan XU ; Jiakang WU ; Wentao ZHOU ; Shasha HAO
Chinese Journal of Blood Transfusion 2024;37(4):477-481
Most solid tumors suffer from inadequate blood perfusion and oxygenation, leading to a hypoxic microenvironment that accelerates tumor progression and adversely impacts prognosis. Thus, improving oxygenation in tumor tissues is crucial for enhancing the sensitivity and efficacy of tumor therapy. Hemoglobin-based oxygen carriers (HBOCs), as a type of oxygen-carrying nanoparticles, can not only carry and release oxygen but also reach the small blood vessels of obstructive microcirculation to deliver oxygen for anoxic tissues and organs, which are difficult for normal red blood cells to pass through. Studies have demonstrated that the application of HBOCs as a potential nanoscale efficient oxygen carrier in tumor therapy can enhance tissue oxygenation and hold great promise for applications in tumor therapy.This review summarizes the impact of hypoxia in tumors and highlights the progress and potential mechanisms of using HBOCs in tumor radiotherapy, chemotherapy, new kinetic therapy and immunotherapy.
3.Therapeutic effect of chemoimmunotherapy on breast cancer sensitized by polymerized human cord hemoglobin in mice: a preliminary study
Shifan ZHENG ; Wentao ZHOU ; Shen LI ; Jiakang WU ; Xunyi YOU ; Jiaxin LIU ; Hong WANG
Chinese Journal of Blood Transfusion 2024;37(3):290-296
【Objective】 To investigate the effect of polymerized human cord hemoglobin (PolyCHb) in chemoimmunotherapy for breast cancer in mice. 【Methods】 A 4T1 breast cancer in situ tumor model was established, and 15 mice were randomly divided into 3 groups: blank group: no intervention; Control group: doxorubicin + PD-1 inhibitor was given intraperitoneal injection of doxorubicin 5 mg·kg-1 once a week and PD-1 inhibitor 12.5 mg·kg-1 once a week; Experimental group: DOX+ a-PD-1+ PolyCHb, the usage of DOX and a-PD-1 was the same as above, PolyCHb: PolyCHb 600 mg·kg-1 was injected into the tail vein, three times a week; The administration period was 4 weeks. During the administration, the tumor volume was recorded 3 times per week, the tumor growth curve of each group was drawn and the tumor inhibition rate was calculated. The mice were killed on the 29th day, and the tumor was removed and weighed to calculate the tumor inhibition rate. Immunofluorescence, HE staining, TUNEL method and immunohistochemistry was used to detect the expression of HIF-1α, observe the pathological changes of tumor tissue, detect the apoptosis of tumor cells, and detect the expression of tumor proliferation index Ki67. 【Results】 Compared with the blank group and the control group, the tumor volume in the experimental group decreased significantly (P<0.05) and the tumor inhibition rate (%) increased significantly (P<0.05). The content of HIF-1α in tumor tissue in experimental group decreased (P<0.05). In the experimental group, the growth area of tumor tissue decreased, accompanied by the increase of necrosis area; The positive rates (%) of apoptosis in tumor tissues of blank group, control group and experimental group were 18.79±0.62, 20.68±1.19 and 41.65±2.99 respectively (F=135.2, P<0.001). In addition, the results of tumor proliferation index Ki67 showed that there was a statistical difference between the control group and the experimental group (P<0.05). 【Conclusion】 PolyCHb increases the sensitivity of chemoimmunotherapy in breast cancer mouse model, and the mechanism may be related to the decrease of HIF-1α expression, the promotion of apoptosis and the inhibition of cell proliferation.
4.Preparation and in vitro evaluation of hemoglobin-paclitaxel dual loaded liposomes for improving tumor hypoxia resistance
Xunyi YOU ; Kehui ZHU ; Jing XIAO ; Jiakang WU ; Shifan ZHENG ; Along ZHANG ; Rui ZHONG ; Hong WANG ; Ye CAO ; Jiaxin LIU
Chinese Journal of Blood Transfusion 2024;37(3):297-303
【Objective】 To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance. 【Methods】 LEHP were prepared by thin-film method, and the particle size, Zeta potential and polydispersity were investigated by nanoparticle size analyzer, and encapsulation efficiency was investigated by high performance liquid chromatography, and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments. 【Results】 The optimal preparation conditions of LEHP was as follows: total phospholipid 36 mM, DPPC∶Dope∶cholesterol molar ratio 7∶2∶1, paclitaxel 3 mg, hydrated with 3 mg·mL-1 Hb-PBS for 30 min at room temperature; The average particle size was (189.17±8.22) nm, polydispersity was 0.14±0.023, paclitaxel encapsulation efficiency was (58.27±2.55)%, hemoglobin content was (0.63±0.05) mg·mL-1. In vitro cell experiments, the killing effect of LEHP was about 1.5 times that of LEP, about 1.2 times that of LEP, and ROS production was about 1.8 times that of LEP. 【Conclusion】 The preparation conditions of LEHP was optimized, and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production, which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.
5.Wound healing in diabetic mice with soluble microneedle-loaded platelet-rich plasma lysate: a preliminary study
Jiakang WU ; Shifan ZHENG ; Xunyi YOU ; Hong WANG ; Yingcan XU ; Rui ZHONG ; Jiaxin LIU
Chinese Journal of Blood Transfusion 2024;37(2):130-137
【Objective】 To prepare microneedles(MNs) loaded with platelet-rich plasma lysate (PL) using Carboxymethyl chitosan (CMCS), and explore the prospect of PL MNs in the treatment of diabetic wounds. 【Methods】 CMCS was used as the basic material, and an appropriate amount of polyvinylpyrrolidone (PVPK-60) was added to prepare needle materials of different concentrations, and the optimal concentration was determined by investigating the needle formation rate, morphological characteristics and mechanical properties, and the growth factor activity in PL MNs was investigated. The diabetic mice were randomly divided into four groups after the back wound was made, the control group did not do any treatment, the PL smear group was treated with PL smearing, the blank MNs group was treated with MNs without PL, and the PL MNs group was treated with PL microneedles. The effect of PL MNs in wound healing in diabetic mice was evaluated through body observation, H&E staining and immunohistochemistry results. 【Results】 When PVPK60 was 40 mg/mL, the needle formation rate was 100%, the array was complete, the needle body was full, and the needle was sharp. According to the results of mechanical-displacement curve and weight pressure change experiment, the prepared PL MNs have good mechanical strength. The results of growth factor analysis indicated that the content of vascular endothelial growth factor (VEGF) in PL was (625±35) pg/mL, and the content of platelet-derived growth factor-BB (PDGF-BB) was (18 741±1 287) pg/mL. After making the MNs, the VEGF content was (183±2) pg/mL, and the PDGF-BB content was (8049±1157) pg/mL. Although the concentration of growth factors decreased, growth factor activity was still preserved.The results of wound healing experiments in diabetic mice showed that the PL MNs group had better healing, and the wound healing rate was different from that of three groups (P<0.01). The results of H&E staining showed that the PL MNs group had fewer inflammatory cell infiltrates and bleeding spots. The number of fibroblasts and new microvascular in the control group was worse than that in the PL MNs group and the PL smear group. The results of immunohistochemistry indicated that the expression of pro-inflammatory factor IL-6 decreased, while anti-inflammatory factor TGF-β and angiogenesis index CD31 increased in the PL MNs group, which were significantly different from those in the other three groups (P<0.01). 【Conclusion】 The PL MNs prepared in this experiment have good mechanical properties, which has a positive effect on the wound healing of diabetic mice, and provides a new idea for diabetic wound healing.
6.Modification effect of overweight and obesity on the association between short term PM 2.5 exposure and high blood pressure in adolescents
Chinese Journal of School Health 2022;43(2):296-299
Objective:
To analyze the association between short term PM 2.5 exposure and high blood pressure in adolescents and its modification effect of overweight and obesity, and to provide a reference for the refined management of students physical health and the scientific prevention and controlling of air pollution.
Methods:
A total of 148 956 junior high school students and senior high school students who passed the annual physical examination data of middle school students in Beijing from 2017 to 2018 were selected; The inverse distance weighted interpolation method was used to get the meteorological elements and air quality of the research area; Linear mixed effect model was used to estimate the cumulative lag effect of short term PM 2.5 exposure on systolic and diastolic blood pressure within 7 days, and analyze the modification effect of overweight and obesity on the association between short term PM 2.5 exposure and high blood pressure in adolescents.
Results:
From September 1, 2017 to June 30, 2018, the average concentration of PM 2.5 was (56.53±45.85)μg/m 3; The detection rate of overweight and obesity was 34.22%, and the detection rate of high blood pressure was 8.03%. The cumulative lag effect of PM 2.5 on systolic blood pressure in overweight and obesity group was the largest at lag07, that is, the daily average concentration of PM 2.5 increased by 10 μg/m 3 was significantly correlated with higher systolic blood pressure ( OR =1.05,95% CI =1.03-1.07); the cumulative lag effect of PM 2.5 on systolic blood pressure in non overweight and obese group was the largest at lag05, that is, the daily average concentration of PM 2.5 increased by 10 μg/m 3 was significantly correlated with higher systolic blood pressure ( OR =1.04,95% CI =1.02-1.06). Short term exposure to PM 2.5 did not affect the high diastolic blood pressure in adolescents. Overweight and obese adolescents were more susceptible to high blood pressure caused by short term PM 2.5 exposure within 3 days of cumulative lag (lag01-lag03).
Conclusion
The short term exposure of PM 2.5 has a significant positive correlation with adolescent blood pressure, and shows a lag effect. Overweight and obese adolescents have higher blood pressure after PM 2.5 short term exposure.
7.Association between short-term exposure of fine particulate matters and blood pressure in children and adolescents
HUO Jiakang, DONG Yanhui, LI Weiming, WU Lijuan, CHEN Li, CHEN Manman, MA Ying, GUO Xiuhua, MA Jun
Chinese Journal of School Health 2021;42(5):723-727
Objective:
To evaluate the association of short-term fine particulate matters (PM2.5) exposure and blood pressure in children and adolescents.
Methods:
A total of 144 813 junior and senior middle school students who participated in the physical examination in the 2017-2018 academic year in a northern city of China, with complete record of demographic characteristics, blood pressure and no history of heart and other important organ diseases were selected as the study subjects. Data on PM2.5 and other pollutants and meteorological data were obtained from the nearest air quality and meteorological monitoring stations of each schools. A generalized linear mixed effect model was used to analyze the association between short-term exposure of PM2.5 and blood pressure.
Results:
The 6 day average concentration of PM2.5 (lag05) increased by 10 μg/m 3 was associated with an increase of 0.177(95%CI=0.148-0.207)mm Hg (1 mm Hg=0.133 kPa) in systolic blood pressure and 4.4%(OR=1.044, 95%CI=1.030-1.058) increase of the prevalence of high systolic blood pressure. And it was also associated with -0.021(95%CI=-0.040--0.002)mm Hg decrease in diastolic blood pressure, but had no significant correlation with the prevalence of high diastolic blood pressure. In general, a 10 μg/m 3 increase of PM2.5 was associated with 3.3% increase in the prevalence of high blood pressure (OR=1.03, 95%CI=1.02-1.05), and difference of boys and girls were found in different lagged days (P<0.05).
Conclusion
Short-term exposure of PM2.5 is associated with increased systolic blood pressure and prevalence of high blood pressure among children and adolescents. Attention should be paid to the prevention of short-term exposure of PM2.5 to protect the health of children and adolescents.
8.Effect modification of overweight and obesity on the relationship between shortterm PM 2.5 exposure and vital capacity in children and adolescents
Chinese Journal of School Health 2021;42(11):1740-1743
Objective:
To analyze the relationship between short term exposure of PM 2.5 and the vital capacity of children and adolescents and the modification effect of overweight and obesity, and to provide a scientific reference for appropriate outdoor activities and strengthening prevention of air pollution.
Methods:
A total of 1 036 273 students who qualified in the annual health examination data of primary and secondary school students in a city from 2017 to 2018 were selected; the meteorological factors and air quality of the study area were obtained by inverse distance weighted interpolation method; the generalized linear mixed model was used to estimate the individual lag effect and average lag effect of PM 2.5 short term exposure on lung capacity with in 7 days, and to analyze the modification effect of overweight and obesity on the relationship between short term PM 2.5 exposure and vital capacity in children and adolescents.
Results:
From September 1, 2017 to June 30, 2018, the average PM 2.5 concentration in this city was 66.36 μg/m 3, the detection rate of overweight and obesity was 33.38%, and the average lung capacity was (2 286.72±956.77)mL. The single lag effect of PM 2.5 on vital capacity was the biggest when lag6, the average daily PM 2.5 concentration increased by 10 μg/m 3 and the decrease of vital capacity of children and adolescents by 2.81(95% CI =2.60-3.03)mL. The average lag effect of PM 2.5 on lung capacity was the largest when lag07, the average concentration of PM 2.5 sliding was significantly correlated with the decrease of lung capacity of children and adolescents by 5.82(95% CI =5.37-6.27)mL every 10 μg/m 3 increase. The prevalence of PM 2.5 short term exposure to pulmonary capacity decreased in overweight and obese children and adolescents was higher ( P <0.01).
Conclusion
The short term exposure of PM 2.5 has a significant negative correlation with the lung capacity of children and adolescents, and there is a lag effect. The decrease of the vital capacity of overweight and obese children and adolescents after PM 2.5 short term exposure is more significant.
9.Diagnostic value of MRI-measured fetal percent predicted lung volume for prognosis of left congenital diaphragmatic hernia
Junjian LYU ; Qiuming HE ; Wei ZHONG ; Hao WEN ; Li HUANG ; Zhe WANG ; Qiang WU ; Jiakang YU ; Hongsheng LIU
Chinese Journal of Perinatal Medicine 2018;21(11):745-749
Objective To evaluate the diagnostic value of MRI-measured fetal percent predicted lung volume (PPLV) for the prognosis of left congenital diaphragmatic hernia (CDH) in fetus. Methods Clinical data of 32 children who were admitted to Women and Children's Medical Center of Guangzhou from September 2012 to December 2017 for prenatally diagnosed left CDH were retrospectively analyzed. These children were divided into two groups, the survival group (n=24) and the death group (n=8), according to the postoperative outcomes at 30 days after CDH repair. Moreover, they were also divided into non-pulmonary hypertension (non-PH) group (n=20) and PH group (n=12), based on whether they suffered from PH or not. Clinical data such as gestational age, birth weight, Apgar score and PPLV values in different groups were compared with t- or Fisher's exact test. The receiver operating characteristic (ROC) curve of the MRI-measured fetal PPLV values of the 32 children was plotted. Results (1) Comparing with the death group, fetal PPLV was significantly higher [(39.5±2.5)% vs (20.4±2.1)%, t=4.27], the gestations on initial diagnosis of CDH was later [(31.6±4.2) vs (25.4±4.6) gestational weeks, t=3.40], Apgar score of the neonates at 5 min was higher (8.7±1.5 vs 5.7±3.8, t=3.26), and fewer cases of PH were reported in the survival group [16.7% (4/24) and 8/8], all P<0.01. The area under the ROC curve of PPLV values for mortality prediction was 0.930 (95%CI: 0.843-1.016, P<0.01). When the PPLV value was 28.55%, its sensitivity and specificity for death prediction in children with left CDH were 100% and 79%, respectively. (2) Comparing with the PH group, fetal PPLV was significantly higher [(41.7±2.6)% vs (23.0±2.0)%, t=4.98], the gestations on initial diagnosis of CDH was later [(32.3±3.4) vs (26.3±5.2) gestational weeks, t=3.81], neonatal Apgar score at 5 min was higher (8.6±1.4 vs 6.8±2.5, t=2.62) and death rate was lower [0(0/20) vs 8/12] in the non-PH group (all P<0.01). The area under the ROC curve of the PPLV values for predicting PH was 0.902 1 (95%CI : 0.800-1.004, P<0.01). When the PPLV value was 33.67%, its sensitivity and specificity for PH prediction was 100% and 75%, respectively. Conclusions Prenatal MRI measurement of PPLV can be used to predict death or as a warning sign of PH in children with left CDH, which may provide evidence for prenatal evaluation and rational clinical decision-making.
10.Meta-analysis of Duhuo Jisheng Decoction Combined with Chemical Medicines in the Treatment of Anky-losing Spondylitis
Yuyun WU ; Qianyi ZHOU ; Jiakang CUI ; Qingping LIU
China Pharmacy 2016;27(21):2945-2947
OBJECTIVE:To systematically review the efficacy of Duhuo jisheng decoction combined with chemical medicines in the treatment of ankylosing spondylitis (AS),and to provide reference for clinical treatment. METHODS:Retrieved from CBM,CJFD,VIP,Wanfang Database,PubMed and EMBase,randomized controlled trials(RCT)about Duhuo jisheng decoction combined with chemical medicines(test group)versus chemical medicines alone(control group)in the treatment of AS were col-lected,Meta-analysis was performed by using Rev Man 5.3 software after data extraction and quality evaluation. RESULTS:Total-ly 6 RCTs were included,involving 382 patients. Results of Meta-analysis showed,the total effective rate [RR=1.35,95%CI(1.20, 1.52),P<0.001],improvement rate of TCM symptoms [RR=1.31,95%CI(1.09,1.57),P=0.004)in test group were significantly higher than control group,and CRP level was lower than contxol group[MD=-6.18,95%CI(-8.49,-3.87),P<0.001],the dif-ference was statistically significant. CONCLUSIONS:Duhuo jisheng decoction combined with chemical medicines shows better effi-cacy than chemical medicines alone,it can improve the TCM symptoms and decrease the CRP level.


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