1.Activation of α7 nAChR improves white fat homeostasis and promotes beige adipogenesis and thermogenesis in obese mice
Hansheng BAO ; Sutong WANG ; Mujie LÜ ; Yongcheng WANG ; Ping JIANG ; Xiao LI
Journal of Southern Medical University 2024;44(3):499-506
Objective To investigate the effects of α7 nicotinic acetylcholine receptor(nAChR)agonist on β3-adrenoceptor agonist-induced impairment of white fat homeostasis and beige adipose formation and heat production in obese mice.Methods Forty obese C57BL/6J mice were randomized into high-fat feeding group,β3-adrenoceptor agonist-treated model group,α7 nAChR agonist group,and α7 nAChR inhibitor group(n=10),with another 10 mice with normal feeding as the blank control group.White adipose tissue from the epididymis of the mice were sampled for HE staining of the adipocytes.The expression levels of TNF-α,IL-1β,IL-10 and TGF-β in the white adipose tissue were determined by ELISA,and the mRNA levels of iNOS,Arg1,UCP-1,PRDM-16 and PGC-1α were detected using RT-qPCR.Western blotting was performed to detect the expression levels of NF-κB P65,p-JAK2,p-STAT3 in the white adipose tissue.Results Compared with those in the blank control group,the mice with high-fat feeding showed significantly increased body weight,more fat vacuoles in the white adipose tissue,increased volume of lipid droplets in the adipocytes,upregulated iNOS mRNA expression and protein expression of TNF-α and IL-1β,and lowered expression of Arg-1 mRNA and IL-10 and TGF-β proteins(P<0.01).Treatment with α7 nAChR significantly reduced mRNA levels of PRDM-16,PGC-1α and UCP-1,lowered TNF-α and IL-1β expressions,increased IL-10 and TGF-β expressions,and reduced M1/M2 macrophage ratio in the white adipose tissues(P<0.05 or 0.01).Conclusion Activation of α7 nAchR improves white adipose tissue homeostasis impairment induced by β3 agonist,promotes transformation of M1 to M2 macrophages,reduces inflammatory response in white adipose tissue,and promote beige adipogenesis and thermogenesis in obese mice.
2.Activation of α7 nAChR improves white fat homeostasis and promotes beige adipogenesis and thermogenesis in obese mice
Hansheng BAO ; Sutong WANG ; Mujie LÜ ; Yongcheng WANG ; Ping JIANG ; Xiao LI
Journal of Southern Medical University 2024;44(3):499-506
Objective To investigate the effects of α7 nicotinic acetylcholine receptor(nAChR)agonist on β3-adrenoceptor agonist-induced impairment of white fat homeostasis and beige adipose formation and heat production in obese mice.Methods Forty obese C57BL/6J mice were randomized into high-fat feeding group,β3-adrenoceptor agonist-treated model group,α7 nAChR agonist group,and α7 nAChR inhibitor group(n=10),with another 10 mice with normal feeding as the blank control group.White adipose tissue from the epididymis of the mice were sampled for HE staining of the adipocytes.The expression levels of TNF-α,IL-1β,IL-10 and TGF-β in the white adipose tissue were determined by ELISA,and the mRNA levels of iNOS,Arg1,UCP-1,PRDM-16 and PGC-1α were detected using RT-qPCR.Western blotting was performed to detect the expression levels of NF-κB P65,p-JAK2,p-STAT3 in the white adipose tissue.Results Compared with those in the blank control group,the mice with high-fat feeding showed significantly increased body weight,more fat vacuoles in the white adipose tissue,increased volume of lipid droplets in the adipocytes,upregulated iNOS mRNA expression and protein expression of TNF-α and IL-1β,and lowered expression of Arg-1 mRNA and IL-10 and TGF-β proteins(P<0.01).Treatment with α7 nAChR significantly reduced mRNA levels of PRDM-16,PGC-1α and UCP-1,lowered TNF-α and IL-1β expressions,increased IL-10 and TGF-β expressions,and reduced M1/M2 macrophage ratio in the white adipose tissues(P<0.05 or 0.01).Conclusion Activation of α7 nAchR improves white adipose tissue homeostasis impairment induced by β3 agonist,promotes transformation of M1 to M2 macrophages,reduces inflammatory response in white adipose tissue,and promote beige adipogenesis and thermogenesis in obese mice.
4.Gouteng Prescription Treats Primary Hypertension with Anxiety Disorder in Patients with Syndrome of Yang Hyperactivity and Heat Toxin: Clinical Efficacy and Impact on Balance of Inflammatory Cytokines
Yongcheng WANG ; Yimei ZHANG ; Xiangdong XU ; Changjing CHEN ; Lin WANG ; Sutong WANG ; Zifang TIAN ; Xiao LI ; Jibiao WU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):138-145
ObjectiveTo explore the clinical efficacy of Gouteng prescription in treating the patients with primary hypertension with anxiety disorder due to yang hyperactivity and heat toxin and the impact of the formula on the balance of inflammatory cytokines. MethodA total of 98 patients diagnosed with primary hypertension and anxiety disorder were randomized into control and observation groups. On the basis of conventional western medicine treatment for hypertension, the control group (47 patients) was treated with Shugan Jieyu capsules for 8 weeks, while the treatment group (51 patients) with Gouteng prescription for 8 weeks. The two groups were compared in terms of the blood pressure level, 24-hour blood pressure variability, Hamilton anxiety scale (HAMA) score, Pittsburgh sleep quality index (PSQI) score, quality of life (SF-36 scale) score, traditional Chinese medicine (TCM) syndrome score and efficacy, incidence of adverse reactions, and the levels of interleukin (IL)-1β, IL-6, IL-10, and IL-4 in the serum of peripheral blood. ResultThe final trial was completed with 95 patients, including 46 in the control group and 49 in the observation group. The treatment in both groups lowered the blood pressure and blood pressure variability (P<0.05, P<0.01). The observation group outperformed the control group in recovering the systolic blood pressure (SBP), 24-hour mean systolic blood pressure (24 h SBP), 24-hour systolic blood pressure variability (24 h SBPV), and 24-hour diastolic blood pressure variability (24 h DBPV) (P<0.05). After treatment, the HAMA and PSQI scores in both groups decreased (P<0.05, P<0.01), and the observation group had lower HAMA and PSQI scores than the control group (P<0.05). Compared with those before treatment, the SF-36 scores in both groups increased (P<0.05, P<0.01). After treatment, the observation group had higher scores of physiological function (PF), bodily pain (BP), social function (SF), role-emotional (RE), and mental health (MH) indicators than the control group (P<0.05). After treatment, the TCM syndrome scores in both groups decreased (P<0.05, P<0.01), and the observation group had lower score than the control group (P<0.05). The total response rate regarding TCM syndrome in the observation group was 85.71% (42/49), which was higher than that (63.04%, 29/46) in the control group (χ2=6.621, P<0.05). The treatment in both groups lowered the levels of pro-inflammatory cytokines (IL-1β, IL-6) and elevated the levels of anti-inflammatory cytokines (IL-10, IL-4) (P<0.05, P<0.01), and the changes were more obvious in the observation group than in the control group (P<0.05). There were no adverse events during the research process. ConclusionGouteng prescription can recover the blood pressure level, reduce blood pressure variability, suppress anxiety state, improve sleep and quality of life, decrease TCM syndrome score, increase total response rate, lower serum IL-1β and IL-6 levels, and elevate serum IL-10 and IL-4 levels in the patients with primary hypertension complicated with anxiety disorder due to yang hyperactivity and heat toxin. It may exert the effects by regulating the balance of pro-inflammatory and anti-inflammatory cytokines.
5.Application of hyaluronic acid microneedles in insulin intelligent delivery system for the treatment of diabetes.
Yongcheng XIAO ; Xiaobin WANG ; Deming XIE
Chinese Journal of Biotechnology 2022;38(9):3433-3442
In this study, insulin (insulin, INS)/Ca3PO4 complex and glucose oxidase (glucose oxidase, GOx)/Cu3(PO4)2 complex were prepared by coprecipitation method. The mineralized insulin (mineralized insulin, m-INS) showed irregular crystalline clusters, and the mineralized glucose oxidase (m-GOx) showed flower spherical morphology, with a diameter of about 1-2 μm. In vitro simulated release experiment showed that m-INS released INS as the pH value of the medium decreased. When the pH value was 4.5, the release amount reached 96.68%. The enzyme activity detection experiment showed that the enzyme activity stability of m-GOx was higher than that of free GOx. It still maintained high activity after 10 days at room temperature, while the activity of GOx was less than 60%. The glucose solution was prepared to simulate the state of normal blood glucose (5.6 mmol/L) and hyperglycemia (22.2 mmol/L). When m-INS and m-GOx were added to the glucose solution, the release amount of INS showed a significant glucose concentration dependence. The higher the glucose concentration, the greater the release amount and release rate of INS. Finally, m-INS, m-GOx and hyaluronic acid (HA) solution were mixed to prepare HA microneedle arrays loaded with m-INS and m-GOx. Type 1 diabetes mice were constructed to evaluate the effect of drug-loaded HA microarray on blood glucose control in diabetic rats. The results show that the HA microneedles loaded with m-INS/m-GOx could deliver drugs effectively. The average blood glucose concentration in diabetic rats dropped to about 7 mmol/L within 1 h, normal blood glucose concentration could be maintained for 10 h, and the overall blood glucose concentration was lower than the level before administration for 36 hours. Compared with HA microneedles loaded with INS only, m-ins microneedles showed better glucose tolerance, longer-lasting glucose control effect and less risk of hypoglycemia. Compared with other sustained-release systems, the preparation process of the core components in this study is simple, efficient, safe and effective, and has great commercial potential.
Animals
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Blood Glucose
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Delayed-Action Preparations/therapeutic use*
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Diabetes Mellitus, Experimental/drug therapy*
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Drug Delivery Systems/methods*
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Glucose Oxidase/chemistry*
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Hyaluronic Acid
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I Blood-Group System
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Insulin/therapeutic use*
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Mice
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P Blood-Group System
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Rats
6.The effects of periacetabular osteotomy in the treatment of borderline developmental dysplasia of the hip
Liqiang ZHANG ; Hong ZHANG ; Dianzhong LUO ; Hui CHENG ; Kai XIAO ; Ningtao REN ; Yongcheng HU
Chinese Journal of Orthopaedics 2021;41(14):966-976
Objective:To investigate the effects of periacetabular osteotomy (PAO) in treating borderline developmental dysplasia of the hip (DDH).Methods:The patients with borderline DDH [lateral center-edge angle (LCEA): 18°-25°) who received PAO with follow-up duration for more than 2 years from January 2011 to January 2018 in our hospital were retrospectively analyzed. The patients in the control group were matched on a 1∶2 ratio based on gender, age, body mass index (BMI) and follow-up duration. There were 66 patients in the 0°≤LCEA<10° group and 66 patients in the 10°≤LCEA<18° group. The LCEA, anterior center-edge angle (ACEA), T?nnis angle, femoral head extrusion index, femoro-epiphyseal acetabular roof (FEAR) index, femoral anteversion angle, West Ontario and McMaster University (WOMAC) index and International Hip Outcome Tool (iHOT-12) were compared among the three groups before operation and the last follow-up.Results:In the preoperative 18°≤LCEA<25° group, three of 33 patients (9.1%) had LCEA, because the only imaging feature suggested acetabular dysplasia, while other parameters were evaluated within the normal range. There were 17 patients with ACEA <20° (51.5%), 24 patients (72.7%) with T?nnis angle >10°, 12 patients (36.4%) with ACEA <20° and T?nnis angle >10°. The positive rate of posterior wall signs in the 18°≤LCEA<25° group (72.7%) was lower than that in the 10°≤LCEA<18° group (77.3%) and the 0°≤LCEA<10° group (90.9%) with statistically significant difference (χ 2=6.417, P=0.040) at preoperation. The positive rate of cross sign (27.3%) and ischial spine sign (48.5%) in the 18°≤LCEA<25° group were higher than those in the 10°≤LCEA<18° group (10.6% and 18.2%, respectively, χ 2=7.002, P=0.030) and the 0°≤LCEA<10° groups (9.1% and 13.6%, respectively, χ 2=16.497, P<0.001). The FEAR index in the 18°≤LCEA<25° group (3.7±8.0) lower than that in the 10°≤LCEA<18° group (4.3±7.9) and the 0°≤LCEA<10° group (11.0±8.8) with significant difference ( F=12.703, P<0.001). In the 18°≤LCEA<25° group, postoperative LCEA increased from 20.4°±1.8° to 37.8°±7.1°, ACEA increased from 18.3°±7.8° to 36.3°±6.3°. T?nnis angle decreased from 12.7°±6.2° to -5.6°±9.2°, the femoral head extrusion index decreased from 22.9%±6.7% to 10.7%±12.2%, the WOMAC index decreased from 20.1±13.4 to 6.0±6.3, and the iHOT-12 score increased from 50.2±19.9 to 90.0±13.7. The above difference before and after surgery was statistically significant ( P<0.05). At the last follow-up, the WOMAC score in the 18°≤LCEA<25° group was 6.0±6.3, wich was less than 10°≤LCEA<18° group (9.3±9.6) and 0°≤LCEA<10° group (12.0±16.0) ( F=6.515, P=0.002). The iHOT-12 score in the 18°≤LCEA<25° group was 90.0±13.7, which was greater than 10°≤LCEA<18° group (77.7±17.3) and 0°≤LCEA<10° group (78.1±20.5) ( F=15.833, P<0.001). Conclusion:After 2 years follow-up, PAO significantly improved bone coverage of femoral head and hip function in patients with borderline DDH. Before surgery, we should pay attention to the comprehensive evaluation of different radiological parameters of the acetabulum, to make better preoperative planning.
7. Surgical treatment of unilateral Isler type II lumbosacral junction injuries with triangular osteosynthesis
Zhaojie LIU ; Jian JIA ; Xin JIN ; Wei TIAN ; Yuxi SUN ; Haotian QI ; Hongchuan WANG ; Xiang XIAO ; Gang LI ; Yongcheng HU
Chinese Journal of Orthopaedics 2019;39(13):833-840
Objective:
To explore the treatment outcome of triangular osteosynthesis (TOS) for the treatment of unilateral Isler type II lumbosacral junction injuries (LSJIs).
Methods:
Data of sixteen patients with unilateral Isler type II LSJIs surgically who were treated in our Hospital from March 2015 to February 2017 were retrospectively analyzed. There were 13 males and 3 females with an average age of 35.5 years (range, 24-61 years). Seven patients were multiple injuries including head, thoracic, musculoskeletal and nerve injuries. According to Isler classification of LSJIs, there were 5 cases of type IIa, 9 of type IIb and 2 of type IIc. All the LSJIs combined with ipsilateral sacral fractures. The sacral fractures were classified by Denis classification with 1 case of zone I, 13 cases of zone II and 2 cases of zone III. According to Tile classification of pelvic fractures, there were 3 cases of type B2, 11 of type C1 and 2 of type C3. There were 3 cases combined with sacral nerve injury among which there were 2 cases of grade II and 1 case of grade III according to Gibbons classification of neurologic deficits. All cases were surgically treated with triangular osteosynthesis. There were 14 cases combined with iliosacral screws fixation in S1 and 2 cases combined with posterior locking plates.
Results:
All patients were followed up for 20.6 months (range, 16-30 months). CT scan was conducted 12 to 24 months after surgery which showed all the sacral fractures were union, and 2 cases achieved bony fusion in L5S1 facets while the other 14 didn’t. According to Majeed’s pelvic injury evaluation, clinical outcomes were rated with excellent in 12 cases, good in 2 cases, fair in 2 cases. The excellent and good rate was 87.5% (14/16) . According to Mears-Velyvis evaluation criterion, there were 14 cases with anatomical reduction and 2 cases with satisfactory reduction. Among the 3 cases with sacral nerve injury, 2 cases were improved from Gibbons grade II to grade I and the other 1 case was improved from Gibbons grade III to grade II, still feeling numbness on the lateral foot. There were no intraoperative complications in all patients such as neurovascular injuries. No incision infection, fat liquefaction and other incision related complications occurred postoperatively. Irritation and pain in iliac spine about prominent implant occurred in 1 case and lumboscaral stiffness in 1 case, in which the symptom relieved and disappeared after implants removal.
Conclusion
Triangular osteosynthesis can provide enough stabilization for Isler type II LSJIs and achieve satisfactory outcomes.
8.Application limitations of sympathetic nerve-mediated thermogenesis of brown/ beige adipose tissue in the treatment of obesity
Dufang MA ; Ping JIANG ; Yongcheng WANG ; Xiao LI
Chinese Journal of Endocrinology and Metabolism 2017;33(7):625-628
Studies on promoting thermogenesis of brown and beige adipose tissue have become a hot topic in various metabolic conditions, which based on the conclusions that brown and beige adipose tissue are able to facilitate weight loss and improve metabolic health.However, recent studies showed that there were several problems for the anti-obesity application via promoting brown/beige adipose tissue thermogenesis.In obese individuals, classical brown adipose tissue presents thermogenesis dysfunction.Moreover, the beige adipose tissue has significantly lower thermogenesis capability compared with brown adipose tissue.On such conditions, excessively excited sympathetic innervation is essential to increase energy consumption in obesity via increasing classic brown adipose thermogenesis and inducing white adipose tissue browning.However, excessive excited sympathetic nerve results in cardiovascular side effects.Additionally, excessive induction of white adipose tissue browning might disrupt the white adipose tissue homeostasis and aggravate the intrinsic metabolic disorders.Therefore, solving these practical application problems of brown/beige adipose tissue is a new research area for improving metabolic disorders.
9.Optimization of Ethanol Extraction Technology forXiao-Xu-MingDecoction by Orthogonal Design with Multi-target
Renjie WANG ; Enli ZHOU ; Miao LI ; Jianping QIN ; Yun WU ; Yongcheng SUN ; Guanhua DU ; Wei XIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(9):1795-1800
This study was aimed to optimize the ethanol extraction technology ofXiao-Xu-Ming (XXM) decoction. The extraction rates of paeoniflorin, ferulic acid, tetrandrine and yield extract were used as comprehensive evaluation indexes. The amount of ethanol, extraction times, extraction time and concentration of ethanol were selected as factors. The orthogonal design was used to optimize ethanol reflux extraction technology of XXM decoction. The results showed that the optimum extraction conditions were as follows: refluxing extracted 3 times with 10 folds, 70% ethanol, 1.5 h for each time. It was concluded that the optimized extraction process was objective, practical, reasonable and stable, which provided experimental basis for industrial production of XXM decoction.
10.Effects of Different Preparation Methods on Content of Ginsenosides Rg1, Re and Rb1 in Yi-Xin-Shu Tablets by HPLC-ELSD
Hongmei YIN ; Dianhong XU ; Juan FU ; Fengjun HE ; Junchao LIU ; Yongcheng SUN ; Wei XIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(11):2280-2284
This paper was aimed to study effects of different preparation methods on the content of ginsenosides Rg1,Re and Rb1 in Yi-Xin-Shu (YXS) tablets by HPLC-ELSD.HPLC-ELSD was used as the detection method.The separation and content of ginsenosides Rg1,Re and Rb1 were used as indexes.The influences of three different preparation methods (i.e.,defatted alcohol extraction and butanol extraction,alcohol extraction and butanol extraction,alcohol extraction and butanol extraction ammonia solution washing) on the effect of YXS tablets were studied.Then,the same content determination method was used to compare the influence of alkali washing treatment to ginsenosides Rg1,Re and Rb1 among different batches of Panax ginseng.The results showed that a good separation of ginsenosides Rg1,Re and Rb1 component peak of YXS tablets was achieved by three kinds of separation methods.The separation degree was greater than 1.5.Ammonia solution washing had some effect on ginsenosides Rg1,Re and Rb1 content,which made the content of ginsenosides Rg1,Re and Rb1 be 1.5-1.8 times to those without alkali washing.No effect was shown on the content of ginsenosides Rg1,Re and Rb1 during ammonia solution washing.It was concluded that some other ginsenosides can be transferred into ginsenosides Rg1,Re and Rb1 in YXS tablets solution after ammonia solution washing.

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