1.Construction of folate receptors and mitochondria targeting celastrol-loaded PAMAM nano-drug delivery system and its in vitro anti-inflammatory effect
Zi-qi JING ; Xue WANG ; Tian-yue YAN ; Yu-jie ZHANG ; Peng-kai MA
Acta Pharmaceutica Sinica 2023;58(3):550-559
Pro-inflammatory macrophages play key regulatory role in the occurrence and development of rheumatoid arthritis (RA). In this study, we constructed a celastrol (Cel)-loaded polyamide-amine dendrimer (PAMAM) drug delivery system, which could target folate receptor and mitochondria. It could target inflammatory macrophages and realize chemo-photothermal synergistic therapy. Using PAMAM as the nano-carrier, folate receptor-targeting group folic acid (FA) and mitochondria-targeting group IR808 (also known as the photothermal agent) were conjugated with PAMAM through amide reaction, and then complexed with anti-inflammatory drug Cel to prepare the FA-PAMAM-IR808/Cel nanocomplex.
2.Advances in antiviral research of adaptor-associated protein kinase 1 (AAK1) inhibitors
Xiang QI ; Song-wei JIANG ; Ying-hui YUAN ; Li XU ; Zi HUI ; Xiang-yang YE ; Tian XIE
Acta Pharmaceutica Sinica 2022;57(7):1991-2002
As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.
3.Nasal colonization of Staphylococcus aureus and nosocomial infection in intensive care unit
Qing-Cao LI ; Qi-Tian MU ; Yan-Zi CHANG ; Wen-Jun LU
Shanghai Journal of Preventive Medicine 2015;(10):617-620
Objective To investigate the relationship between nasal colonization of Staphylococcus aureus(SA) and nosocomial infection in intensive care unit(ICU), and observe the therapeutic effect of Anerdian III in nasal decolonizaion. Methods Bacterial cultures were made by means of nasal swabs among inpatients whom the occurrence of nosocomial infection were observed.Patients with SA colonization were randomly divided into two groups:control and treatment.Control group were given regular treatment, and treatment group were administered Anerdian III in addition to regular treatment.Then the clearance rate of SA and the occurrence of nosocomial infection of two groups were observed. Results A total of 751 patients were enrolled, of whom 108(14.4%) were with nosocomial infection and 85(11.3%) with SA nasal colonization. Methicillin resistant Staphylococcus aureus ( MRSA ) was detected in 33 patients (4.4%).The nosocomial infection rate of patients with MRSA colonization was 51.5%, which was significantly higher than those in patients with other bacterial colonization(P<0.05).The SA clearance rate in treatment group was significantly higher than that in control group(81.4% vs.42.8%,P<0.05).The nosocomial infection rate in treatment group was significantly lower than that in control group ( 16 .3% vs. 40.5%,P <0.05).After decolonization treatment,the nosocomial infection rate of patients with MRSA colonization was significantly lower than that in control group(25.0% vs.76.5%,P <0.05). Conclusion The incidence rate of nosocomial infection in patients with MRSA nasal colonization is markedly increased in ICU, and the decolonization treatment by Anerdian III increases the clearance rate of nasal SA and decreases the incidence rate of nosocomial infection.
4.Not Available.
Xiao ZHANG ; Bin WANG ; Gong ying ZHANG ; Jun zhe TIAN ; Zi wei HE ; Xi HE ; Yi qi ZHAO ; Zhi qing YAO ; Lu TIAN ; Shi lin LI
Journal of Forensic Medicine 2022;38(4):545-550
5.The pro-angiogenesis effect of Pitavastatin in the Klotho gene-knockout mice.
Yue-Lan ZHANG ; Wen TIAN ; Zi-Xin ZHANG ; Ding-Yin ZENG ; Guo-Xian QI
Chinese Journal of Applied Physiology 2006;22(2):163-167
AIMTo discuss the effect of Pitavastatin on angiogenesis in vivo and its mechanism in Klotho heterozygous deficient mice.
METHODSThe heterozygous deficient Klotho mice (kl +/-) and wild mice (kl +/+) from the same litter were used to establish the animal model of hind-limb ischemia and grouped into control and Pitavastatin group, respectively. Hind-limb blood flow was evaluated using Laser Doppler perfusion imager (LDPI) before treatment and after operation of hind-limbs. The capillaries in muscle of limbs were counted by means of CD-31 labeled immuno-fluorescence. The phosphorylation of Akt (Protein kinase B) in cells was measured by direct immunohistochemical technique. The expression of vascular endothelial growth factors (VEGFs) in muscle of limbs was assessed using Western blotting.
RESULTSAfter treatment of Pitavastatin, the blood flow in ischemic limbs of the Kl +/- and wild mice improved obviously, the ratio of blood flow area in ischemic limb to that in non-ischemic limb increased and the density of capillaries increased in ischemic limbs of the Kl +/- and wild mice. Pitavastatin enhanced the phosphorylation of Akt and the expression of VEGF in ischemic limbs of the Kl +/- and wild mice.
CONCLUSIONPitavastatin has the pro-angiogenesis effect in vivo and the VEGF-p-Akt-NO pathway may be involved in the mechanism of the effect of Pitavastatin.
Angiogenesis Inducing Agents ; pharmacology ; Animals ; Heterozygote ; Ischemia ; Male ; Mice ; Mice, Knockout ; Quinolines ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism
6.Comparative study on the clinical results of locking proximal humerus plate (LPHP) and traditional plates in the treatment of proximal humerus fractures in the young and middle-aged patients.
Zi-jian SHENG ; Yue-hong MA ; Si-qi TIAN ; Jian-yue GU
China Journal of Orthopaedics and Traumatology 2008;21(9):684-685
7.Co-delivery of Tim-3 mAb and sorafenib enhanced chemoimmunotherapy for hepatocellular carcinoma using "responsive shell-peeling" mesoporous silica nanoparticles
Sheng-jun MU ; Xiao SANG ; Wei-wei MU ; Tian-qi WANG ; Rui YANG ; Zi-peng ZHANG ; Yong-jun LIU ; Na ZHANG
Acta Pharmaceutica Sinica 2022;57(1):200-210
Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively.
8.Effect of oxidative stress in development of acute high altitude response during the process of strong physical work at high altitude.
Sheng-Yue YANG ; En-Zhi FENG ; Zi-Qiang YAN ; Wei HE ; Zhong-Xin TIAN ; He YIN ; Li-Fu MA ; Qi-Quan ZHOU ; Zi-Fu SHI
Chinese Journal of Applied Physiology 2011;27(4):457-460
OBJECTIVETo assess the effect of oxidative stress in development of acute high altitude response (AHAR) during the process of strong physical work at high altitude and its change after return to lower altitude.
METHODSNinety-six officers and soldiers of rapid entering into high altitude (3 700 m) with strong physical work were analyzed, all subjects were male, aged 18-35 years. According to the symptomatic scores of AHAR were divided into 3 groups: severe AHAR (group A, n = 24), mild AHAR (group B, n = 47) and without AHAR (group C, n = 25). Levels in serum 8-iso prostaglandinF2alpha(8-iso-PGF2alpha), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at higher altitude stayed 50 d and after return to lower altitude (1 500 m) 12 h and 15 d, and 50 healthy volunteers (group D) at 1 500 m altitude served as controll.
RESULTSLevels of serum 8-iso-PGF2alpha and MDA [(9.53 +/- 0.47) microg/L, (8.91 +/- 0.39) micromol/L] were significantly higher in group A than those in group B [(8.34 +/- 0.42) microg/L, (7.31 +/- 0.32) micromol/L] , group C [(7.02 +/- 0.48) microg/L, (6.41 +/- 0.23) micromol/L] and group D [(5.13 +/- 0.56) microg/L, (5.48 +/- 0.33) micromol/L], (all P < 0.01), and serum SOD [(52.08 +/- 3.44) micro/ml] was significantly lower in group A than that in group B [62.27 +/- 2.54) micro/ml], group C [(71.99 +/- 3.35) micro/ml] and group D [(80.78 +/- 3.44) micro/ ml] (all P < 0.01), there were significant differences between group B and C, C and D (all P < 0.01). At altitude 3 700 m 50 d, AHAR scores was positively correlated with serum 8-iso-PGF2alpha and MDA (all P < 0.01), negatively correlated with SOD (P < 0.01). Serum 8-iso-PGF2alpha and MDA were negatively correlated with SOD (all P < 0.01). Levels of serum 8-iso-PGF2alpha and MDA were significantly higher at altitude of 3 700 m 50 d than those at altitude of 1 500 m 12 h,15 d in group D (all P < 0.01), and serum SOD was significantly lower than that at 1 500 m 12 h,15 d in group D (all P < 0.01), there were significantly difference between at 1 500 m 12 h and 15 d (all P < 0.01), there were no difference between at 15 d in group D (all P > 0.05).
CONCLUSIONThe more serious of oxidative stress and oxidative/antioxidative imbalance, the more serious of AHAR, oxidative stress and oxidative/antioxidative imbalance may be involved in the development of AHAR. The changes were obviously improved after return to lower altitude 12 h, and recovered to normal after 15 d.
Adolescent ; Adult ; Altitude ; Altitude Sickness ; physiopathology ; Humans ; Male ; Oxidative Stress ; physiology ; Physical Exertion ; physiology ; Young Adult
9.The prevalence of hepatitis C virus (HCV) subtypes in Chinese HIV-1/HCV co-infected individuals
Jing LIU ; Yang YANG ; Ju-Li GONG ; Zi-Ning ZHANG ; Min ZHANG ; Ya-Nan WANG ; Yong-Jun JIANG ; Zhong-Tian QI ; Qi-Chao PAN ; Ping ZHONG ; Hong SHANG
Chinese Journal of Epidemiology 2009;30(7):663-667
Objective To better understand the prevalence and geographic distribution of genotypes/subtypes on HCV and the relationship between HCV genotypes/subtypes and HIV infection disease progression in the HIV-1/HCV co-infected individuals living in high HIV-1 prevalent areas in China. Methods 186 plasma samples were collected from HIV-1 seropositive individuals infected through paid blood donors (PBD), injecting drug users (IDUs) or sexual contact, living in most severely affected provinces, Henan, Yunnan, Xinjiang, Jilin and Liaoning provinces. Samples with HCV viral load >1000 cop/ml were amplified by RT-nested PCR, sequenced and phylogenetically analyzed for genotyping/subtyping of HCV. HIV-1, HCV viral loads and CD4 T lymphocytes were measured for all subjects. Results (1) HCV were identified as 1 a (1.7%), 1 b (39.9%), 2a (17.9%), 3a (10.4%), 3b (15.6%), 6a (1.2%), 6n (6.4%), and a newly unclassified subtype (7.5%). HCV 2a and lb subtypes predominated in PBD in Henan, 3a and 3b in IDUs in Xinjiang and Yunnan, and 6 genotype/subtypes in IDU in Yunnan. (2) There were no significant differences in CD4 T cell counts among the different HCV subtypes. (3) The viral load of HCV RNA in lb subtype was higher than that of non-1b subtype, however, no significant differences in HIV-1 viral loads and CD4 T cell counts were found between Ib and non-1b subtype. Both HIV and HCV viral loads were lower in 2a than non-2a subtype. Conclusion The prevalence of HCV genotype/subtype in HIV-1/FICV co-infected individuals was associated with geographic areas and transmission routes. HCV subtypes had no direct correlation with HIV infection disease progression.
10.Long-term outcome of antireflux surgery for gastroesophageal reflux disease.
Qi-zhang WANG ; Zhi-chao WANG ; Jun-feng LIU ; Bao-qing LI ; Fu-shun WANG ; Fu-min CAO ; Zi-qiang TIAN ; Yue-feng ZHANG
Chinese Journal of Surgery 2006;44(2):93-96
OBJECTIVETo investigate the long-term outcomes of various antireflux procedures for gastroesophageal reflux disease (GERD).
METHODSBetween November 1988 and January 2004, 129 patients with GERD underwent antireflux procedures. Six kinds of antireflux procedures were performed including Nissen fundoplication, cardiac oblique invagination (COI) procedure, Belsey Mark IV, Toupet, Thal and Dor procedures. One hundred and sixteen patients were followed up. Esophageal manometry study was carried out in 95 patients preoperatively and 51 postoperatively. 24-hour esophageal pH monitoring were carried out in 56 patients preoperatively and 35 postoperatively. Esophagoscopy were performed in all patients before operation and 48 cases after operation.
RESULTSClinical symptom scores reduced significantly from 4.1 +/- 0.4 before surgery to 1.1 +/- 1.0 after surgery (t = 27.21, P < 0.01). The outcome of surgery showed excellent in 42 cases (36.2%), good in 60 (51.7%), fair in 7 (6.0%), poor in 7 (6.0%). The long-term follow-up showed excellent or good results in 87.9% of patients. There was no significant difference in Nissen fundoplication, COI procedure and Belsey Mark IV.
CONCLUSIONSThere are significant differences in symptom score, esophageal manometry, 24-hour esophageal pH monitoring and esophagoscopy pre- and post-operatively. There is no significant difference in Nissen fundoplication, COI procedure and Belsey Mark IV.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Fundoplication ; Gastroesophageal Reflux ; etiology ; surgery ; Hernia, Hiatal ; complications ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome