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1.
Acta Pharmaceutica Sinica ; (12): 375-384, 2022.
Article in Chinese | WPRIM | ID: wpr-922926

ABSTRACT

Drug repositioning provides new clinical indications for existing drugs. The imbalance between body's "immune-inflammation" regulation is one of the important factors in the occurrence and development of diabetic nephropathy (DN). Chinese patent medicine Kunxian capsule is clinically used for treating rheumatoid arthritis with satisfying immune-modulatory and anti-inflammatory actions. Notably, accumulating clinical evidence based on small cohorts had shown that Kunxian capsule may be used to treat DN. But the underlying pharmacological mechanisms remain unclear. Therefore, this study integrated "drug target-disease gene-biological pathway-function module" multi-level associated network analysis, and in vivo and in vitro experiments, to verify the pharmacological effects of Kunxian capsules in DN and to elucidate its molecular mechanisms. The experimental protocol was reviewed by the Laboratory Animal Welfare and Ethics Committee of China Academy of Chinese Medical Sciences, and it complies with the relevant regulations on laboratory animal welfare and ethics. As a result, the network analysis showed that the candidate targets of Kunxian capsule against DN were significantly involved into various functional modules which were related to modulation of immune-inflammation system, basement membrane lesion, abnormal hemorheology, energy metabolism and hormone metabolism, and the number of targets enriched by PI3K/AKT/NF-κB pathway is the largest. In addition, both in vivo and in vitro experiments demonstrated that Kunxian capsule by gavage effectively reduced blood glucose, improved insulin resistance, reduced blood lipid, inhibited renal extracellular matrix protein production and renal inflammation, improved renal function and pathological damages, and inhibited the activity of PI3K/AKT/NF-κB/TNF-α/IL-1β pathway in diabetic nephropathy rats. Collectively, these findings suggest the therapeutic potentials of Kunxian capsule to alleviate DN by regulating the imbalance of immune-inflammation system.

2.
Article in Chinese | WPRIM | ID: wpr-907720

ABSTRACT

Objective:By establishing the rats model of sepsis induced by endotoxin, exploring the effects of agmatine on the apoptosis of splenocyte and dendritic cells in the septic rats.Methods:SD rats ( healthy and clean, male, 90) were randomly(random number) divided into control groups, endotoxin groups and agmatine groups, 30 rats per group. The control groups were injected with normal saline via femoral vein (10 mL/kg), endotoxin groups were injected with lipopolysaccharide via femoral vein (10 mg/kg), agmatine groups were injected with lipopolysaccharide via femoral vein (10 mL/kg) and intraperitoneal injected of agmatine (200 mg/kg).The three groups were randomly selected 10 rats separately at 0 h, 12 h, 24 h (marked as 0 h, 12 h, 24 h subgroups, n=10) , anesthetized to death. Weigh the spleen; HE staining was used to observe the pathological changes of the spleen; The cell apoptosis of splenocyte and dendritic cells were detected by flow cytometry. The results were statistically analyzed using SPSS 17.0 software, analyzed by independent sample t test, P<0.05 was considered statistically significant. Results:The weights (g) of spleen in 12 h (1.2633±0.0652) , 24 h (1.5576±0.0711) subgroups of the endotoxin groups were increased significantly than the corresponding subgroups[(0.8876±0.0361),(0.9079±0.0425)]of the control groups ( P<0.05) , the 12 h (1.1052±0.0585) , 24 h (1.3262±0.0682) subgroups of the agmatine groups were decreased significantly than the corresponding subgroups of the endotoxin groups ( P<0.05) . HE staining showed that the spleen tissue inflammatory reaction in the endotoxin groups were worse than the control group ( P<0.05) , the agmatine groups were better than the endotoxin group ( P<0.05) . The apoptosis rates of the splenocyte[(13.31±1.26)、(19.53±1.68)]and dendritic cells[(19.5±1.52)、(16.09±1.15)]in the spleen from 12 h, 24 h subgroups of the endotoxin groups were significantly higher than the corresponding subgroups[(6.27±0.71),(6.01±0.67) and (4.99±0.51)、(5.30±0.66)]of the control groups ( P<0.05) , the 12 h[(9.19±0.95),(12.19±1.25)], 24 h [(12.71±1.19),(10.76±1.09)subgroups of the agmatine groups were significantly lower than the corresponding subgroups of the endotoxin groups ( P<0.05) ; The apoptosis rates of the splenocyte in the 24 h subgroups of the endotoxin groups and the agmatine groups were significantly higher than the 12 h subgroups of the same group ( P<0.05) , but the apoptosis rates of the dendritic cells were significantly lower than the 12h subgroups of the same group ( P<0.05) . Conclusion:The apoptosis of splenocyte and dendritic cells were closely related to the occurrence and development of sepsis, Agmatine could inhibit the apoptosis of splenocyte and dendritic cells the rats with sepsis.

3.
Journal of Leukemia & Lymphoma ; (12): 353-356, 2021.
Article in Chinese | WPRIM | ID: wpr-907183

ABSTRACT

Objective:To improve awareness of the diagnosis and treatment of splenic histiocytic sarcoma.Methods:The clinical data of one patient with splenic histiocytic sarcoma who was admitted to First Teaching Hospital of Tianjin University of Traditional Chinese Medicine in July 2020 were retrospectively analyzed, and the relevant domestic and foreign literature was reviewed.Results:The patient was diagnosed as splenic histiocytic sarcoma by histopathological and immunohistochemical examinations. The methylprednisolone combined with cyclosporine was ineffective. The patient received a total splenectomy, followed by chemotherapy with VECD and CHOP regimens. The patient's condition was stable during the 5-month follow-up after the operation. The result of bone puncture showed that there was no infiltration of histocytic sarcoma, and hematological remission was obtained.Conclusions:Splenic histocytic sarcoma is a highly malignant tumor with insidious onset, unclear pathogenesis, and lack of specificity in clinical manifestations and imaging examinations. The diagnosis depends on pathological biopsy and immunohistochemistry, and needs to be differentiated from other malignant tumors of lymphoid hematopoietic tissue. At present, there is no best treatment for splenic histiocytic sarcoma, and most patients have a poor prognosis.

5.
Cancer Research and Clinic ; (6): 789-793, 2021.
Article in Chinese | WPRIM | ID: wpr-912968

ABSTRACT

Some primary bone tumors are prone to hematogenous metastasis and after that, the therapeutic effect is not that good and prognosis is poor. Circulating tumor cells (CTC) shed from the tumor cells of primary or metastatic focus and then enter into blood circulation. CTC may appear in the early stage of the tumor, which can implant in distant organs to form metastatic sites and self-implant in the primary sites leading to the tumor recurrence; CTC are closely related with the prognosis of patients with tumors. In most primary bone tumors, CTC are heterogeneous compared with primary tumor cells. Studying CTC from various aspects can provide a basis for the early diagnosis and treatment of primary bone tumors. This review summarizes the current researches of CTC in common primary bone tumors, and expects the future of research direction and application practice in clinic.

6.
Chinese Journal of Orthopaedics ; (12): 1647-1654, 2021.
Article in Chinese | WPRIM | ID: wpr-910759

ABSTRACT

Osteosarcoma, the most common primary bone tumor in children and adolescents, is characterized by high malignancy, rapid progression and high metastatic potential. However, no significant progress has been made in treating osteosarcoma recently. The prognosis of osteosarcoma is usually unsatisfied. One of the main reasons is that we cannot be able to identify the Achilles heel of osteosarcoma. A growing number of evidence suggests that different types of RNA play various roles in the development of osteosarcoma. The competing endogenous RNA (ceRNA) is a newly emerging theory, which can propose messenger RNA (mRNA), long non-coding RNA (lncRNA), pseudogene and other different transcripts. Therefore, it can play a role in the regulation of microRNA (miRNA) through competition. In the latest researches, it is shown that the interaction of these transcripts play an important role in the occurrence and development of osteosarcoma by mediating biological processes such as proliferation, apoptosis, metastasis and chemotherapy resistance of osteosarcoma cells. In addition, these different types of transcripts may provide new biomarkers and potential therapeutic targets for osteosarcoma. The present studies review the development of ceRNA hypothesis, summarizes existing knowledge system of ceRNA, and develop a systematic review of the role of different types of ceRNA in the pathogenesis and biological function of osteosarcoma. This review could lay the foundation for the basic and clinical study of osteosarcoma and promote the early diagnosis and treatment effects of osteosarcoma.

7.
Chinese Journal of Orthopaedics ; (12): 186-194, 2021.
Article in Chinese | WPRIM | ID: wpr-884695

ABSTRACT

Osteoarthritis (OA) is a common degenerative disease. Its most significant pathological change is destruction of articular cartilage and the main clinical symptoms are pain and dysfunction of joints. Recent studies have shown that the expression of non-coding RNA (ncRNA) in chondrocytes can abnormally up-regulate or down-regulate and alter the activities of chondrocytes like their proliferation, migration and apoptosis, thus leading to the occurrence and development of osteoarthritis. Exosomes are extracellular vesicles with a diameter of 40-100 nm, which are secreted in intercellular fluid, act as medium of intercellular communication. They protect ncRNA, protein, lipid and other bioactive materials from enzymatic degradation by encapsulating them and transferring to sibling chondrocytes, due to their good tissue permeability. They can also improve communication between cells and regulate the activities of chondrocytes. Thus, exosomes behave like gene carriers. The ncRNA carried by exosomes can supplement or adsorb the abnormal ncRNA in chondrocytes, so as to regulate the activity of chondrocytes, and is therefore considered as a possible candidate with capabilities to repair cartilages. In this study we reviewed existing literatures related to the roles and effects of exosome miRNA, lncRNA and circRNA on osteoarthritis. We also reviewed the pathogenesis of exosome ncRNA in osteoarthritis.

8.
Article in Chinese | WPRIM | ID: wpr-883156

ABSTRACT

Metabolic bone disease(MBD) in preterm infant is a disorder of calcium and phosphorus metabolism that leads to a decrease in bone mineral content, resulting in clinical, biochemical, and imaging changes.It occurs mostly in very low birth weight and extremely low birth weight newborns.The clinical symptoms usually occur from 6 to 12 weeks after birth, mainly manifested as dyspnea accompanied by mechanical ventilation for a long time, rickety-like changes, and even fracture in severe cases.At present, diagnosis of MBD is characterized by biochemical markers, radiology and ultrasound.As the clinical manifestations of MBD in prematurity occur late, early screening and prevention for high-risk groups play an important role to reduce the risk of MBD.

10.
Protein & Cell ; (12): 7-28, 2021.
Article in English | WPRIM | ID: wpr-880895

ABSTRACT

Mammalian fertilization begins with the fusion of two specialized gametes, followed by major epigenetic remodeling leading to the formation of a totipotent embryo. During the development of the pre-implantation embryo, precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality, but the underlying molecular mechanisms remain elusive. For the past few years, unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development, taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies. The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals, including DNA methylation, histone modifications, chromatin accessibility and 3D chromatin organization.


Subject(s)
Animals , Chromatin Assembly and Disassembly , DNA Methylation , DNA Transposable Elements , Embryo, Mammalian , Embryonic Development/genetics , Epigenesis, Genetic , Epigenome , Female , Fertilization/physiology , Gene Expression Regulation, Developmental , Histone Code , Histones/metabolism , Male , Mice , Oocytes/metabolism , Spermatozoa/metabolism
11.
Journal of Medical Postgraduates ; (12): 708-714, 2020.
Article in Chinese | WPRIM | ID: wpr-822588

ABSTRACT

ObjectiveThe methods based on bladder cancer markers which could be applied to early diagnosis and postoperative recurrence monitoring of bladder cancer were current research hotspots. This study aims to screen aptamers that specifically recognize human bladder cancer cell lines (EJ, T24, BIU87) through cell-based systematic evolution of ligand by exponential enrichment (CELL-SELEX).MethodsFor CELL-SELEX screening, bladder cancer cell lines EJ, T24, and BIU87 were used as positive control cells. HCV 29 (human normal urothelial cell line), 293T (human embryonic kidney cell line), huh7 (human hepatocellular carcinoma cell line) were used as negative control cells. PCR upstream primers were labeled with FITC, downstream primer was labeled with Biotin. ssDNA fragments collected from each round were amplified by PCR, and the amplified product was then purified using a DNA purification Kit. The biotin-streptavidin magnetic separation methods were used to isolate the PCR product to obtain secondary FITC-ssDNA for the next CELL-SELEX round. The screening process was monitored by flow cytometry. ssDNA pool with the highest binding rates to bladder cancer cell lines(EJ, T24, and BIU87) was selected to PCR amplification, product purification, molecular cloning, and sequencing. According to the sequencing results, the secondary structure of the aptamer was pre-simulated by Dnaman software. Aptamer labeled with FITC was synthesized in vitro, flow cytometry was used to detect the binding rate of the aptamer to bladder cancer cell lins (EJ, T24 and BIU87).ResultsWith the advance of the CELL-SELEX process, the binding rate of FITC-ssDNA to bladder cancer cell lins (EJ, T24, and BIU87) increased gradually. By the 15th round, the binding rate of FITC-ssDNA to EJ cells reached the highest level. The apt1 had the highest enrichment among the 15th round ssDNA pool. By the 18th round, the binding rate of FITC-ssDNA to T24 or BIU87 cells reached the highest level. The apt2 and apt3 had the highest enrichment among the 18th round ssDNA pool. DNA structure prediction showed that the secondary structure of apt1, apt2, and apt3 was mainly stem-loop structure. Flow cytometry showed that the highest binding rate was FITC-apt1 to EJ cells, FITC-apt2 to T24 cells, and FITC-apt3 to BIU87 cells, respectively. There is no significant combination between these aptamers with the negative cells.ConclusionIn this study, three kinds of aptamers with high specificity for bladder cancer cell lines were successfully screened by CELL-SELEX. The apt1 can specifically recognize EJ cells, apt2 can specifically recognize T24 cells and apt3 can specifically recognize BIU87 cells, all of which provide experimental evidence for early diagnosis and targeted therapy technology research of bladder cancer.

12.
Chinese Medical Journal ; (24): 2437-2443, 2020.
Article in English | WPRIM | ID: wpr-877835

ABSTRACT

BACKGROUND@#Epithelial to mesenchymal transition (EMT) is strongly linked with tumor invasion and metastasis, which performs a vital role in carcinogenesis and cancer progression. Emerging evidence suggests that microRNAs (miRNAs) expression are closely associated to EMT by regulating targeted genes. MiR542 has been found to be involved in the EMT program and bound up with various cancers. However, the functions of miR542 and its underlying mechanism in glioblastoma multiforme (GBM) remain largely unknown. In the current study, we investigated the effect of astrocyte elevated gene-1 (AEG-1) on U251 cells aggressiveness, proliferation, apoptosis, and cell cycle.@*METHODS@#The screening of targeted miRNAs was performed, as well as the functional roles and mechanisms of miR542 were explored.@*RESULTS@#MiR542 was selected as the target because of the most significantly differential expression and this high level of expression negatively correlated with cell migration and proliferation, which suggested that miR542 could be a novel tumor suppressor. Moreover, we confirmed that AEG-1 was a direct targeted gene of miR542 by luciferase activity assay, reverse transcription-polymerase chain reaction, and immunoblotting analysis. Furthermore, miR542 suppressed the expression of AEG-1, which upgraded the level of E-cadherin and degraded Vimentin expression contributing to retraining EMT.@*CONCLUSION@#The in vitro findings demonstrated that miR542 inhibited the migration and proliferation of U251 cells and suppressed EMT through targeting AEG-1, indicating that miR542 may be a potential anti-cancer target for GBM.


Subject(s)
Astrocytes , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Humans , MicroRNAs/genetics , Neoplasm Invasiveness/genetics
13.
Chinese Medical Journal ; (24): 301-309, 2020.
Article in English | WPRIM | ID: wpr-781588

ABSTRACT

BACKGROUND@#Mesenchymal stem or stromal cells (MSCs) derived from the induced pluripotent stem cells (iPSCs) have uniform biological activity, which makes the clinical application of MSCs in bone repair possible. Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration. The aim of this work was to evaluate the effects of semaphorin 3A (Sema3A) and hypoxia inducible factor 1 subunit alpha (HIF1α) co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs.@*METHODS@#Sema3A and HIF1α were linked together with the three (GGGGS; G, glycine; S, serine) peptide fragment, and their co-expression in iPSC-MSCs was mediated by a lentiviral vector. The fusion protein retained the immune reactivity for both Sema3A and HIF1α as determined with Western blotting. iPSC-MSCs were infected with overexpression lentivirus (oeLenti) as negative control, oeLenti-Sema3A, oeLenti-HIF1α or oeLenti-Sema3A-HIF1α lentiviruses.@*RESULTS@#Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs (the activity and/or expression of osteoblast markers, such as alkaline phosphatase, osteopontin, and osteocalcin, were upregulated), and suppressed cell survival. The Sema3A-HIF1α fusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival. We further seeded iPSC-MSCs modified by SemaA-HIF1α overexpression onto hydroxyapatite (HA) scaffolds, and evaluated their growth and differentiation on this three-dimensional material. Additional data indicated that, as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes, cells cultured in HA scaffolds grew (blank vs. HA scaffolds: 0.83 vs. 1.39 for survival) and differentiated better (blank vs. HA scaffolds: 11.29 vs. 16.62 for alkaline phosphatase activity).@*CONCLUSION@#Modifying iPSC-MSCs with pro-osteogenic (Sema3A) and pro-survival (HIF1α) factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair.

14.
Chinese Journal of Orthopaedics ; (12): 1126-1134, 2020.
Article in Chinese | WPRIM | ID: wpr-869057

ABSTRACT

Malignant bone tumors, one of the most common bone tumors includes osteosarcoma, Ewing's sarcoma, multiple myeloma, and metastatic bone tumors etc. These tumors are often accompanied by distant metastatic lesions at time of diagnosis, leading to low 5-year survival rates. At present, the use of biomarkers for early detection in order to facilitate early treatment are very limited. Therefore, most medical researchers are exploring the roles of exosomes in detecting malignant bone tumors. Exosomes are extracellular microvesicles secreted by different types of cells, which exist in a variety of body fluids. They are new intercellular information carriers that play important physiological roles. Current literature have reported that the RNA contained in exosomes (such as mRNA, miRNAs, lncRNAs and circRNAs) play important roles in the incidence as well as development of malignant bone tumors. However, the previous studies mostly focused on the roles of exosomal RNA in malignant bone tumor diseases, in tumor cell proliferation or apoptosis, transfers, evasion of immune surveillance and chemotherapy drug resistance etc. However, exosomal RNAs may function in the whole process of the disease progression via regulation networks. Our review of existing literature revealed that exosomal RNAs affacted the proliferation, metastasis, immune evasion and drug resistance of five common malignant bone tumors; Osteosarcoma, Ewing sarcoma, Chondrosarcoma, multiple myeloma, and metastatic bone tumors. Therefore, by elucidating on the mechanism of exosomal RNAs in the occurrence and development of malignant bone tumors, this study, could provide new ideas for early diagnosis, concomitant diagnosis, efficacy estimation (chemotherapy, radiotherapy and immunotherapy, etc.) as well as assessing the prognosis of malignant bone tumors.

15.
Article in English | WPRIM | ID: wpr-822671

ABSTRACT

@#Among the main reasons for re-emergence of vaccine preventable diseases were missed or incomplete immunization schedule. The supplementary immunization activity (SIA) is an important intervention done to provide complete immunization coverage among those children. Better outcome came along with good knowledge and perception on the program. Thus, this study aims to assess the level of knowledge and perception of the mothers towards SIA program. A cross-sectional study was conducted among mothers with children ≤ 15 years old in Cheras, Kuala Lumpur. Data was collected by interview using the guided questionnaire consists of four sections to assess the socio demographic, socio economic, knowledge and perception regarding SIA. The questionnaire was validated for internal consistency with Cronbach’s alpha 0.461 for knowledge and 0.729 for perception. A total of 105 respondents with the median age of 33 years (IQR: 28-38) with majority of them are Malays (82.9%), Muslim (83.8%), married (97.1%) and (57.1%) with 1- 2 child in the family. Half of them were from low income family (46.7%) and had secondary education level (54.3%) and were housewives (47.6%). One third of the respondents (33%) never heard about SIA before. Overall had poor knowledge (82.9%) and perception (95.2%) towards SIA. There is a significant association between the level of knowledge on SIA with household income (χ

16.
Article in Chinese | WPRIM | ID: wpr-817827

ABSTRACT

The virus is a major pathogen of respiratory tract infection in children. Detection of viral etiology of respiratoty illnesses can provide valuable information to direct the management of patients over the different clinical manifestations. The procedures of the collection,transport and processing of specimens is the most error-prone parts in microbiological testing. Clinicians also lack sufficient understanding of the procedures and clinical value for respiratory virus detection. The paper covers the main content of Advice on Collection,Transport and Detection of Microbiological Testing Specimen in Children with Respiratory Infection(Focusing on Virus),the importance and problems involved in specimen collection,laboratory testing of respiratory viruses,and interpretation of the results.

17.
Acta Pharmaceutica Sinica B ; (6): 1145-1162, 2019.
Article in English | WPRIM | ID: wpr-815863

ABSTRACT

Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015-2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.

18.
Article in Chinese | WPRIM | ID: wpr-792262

ABSTRACT

Objective: To observe the effects of acupuncture combined with isokinetic eccentric exercise on pain and motor function in patients with knee osteoarthritis (KOA). Methods: Sixty-four patients with KOA were randomly divided into an observation group and a control group, with 32 cases in each group. The observation group received acupuncture and isokinetic eccentric exercise, and the control group received isokinetic eccentric exercise and oral intake of meloxicam tablets. Both groups were treated for 4 weeks. Before and after treatment, the visual analog scale (VAS) score, the lysholm knee scale (LKS) score, and the quadriceps peak torque (PT) were evaluated. Results: The total effective rate was 93.8% in the observation group, versus 81.3% in the control group. The difference between the two groups was statistically significant (P<0.05). After treatment, the VAS scores of the two groups were lower than those before the treatment; both LKS score and quadriceps PT were higher than those before treatment, and the differences were statistically significant (allP<0.05). The VAS score, LKS score and quadriceps PT (angular velocity was 60 °/s) of the observation group were significantly different from those of the control group (all P<0.05). Conclusion: Acupuncture plus isokinetic eccentric exercise is effective in treating KOA. The combined treatment can reduce the pain of KOA patients, improve joint function, strengthen quadriceps, improve joint stability, and its curative effect is better than isokinetic eccentric exercise plus oral intake of meloxicam tablets.

19.
Acta Pharmaceutica Sinica ; (12): 540-546, 2019.
Article in Chinese | WPRIM | ID: wpr-780141

ABSTRACT

Carbon monoxide (CO) is an important chemical gas messenger molecule in the body with anti-inflammatory activity. As an active substance in gaseous state, the method for its safe and effective delivery towards the lesion sites remains to be established. Based on the natural affinity of carbon monoxide to hemoglobin, a main component of red blood cells (RBCs), this study proposes a carbon monoxide-red blood cell (CO-RBC) composite system, and tested its therapeutic effect against lung injury in an animal model. The mouse model of septic lung injury was adopted, and the carbon monoxide release molecule (CORM-2) was used as a positive control. CO-RBC system was characterized by CO release, stability, toxicity and in vivo lung targeting. The expression of intercellular adhesion molecule (ICAM-1) and pulmonary surfactant protein-A (SP-A) were evaluated in the animal model and the therapeutic effect of CO-RBC system for sepsis was measured by inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as survival time of mice and pathological changes of the lung. Our results show that CO-RBC system exhibited satisfactory stability with negligible CO release during 48 h storage under nitrogen protection, while the CO release was about 70% within 12 h under physiological condition, in contrast to CO burst release from CORM-2. The CO-RBC system showed no significant toxicity in the animal model, and in vivo fluorescence imaging results showed effective accumulation in the lungs, supporting its lung targeting effects. The secretion of TNF-α and IL-6 in the CO-RBC group was significantly lower than that in other groups, the degree of pulmonary interstitial edema was relieved, the white blood cell infiltration was decreased, and the survival rate was significantly improved. Therefore, the CO-RBC system has a significant inhibitory effect on the pulmonary inflammatory response in septic mice compared with CORM-2. This system provides a new hope for therapeutic treatment of sepsis.

20.
Article in Chinese | WPRIM | ID: wpr-701121

ABSTRACT

AIM:To explore the effect of curcumin(Cur)and curcuminoids(Y20 and 6B)on the expression of secretory leukocyte protease inhibitor(SLPI), tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)induced by Streptococcus pneumoniae(SP)and the possible mechanism.METHODS:BEAS-2B cells incubated with SP were set up as an inflammation model of pneumonia.The mRNA levels of SLPI at 1 h,3 h,6 h and 9 h,and the mRNA expression of TNF-αand IL-1βat 3 h,6 h and 9 h in control group,SP infection group,Cur treatment group,Y20 treatment group and 6B treatment group were measured by qPCR.The protein levels of TNF-αand IL-1βin the culture supernatant were measured by ELISA.The protein levels of Toll-like receptor 2(TLR2)and phosphorylated nuclear factor-κB(p-NF-κB) p65 at 3 h,6 h and 9 h were determined by Western blot.RESULTS:The mRNA level of SLPI was increased in Cur, Y20 and 6B treatment groups compared with SP group(P<0.05).The protein levels of TLR2 and p-NF-κB p65 were sig-nificantly increased after SP stimulation.After treatment with Cur,Y20 and 6B,the protein levels of TLR2 and p-NF-κB p65 were significantly decreased(P<0.05).The levels of TNF-αand IL-1βwere significantly increased after SP stimula-tion.Cur,Y20 and 6B significantly decreased the levels of TNF-αand IL-1βin the supernatant(P<0.05).CONCLU-SION: Cur, Y20 and 6B increase SLPI expression, reduce the expression of inflammatory cytokines TNF-αand IL-1β. The possible mechanism might be associated with inhibiting TLR 2 expression and down-regulating the transcriptional activity of NF-κB.

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