Adolescent ; Adult ; Aged ; Bone Marrow ; pathology ; Child ; Female ; Humans ; Lymphoma, Non-Hodgkin ; diagnosis ; pathology ; Male ; Middle Aged ; Spleen ; pathology ; Young Adult

Objective To explore the mechanism of vessel endothelial dysfunction in rats under intermittent hypoxia (IH). Methods The respiratory simulation system was used to simulate IH. Sixty C57BL/6J rats (male) were randomized into control group and IH group. The rats of IH group were exposed to IH 8 hours per day for 6 weeks. The serum levels of hypoxia inducible factor (HIF)-1a and stromal cell derived factor (SDF)-1a were assessed by ELISA. The serum levels of reactive oxygen species (ROS) were detected in two groups. The serum expression of miR-199a-5p was detected by real-time fluorescent quantitative PCR in two groups. The dual luciferase report system and point mutation test were used to verify target gene for HIF-1a. Results The serum levels of HIF-1a and SDF-1a were significantly higher in IH group than those of control group (μg/L:1.60±0.02 vs. 1.19±0.02, 1 823.00±8.97 vs. 1 444.00±17.90, P<0.01). The serum level of ROS was significantly higher in IH group than that of control group (U/mL:487.66±35.73 vs. 211.57±23.82, P<0.01). The serum level of miR-199a-5p expression was significantly lower in IH group compared to that of control group (1.31±0.07 vs. 3.47± 0.17, P<0.01). The result of dual luciferase reporter gene detection confirmed that target gene of miR-199a-5p was HIF-1a. Conclusion The serum level of miR-199a-5p is decreased first due to IH, and then its target gene (HIF-1a) is increased. HIF-1a can induce the increased level of SDF-1a, and its receptor (CXCR-4 ) is also increased. Finally, HIF-1a can increase the serum level of ROS, resulting in the endothelial dysfunction.

OBJECTIVEThe study was aimed to investigate the inhibitory effect and mechanism of astragaloside IV (ASI) on the activation of microglial cells.

METHODAfter pre-incubated with ASI for 2 h, microglial cells BV-2 were stimulated with interferon-γ (IFN-γ) for 1. 5 h and 24 h, respectively. Secretion of nitric oxide (NO) in the medium was measured by Griess method. Production of tumor necrosis factor alpha (TNF-α) was detected by ELISA approach. Cellular gene expressions of CD11b, TNF-α, interleukin 1β (IL-1β) and induced nitric oxide synthase (iNOS) were examined by quantitative-PCR analysis. Total and phosphorylation of STAT1, IκB and NF-κB was analyzed by Western blot method.

RESULTASI could significantly inhibit the increased secretion of TNF-α and NO from BV-2 cells upon IFN-γ stimulation (P < 0.001). Further study showed that ASI significantly down-regulated gene expression of IL-1β and TNF-α (P < 0.01, P < 0.05) and exhibited a trend to reduce that of iNOS. IFN-γ and ASI have no obvious effect on gene expression of CD11b. Moreover, ASI inhibited the phosphorylation of STAT1, IκB and NF-κB elicited by IFN-γ stimulation.

CONCLUSIONASI could restrain microglial activation through interfering STAT1/IκB/NF-κB signaling pathway, reducing gene expres- sion of IL-1β and TNF-α, and thus inhibiting the production of proinflammatory mediators such as NO and TNF-α.

Animals ; Astragalus Plant ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; I-kappa B Proteins ; genetics ; metabolism ; Interferon-gamma ; genetics ; metabolism ; Mice ; NF-kappa B ; genetics ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; STAT1 Transcription Factor ; genetics ; metabolism ; Saponins ; pharmacology ; Signal Transduction ; drug effects ; Triterpenes ; pharmacology

ObjectiveTo investigate the gene expression profiling of articular chondrocyte and the function and pathway of the differentially expressed genes in patients with osteoarthritis (OA) by using gene microarray technique.MethodsThree patients with OA,three patients with rheumatoid arthritis(RA) and three traumatic controls without arthritis were selected and were divided into OA versus RA and OA versus the traumatic control groups,and their articular cartilage cells were cultivated.The gene expression profiling was performed by human genome oligonucleotide microarray technique.The differences of gene expression of the articular chondrocyte in OA versus RA group and OA versus the traumatic control group were compared respectively by two class unpaired test using significant analysis of microarray software.The function and pathway of these differentially expressed genes were analyzed by using the database of Molecule Annotation System.ResultsThe number of differentially expressed genes was 145 when OA compared with the traumatic control,in which 70 were up-regulated and 75 were down-regulated; and the number was 281 when OA were compared with RA,in which 94 were up-regnlated and 187 were down-regulated.The Gene Onto-logy (GO) functions of the differentially expressed genes of OA in each group were related to pathological and immune courses including cellular process,physiological process,cell division,biological regulation and cell signal transduction.The statistically significant pathways of these genes in each group included apoptosis pathway,cell cycle pathway,P53 signaling pathway,Fas signaling pathway,NO pathway,apeptotic cascade pathway,focal adhesion pathway, ECM-receptor interaction pathway, tight junction pathway, adhesive bonding pathway,actin cytoskeleton regulation pathway,bone remodeling pathway,chondroitin sulfate biosynthesis pathway,Jak-STAT signaling pathway,Wnt signaling pathway,Toll recepor signaling pathway,cell adhesion molecules pathway,T cell receptor signaling pathway,and s o on (P＜0.05).They displayed not only marked dif-ferences in GO function and gene pathway of differentially expressed genes between OA versus RA group and OA versus the traumatic control group,but also displayed the significant overlapping of the differentially expressed genes and pathways between the two groups.ConclusionThe differentially expressed genes and pathways of articular chondrocytes involve apoptosis,extracellular matrix and cytokines in OA,which contri-bute to further study of early warning genes of OA.

Objective To determine whether acute withdrawal of simvastatin treatment in healthy normocholesterolemic men impairs the brachial artery endothelial function.Methods The study was performed on 16 healthy,young male subjects with desirable serum levels of cholesterol.They were administered with simvastatin(20 mg/d)for 4 weeks.Endothelial dependent flow-mediated vasodilation (FMD)was assessed on the brachial artery using high-resolution ultrasound,and fasting serum lipid profiles as well as vasoactive substances[NO,endothelin(ET)and 6-keto-PGF1α] were measured.The parameters mentioned above were obtained at indicated time points before and after simvastatin treatment. Resuts Simvastatin treatment for 4 weeks significantly improved FMD and reduced low density LDL-C and total TC levels.Withdrawal of simvastatin.however,resulted in dramatic impairment of endothelium- dependent relaxation on the first day after with drawal [(4.6±0.48)%and(10.9±0.89)%,P＜0.01 ], Furthermore,FMD decreased significantly as compared with baseline level[(4.6±0.48)%vs(6.4±0.47)%,P＜<0.01].Serum NO level varied according to the change of endothelial-dependent relaxation(γ=0.496,P＜0.01).After discontinuing simvastatin therapy,plasma ET increased and plasma 6-keto-PGF1α decreased progressively.In addition,serum TC and LDL-C were not significantly modified during the initial 2 days.No correlation was shown between FMD and serum LDL-C level(γ=-0.172,P=0.101). Conclusions Withdrawal of simvastatin not only abrogates the beneficial effect on endothelial function of healthy normocholesterolemic men rapidly,but also induces further endothelial deterioration as compared with pretreatment status.This adverse effect is independent of serum cholesterol.The underlying mechanism may be related to the suppression of endothelial NO production.

Objective To compare the differences of lung pathological changes of acute lung injury in mice in-duced by lipopolysaccharide ( LPS) and graphite particles, and to explore the possible mechanisms of acute lung injury in-duced by fine particles of different origins.Methods 140 male specific-pathogen-free Kunming mice weighing 18-20 g were randomly divided into 7 experimental groups, in addition to the normal control group.The experimental groups were treated by intratracheal instillation of LPS solution or graphite powder suspension in different doses, respectively, to induce acute lung injury in the mice.The mortality of the mice was observed, and pathological changes of the lung tissues were ex-amined by light and transmission electron microscopy.Western blot was used to detect the protein expression of neutrophil elastase ( NE) in lung tissues , and real-time quantitative PCR was used to detect mRNA expression of monocyte chemotac-tic protein-1 ( MCP-1) in the lung tissue .Results Compared with the normal control group, some pathological changes were observed in the lung tissues of the groups L ( LPS) and G ( graphite) .There were numerous macrophages in the lung tissues in the group G mice, and exudate, mainly neutrophils, in the lung tissues of the group L.The NE protein expres-sion in the lung tissue was significantly higher than that of the normal control group ( P<0.05) , and there was also a sig-nificant difference between the groups L and G (P<0.05).The MCP-1 mRNA expression in lung tissues was higher in the control group (P<0.01), and there was also a significant difference between the groups L and G (P<0.01).Conclu-sions Diverse types of particulate matters induce different pathological changes in the lungs, therefore the mechanism may also be different in the inflammatory responses.It means that the lung injuries caused by fine particles of mixed composition may have complex mechanisms.

Objective To investigate the effect of dapagliflozin on blood pressure variability(BPV)and left ventricular mass index(LVMI)in patients with type 2 diabetes mellitus(T2DM)and hypertension.Methods Patients with T2DM complicated with hypertension admitted to Lishui Central Hospital from August 2021 to August 2022 were selected as the study subjects,and were treated with conventional treatment(control group)and dapagliflozin treatment(test group),respectively.The changes of BPV index,LVMI,blood glucose level and the incidence of adverse reactions were compared between the two groups.Results A total of 94 patients with T2DM and hypertension were included in the study,including 47 patients in the test group and 47 in the control group.The 24-hour diastolic blood pressure(DBP),24-hour systolic blood pressure(SBP),24-hour systolic standard deviation(SSD),24-hour diastolic standard deviation(DSD),fasting blood glucose(FBG),2-hour blood glucose(PG),glycated hemoglobin glycosylated hemoglobin(HbA1c),body mass index(BMI)and LVMI of the patients with T2DM and hypertension were significantly decreased in the two groups(P<0.05),and the 24-hour SBP,24-hour DBP,24-hour SSD,24-hour DSD,FPG,2-hour PG,HbA1c,BMI and LVMI in the test group were lower than those in the control group(P<0.05).The total incidence of adverse reactions between the test group and the control group was 10.64% and 4.26% ,respectively,and the difference was not statistically significant(P>0.05).Conclusion Dapagliflozin can reduce LVMI and improve BPV and blood glucose levels in patients with T2DM and hypertension,and has a good safety profile.

Objective To investigate the process and mechanism of neointimal formation,the level of angiotensin Ⅱ and angiotensin ( 1-7 ),the expression of angiotensin converting enzyme 2 ( ACE2 ),angiotensin Ⅱ type 1 receptor (AT1R),extracellular signal regulated kinase (ERK) and the effects of valsartan on them after aortic balloon injury in rats.Methods Aortic endothelial denudation of rats was induced by 2F balloon catheter. Thirty-six rats were randomly allocated into three groups:Group 1 (n =12):controls; Group 2 (n =12):aortic balloon injury; Group 3 (n =12):valsartan (20 mg · kg 1 ·d-1 ) given from 1 day before injury to 14 and 28 days after aortic injury.The expression of ACE2 and AT1,the level of P-ERK,Ang Ⅱ,Ang ( 1-7 ) and intimal thickening were investigated by RT-PCR technique,immunohistochemistry. Western blot, radioimmunological method, enzymelinked immunosorbent assay (ELISA) and HE stain,respectively.Results (1)The proliferation of vascular smooth muscle cells (VSMC) and the intimal thickening were evidenced at day 14 and 28 after aortic balloon injury. (2) The mRNA and protein expressions of ACE2 decreased significantly,but AT1R mRNA and protein expression increased significantly at day 14 and 28 after balloon injury.(3) The level of Ang Ⅱ and p-ERK increased and Ang(1-7) reduced after balloon injury.(4)Valsartan not only attenuated the proliferation of VSMC and the intimal thickening but also upregulated the expression of ACE2 and the level of Ang (1 7) and downregulated the expression of AT1 R and the level of Ang Ⅱ,p-ERK in this model.Conclusion Intimal thickening after balloon injury is linked with reduced expression of ACE2.Valsartan can inhibit the intimal thickening possibly by upregulating ACE2 and Ang(1-7) and downregulating AT1 in this model.

BACKGROUND: As an ideal scaffold of cartilage tissue engineering, demineralized bone matrix (DBM) has been widespread used. But some of biological characters remain poorly understood.OBJECTIVE: To determine the degradation capacity, interval porosity and adhesion rate of mesenchymal stem cells (MSCs) onto DBM in vitro.DESIGN, TIME AND SETTING: An observation experiment in vitro was complicated in Institute of Orthopedics, Second Hospital of Lanzhou University from January 8~(th) to April 15~(th) in 2005 and Central Laboratory of Guilin Medical University from August 1~(st) to November 15~(th) in 2007.MATERIALS: One chinchilla rabbit was killed under anesthesia. Referring to the method described by Urist, DBM was made by cancellated bone harvested from metaphysis and vertebral body METHODS: DBM was soaked into phosphate buffered solution to determine its degradation capacity; liquid replacement method was used to test its interval porosity; The 3~(rd) passage MSCs at a concentration of 1×10~8/L were cocultured with DBM in vitro and adhesion rate of MSCs onto DBM was tested using cytometry.MAIN OUTCOME MEASURES: The degradation capacity, interval porosity and adhesion rate of MSCs onto DBM.RESULTS: The degradation rate of DBM was accelerated with the prolonging of time, and the complete degrading time was about 10-12 weeks; The holing rate tested was (77.15±3.44)%; The 3~(rd) passage cells had a higher adhesive rate of 71.25% onto DBM.CONCLUSION: DBM degradation curve is consistent with MSCs proliferation curve, indicating a satisfactory adhesion capacity and interval porosity and DBM is an ideal biological scaffold material for cartilage tissue engineering.