111 research outputs found
The effects of intro-oral parathyroid hormone on the healing of tooth extraction socket: an experimental study on hyperglycemic rats
Objective: To investigate the effects of intro-oral injection of parathyroid hormone (PTH) on tooth extraction wound healing in hyperglycemic rats. Methodology: 60 male Sprague-Dawley rats were randomly divided into the normal group (n=30) and DM group (n=30). Type 1 diabetes mellitus (DM) was induced by streptozotocin. After extracting the left first molar of all rats, each group was further divided into 3 subgroups (n=10 per subgroup), receiving the administration of intermittent PTH, continuous PTH and saline (control), respectively. The intermittent-PTH group received intra-oral injection of PTH three times per week for two weeks. A thermosensitive controlled-release hydrogel was synthesized for continuous-PTH administration. The serum chemistry was determined to evaluate the systemic condition. All animals were sacrificed after 14 days. Micro-computed tomography (Micro-CT) and histological analyses were used to evaluate the healing of extraction sockets. Results: The level of serum glucose in the DM groups was significantly higher than that in the non-DM groups (p<0.05); the level of serum calcium was similar in all groups (p>0.05). Micro-CT analysis showed that the DM group had a significantly lower alveolar bone trabecular number (Tb.N) and higher trabecular separation (Tb.Sp) than the normal group (p<0.05). The histological analyses showed that no significant difference in the amount of new bone (hard tissue) formation was found between the PTH and non-PTH groups (p>0.05). Conclusions: Bone formation in the extraction socket of the type 1 diabetic rats was reduced. PTH did not improve the healing of hard and soft tissues. The different PTH administration regimes (continuous vs. intermittent) had similar effect on tissue healing. These results demonstrated that the metabolic characteristics of the hyperglycemic rats produced a condition that was unable to respond to PTH treatment
Ginkgolide B Reduces Atherogenesis and Vascular Inflammation in ApoE−/− Mice
To investigate whether ginkgolide B (a platelet-activating factor inhibitor) affects vascular inflammation in atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice.Human platelets were used to evaluate the effects of ginkgolide B on platelet aggregation and signal transduction. Ginkgolide B attenuated platelet aggregation and inhibited phosphatidylinositol 3 kinase (PI3K) activation and Akt phosphorylation in thrombin- and collagen-activated platelets. ApoE(-/-) mice were administered a high-cholesterol diet for 8 weeks. Plasma platelet factor 4 (PF4) and RANTES (regulated upon activation, normal T-cell expressed, and secreted protein) were then measured using an enzyme-linked immunosorbent assay. Scanning electron microscopy and immunohistochemistry were used to determine atherosclerotic lesions. Ginkgolide B decreased plasma PF4 and RANTES levels in ApoE(-/-) mice. Scanning electron microscopic examination showed that ginkgolide B reduced aortic plaque in ApoE(-/-) mice. Immunohistochemistry analysis demonstrated that ginkgolide B diminished P-selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE(-/-) mice. Moreover, ginkgolide B suppressed macrophage and vascular cell adhesion protein 1 (VCAM-1) expression in aorta lesions in ApoE(-/-) mice. Similar effects were observed in aspirin-treated ApoE(-/-) mice.Ginkgolide B significantly reduced atherosclerotic lesions and P-selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE-/- mice. The efficacy of ginkgolide B was similar to aspirin. These results provide direct evidence that ginkgolide B inhibits atherosclerosis, which may be associated with inhibition of the PI3K/Akt pathway in activated platelets
Infection of liver sinusoidal endothelial cells with Muromegalovirus muridbeta1 involves binding to neuropilin-1 and is dynamin-dependent
Liver sinusoidal endothelial cells (LSEC) are scavenger cells with a remarkably
high capacity for clearance of several blood-borne macromolecules and
nanoparticles, including some viruses. Endocytosis in LSEC is mainly via the
clathrin-coated pit mediated route, which is dynamin-dependent. LSEC can also
be a site of infection and latency of betaherpesvirus, but mode of virus entry into
these cells has not yet been described. In this study we have investigated the role
of dynamin in the early stage of muromegalovirus muridbeta1 (MuHV-1, murid
betaherpesvirus 1, murine cytomegalovirus) infection in mouse LSECs. LSEC
cultures were freshly prepared from C57Bl/6JRj mouse liver. We first examined
dose- and time-dependent effects of two dynamin-inhibitors, dynasore and
MitMAB, on cell viability, morphology, and endocytosis of model ligands via
different LSEC scavenger receptors to establish a protocol for dynamin-inhibition
studies in these primary cells. LSECs were challenged with MuHV-1 (MOI 0.2) ±
dynamin inhibitors for 1h, then without inhibitors and virus for 11h, and nuclear
expression of MuHV-1 immediate early antigen (IE1) measured by immune
fluorescence. MuHV-1 efficiently infected LSECs in vitro. Infection was
significantly and independently inhibited by dynasore and MitMAB, which block
dynamin function via different mechanisms, suggesting that initial steps of
MuHV-1 infection is dynamin-dependent in LSECs. Infection was also reduced
in the presence of monensin which inhibits acidification of endosomes.
Furthermore, competitive binding studies with a neuropilin-1 antibody blocked
LSEC infection. This suggests that MuHV-1 infection in mouse LSECs involves
virus binding to neuropilin-1 and occurs via endocytosis
DEVELOPMENT OF A KIND OF FLAVORING TABLETS FOR CHILDREN'S USE
Objective: In this study, based on children's medication preferences, Synsepalum dulcificum and Siraitia grosvenorii as raw material were used to develop a flavoring medicine for children. Methods: Synsepalum dulcificum and Siraitia grosvenorii as the raw material were applied to extract the Synsepalum dulcificum powder and Siraitia grosvenorii powder respectively, according to the orthogonal test design; the optimal proportion of flavoring powder was obtained. Low-substituted hydroxypropyl cellulose(L-HPC), polyvinylpolypyrrolidone(PVPP), sodium carboxymethyl starch(CMS-Na), microcrystalline cellulose(MCC) were taken, according to the orthogonal test design the optimum proportion of auxiliary materials, then the flavoring tablets was prepared according to the preparation process. Results: Through orthogonal test design, the optimum ratio of Synsepalum dulcificum: Siraitia grosvenorii was 1:3, and mixing them up in proportion; the optimum ratio of L-HPC: PVPP: CMS-Na: MCC was 10: 8: 3: 6, and mix them up in proportion. Equal amounts of sugar and salt were obtained by mass ratio of 1 to 1. Mixing 1/3 amount of flavoring powder with 3/4 amount of auxiliary materials, using 20% ethanol as a wetting agent, using the remaining sugar as a filler, and granulating. After the granules were dried and whole grain, add the remaining auxiliary materials and magnesium stearate were added, then the flavoring tablets were prepared. Conclusion: The effects of this formula were prominent, which could effectively intervene the taste of children's medicine; solve the practical problems concerning taking medications in children. Keywords: Synsepalum dulcificum; Siraitia grosvenorii; drug use in children; flavoring tabletsÂ
Changes in the proteome and secretome of rat liver sinusoidal endothelial cells during early primary culture and effects of dexamethasone
Introduction
Liver sinusoidal endothelial cells (LSECs) are specialized fenestrated scavenger endothelial
cells involved in the elimination of modified plasma proteins and tissue turnover waste macromolecules from blood. LSECs also participate in liver immune responses. A challenge
when studying LSEC biology is the rapid loss of the in vivo phenotype in culture. In this
study, we have examined biological processes and pathways affected during early-stage
primary culture of rat LSECs and checked for cell responses to the pro-inflammatory cytokine interleukin (IL)-1β and the anti-inflammatory drug dexamethasone.
Methods
LSECs from male Sprague Dawley rats were cultured on type I collagen in 5% oxygen atmosphere in DMEM with serum-free supplements for 2 and 24 h. Quantitative proteomics
using tandem mass tag technology was used to examine proteins in cells and supernatants.
Validation was done with qPCR, ELISA, multiplex immunoassay, and caspase 3/7 assay.
Cell ultrastructure was examined by scanning electron microscopy, and scavenger function
by quantitative endocytosis assays.
Results
LSECs cultured for 24 h showed a characteristic pro-inflammatory phenotype both in the
presence and absence of IL-1β, with upregulation of cellular responses to cytokines and
interferon-γ, cell-cell adhesion, and glycolysis, increased expression of fatty acid binding
proteins (FABP4, FABP5), and downregulation of several membrane receptors (STAB1,
STAB2, LYVE1, CLEC4G) and proteins in pyruvate metabolism, citric acid cycle, fatty acid elongation, amino acid metabolism, and oxidation-reduction processes. Dexamethasone
inhibited apoptosis and improved LSEC viability in culture, repressed inflammatory and
immune regulatory pathways and secretion of IL-1β and IL-6, and further upregulated
FABP4 and FABP5 compared to time-matched controls. The LSEC porosity and endocytic
activity were reduced at 24 h both with and without dexamethasone but the dexamethasone-treated cells showed a less stressed phenotype.
Conclusion
Rat LSECs become activated towards a pro-inflammatory phenotype during early culture.
Dexamethasone represses LSEC activation, inhibits apoptosis, and improves cell viability
Liver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIB, yet maintain a preserved fenestration the Glmp gt/gt mouse model of slowly progressing liver fibrosis
Liver sinusoidal endothelial cells (LSECs) are fenestrated endothelial cells with a unique,
high endocytic clearance capacity for blood-borne waste macromolecules and colloids. This
LSEC scavenger function has been insufficiently characterized in liver disease. The
Glmpgt/gt mouse lacks expression of a subunit of the MFSD1/GLMP lysosomal membrane
protein transporter complex, is born normal, but soon develops chronic, mild hepatocyte
injury, leading to slowly progressing periportal liver fibrosis, and splenomegaly. This study
examined how LSEC scavenger function and morphology are affected in the Glmpgt/gt
model. FITC-labelled formaldehyde-treated serum albumin (FITC-FSA), a model ligand for
LSEC scavenger receptors was administered intravenously into Glmpgt/gt mice, aged 4
months (peak of liver inflammation), 9–10 month, and age-matched Glmpwt/wt mice. Organs
were harvested for light and electron microscopy, quantitative image analysis of ligand
uptake, collagen accumulation, LSEC ultrastructure, and endocytosis receptor expression
(also examined by qPCR and western blot). In both age groups, the Glmpgt/gt mice showed
multifocal liver injury and fibrosis. The uptake of FITC-FSA in LSECs was significantly
reduced in Glmpgt/gt compared to wild-type mice. Expression of LSEC receptors stabilin-1
(Stab1), and mannose receptor (Mcr1) was almost similar in liver of Glmpgt/gt mice and agematched controls. At the same time, immunostaining revealed differences in the stabilin-1
expression pattern in sinusoids and accumulation of stabilin-1-positive macrophages in
Glmpgt/gt liver. FcγRIIb (Fcgr2b), which mediates LSEC endocytosis of soluble immune
complexes was widely and significantly downregulated in Glmpgt/gt liver. Despite increased collagen in space of Disse, LSECs of Glmpgt/gt mice showed well-preserved fenestrae organized in sieve plates but the frequency of holes >400 nm in diameter was increased, especially in areas with hepatocyte damage. In both genotypes, FITC-FSA also distributed to
endothelial cells of spleen and bone marrow sinusoids, suggesting that these locations may
function as possible compensatory sites of clearance of blood-borne scavenger receptor
ligands in liver fibrosis
Study on Anti-inflammatory and Analgesic Effect of FangXiangTongLuo-cervical Plaster
Objective: To study the anti-inflammatoryandanalgesic effects of FangXiangTongLuo-cervical Plaster. Methods: Preparation of FangXiangTongLuo cervical ointment. Using the model of the mouse ear swelling inflammation which is caused by xylene. The analgesic mode of hot-plate method and acetic acid wrinkle method, in order to study the anti - inflammatory and analgesic effects of FangXiangTongLuo-cervical Plaster. Result: The results showed that Fangxiangtongluo cervical plaster can effectively reduce the number of writhing in acetic acid-induced mice and increase the rate of writhing inhibition and analgesic percentage (p<0.01). In the hot plate experiment, Fangxiangtongluo cervical plaster can effectively improve the pain threshold of mice. With the increase in medication time, it can also significantly extend the time of the first mouse licking foot, thereby increasing the pain threshold of the mice. At the same time, Fangxiangtongluo cervical plaster can also significantly inhibit the degree of swelling of the mouse auricle caused by xylene, reducing the exudation of inflammatory substances in the body of mice. Conclusion: Fangxiangtongluo cervical plaster has significant anti-inflammatory and analgesic effects
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