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Psoriasis is an autoimmune disease presented in the context of inflammation， and it mainly results from proliferation and differentiation defects of keratinocytes and abnormal immune response. However， some cellular and molecular mechanisms remain unclear. Although a variety of drugs and physiotherapies are applicable to this disease， they can only be utilized for a short-term period considering their transient effect， high cost， and serious adverse reactions. It is difficult to achieve satisfactory long-term results in the treatment of psoriasis. With the development of network pharmacology and molecular biology and the modernization of traditional Chinese medicine （TCM）， the multi-component and multi-target characteristics of TCM have become prominent， promoting the in-depth research on TCM by doctors and scholars. Nevertheless， there is no detailed summarization on the mechanisms of TCM in interfering with T helper 17 （Th17）/regulatory T （Treg） cell balance to prevent and treat psoriasis. After reviewing the recent literature data， this paper has found that Chinese herbal monomers， active ingredients， and compounds obviously regulate the Th17/Treg axis in psoriasis. Th17 cells have a pro-inflammatory effect， while Treg cells are responsible for maintaining peripheral tolerance. They function in a mutually exclusive manner， and maintaining the Th17/Treg balance helps to effectively reduce inflammatory reaction and regulate immune homeostasis. As revealed by a series of clinical and experimental studies carried out based on the Th17/Treg axis in psoriasis， reducing the percentage of Th17 cells，increasing the percentage of Treg cells，and regulating the levels of related cytokines and transcription factors are conducive to alleviating inflammation and regaining immune homeostasis，which has provided new ideas for further elucidating the pathological mechanism of psoriasis and alternative plans for developing new treatments against psoriasis.
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OBJECTIVE: To investigate the effects of GnRH agonist and antagonist protocols on preimplantation genetic testing outcomes of chromosomal translocation carriers.METHODS: The clinical data of 226 patients with chromosomal translocation were analyzed retrospectively between Jan. 2015 and Dec. 2017 in Shengjing Hospital Affiliated to China Medical University.The patients were divided into GnRH agonist group(174 cases)and GnRH antagonist group(52 cases),then the duration of gonadotropin stimulation,dosage of gonadotropin used,embryonic quality,normal and balanced embryo numbers,per transfer cyclepregnancy rate,abortion rate and continuous pregnancy rate and accumulated pregnancy rate were analyzed.RESULTS: There were no statistical differences in the number of retrieved oocytes,number of MⅡ oocytes,fertilization rate,cleavage rate,blastocyst formation rate,number of high-quality embryo,number of blastocyst biopsy,normal and balanced embryo numbers,per transfer cycle pregnancy rate,abortion rate,continuous pregnancy rate or accumulated pregnancy rate between GnRH agonist group and GnRH antagonist group(P>0.05).The duration of gonadotropin stimulation(9 d vs. 10 d)and dosage of gonadotropin(2100 U vs. 2400 U)used in the GnRH antagonist group were significantly less than the GnRH agonist group(P<0.05).CONCLUSION: There are no significant differences in embryo quality or pregnancy rate between the GnRH agonist group and antagonist group during preimplantation genetic testing,but the GnRH antagonist group have an advantage in Gn duration and dosage.
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OBJECTIVE: To investigate the uptake and transport properties of micelles across Madin Darby canine kidney (MD-CK) cells. METHODS: Coumarin 6 loaded PEG-PLA (PEG3000-PLA3000) micelles were prepared by solvent evaporation method, and the HPLC determination method of coumarin 6 was constructed. Competition uptake of blank micelles with coumarin 6 micelles was studied. Temperature and inhibitors effect on transport of micelles across MDCK cell monolayer were studied, the concentration of Ca and EGTA were also studied. RESULTS: Coumarin 6 micelles could be internalized into cells very quickly, and the uptake of micelles could be inhibited by blank micelles. The transport of micelles was affected by temperature and inhibitors, which means that this process is an active and energy-dependent process. The concentration of Ca2+ and EGTA could affect the transport of the micelles, which means micelles could transport across the cell monolayer via paracellular pathway. The amount of transported coumarin 6 micelles was rather limited compared with coumarin 6 micelles added to the apical side. CONCLUSION: Micelles transport across MDCK cell monolayer via both paracellular and transcellular pathway at the same time.
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Objective To observe the expression of hypoxia-inducible factor 1 α (HIF-1α) in rat brain after hypoxia-ischemia(HI),and to explore the possible mechanism of L-thyroxine (L-T4) on HIF-1α expression.Methods Sixty-four postnatal 7-day Sprague-Dawley rats were randomly divided into 4 groups:the sham operation group,HI group,menstruum-treated group and L-T4-treated group.HIBD models were generated according to Rice model method.The rats in menstruum-treated group and L-T4-treated group were respectively administrated of intraperitoneal injection of menstruum with the equal volume and 2 μg/100g L-T4,once a day,for 5 days.The expressions of HIF-1α and phospho-protein kinase B(p-Akt) protein were detected by means of immunohistochemistry.Reverse transcription-polymerase chain reaction was used to detect the level of HIF-1α mRNA.Results The levels of p-Akt protein(50.168 ±4.259),HIF-1α protein (72.795 ±6.121) and HIF-1α mRNA (0.448 ± 0.035) were upregulated compared with those in the sham operation group (8.080 ±0.369,38.581 ± 2.846,0.174 ± 0.015),and the differences were significant (all P ＜ 0.05).The levels of p-Akt protein (82.765 ± 6.271),HIF-1 α protein (117.350 ± 9.374) and HIF-1 α mRNA (0.618 ± 0.042) in L-T4-treated group were higher than those in HI group,and the differences were significant (all P ＜ 0.05).The level of HIF-1 α protein was positively correlated with p-Akt protein in HI group and L-T4-treated group [r(HI) =0.635,P=0.048;r(L-T4) =0.694,P=0.026].Conclusions L-T4 can upregulate HIF-1α mRNA and protein expression in neonatal rats with hypoxia-ischemia brain damage.Phosphatidylinositol-3-kinase/protein kinase B signaling pathway may be involved in L-T4 upregulating HIF-1α mRNA and protein expression.
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<p><b>OBJECTIVE</b>Based on establishment of four rat models of experimental pulmonary hypertension (PH), the authors examined the inhibition of matrix metalloproteinases (MMPs) by doxycycline and its effect on the development of PH and associated pulmonary vascular remodeling.</p><p><b>METHOD</b>Healthy male Sprague-Dawley rats (weight 350 g to 400 g) were randomly divided into nine groups: Normal control group (N), four model groups (H, M, P, PM) and their corresponding drug intervention groups (HD, MD, PD, PMD) in which doxycycline was given by gavage at a 20 mg/kg daily dosage. On day 28 (day 35 for PM and PMD models), the animals were catheterized to record mean pulmonary arterial pressure (mPAP) and then sacrificed. Fulton Index [RV/(LV + S)] was measured immediately. Morphometric parameters, including percent vascular wall thickness and muscularization of non-muscularized peripheral pulmonary arterioles were determined microscopically. The activity of MMPs was measured by gelatin zymography in the lung tissue.</p><p><b>RESULTS</b>(1) Rats in all model groups (H, M, P, PM) developed significant pulmonary arterial hypertension and right ventricular hypertrophy in comparison with their corresponding drug intervention groups (HD, MD, PD, PMD) and normal control group (N) (P < 0.01). For example, mPAP (mm Hg)(1 mm Hg = 0.133 kPa):N: 18.10 +/- 1.45, H: 27.20 +/- 1.55, HD: 23.90 +/- 2.13; Fulton Inedx(%):N: 23.41 +/- 1.84, H: 34.44 +/- 2.70, HD: 27.55 +/- 2.45. (2) The percent vascular wall thickness (WT%) and percentage of muscularization of non-muscular pulmonary arterioles were significantly increased in all model groups compared with drug intervention groups and normal group (P < 0.01). For example, WT%:N: 10.90 +/- 3.11, H:41.41 +/- 5.21, HD: 17.73 +/- 3.12; Muscularization(%):N: 13.83 +/- 3.72, H: 44.93 +/- 2.43, HD: 29.89 +/- 4.45. (3) The activity of MMPs was inhibited by doxycycline effectively as assessed by gelatin zymography (P < 0.01). For example, the activity of MMP2 (A x 10(3)):N: 1.43 +/- 0.24, H: 3.58 +/- 0.28, HD: 2.29 +/- 0.31.</p><p><b>CONCLUSION</b>Doxycycline attenuated PH and associated pulmonary vascular remodeling in all rat PH models. The study suggests that high expression and enhanced activity of MMPs may play a brutial role in the development of PH. Such phenomenon seems to be common in a variety of PH models of different etiology.</p>
Subject(s)
Animals , Male , Rats , Disease Models, Animal , Doxycycline , Pharmacology , Hypertension, Pulmonary , Metabolism , Matrix Metalloproteinases , Metabolism , Pulmonary Artery , Metabolism , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To establish a human ovarian cancer-bearing mouse model via orthotopic transplantation of human HO-8910 cells expressing green fluorescent protein (GFP).</p><p><b>METHODS</b>GFP-expressing human ovarian carcinoma HO8910/GFP cells (2 x 10(6)) in exponential phase of growth were inoculated subcutaneously in nude mice, and the generated tumor tissues were collected and transplanted below the capsule of the left ovary of 6 nude mice. The growth of the tumors was observed in vivo using a fluorescence stereomicroscope. The nude mice were sacrificed 4 weeks after transplantation to assess the tumor growth and metastasis.</p><p><b>RESULTS</b>The tumors showed progressive growth at the orthotopic sites in all animals. Two weeks after the transplantation, green fluorescent mass was observed at the left costovertebral angle, and the mass increased thereafter and invaded or metastasized to the peritoneum, omentum, spleen, liver, uterus, and the pelvic lymph nodes, with a metastatic rate as much as 66.7%.</p><p><b>CONCLUSION</b>The nude mouse model bearing orthotopic human ovarian carcinoma expressing GFP has been successfully established.</p>
Subject(s)
Animals , Female , Mice , Cell Line, Tumor , Disease Models, Animal , Green Fluorescent Proteins , Genetics , Metabolism , Mice, Nude , Microscopy, Fluorescence , Neoplasm Transplantation , Neoplasms, Experimental , Genetics , Metabolism , Pathology , Ovarian Neoplasms , Genetics , Metabolism , Pathology , Transplantation, HeterologousABSTRACT
<p><b>OBJECTIVE</b>To explore the role of expression of connective tissue growth factor (CTGF) in pulmonary vascular remodeling of pulmonary hypertensive rats, and investigate the regulation of CTGF expression by simvastatin in this animal model.</p><p><b>METHODS</b>Eighty male Sprague-Dawley rats (350 to 400 g) were randomized to 7 groups. The rats in group PM(1 - 21) (n = 10) and PM(1 - 35) (n = 12) were treated with pneumonectomy + monocrotaline (MCT), and sacrificed at the 21st or 35th experimental day;those in groups PMS(1 - 35) (n = 12), PMS(21 - 35) (n = 12), PMV(1 - 35) (n = 12) and PMV(21 - 35) (n = 12) were given daily lavage of simvastatin (or vehicle) as intervention measure which began from the 1st and 21st experimental days, respectively; additional 10 rats were used as control without any intervention. The animals were sacrificed at the end of experiment (35 th day) as hemodynamic measurements and study on the morphological parameters relevant to pulmonary vascular remodeling were performed on each group of rats. The expression of ET-1 mRNA, CTGF mRNA and protein, and synthesis of collagen in these pneumonectomized, MCT-treated rats were compared between control and rats treated with simvastatin.</p><p><b>RESULTS</b>Rats in PM(1 - 35) Group developed severe PAH (mPAP = 39.75 +/- 3.62 mm Hg) (1 mm Hg = 0.133 kPa), right ventricular hypertrophy [RV/(LV + S) ratio = 0.627 +/- 0.040], and arterial medial hypertrophy (WT% = 61.73 +/- 5.39), these parameters of the control animals were 17.10 +/- 1.20 mm Hg, 0.262 +/- 0.018 and 14.71 +/- 1.16, respectively. CTGF mRNA and protein were mainly located in pulmonary arterial smooth muscle cells and interstitial macrophage shown by in situ hybridization and immunohistochemistry, respectively. The expression of ET-1 mRNA and CTGF mRNA detected by fluorescent quantitative RT-PCR in Group PM(1 - 35) were significantly increased in comparison with controls, and so did the CTGF protein expression determined by Western blotting in these diseased rats. The content of hydroxyproline (1.30 +/- 0.19 microg/mg wet lung) was remarkably higher than that of control animals (0.56 +/- 0.10 microg/mg wet lung). The up-regulation of ET-1 and CTGF gene expression, and elevated synthesis of hydroxyproline were reversed in rats intervened with simvastatin. The pulmonary hypertension, right ventricular hypertrophy and medial hypertrophy were attenuated in all simvastatin-treated rats no matter the intervention was initiated from the beginning or midway of the study.</p><p><b>CONCLUSION</b>The up-regulation of CTGF gene expression may play an important role in the development of pulmonary vascular remodeling in PAH. Simvastatin can prevent and, to some extent, reverse the vascular remodeling via down-regulation of CTGF gene expression.</p>
Subject(s)
Animals , Male , Rats , Connective Tissue Growth Factor , Metabolism , Down-Regulation , Hypertension, Pulmonary , Metabolism , Rats, Sprague-Dawley , Simvastatin , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate calcium-phosphate coating on commercial pure titanium substrate using a fast biomimetic procedure.</p><p><b>METHODS</b>The titanium specimens were divided into two groups, group A and group B. The specimens of group A were only treated with the mixture of H2SO4/HCl for 30 min. The specimens of group B were treated with the mixture of H2SO4/HCl for 30 min, immersed into 5 mol/L NaOH solution at 60 degrees C for 24 h, and then heated to 600 degrees C and maintained for 1 h. All specimens were soaked into simulated body fluid-A (SBF) and SBF-B for each day. The surface morphology was observed by field scanning electron microscopy.</p><p><b>RESULTS</b>Dense calcium-phosphate coating deposited on all the titanium surfaces of two groups. The calcium-phosphate coating consisted of spheric structure with a diameter of 1 approximately 3 microm, which was proved to be hydroxycarbonate apatite with the analysis of X-ray diffraction.</p><p><b>CONCLUSIONS</b>Thin hydroxycarbonate apatite coating can deposited on pure titanium using a fast biomimetic procedure.</p>
Subject(s)
Apatites , Chemistry , Coated Materials, Biocompatible , Chemistry , Dental Implants , Surface Properties , Titanium , Chemistry , X-Ray DiffractionABSTRACT
<p><b>OBJECTIVE</b>To compare the surface apposition and the bone response at early period of implantation in two differently treated implants.</p><p><b>METHODS</b>The implants were subject to double acid-etched-H2O2/HCl-heat treatment and double acid-etching treatment, and then randomly implanted into the tibia of rabbits. After 2, 4, 8 weeks of follow up, the bone specimens containing implants were prepared and examined by a field emission SEM and EDX.</p><p><b>RESULT</b>A layer rich with calcium and phosphorus was clearly demonstrated on the implants surface of both groups after 2 weeks of implantation, but it was mostly disappeared after 4 weeks. There were large amounts of osteoblasts cells on double acid-etched-H2O2/HCl-heat treated implants surface indicating the initiation of osteogenesis. After 8 weeks of implantation some new bones were attached on the implants surface in both groups, more bones attached were shown on double acid-etched- H2O2/HCl-heat treated implants surface.</p><p><b>CONCLUSION</b>A calcium and phosphorus-rich layer was formed on the implants surface of both groups at early period of implantation.</p>