ABSTRACT
The aim of this study was to investigate the expression of macrophage migration inhibitory factor (MMIF),hypoxia-inducible factor-1 α (HIF-1 αt) and vascular endothelial growth factor (VEGF) in the serum and endometrial tissues of patients with endometriosis (EM) and the clinical significance.Eighty EM patients [American Reproductive Association stage I (n=20),stage Ⅱ (n=22),stage Ⅲ (n=21) and stage Ⅳ (n=17)] were enrolled and divided into mild (10-14 points,n=28),moderate (16-24 points,n=27) and severe (26-30 points,n=25) dysmenorrhea groups.The control group included 40 healthy women of childbearing age who underwent routine healthcare examinations in the enrolment period.The expression of MMIF,HIF-1α and VEGF in the serum and endometrial tissues was measured by enzyme-linked immunosorbent assay and Western blotting,respectively.Meanwhile,the sensitivity and specificity of serum MMIF,HIF-1α,and VEGF when separately used as single indexes or jointly used as one index were examined as well.The results showed that serum concentrations of MMIF,HIF-1α,and VEGF were significantly higher in EM patients than in controls (P＜0.05).The expression of all three proteins in both serum and endometrial tissues increased significantly with the R-AFS stage (P＜0.05) and with dysmenorrheal severity (P＜0.05).The sensitivity and specificity of the combined detection of serum MMIF,HIF-1α,and VEGF levels were significantly higher than those of single index detection (P＜0.05).In conclusion,the expression of MMIF,HIF-1α,and VEGF in the serum and endometrial tissues may be used to assess the stage of EM and the severity of dysmenorrhea.Combined evaluation of MMIF,HIF-1α,and VEGF significantly improves the diagnostic sensitivity and specificity.
ABSTRACT
The aim of this study was to investigate the expression of macrophage migration inhibitory factor (MMIF),hypoxia-inducible factor-1 α (HIF-1 αt) and vascular endothelial growth factor (VEGF) in the serum and endometrial tissues of patients with endometriosis (EM) and the clinical significance.Eighty EM patients [American Reproductive Association stage I (n=20),stage Ⅱ (n=22),stage Ⅲ (n=21) and stage Ⅳ (n=17)] were enrolled and divided into mild (10-14 points,n=28),moderate (16-24 points,n=27) and severe (26-30 points,n=25) dysmenorrhea groups.The control group included 40 healthy women of childbearing age who underwent routine healthcare examinations in the enrolment period.The expression of MMIF,HIF-1α and VEGF in the serum and endometrial tissues was measured by enzyme-linked immunosorbent assay and Western blotting,respectively.Meanwhile,the sensitivity and specificity of serum MMIF,HIF-1α,and VEGF when separately used as single indexes or jointly used as one index were examined as well.The results showed that serum concentrations of MMIF,HIF-1α,and VEGF were significantly higher in EM patients than in controls (P＜0.05).The expression of all three proteins in both serum and endometrial tissues increased significantly with the R-AFS stage (P＜0.05) and with dysmenorrheal severity (P＜0.05).The sensitivity and specificity of the combined detection of serum MMIF,HIF-1α,and VEGF levels were significantly higher than those of single index detection (P＜0.05).In conclusion,the expression of MMIF,HIF-1α,and VEGF in the serum and endometrial tissues may be used to assess the stage of EM and the severity of dysmenorrhea.Combined evaluation of MMIF,HIF-1α,and VEGF significantly improves the diagnostic sensitivity and specificity.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of Xinfeng Capsule (XFC) on ankylosing spondylitis (AS) patients' symptoms and signs, serum immunoglobulin levels, peripheral blood lymphocyte autophagy protein, autophagy gene, and to explore its mechanism.</p><p><b>METHODS</b>Totally 59 AS patients were assigned to the treatment group (39 cases) and the control group (20 cases) according to random digit table. Patients in the treatment group received XFC, 0.5 g each pill, three pills each time, 3 times per day, while those in the control group received sulfasalazine (SASP), 0.25 g per tablet, 4 tablets each time, twice per day. Three months consisted of one therapeutic course. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were statistically calculated. Serum immunoglobulins (IgG1, IgG2, IgG3, IgG4, IgA , SIgA, and IgM) were detected using ELISA. Changes of Beclin1, LC3-II, phosphatidylinositol 3-kinase (PI3K), Akt, the mammalian target of rapamycin (mTOR) were detected using Western blot. Serum autophagy related genes such as Atg1, Atg5, Atg12, Atg13, and Atg17 were detected using the polymerase chain reaction (PCR). The correlation between immunoglobulin subtypes and autophagy gene in AS patients using Spearman correlation.</p><p><b>RESULTS</b>Compared with before treatment, BASDAI, IgG1, lgG3, and IgA decreased (P < 0.01); PI3K, Akt, and mTOR protein expressions decreased (P < 0.01); ATG1, ATG12, ATG13, and ATG17 mRNA expressions decreased, ATG5 mRNA expression increased (P < 0.01) in the treatment group. But BASDAI, IgG1, and IgA levels decreased (P < 0.05, P < 0.01); PI3K, Akt, and mTOR protein expressions decreased (P < 0.05); ATG1 and ATG13 mRNA expressions decreased (P < 0.05, P < 0.01) in the control group. Compared with the control group, BASDAI, IgG1, and IgA levels decreased (P < 0.05); PI3K, Akt, mTOR protein expressions decreased (P < 0.01); ATG12 and ATG17 mRNA expression decreased, ATG5 mRNA expression increased (P < 0.01) in the XFC group. Correlation analysis showed AS patients' IgG1, IgG2, IgG3, IgA, SIgA, IgM had negative correlation with ATG17; IgG4 and ATG17 were positively correlated (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>XFC could elevate clinical efficacy of AS patients and enhance their autophagy, which might be achieved by acting on PI3K/Akt/mTOR signal, affecting autophagy gene and autophagy protein expression, taking part in the regulation of proliferation and differentiation of lymphocyte B, and strengthen humoral immunity.</p>
Subject(s)
Humans , Apoptosis Regulatory Proteins , Metabolism , Autophagy , Beclin-1 , Capsules , Drugs, Chinese Herbal , Therapeutic Uses , Immunoglobulin A , Blood , Immunoglobulin G , Blood , Immunoglobulin M , Blood , Lymphocytes , Membrane Proteins , Metabolism , Phosphatidylinositol 3-Kinases , Metabolism , Spondylitis, Ankylosing , Drug Therapy , Sulfasalazine , Therapeutic Uses , TOR Serine-Threonine Kinases , MetabolismABSTRACT
Fraxinellone, the major component of Cortex Dictamni, is naturally degraded limonids compound. Fraxinellone has significant anti-inflammatory activity in acute liver injury model. However, the low solubility and permeability of fraxinellone limited its potential application and even therapeutic effects. The aim of the paper is to increase oral bioavailability of fraxinellone, thus improving its hepatoprotection effect in vivo. We evaluated the effects of different pH values and different solubilizer (PEG 6000, PVP K30, HP-beta-CD, F68 and SDS) on the solubility of fraxinellone. The results showed that HP-beta-CD increased solubility of fraxinellone up to 155 times compared to that of water. More than 2. 1 mg mL1 fraxinellone can be resolved when adding 20% HP-beta-CD. Mouse acute liver injury model induced hy CCl4 was used to evaluate in vivo activity of fraxinellone with or without HP-beta-CD. The result shows that the hepatoprotective activity of fraxinellone in 20% HP-beta-CD solution has been significantly improved compared with that of fraxinellone solution without HP-beta-CD: the former inhibited 59 percent the increase of enzyme activity of ALT in liver, while the latter only inhibited 20 percent. A LC-MS/MS method was also developed to determine the oral bioavailability of fraxinellone. Fraxinellone solution with or without HP-betaCD were administered intra-gastrically to rats, and it was found that the bioavailahility of fraxinellone with HP-beta-CD was 23%, while only 5% without HP-beta-CD. The result showed that HP-beta-CD can significantly increase the solubility and permeability of fraxinellone, and improve bioavailability 3. 5 fold in vivo acute liver injury model as well as administration.