Humans ; Kidney Diseases ; genetics ; Mutation ; WT1 Proteins ; genetics

Complement Factor H ; genetics ; Hemolytic-Uremic Syndrome ; genetics ; Humans

Autoimmune diseases (AID) are characterized by autoimmune disorder, as autologous tissue is attacked by the autoimmune system. It is reported that the imbalance of autoimmune tolerance and ingrained inflammatory response are the core events of AID undoubtedly. Peroxisome proliferator-activated receptor γ (PPARγ) which belongs to the nuclear hormone receptor superfamily is a ligand activated transcription factor. PPARγ combines with retinoid X receptor (RXR) to form heterodimer. When PPARγ is activated, the complex regulates gene expression by binding to a specific peroxisome proliferator response element (PPRE). In addition, PPARγ has diversified biological functions, playing important roles in regulating metabolism, controling inflammation, modulating glucose and lipid metabolism, ameliorating atherosclerosis, anti-tumor, and regulating immune response. However, recently researches indicate that PPARγ participates in the pathogenesis of AID. PPARγ plays key roles in regulating activation and polarization of macrophages, function of dendritic cells, proliferation and differentiation of T cells, and modulation of the function of related stromal cells. This article summarizes the biological functions and signal transduction pathways of PPARγ and the protective effects of agonists of PPARγ on AID, aiming to provide theoretical support for the research of mechanism and prevention and treatment of AID.

OBJECTIVETo explore the effect of Modified Hangqi Chifeng Decoction (MHCD) on levels of collagen type IV (Col IV), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) in extracellular matrix (ECM) of glomerular mesangial cells (GMCs) in LPS induced mice.

METHODSNormal serum and telmisartan, high, medium, low dose MHCD containing serums were prepared by using serum pharmacology method. GMCs were cultured in vitro. The proliferation of mesangial cells were induced using LPS as stimulating factor. GMCs were divided into six groups, i.e., the normal group, the model group, the telmisartan group, high, medium and low dose MHCD groups. Col IV content in the supernatant of mesangial cells was detected using ELISA. Protein expressions of MMP-2 and TIMP-2 were detected using Western blot.

RESULTSCompared with the normal group, Col IV content obviously increased in the model group after 72-h LPS stimulation; protein expressions of MMP-2 and TIMP-2 were obviously up-regulated, and MMP-2/TIMP-2 ratio was down-regulated in the model group (P < 0.01). Compared with the model group, Col IV content obviously decreased in high and medium dose MHCD groups and the telmisartan group (P < 0.01); protein expressions of MMP-2 were obviously down-regulated in medium and low dose MHCD groups (P < 0.01, P < 0.05); the protein expression of TIMP-2 was obviously down-regulated in high, medium, low dose MHCD groups and the telmisartan group (P < 0.01). The pro- tein expression of TIMP-2 was obviously lower in the high dose MHCD group than in the low dose MHCD group (P < 0.01). MMP-2/TIMP-2 ratio was obviously up-regulated in the telmisartan group, high and medium dose MHCD groups (P < 0.01).

CONCLUSIONMHCD could regulate disordered MMP-2/TIMP-2 ratio in LPS induced ECM, inhibit excessive production of Col IV in ECM, promote the degradation of ECM, reduce the accumulation of ECM, thereby, delaying the process of glomerular sclerosis.

Animals ; Cells, Cultured ; Collagen Type IV ; metabolism ; Extracellular Matrix ; metabolism ; Kidney Glomerulus ; cytology ; Matrix Metalloproteinase 2 ; metabolism ; Mesangial Cells ; drug effects ; Mice ; RNA, Messenger ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism

To study the relation between drug release and the drug status within curcumin-loaded microsphere, SPG (shirasu porous glass) membrane emulsification was used to prepare the curcumin-PLGA (polylactic-co-glycolic acid) microspheres with three levels of drug loading respectively, and the in vitro release was studied with high-performance liquid chromatography (HPLC). The morphology of microspheres was observed with scanning electron microscopy (SEM), and the drug status was studied with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and infrared analysis (IR). The drug loading of microspheres was (5.85 ± 0.21)%, (11.71 ± 0.39)%, (15.41 ± 0.40)%, respectively. No chemical connection was found between curcumin and PLGA. According to the results of XRD, curcumin dispersed in PLGA as amorphous form within the microspheres of the lowest drug loading, while (2.12 ± 0.64)% and (5.66 ± 0.07)% curcumin crystals was detected in the other two kinds of microspheres, respectively, indicating that the drug status was different within three kinds of microspheres. In the data analysis, we found that PLGA had a limited capacity of dissolving curcumin. When the drug loading exceeded the limit, the excess curcumin would exist in the form of crystals in microspheres independently. Meanwhile, this factor contributes to the difference in drug release behavior of the three groups of microspheres.
Calorimetry, Differential Scanning ; Curcumin ; chemistry ; Drug Liberation ; Lactic Acid ; Microscopy, Electron, Scanning ; Microspheres ; Polyglycolic Acid ; X-Ray Diffraction

To investigate the effect of compound Chinese traditional medicine PC-SPES II I in inhibiting proliferation of human prostate cancer cell LNCaP based on the androgen receptor (AR) signaling pathway. The effect of PC-SPES II on LNCaP cell proliferation was detected by MTT assay. According to the findings, at the mass concentration of 180-1 440 mg x L(-1), PC-SPES II significantly inhibited the proliferation of LNCaP cells; the IC50 of PC-SPES II at 24 h and 48 h were 311.48, 199.01 mg x L(-1), respectively. The flow Cytometry detection showed 240 mg x L(-1) PC-SPES II arrested cells in G2/M phase, and an obvious apoptotic peak appeared before G0/G1 peak and rose over time. Meanwhile, Hoechst 33258 staining revealed apoptotic cellular morphology. Annexin V-FITC/PI staining manifested an increase in apoptotic cell ratio at the PC-SPES II concentration of 480 mg x L(-1) in a dose dependent manner. The prostate specific antigen (PSA) secretion of LNCaP cells was tested by PSA ELISA kit. Besides, compared with 25 mg x L(-1) Bic, 480 mg x L(-1) PC-SPES II significantly reduced the cell secretion of PSA. The AR and PSA mRNA and protein expressions were detected by qRT-PCR and Western blot. According to the results, after the induction of LNCaP cells with synthetic androgen 25 μg x L(-1) R1881, 240-480 mg x L(-1) PC-SPES II notably down-regulated the AR and PSA mRNA and protein expressions and inhibited the translocation of AR from cytoplasm to nucleus. In summary, PC-SPES II significantly can inhibit the in vitro proliferation of LNCaP cells and arrest cell cycle arrest in G2/M phase. Its mechanism may be associated with the down-regulation of the AR and PSA expressions and the inhibition of AR nuclear translocation.
Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Male ; Prostate-Specific Antigen ; genetics ; metabolism ; Prostatic Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Receptors, Androgen ; genetics ; metabolism ; Signal Transduction ; drug effects

AIM: To investigate the early changes of retinal function in diabetic patients detected by multifocal electroretinogram (mfERG).METHODS: The first-order kernel responses of mfERG were recorded from eyes of 33 normal control subjects,63 diabetic patients without retinopathy and 43 diabetic patients with background retinopathy. The response densities and implicit times of N1 and P1 were compared among the control, diabetic patients without retinopathy and diabetic patients with retinopathy.RESULTS: The response densities of N1 and P1 in central 3 rings were reduced significantly in diabetic eyes with and without retinopathy. And the implicit times of N1 and P1 were delayed significantly only in diabetic eyes with retinopathy.CONCLUSION: mfERG can detect the early changes of retinal function quantitatively in diabetic patients. Analysis of response densities and implicit times of N1 and P1 can reflect the progress of local retinal dysfunction in diabetes.

Objective To evaluate the value of ultrasound (US) in assessment knee joint inflammation in patients with juvenile rheumatoid arthritis(JRA).Methods US scans of the knees obtained in 30 children at clinically active stage; JRA was compared with those obtained in 30 healthy children and 10 JRA patients in clinical remission.Results Changes in synovial membrane thickness and presence of fluid in suprapatellar bursa showed statistically significant differences between JRA patients with active disease and the other subjects.Alterations in contour of the articular cartilage were demonstrated in 10 knees of patients with JRA.Conclusion US is a simple sensitive and reliable methods for the assessment and monitoring of knee joint involvement in JRA.

Objective To investigate the current status of coal-burning endemic fluorosis and the fluoride content in foods and drinking water in Hongya County,Sichuan Province.Methods Dental fluorosis and urinary fluoride were suveyed in children of 8～12 years old in two schools which repectively located in Gaomiao and Wawushan Town.The adults above 20 years old underwent clinical examination.At the same time,fifty adults above 20 years old in Garden Village were chosen to take forearm and calf X-ray films to find out the evidence of skeletal fluorosis.The content of fluoride in food such as bacon,corn,dry capsicum in Sanxing Village in Gaomiao Town and Futian Village in Wawushan Town as well as drinking water in five families in Sanxing Village were determined.Results The dental fluorosis rate of children was 40.76%(161/395),the dental fluorosis index was 0.86 in Gaomiao Town.The dental fluorosis rate of children was 14.36%(82/571),the dental fluorosis index was 0.31 in Wawushan Town.The medium value of the urine fluoride was 0.81 mg/L.ranged 0.16～3.89 mg/L.The positive rate oi the clinical examination of skeletal fluorosis was 5.27%(27/512),the X-rays detective rate was 4.00%(2/50).The medium value in bacon,corn,dry capsicum were 6.00,0.64,1.49 mg/kg.The averaged content of the fluoride in drinking water(0.14±0.06)mg/L of local household was within the eligible limitation.Conclusions It is currently a mild endemic disease in Hongya Country,its incidence is reduced apparently,pathogenetic environmental fluoride content is reduced.The main source of fluoride is from the preserved ham contaminated with fluoride,which is epidemiologically significant in endemic area of Hongya County.Defluoriding countermeasures should be taken in the endemic areas.

Pro-inflammatory macrophages play key regulatory role in the occurrence and development of rheumatoid arthritis (RA). In this study, we constructed a celastrol (Cel)-loaded polyamide-amine dendrimer (PAMAM) drug delivery system, which could target folate receptor and mitochondria. It could target inflammatory macrophages and realize chemo-photothermal synergistic therapy. Using PAMAM as the nano-carrier, folate receptor-targeting group folic acid (FA) and mitochondria-targeting group IR808 (also known as the photothermal agent) were conjugated with PAMAM through amide reaction, and then complexed with anti-inflammatory drug Cel to prepare the FA-PAMAM-IR808/Cel nanocomplex. In vitro characterization results showed that the drug loading efficiency of the nanocomplex was 50.90%, particle size was between 130 and 160 nm, average potential was between 1.0 and 3.5 mV, the drug release showed pH sensitivity, temperature reached to 42.5 ℃ after near-infrared (NIR) light irradiation for 10 min. In vitro cellular uptake experiments showed that the nanocomplex had obvious folate receptor-targeting and mitochondria-targeting ability. Following irradiation with NIR light, the cytotoxicity and cellular apoptosis enhanced. The secretion of pro-inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and nitric oxide (NO) decreased in a concentration-dependent manner. This study provided insights for the development of novel anti-RA nanomedicines.