Dangui Huoxue Preparation (DHP) Ameliorates Skin Fibrosis, Inflammation, and Vasculopathy in the Bleomycin-Induced Murine Model of Systemic Sclerosis.

Systemic sclerosis (SSc) is an immune-mediated rheumatic disease that is characterized by fibrosis of the skin and internal organs and vasculopathy with poor prognosis. Dangui Huoxue Preparation (DHP) is a clinically effective traditional Chinese herbal formula for the treatment of SSc in the hospital. This study aims to investigate the therapeutic effects and underlying molecular mechanisms of DHP in the treatment of SSc. SSc mice models are induced by bleomycin (BLM). Tissues of DHP group, normal control group, and positive control drug Sanqi Tongshu Capsule (STC) group are collected for inflammation, fibrosis, and vasculopathy. Also, the human dermal fibroblasts (HDF) stimulated with TGF-ß1 are analyzed for in vitro study. The expression levels of MCP-1, IFN-γ, IL-1ß, IL-10, Fizz1, iNOS, and IL12p40, and the mRNA levels of Col1a1, Col1a2, Col3a1, and Col5a1 are significantly decreased in all DHP groups and STC group compare with those in the BLM group. The main drug of DHP inhibits the proliferation and migration of HDF, reduces Ctgf, Itgb3, Itgb5 expression, and also inhibits the Smad3 pathway. In conclusion, DHP can ameliorate SSc skin inflammation, fibrosis, and vasculopathy, possibly suppressing the TGF-ß1/Smad3 signaling pathway through extracellular and intracellular mechanisms.

Pathogenic Characteristics of Th17 Cells Based on the IL-17 Signaling Pathway in the Regulation of Sebaceous Gland Lipoprotein Metabolism in an Acne Rat Model.

BACKGROUND: Acne is a common and chronic inflammatory dermatosis of sebaceous gland units of the human hair follicle. Acne is closely related to immune cytokines and cells including T helper 17cells (Th17 cells). Mis-regulated glycolipid metabolism also plays a vital role in the process. OBJECTIVE: This investigation aimed to explore the role of IL-17 in signaling pathways controlling sebaceous gland lipoprotein metabolism in a rat model of acne. METHODS: We generated the rat ear acne model, and investigated the pathological changes of acne skin tissue by histological analysis and the changes in the critical factors including DEFB1, GPR65, FADS1, and FADS2 by Western Blot in this model. RESULTS: There were more Th17 cells in the rat ear acne model than in the control mice. The expression levels of DEFB1, GPR65, FADS1, FADS2 and MOGAT1 were significantly upregulated in serum and tissue from rat acne model, which could be concluded that the Th17 cells play a major role in the pathogenesis of acne based. CONCLUSION: Although acne is associated with immune effects and glycolipid metabolism, inhibition of IL-17 signaling pathway might be a novel way for acne therapy. Our findings also suggest a new strategy for targeted therapy of acne.

Prediction of a Competing Endogenous RNA Co-expression Network by Comprehensive Methods in Systemic Sclerosis-Related Interstitial Lung Disease.

Systemic sclerosis (SSc) is an immune-mediated connective tissue disease characterized by fibrosis of multi-organs, and SSc-related interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality. To explore molecular biological mechanisms of SSc-ILD, we constructed a competing endogenous RNA (ceRNA) network for prediction. Expression profiling data were obtained from the Gene Expression Omnibus (GEO) database, and differential expressed mRNAs and miRNAs analysis was further conducted between normal lung tissue and SSc lung tissue. Also, the interactions of miRNA-lncRNA, miRNA-mRNA, and lncRNA-mRNA were predicted by online databases including starBase, LncBase, miRTarBase, and LncACTdb. The ceRNA network containing 11 lncRNAs, 7 miRNAs, and 20 mRNAs were constructed. Based on hub genes and miRNAs identified by weighted correlation network analysis (WGCNA) method, three core sub-networks-SNHG16, LIN01128, RP11-834C11.4(LINC02381)/hsa-let-7f-5p/IL6, LINC01128/has-miR-21-5p/PTX3, and LINC00665/hsa-miR-155-5p/PLS1-were obtained. Combined with previous studies and enrichment analyses, the lncRNA-mediated network affected LPS-induced inflammatory and immune processes, fibrosis development, and tumor microenvironment variations. The ceRNA network, especially three core sub-networks, may be served as early biomarkers and potential targets for SSc, which also provides further insights into the occurrence, progression, and accurate treatment of SSc at the molecular level.

Insulin-like growth factor binding protein 7 as a candidate biomarker for systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease clinically characterised by skin and internal organs fibrosis with high mortality. However, the pathogenesis of SSc is still controversial and the effect of the current treatment is far from satisfactory. We aimed to find out novel candidate genes related to the pathological process in SSc. METHODS: In this study, the weighted correlation network analysis (WGCNA) was conducted to identify the key module and hub genes most related to SSc in GSE58095, a microarray dataset from the Gene Expression Omnibus (GEO) database. Also, the key module was analysed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then we validated hub genes in other datasets (GSE32413, GSE125362, GSE45485, GSE76885, GSE95065). The serum of 37 patients with SSc and 25 healthy control subjects (HCs) were recruited and detected by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Five interested genes (IGFBP7, LRRC32, STMN2, C1QTNF5, CPXM1) were up-regulated in SSc microarray datasets from the GEO. And the level of serum IGFBP7, which encodes a secreted protein, was upregulated in SSc patients-also in dcSSc patients and SSc with ILD patients. CONCLUSIONS: Among the five interested genes, the IGFBP7 was a novel candidate gene for SSc and may be served as potential target and early biomarker for accurate treatment, which also provides further insights into the pathogenesis of SSc at the molecular level.

Comparative efficacy and safety of immunosuppressive therapies for systemic sclerosis related interstitial lung disease: A Bayesian network analysis.

Objectives: Immunosuppressive therapies for the treatment of patients with systemic sclerosis (SSc) and SSc related interstitial lung diseases (SSc-ILD) include cyclophosphamide (CYC), mycophenolate mofetil (MMF), azathioprine (AZA) and methotrexate (MTX). The objectives were to compare and rank these therapies in term of forced vital capacity (FVC) % predicted, diffusing capacity of the lung for carbon monoxide (DLco) % predicted and adverse events (AEs).Methods: We present pooled estimates of mean difference (MD) and odds rates (ORs) with 95% confidence intervals (CIs) among different therapies. We also ranked these agents with surface under the cumulative ranking probability (SUCRA).Results: CYC plus AZA had the highest SUCRA probability (70%) on reducing risk of the deterioration of FVC compared with CYC, observation (OBS), MMF and AZA. While for the prevention of the deterioration of DLco, MMF showed the highest SUCRA probability (76%) compared with others. Moreover, AZA showed the lowest probability (32%) for AEs among active interventions.Conclusions: CYC plus AZA was the preferred immunosuppressive strategies compared to others on preventing the deterioration of FVC. MMF resulted with the highest probability as the best in preventing the deterioration of DLco. Monotherapy of AZA was less pulmonary function benefit but related less AEs.

Modification of garlic skin dietary fiber with twin-screw extrusion process and in vivo evaluation of Pb binding.

This study investigated the effects of a twin-screw extrusion-cooking process on the modification of garlic skin dietary fiber (DF) under optimal conditions (feed moisture 25%, extrusion temperature 170 °C and screw speed 170 rpm). The evaluation of the soluble dietary fiber (SDF) from the extruded garlic skin on the capacity of Pb binding was determined in vivo. Compared with the untreated garlic skin, the content of extruded garlic skin SDF increased from 5.31 ±â€¯0.58% to 15.87 ±â€¯0.88%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) images demonstrated that the macromolecules deteriorated to form smaller SDF fractions during extrusion. Moreover, differential scanning calorimetry (DSC) spectra showed the thermal stability of the extruded SDF was highly improved after extrusion. Additionally, in vivo experimental results indicated that the addition of extruded DF significantly reduced the Pb absorptivity of rats with exposed Pb concentrations at 20, 100 and 200 mg/kg. The findings showed that the extruded garlic skin DF has a positive effect on Pb binding.

The effect of 595 nm pulsed dye laser on connective tissue growth factor (CTGF) expression in cultured keloid fibroblasts.

OBJECTIVE: To investigate the effect of pulsed dye laser (PDL 595 nm) on the proliferation and expression of connective tissue growth factor (CTGF) in cultured keloid fibroblasts. MATERIALS AND METHODS: Cultured keloid fibroblasts were exposed to pulsed dye laser irradiation at fluences of 6, 8, and 10 J/cm(2) , with pulse durations of 1.5, 3, and 10 ms. The viability of keloid fibroblasts was measured with CCK-8 at 72, 24, and 12 hours prior to irradiation. Subsequently, viability was measured at 12, 24, and 72 hours post-irradiation. Additionally, the fibroblast cell cycle and apoptosis rate were measured by flow cytometry. Finally, keloid fibroblasts underwent real-time polymerase chain reaction (PCR) and Western blot to investigate the CTGF mRNA and protein expression after PDL irradiation. The untreated cultured keloid fibroblasts served as controls. RESULTS: The proliferation of keloid fibroblasts was significantly inhibited after PDL irradiation. Both CTGF mRNA and protein expression were significantly down-regulated in 1.5, 3, and 10 ms pulse duration groups, in a dose dependent manner (P < 0.05). However, there was no statistically significant difference between groups of different pulse duration in 6, 8, and 10 J/cm(2) fluence ranges (P > 0.05). CONCLUSIONS: Within certain fluence ranges, pulsed dye laser can effectively suppress the growth of keloids and significantly down-regulate CTGF mRNA and CTGF expression.

Pretreatment of garlic powder using sweep frequency ultrasound and single frequency countercurrent ultrasound: optimization and comparison for ACE inhibitory activities.

The sweep frequency ultrasound (SFU) and single frequency countercurrent ultrasound (SFCU) pretreatments were modeled and compared based on production of angiotensin I-converting enzyme (ACE) inhibitory peptides from garlic hydrolysates. Two mathematical models were developed to show the effect of each variable and their combinatorial interactions on ACE inhibitory activity. The optimum levels of the parameters in SFU were determined using uniform design, which revealed these as follows: total ultrasonic time 1.5 h, on-time of pulse 18 s and off-time of pulse 3 s. Under optimized conditions, the experimental values of SFU and SFCU were 65.88% and 67.78%, which agreed closely with the predicted values of 63.44% and 67.33%. The SFU and SFCU pretreatments both resulted in higher ACE inhibitory activity compared with untreated garlic (p<0.05). However, there were no significant differences in the ACE inhibitory activities and IC50 values obtained from SFCU and SFU pretreatments under optimum conditions (p>0.05).

The effect of flashlamp pulsed dye laser on the expression of connective tissue growth factor in keloids.

OBJECTIVE: To investigate connective tissue growth factor (CTGF) expression before and after pulsed dye laser (PDL, 595 nm) treatment, and to better understand the mechanism of PDL treatment of keloids. METHOD: Twenty-six patients with keloids were recruited for this study. For each patient, two keloids of similar anatomic location, duration, texture, and appearance were chosen for study; one of these keloids was treated and the other served as a control. Three sessions of PDL treatment, with pulse duration of 1.5 milliseconds, spot size 7 mm, DCD duration 20 milliseconds/delay 10 milliseconds and fluence of 10 J/cm(2), were performed on the keloids at 3- to 4-week intervals. Punch biopsies were performed both on the treated and untreated keloids prior to the first treatment and after the final treatment. The specimens underwent realtime polymerase chain reaction (PCR) and immunohistochemistry (IHC) to investigate the CTGF mRNA and protein expression after PDL treatment. RESULTS: According to realtime PCR, the CTGF mRNA was significantly down-regulated after PDL treatment in 80.77% of patients as compared to the control group. IHC investigation showed that after treatment the CTGF positive cells also significantly decreased in number as compared to the control group in 80.77% of patients. Using the Vancouver scar scale (VSS), there was an average decrease of 20.85 ± 12.33% after PDL treatment. CONCLUSIONS: Pulsed dye laser treatment of keloids significantly down-regulates the expression of CTGF in most cases. This may partially explain the mechanism of action of PDL treatment of keloids.

[Studies on HPLC-ELSD fingerprint of the Coleus forskohlii introduced in Tongcheng].

OBJECTIVE: To establish HPLC-ELSD fingerprint of Coleus forskohlii. METHODS: Chromatographic fingerprint of Coleus forskohlii was investigated by HPLC-ELSD and gradient elution mode was applied to chromatographic separation. RESULTS: The HPLC-ELSD fingerprint of Coleus forskohlii was established preliminarily. CONCLUSION: HPLC-ELSD fingerprint method is repeated and can be used in quality control of Coleus forskohlii. The active constituent in Coleus forskohlii is probably at equal pace between introduced in Tongcheng and provenance.

Bioactive compounds from Peperomia pellucida.

Five new compounds (1-5), including two secolignans, two tetrahydrofuran lignans, and one highly methoxylated dihydronaphthalenone, were isolated from the whole plant of Peperomia pellucida. These compounds were accompanied by the known peperomins A, B, C, and E, 7,8-trans-8,8'-trans-7',8'-cis-7,7'-bis(5-methoxy-3,4-methylenedioxyphenyl)-8-acetoxymethyl-8'-hydroxymethyltetrahydrofuran, 7,8-trans-8,8'-trans-7',8'-cis-7-(5-methoxy-3,4-methylenedioxyphenyl)-7'-(4-hydroxy-3,5-dimethoxyphenyl)-8,8'-diacetoxymethyltetrahydrofuran, sesamin, and isoswertisin. New structures were elucidated mainly by NMR and MS techniques, and anticancer activities evaluated in HL-60, MCF-7, and HeLa cell lines. Compound 1 and peperomin E show growth inhibitory effects on the three cancer cell lines with IC(50) values ranging between 1.4 and 9.1 and between 1.8 and 11.1 microM, respectively. Compound 2 has a weak suppressive activity on HL-60 cells (IC(50) = 10.8 microM), while 7,8-trans-8,8'-trans-7',8'-cis-7,7'-bis(5-methoxy-3,4-methylenedioxyphenyl)-8-acetoxymethyl-8'-hydroxymethyltetrahydrofuran exhibits estrogen-like properties (EC(50) = 3.1 microM) in CV-1 cells transfected with human estrogen receptor (ERalpha).