Quercetin inhibits the amphiregulin/EGFR signaling-mediated renal tubular epithelial-mesenchymal transition and renal fibrosis in obstructive nephropathy.

Quercetin is a widely distributed, bioactive flavonoid compound, which displays potential to inhibit fibrosis in several diseases. The purpose of our study was to determine the effect of quercetin treatment on renal fibrosis and investigate the mechanism. Human proximal tubular epithelial cells (HK-2) stimulated by transforming growth factor-ß1 (TGF-ß1) and a rat model of unilateral ureter obstruction (UUO) that contributes to fibrosis were used to investigate the role and molecular mechanism of quercetin. PD153035 (N-[3-Bromophenyl]-6,7-dimethoxyquinazolin-4-amine) was used to inactivate EGFR (epidermal growth factor receptor). The level of fibrosis, proliferation, apoptosis, and oxidative stress in HK-2 were measured. All data are presented as means ± standard deviation (SD). p-value < .05 was considered statistically significant. In UUO rats, quercetin reduced the area of fibrosis as well as inflammation, oxidative stress, and cell apoptosis. In cultured HK-2 cells, quercetin significantly ameliorated the EMT induced by TGF-ß1, which was accompanied by increased amphiregulin (AREG) expression. Moreover, quercetin inhibited AREG binding to the EGFR receptor, thereby further affecting other downstream pathways. Quercetin may alleviate fibrosis in vitro and in vivo by inhibiting the activation of AREG/EGFR signaling indicating a potential therapeutic effect of quercetin in renal fibrosis.

Ascorbic acid mitigates the deleterious effects of nicotine on tendon stem cells.

Purpose: Nicotine causes tendon degeneration, whereas ascorbic acid imparts beneficial effects on tendon cells. Tendon stem cells (TSCs) play a vital role in maintaining tissue integrity and promoting restoration of structure and function after tendon injury. In the present study, cell culture experiments were performed to determine the effects of nicotine on TSCs and whether ascorbic acid supplementation could antagonize the action of high concentration nicotine. Methods: After treatment with nicotine and ascorbic acid, TSC proliferation, migration, stemness, apoptosis, and differentiation were analyzed. Results: TSC proliferation and expression of stem cell markers were significantly impaired by a high concentration of nicotine (1000 ng/mL), but a lower concentration (100 ng/mL) induced proliferative effects in TSCs. Moreover, the highest concentration of nicotine tested (1000 ng/mL) significantly inhibited the migratory ability of TSCs, while relatively high concentrations (100 and 1000 ng/mL) significantly (p < 0.05) up-regulated non-tenocyte genes. When ascorbic acid was added, the inhibitory effects of nicotine on the proliferation, migration, and stemness of TSCs were reversed. In addition, flow cytometry analysis showed that these nicotine concentrations could induce cell apoptosis, while the addition of ascorbic acid inhibited apoptosis. Conclusion: Addition of ascorbic acid partially reversed the inhibitory effect of a high concentration of nicotine. These findings indicate that while nicotine impairs the biological characteristics of TSCs, ascorbic acid can mitigate these deleterious effects and, therefore, may be useful for decreasing nicotine-induced tendon degeneration.

Adjuvant treatment with crude rhubarb for patients with systemic inflammation reaction syndrome/sepsis: a meta-analysis of randomized controlled trials.

OBJECTIVE: The objective of this study is to evaluate the benefits of adjuvant treatment with crude rhubarb in patients with systemic inflammation reaction syndrome/sepsis by conducting a meta-analysis. METHODS: We conducted a systematic literature search of medical electronic databases (up to October 2013). Only randomized controlled trials (RCTs) assessing adjuvant treatment with crude rhubarb in septic patients were included. RESULTS: A total of 15 RCTs with 869 patients were identified. Pooled analysis showed that interleukin 6 (standardized mean differences [SMDs], -1.30; 95% confidence intervals [CIs], -1.94 to -0.66), tumor necrosis factor α (SMD, -0.95; 95% CI, -1.55 to -0.36), procalcitonin (SMD, -1.50; 95% CI, -2.20 to -0.80), von Willebrand factor (mean differences [MDs], -144.11; 95% CI, -253.87 to -34.35), prothrombin time (MD, -2.38; 95% CI, -2.67 to -2.10), acute physiology and chronic health evaluation II scores (MD, -4.51; 95% CI, -5.30 to -3.73), and gastrointestinal dysfunction (risk ratio, 0.28; 95% CI, 0.16-0.49) were significantly reduced after treatment with crude rhubarb. Platelet number (MD, 58.16; 95% CI, 51.16-65.15) was significantly increased. However, crude rhubarb therapy did not significantly reduce 28-day mortality (risk ratio, 0.60; 95% CI, 0.36-1.00) compared with the usual treatment. CONCLUSIONS: Adjuvant treatment with crude rhubarb appears to have additional benefits in septic patients. Antiinflammation and anticoagulant/antiaggregant properties may be its potential mechanism.

HGF inhibits TGF-ß1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat.

Both myofibroblast differentiation and extracellular matrix (ECM) deposition are essential components of scar formation in tendons, and hepatocyte growth factor (HGF) is reported to prevent fibrogenic responses in tendons. Matrix metalloproteinases-2(MMP-2) is also involved in the healing process in tendons. Whether HGF protects healed Achilles tendons from injury-induced scar formation and the mechanisms are unknown. Daily for 2 weeks after wounding, except for the non-surgical control group, the Achilles tendons in rats were locally injected with HGF (100 ng 50 µl(-1) per mouse) or phosphate-buffered saline (PBS). Histological examination showed HGF ameliorated disorganized collagen fibers caused by surgical incisions in rats. After transforming growth factor beta-1 (TGF-ß1) induced fibrogenic responses in primary Achilles tendon fibroblasts in rats, HGF treatment for 24 h reduced α-smooth muscle actin (α-SMA) (0.60 ± 0.07-fold, P < 0.05) and type III collagen expression (0.39 ± 0.07-fold, P < 0.05). Moreover, HGF elevated MMP-2 expression (1.23 ± 0.11-fold, P < 0.05). The MMP-2 inhibitor, tissue inhibitors of metalloproteinase-1 (TIMP-1), partially blocked the inhibitory effects of HGF on α-SMA expression (from 0.60 ± 0.07-fold to 0.83 ± 0.07-fold, P < 0.05) and type III collagen expression (from 0.39 ± 0.06-fold to 0.86 ± 0.08-fold, P < 0.05). These results indicate HGF attenuates TGF-ß1-induced fibrogenic responses in Achilles tendon, which was mediated by MMP-2. These results will aid in developing effective therapeutic approaches for the dysfunctional repair in Achilles tendons.

Treatment of pediatric Ogilvie's syndrome with low-dose erythromycin: a case report.

Acute colonic pseudo-obstruction is a poorly understood syndrome, characterized by the signs, symptoms and radiological pattern of a large bowel obstruction without evidence for a mechanical obstruction. We report a case of a 2-year old boy who presented with progressive abdominal distention, vomiting and abdominal pain on postoperative d 3. Plain abdominal z-ray showed markedly dilated large bowel. Mechanical colonic obstruction was ruled out with hypaque enema. Ogilvie's syndrome was suspected. The patient received treatment with oral erythromycin which had an immediate beneficial effect. During the 6 mo follow-up, no recurrences of symptoms were observed. We provide a safe and effective therapy for Ogilvie's syndrome in pediatric individuals.