Water extract of processed Hydrangea macrophylla (Thunb.) Ser. leaf attenuates the expression of pro-inflammatory mediators by suppressing Akt-mediated NF-κB activation

Although Hydrangea macrophylla is native to Northeast Asia and widely cultivated in many parts of the world, no studies on its anti-inflammatory effects have been reported. In this study, we evaluated the anti-inflammatory effect of a water extract of processed H. macrophylla leaf (WH) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. WH inhibited the expression of LPS-stimulated pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumor necrosis factor-α (TNF-α), as well as their regulatory genes inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α without any accompanying cytotoxicity. Moreover, WH significantly suppressed the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB), as well as the nuclear translocation of the NF-κB subunits, p65 and p50 by suppressing of IκBα phosphorylation and degradation. WH also increased Akt dephosphorylation, leading to the suppression of the DNA-binding activity of NF-κB in LPS-stimulated RAW264.7 macrophage cells. Our results indicate that WH downregulates the expression of pro-inflammatory mediators such as NO, PGE₂, and TNF-α by suppressing the Akt-mediated NF-κB activity in LPS-stimulated RAW264.7 macrophage cells.     

Acanthopanax senticosus exerts neuroprotective effects through HO-1 signaling in hippocampal and microglial cells

Extracts of Acanthopanax senticosus, a traditional herb commonly found in Northeastern Asia, are used for treating neurodegenerative disorders such as ischemia and depression. However, the mechanisms of its neuroinflammatory and cytoprotective effects have not been investigated. We examined the mechanism of A. senticosus activity in anti-neuroinflammatory and neuroprotective processes. HO-1 is an inducible enzyme present in most cell lines. ASE increased HO-1 expression, which reduced LPS-induced nitric oxide/ROS production in BV2 cells. Moreover, the induction of HO-1 expression protected cells against glutamate-induced neuronal cell death. Activation of the p38-CREB pathway and translocation of Nrf2 are strongly involved in ASE-induced HO-1 expression. Our results showed that ASE-induced HO-1 expression through the p38-CREB pathway plays an important role in the generation of anti-neuroinflammatory and neuroprotective responses. ASE also increases the translocation of Nrf2 to regulate HO-1 expression. Furthermore, our results indicate that ASE serves as a potential therapeutic agent for neuronal disorders.     

Gastroprotective Effect of the Three Glucuronopyranoside Flavonoids in Rats

In this study, we investigated the protective action of glucuronopyranoside flavonoids (QGC, AGC, LGC) on gastritis in rats. QGC, AGC and omeprazole decreased the gastric volume significantly, and each ID₅₀ was 0.75, 0.54 and 8.5 mg/kg, respectively, thus the order of potency was AGC, QGC and omeprazole. They also decreased acid output, and each ID₅₀ was 7.81, 0.58 and 6.71 mg/kg, respectively, thus the order of potency was AGC, omeprazole and QGC. They inhibited gastritis induced by indomethacin, and it recovered significantly by increasing the GSH levels in gastritis. The gastric MPO activity in the gastritis group increased more than in the normal group. QGC, LGC, or AGC administration reduced moderately the MPO activity in a dose-dependent manner. This study demonstrated that AGC, QGC, or LGC showed potent efficacy on the gastritis, by preventing oxidative stress. These results suggest that QGC, AGC, or LGC have gastroprotective effect in rats.     

Pancreatic neuroendocrine tumour (PNET): Staging accuracy of MDCT and its diagnostic performance for the differentiation of PNET with uncommon CT findings from pancreatic adenocarcinoma

Purpose

To investigate staging accuracy of multidetector CT (MDCT) for pancreatic neuroendocrine tumour (PNET) and diagnostic performance for differentiation of PNET from pancreatic adenocarcinoma.

Material and methods

We included 109 patients with surgically proven PNET (NETG1?=?66, NETG2?=?31, NEC?=?12) who underwent MDCT. Two reviewers assessed stage and presence of predefined CT findings. We analysed the relationship between CT findings and tumour grade. Using PNETs with uncommon findings, we also estimated the possibility of PNET or adenocarcinoma.

Results

Accuracy for T stage was 85–88 % and N-metastasis was 83–89 %. Common findings included well circumscribed, homogeneously enhanced, hypervascular mass, common in lower grade tumours (p?<?0.05). Uncommon findings included ill-defined, heterogeneously enhanced, hypovascular mass and duct dilation, common in higher grade tumours (p?<?0.05). Using 31 PNETs with uncommon findings, diagnostic performance for differentiation from adenocarcinoma was 0.760–0.806. Duct dilatation was an independent predictor for adenocarcinoma (Exp(B)?=?4.569). PNETs with uncommon findings were associated with significantly worse survival versus PNET with common findings (62.7 vs. 95.7 months, p?<?0.001).

Conclusion

MDCT is useful for preoperative evaluation of PNET; it not only accurately depicts the tumour stage but also prediction of tumour grade, because uncommon findings were more common in higher grade tumours.

Key Points

? CT accurately depicts the T stage and node metastasis of PNET. ? Uncommon findings were more common in higher grade tumours. ? CT information may be beneficial for optimal therapeutic planning.

     

Korean Guidelines for the Diagnosis and Management of Dry Eye: Development and Validation of Clinical Efficacy

Purpose

To evaluate the clinical efficacy of newly developed guidelines for the diagnosis and management of dry eye.

Methods

This retrospective, multi-center, non-randomized, observational study included a total of 1,612 patients with dry eye disease who initially visited the clinics from March 2010 to August 2010. Korean guidelines for the diagnosis and management of dry eye were newly developed from concise, expert-consensus recommendations. Severity levels at initial and final visits were determined using the guidelines in patients with 90 ± 7 days of follow-up visits (n = 526). Groups with different clinical outcomes were compared with respect to clinical parameters, treatment modalities, and guideline compliance. Main outcome measures were ocular and visual symptoms, ocular surface disease index, global assessment by patient and physician, tear film break-up time, Schirmer-1 test score, ocular surface staining score at initial and final visits, clinical outcome after three months of treatment, and guideline compliance.

Results

Severity level was reduced in 47.37% of patients treated as recommended by the guidelines. Younger age (odd ratio [OR], 0.984; p = 0.044), higher severity level at initial visit, compliance to treatment recommendation (OR, 1.832; p = 0.047), and use of topical cyclosporine (OR, 1.838; p = 0.011) were significantly associated with improved clinical outcomes.

Conclusions

Korean guidelines for the diagnosis and management of dry eye can be used as a valid and effective tool for the treatment of dry eye disease.