Anti-inflammatory effects of Radix Gentianae Macrophyllae (Qinjiao), Rhizoma Coptidis (Huanglian) and Citri Unshiu Pericarpium (Wenzhou migan) in animal models

<p>Abstract</p> <p>Background</p> <p>KHU14, an ethanolic extract of <it>Radix Gentianae Macrophyllae </it>(<it>Qinjiao</it>), <it>Rhizoma Coptidis </it>(<it>Huanglian</it>) and <it>Citri Unshiu Pericarpium </it>(<it>Wenzhou migan</it>) was tested for its anti-inflammatory effects.</p> <p>Methods</p> <p>Three out of 20 herbs were found to have anti-inflammatory effects. The formulation of these herbs, i.e. KHU14 was tested for croton oil-induced ear edema, carrageenan-induced paw edema, acetic acid-induced capillary permeability, cotton pellet and delayed type hypersensitivity.</p> <p>Results</p> <p>KHU14 exhibited anti-inflammatory effects in animal models of acute and chronic inflammation. The anti-inflammatory activity of KHU14 observed was comparable to that of celecoxib. KHU14 inhibited the production of NO and PGE₂in LPS/IFN-gamma-stimulated peritoneal macrophages, and reduced edema and the amount of infiltrated cells in animal models.</p> <p>Conclusion</p> <p>KHU14 exhibited anti-inflammatory effects as demonstrated in typical immunological tests for anti-inflammation <it>in vitro </it>and <it>in vivo</it>.</p

A novel gene mutation, c.82delC (p.Arg28 Alafs5), in a Korean family with X-linked agammaglobulinemia

X-linked agammaglobulinemia (XLA) is a hereditary humoral immunodeficiency that results from Bruton’s tyrosine kinase (BTK) gene mutations. These mutations cause defects in B-cell development, resulting in the virtual absence of these lymphocytes from the peripheral circulation. Consequently, this absence leads to a profound deficiency of lg all isotypes, and an increased susceptibility to encapsulated bacterial infections. A 15-month-old Korean boy presented with recurrent sinusitis and otitis media after 6 months of age, and had a family history of 2 maternal uncles with XLA. Laboratory tests revealed a profound deficiency of Ig isotypes, and a decreased count of CD19+ B cells in the peripheral circulation. Based on his family history and our laboratory test results, he was diagnosed with XLA. We performed BTK gene analysis of peripheral blood samples obtained from family members to confirm the diagnosis. Mutational analysis revealed a novel hemizygous frameshift mutation (c.82delC, p.Arg28Alafs*5), in the BTK gene. His mother and maternal grandmother were heterozygous carriers of this mutation and his two maternal uncles were hemizygous at the same position. After XLA diagnosis, intravenous immunoglobulin (400 mg/kg, monthly) treatment was initiated; recurrent sinusitis and otitis media were subsequently brought under control. To our knowledge, this is the first reported case of a Korean pedigree with a novel mutation in the BTK gene

Intra-mitochondrial Assembly of Peptide Amphiphiles for Cancer Therapy

The intracellular assembly of small molecules presents an innovative and creative strategy to alter the cellular functions via the interactions between assembled structure and cell components, which can ultimately leads to the exploration of unrevealing mechanisms inside the cell. In here we present, for the first time, the self-assembly of peptide amphiphile inside the mitochondria of tumor cells. We have designed mitochondria targeting short peptide, mito-FF with triphenylphosphonium (TPP) as a targeting ligand and pyrene as a fluorophore. The peptide is capable of forming fibrous morphology under physiological condition. The assembly inside the mitochondria was confirmed by the environment dependent fluorescence emission of pyrene moiety in the peptide assembly of mito-FF, using confocal microscopy. The intra-mitochondrial assembly induced significant dysfunction of mitochondria which was indicated by the production of reactive oxygen species (ROS). The self-assembly process was driven by the high mitochondriaaccumulation of peptides due to the highly negative inner membrane potential of cancer cell mitochondria. Since the intra-mitochondrial assembly is restricted towards cancer cells, the cytotoxicity analysis of mito-peptides showed the significant toxicity specifically towards carcinoma cells which consequently leads to the programmed cell death. A series of mito-peptide were designed and studied the impact of assembly to induce cancer specific mitochondria dysfunction

High serum TGF-alpha predicts poor response to lapatinib and capecitabine in HER2-positive breast cancer

Lapatinib and capecitabine combination therapy is effective in trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the biomarkers from serum of patients receiving lapatinib and capecitabine Patients received lapatinib 1,250 mg once daily and capecitabine 2,000 mg/m(2)/day, day 1-14, every 3 weeks. Serum samples were obtained before treatment initiation. Levels of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), extracellular domains of EGFR and HER2 were measured by enzyme-linked immunosorbent assay. The effect of TGF-alpha on in vitro sensitivity of SK-BR-3 cells to lapatinib was investigated. Sixty-four patients were included. Response rate was significantly higher in patients with low serum TGF-alpha (a parts per thousand currency sign3.75 pg/ml) compared to high TGF-alpha (> 3.75 pg/ml) [61.1% (11/18) vs. 17.4% (8/46), respectively; P = 0.001]. Low serum TGF-alpha was independently associated with better response in multivariate analysis [adjusted odds ratio, 8.96; 95% confidence interval (CI) 2.4-34.2]. Time-to-progression tended to be shorter in patients with high serum TGF-alpha compared to low TGF-alpha [median 3.8 months (95% CI 2.3-5.4) vs. 6.5 (95% CI 6.1-6.8), respectively; P = 0.067]. We confirmed that TGF-alpha diminished the sensitivity of SK-BR3-cells to lapatinib in vitro. The in vitro antiproliferative effect of cetuximab in combination with lapatinib was higher than that of lapatinib alone in SK-BR3-cells exposed to TGF-alpha. These data suggest that TGF-alpha plays a role in resistance to lapatinib and capecitabine therapy among HER2-positive breast cancer

Office blood pressure threshold of 130/80 mmHg better predicts uncontrolled out‐of‐office blood pressure in apparent treatment‐resistant hypertension

Abstract The objective of this study was to compare the diagnostic accuracy of office blood pressure (BP) threshold of 140/90 and 130/80 mmHg for correctly identifying uncontrolled out‐of‐office BP in apparent treatment‐resistant hypertension (aTRH). We analyzed 468 subjects from a prospectively enrolled cohort of patients with resistant hypertension in South Korea (clinicaltrials.gov: NCT03540992). Resistant hypertension was defined as office BP ≥ 130/80 mmHg with three different classes of antihypertensive medications including thiazide‐type/like diuretics, or treated hypertension with four or more different classes of antihypertensive medications. We conducted different types of BP measurements including office BP, automated office BP (AOBP), home BP, and ambulatory BP. We defined uncontrolled out‐of‐office BP as daytime BP ≥ 135/85 mmHg and/or home BP ≥ 135/85 mmHg. Among subjects with office BP < 140/90 mmHg and subjects with office BP < 130/80 mmHg, 66% and 55% had uncontrolled out‐of‐office BP, respectively. The prevalence of controlled and masked uncontrolled hypertension was lower, and the prevalence of white‐coat and sustained uncontrolled hypertension was higher, with a threshold of 130/80 mmHg than of 140/90 mmHg, for both office BP and AOBP. The office BP threshold of 130/80 mmHg was better able to diagnose uncontrolled out‐of‐office BP than 140/90 mmHg, and the net reclassification improvement (NRI) was 0.255. The AOBP threshold of 130/80 mmHg also revealed better diagnostic accuracy than 140/90 mmHg, with NRI of 0.543. The office BP threshold of 130/80 mmHg showed better than 140/90 mmHg in terms of the correspondence to out‐of‐office BP in subjects with aTRH