Suyeong Nam

The Cardiac Biomarker Sodium-Calcium Exchanger (NCX-1) Can Differentiate between Heart Failure and Renal Failure: A Comparative Study of NCX-1 Expression in Dogs with Chronic Mitral Valvular Insufficiency and Azotemia

BACKGROUND The sodium-calcium exchanger (NCX-1), an established cardiac biomarker, was postulated previously as differentiating between heart failure (HF) and renal failure (RF) in dogs. The effect of azotemia on NCX-1 expression has not been studied. HYPOTHESIS In contrast to other cardiac biomarkers (eg, N-terminal-proBNP), we hypothesized that the expression level of NCX-1 is not influenced by either azotemia or decreased renal clearance. ANIMALS Fifteen client-owned healthy control dogs, 14 dogs with chronic mitral valvular insufficiency (CMVI), classified based on severity of the disease by the established International Small Animal Cardiac Health Council classification system, and 15 dogs with RF, grouped according to the International Renal Interest Society stage classification. METHODS A comparative study of the expression levels of NCX-1, evaluated in peripheral blood samples from dogs with HF, RF, and healthy controls by quantitative PCR. RESULTS NCX-1 expression was significantly increased in moderate (2.99±0.61 [fold changes relative to normal group]) to severe (4.35±1.44) CMVI dogs (P<.01). In contrast, NCX-1 expression was not increased in the azotemic dogs. Furthermore, there was also no correlation between increased concentrations of creatinine and urea nitrogen in serum and NCX-1 expression in the RF group. CONCLUSIONS AND CLINICAL IMPORTANCE Azotemia likely does not affect NCX-1 expression.

Angelica gigas Nakai extract-loaded fast-dissolving nanofiber based on poly(vinyl alcohol) and Soluplus for oral cancer therapy

A poly(vinyl alcohol) (PVA) and Soluplus (SP)-based nanofiber (NF) mat was fabricated using an electrospinning method for the delivery of Angelica gigas Nakai (AGN) extract (ext) to oral cancers. AGN/SP NF (mean diameter: 75±26nm; entrapment efficiency: 84.6±18.6%) and AGN/PVA/SP NF (mean diameter: 170±35nm; entrapment efficiency: 81.0±10.1%) were fabricated using an electrospinning method. Amorphization of AGN EtOH ext was verified by X-ray diffractometry (XRD) analysis during the electrospinning process for the fabrication of NF structures. The AGN/PVA/SP NF group exhibited instant wetting (within 2s) and rapid disintegration (within 3min) properties compared with those in the AGN/PVA NF group, assuring the successful and conventional application of AGN/PVA/SP NF film in the oral cavity without the intake of beverages. After the spontaneous dispersion of NF in the aqueous media, it was converted to nanoparticles with a narrow size distribution. In YD-9 cells (oral squamous cell carcinoma from buccal cheek), the anti-proliferation activity was ordered as follows: AGN EtOH ext suspension < AGN/PVA NF < AGN/PVA/SP NF. All of these findings indicated that AGN/PVA/SP NF can be used as a fast-dissolving mat formulation for the therapy of oral cancers.

Nanocomposites based on Soluplus and Angelica gigas Nakai extract fabricated by an electrohydrodynamic method for oral administration.

Nanocomposites (NCs) based on Soluplus (SP) were fabricated by an electrohydrodynamic (EHD) method for the oral delivery of Angelica gigas Nakai (AGN). Nano-sized particles were obtained after dispersing the resultant, produced by the EHD technique, in the aqueous environment. AGN/SP2 (AGN:SP=1:2, w/w) NC dispersion in aqueous media exhibited a 130nm mean diameter, narrow size distribution, and robust stability in the tested concentration range of the ethanol extract of AGN (AGN EtOH ext) and at pH 1.2 and 6.8. Amorphization of the components of AGN and their interactions with SP in the AGN/SP2 NC formulation were demonstrated by X-ray diffractometry (XRD) analysis. The released amounts of decursin (D) and decursinol angelate (DA), major components of AGN, from NCs were improved compared with those from the AGN EtOH ext group at both pH 1.2 and 6.8. As D and DA can be metabolized into decursinol (DOH) in the liver after oral administration, the DOH concentrations in plasma were quantitatively determined to evaluate the oral absorption of AGN. In a pharmacokinetic study in rats, higher oral absorption and the maximum concentration in plasma (Cmax) were presented in the AGN/SP2 NC group compared with the AGN EtOH ext and AGN NC groups. These findings indicate the successful application of developed SP-based NCs for the oral delivery of AGN.

Fabrication of polymer matrix-free nanocomposites based on Angelica gigas Nakai extract and their application to breast cancer therapy

Nanocomposites (NCs) based on the ethanol extract of Angelica gigas Nakai (AGN EtOH ext) were developed for breast cancer therapy. Polymer matrix-free nano-sized particles based on the extract of natural product were fabricated using a modified emulsification-solvent evaporation method. Without the use of polymer matrix, toxicity can be minimized and the clinical application may be assured. AGN NCs with approximately 200nm mean diameter, narrow size distribution, and negative zeta potential were prepared in this study. Sustained release of decursin (D) and decursinol angelate (DA) (as major components of AGN) from AGN NCs was observed at pH 7.4. Cellular accumulation efficiency and intracellular distribution of AGN NCs were evaluated in MCF-7 (human breast adenocarcinoma) cells. According to the results of antiproliferation assay in MCF-7 cells, IC50 value of AGN NCs group (27.4±4.0μg/mL) was lower than that of AGN EtOH ext group (75.3±13.7μg/mL) (p<0.05). Also, the percentage of apoptotic events of AGN NCs group was significantly higher than that of AGN EtOH ext group (p<0.05). All these findings suggest that developed AGN NCs can be used as one of promising nanosystems for the therapy of breast cancers.

Antiproliferation of keratinocytes and alleviation of psoriasis by the ethanol extract of Artemisia capillaris

The therapeutic potentials of the ethanol extract of Artemisia capillaris (ACE) for psoriasis were verified in HaCaT cells (as an immortalized human keratinocyte cell line) and imiquimod (IMQ)‐induced psoriasis‐like mouse models. In HaCaT cells, IC50 value of ACE was 37.5 μg/ml after incubating for 72 hr. The antiproliferation activity of ACE in HaCaT cells was further verified by apoptosis assays. The percentage of apoptotic population in ACE‐treated group was significantly higher than that of control group (p < .05). The result of cell cycle arrest assay also supported the observed antiproliferation efficacy of ACE in HaCaT cells. In IMQ‐induced psoriasis‐like mouse models, the Psoriasis Area and Severity Index score of ACE (50 mg/ml; ACE50)‐treated group was significantly lower than that of IMQ group on Day 4 (p < .05). After topical application of ACE on psoriasis‐like lesion for 4 days, the epidermal thickness of (IMQ + ACE50) group was significantly lower than that of IMQ group (p < .05). The expression levels of Ki‐67 and intracellular adhesion molecule‐1 in excised skin tissues of (IMQ + ACE50) group were also lower than those of IMQ group. All these findings suggest that ACE can be used as a promising antipsoriatic agent.

Development of Resveratrol-Loaded Herbal Extract-Based Nanocomposites and Their Application to the Therapy of Ovarian Cancer

Resveratrol (RSV) and the ethanol extract of Angelica gigas Nakai (AGN Ex)-based nanoparticles (NPs) were prepared using the nanocrystal concept. AGN/RSV NPs with 224 nm hydrodynamic size, unimodal size distribution, and negative zeta potential values were developed with the emulsification and solvent evaporation techniques. The crystalline properties of AGN Ex and RSV were transformed during the emulsification and solvent evaporation processes, thus, AGN NPs and AGN/RSV NPs exhibited amorphous states. AGN/RSV NPs held up their initial hydrodynamic size after 24 h of incubation in serum-included media. Sustained release profiles (for 5 days) of decursin (D) and decursinol angelate (DA) (the representative markers of AGN Ex) and RSV were observed at normal physiological pH (pH 7.4). In ovarian cancer (SKOV-3) cells, although AGN/RSV NPs showed a lower cellular entry rate rather than AGN NPs, the cellular accumulated amount of AGN/RSV NPs was similar with that of AGN NPs after 4 h of incubation. The antiproliferation efficiency of AGN/RSV NPs group was significantly higher than the AGN Ex, AGN NPs, and AGN NPs + RSV groups in SKOV-3 cells. AGN/RSV NPs can be one of the promising candidates for therapeutic nanoplatforms against ovarian cancers.

Therapeutic Efficacies of Artemisia capillaris Extract Cream Formulation in Imiquimod-Induced Psoriasis Models

A cream formulation containing Artemisia capillaris (AC) extract (ACE) was developed for psoriasis therapy. Although ACE can be dissolved in organic solvents, its topical application is restricted because of toxicities. Therefore, a cream formulation was developed for the convenient and safe local application of ACE on skin lesions. The antipsoriatic properties of the ACE cream were evaluated using an imiquimod- (IMQ-) induced psoriasis-like mouse model. In psoriasis-like mouse models, the cumulative score (redness, thickness, and scaling) of the IMQ + ACE cream group was significantly lower than those of the other groups on day 4 (p < 0.05). The results of the hematoxylin and eosin staining of skin tissues revealed that the epidermal thickness value of the IMQ + ACE cream group was significantly lower than those of the other experimental groups (p < 0.05). The expression level of intracellular adhesion molecule-1 (ICAM-1), which indicates the leukocyte infiltration into the skin and subsequent interactions with keratinocytes, was also lower in the IMQ + ACE cream group than in the IMQ group. These results indicate that ACE cream formulation could be used safely and conveniently for psoriasis treatment.

Polydopamine-coated nanocomposites of Angelica gigas Nakai extract and their therapeutic potential for triple-negative breast cancer cells

Polydopamine (PD)-coated nanocomposites (NCs) based on the ethanol extract of Angelica gigas Nakai (AGN EtOH ext) were fabricated and evaluated for breast cancer therapy. AGN NCs were prepared using a modified emulsification-solvent evaporation method and were further incubated in dopamine solution (at pH 8.6) to be covered with the PD layer. PD-AGN NCs with a 213-nm mean diameter, narrow size distribution, and negative zeta potential values were fabricated in this study. Less negative (close to zero) zeta potential value of PD-AGN NCs than that of AGN NCs implied the existence of the PD layer in the outer surface of NCs. The PD layer in PD-AGN NCs was also identified by X-ray photoelectron spectroscopy (XPS) and ultraviolet (UV)/visible absorption analyses. The sustained release of decursin (D) and decursinol angelate (DA), as major active pharmacological components of AGN, was observed in both AGN NCs and PD-AGN NCs. Enhanced cellular binding property of PD-AGN NCs, compared to AGN NCs, in MDA-MB-231 (human breast adenocarcinoma; triple-negative breast cancer) cells was observed. Improved anticancer activities of PD-AGN NCs compared with those of AGN EtOH ext and AGN NCs were also shown in MDA-MB-231 cells. The developed PD-AGN NCs may be used as remarkable platform nanocarriers for efficient breast cancer therapy.

Phloretin-loaded fast dissolving nanofibers for the locoregional therapy of oral squamous cell carcinoma

Fast dissolving nanofiber (NF) composed of poly(vinyl alcohol) (PVA) and d-α-tocopheryl polyethylene glycol succinate (TPGS) was developed for locoregional delivery of phloretin to oral cancers. PVA/TPGS/phloretin NF with 321nm mean diameter and >90% drug entrapment efficiency was fabricated by an electrospinning method. Transformation of drug from crystalline to amorphous state was identified by solid-state studies. NF structure was changed to nanoparticles after its dispersing in the aqueous medium. PVA/TPGS/phloretin NF exhibited fast wetting property and smaller hydrodynamic size of dispersion, compared with PVA/phloretin NF. The amphiphilic property of TPGS also contributed to the improved drug release from PVA/TPGS/phloretin NF. The anticancer activities of phloretin, via the inhibition of glucose uptake into the cancer cells, in NFs were assessed in YD-9 cells (oral squamous cell carcinoma from buccal cheek). The antiproliferation efficacy of PVA/TPGS/phloretin NF was significantly higher than that of phloretin solution and PVA/phloretin NF (p<0.05). Higher apoptotic events were also observed in PVA/TPGS/phloretin NF group rather than phloretin solution and PVA/phloretin NF groups (p<0.05). All these results support that PVA/TPGS/phloretin NF can be a promising fast dissolving formulation for the treatment of oral cancers.