Kink-Controlled Gold Nanoparticles for Electrochemical Glucose Oxidation.

Enzymes in nature efficiently catalyze chiral organic molecules by elaborately tuning the geometrical arrangement of atoms in the active site. However, enantioselective oxidation of organic molecules by heterogeneous electrocatalysts is challenging because of the difficulty in controlling the asymmetric structures of the active sites on the electrodes. Here, we show that the distribution of chiral kink atoms on high-index facets can be precisely manipulated even on single gold nanoparticles; and this enabled stereoselective oxidation of hydroxyl groups on various sugar molecules. We characterized the crystallographic orientation and the density of kink atoms and investigated their specific interactions with the glucose molecule due to the geometrical structure and surface electrostatic potential.

Green tea extract ameliorates macrophage-driven emphysematous lesions in chronic obstructive pulmonary disease induced by cigarette smoke condensate.

Chronic obstructive pulmonary disease (COPD) is an important lung disease characterized by complicated symptoms including emphysema. We aimed to explore the mechanisms underlying the protective effect of green tea extract (GTE) on cigarette smoke condensate (CSC)-induced emphysema by demonstrating the reduction of macrophage-induced protease expression through GTE treatment in vivo and in vitro. Mice were intranasally administered 50 mg/kg CSC once a week for 4 weeks, and doses of 100 or 300 mg/kg GTE were administered orally once daily for 4 weeks. GTE significantly reduced macrophage counts in bronchoalveolar lavage fluid and emphysematous lesions in lung tissues in CSC-exposed mice. In addition, GTE suppressed CSC-induced extracellular signal-regulated kinase (ERK)/activator protein (AP)-1 phosphorylation followed by matrix metalloproteinases (MMP)-9 expression as revealed by western blotting, immunohistochemistry, and zymography in CSC-instilled mice. These underlying mechanisms related to reduced protease expression were confirmed in NCI-H292 cells stimulated by CSC. Taken together, GTE effectively inhibits macrophage-driven emphysematous lesions induced by CSC treatment, and these protective effects of GTE are closely related to the ERK/AP-1 signaling pathway, followed by a reduced protease/antiprotease imbalance. These results suggest that GTE can be used as a supplementary agent for the prevention of emphysema progression in COPD patients.

Magnetic Control of the Plasmonic Chirality in Gold Helicoids.

Chiral plasmonic nanostructures have facilitated a promising method for manipulating the polarization state of light. While a precise structural modification at the nanometer-scale-level could offer chiroptic responses at various wavelength ranges, a system that allows fast response control of a given structure has been required. In this study, we constructed uniformly arranged chiral gold helicoids with cobalt thin-film deposition that exhibited a strong chiroptic response with magnetic controllability. Tunable circular dichroism (CD) values from 0.9° to 1.5° at 550 nm wavelength were achieved by reversing the magnetic field direction. In addition, a magnetic circular dichroism (MCD) study revealed that the gap structure and size-related surface plasmon resonance induced MCD peaks. We demonstrated the transmitted color modulation, where the color dynamically changed from green-to-red, by controlling the field strength and polarizer axis. We believe current work broadens our understanding of magnetoplasmonic nanostructure and expands its potential applicability in optoelectronics or optical-communications.

Delta/Notch-like Epidermal Growth Factor-Related Receptor (DNER), a Potential Prognostic Marker of Gastric Cancer Regulates Cell Survival and Cell Cycle Progression.

Upregulation of the expression of Delta/notch-like epidermal growth factor-related receptor (DNER) and its oncogenic role have been reported in several cancers, including gastric, breast, and prostate cancers. This study aimed to investigate the oncogenic role of DNER and the mechanisms behind its oncogenic role in gastric cancer. Analysis of the RNASeq data of gastric cancer tissues obtained from the TCGA database revealed that the expression of DNER was associated with the pathology of advanced gastric cancer and the prognosis of patients. DNER expression was increased upon stem cell-enriching cancer spheroid culture. Knockdown of DNER expression inhibited cell proliferation and invasion, induced apoptosis, enhanced chemosensitivity, and decreased spheroid formation of SNU-638 gastric cancer cells. DNER silencing elevated the expression of p53, p21cip/waf, and p27, and increased G1 phase cells at the expense of S phase cells. Knockdown of p21cip/waf expression in the DNER-silenced cells partially restored cell viability and S phase progression. DNER silencing also induced the apoptosis of SNU-638 cells. While both cleaved caspases-8 and 9 were detected in adherent cells, only cleaved caspase-8 was found to have increased in spheroid-cultured cells, suggesting a distinct activation pattern of caspase activation depending on the growth condition. Knockdown of p53 expression rescued the DNER-silenced cells from apoptosis and partially restored cell viability. In contrast, overexpression of the Notch intracellular domain (NICD) decreased the expression of p53, p21cip/waf, and cleaved caspase-3 in DNER-silenced cells. Moreover, NICD expression fully reverted the cell viability reduction, arrest in the G1 phase, and elevated apoptosis caused by DNER silencing, thereby suggesting activation of Notch signaling by DNER. Expression of a membrane-unbound mutant of mDNER also decreased cell viability and induced apoptosis. On the other hand, TGF-ß signals were found to be involved in DNER expression in both adherent and spheroid-cultured cells. DNER could therefore be a link connecting TGF-ß signaling to Notch signaling. Taken together, DNER regulates cell proliferation, survival, and invasive capacity of the gastric cancer cells through the activation of Notch signaling, which may facilitate tumor progression into an advanced stage. This study provides evidences suggesting that DNER could be a potential prognostic marker, a therapeutic target, and a drug candidate in the form of a cell-free mutant.

Electronic Mechanism of In Situ Inversion of Rectification Polarity in Supramolecular Engineered Monolayer.

This Communication describes polarity inversion in molecular rectification and the related mechanism. Using a supramolecular engineered, ultrastable, binary-mixed self-assembled monolayer (SAM) composed of an organic molecular diode (SC11BIPY) and an inert reinforcement molecule (SC8), we probed a rectification ratio (r)-voltage relationship over an unprecedentedly wide voltage range (up to |3.5 V|) with statistical significance. We observed positive polarity in rectification at |1.0 V| (r = 107), followed by disappearance of rectification at ∼|2.25 V|, and then eventual emergence of new rectification with the opposite polarity at ∼|3.5 V| (r = 0.006; 1/r = 162). The polarity inversion occurred with a span over 4 orders of magnitude in r. Low-temperature experiments, electronic structure analysis, and theoretical calculations revealed that the unusually wide voltage range permits access to molecular orbital energy levels that are inaccessible in the traditional narrow voltage regime, inducing the unprecedented in situ inversion of polarity.

Understanding the impact of more realistic low-dose, prolonged engineered nanomaterial exposure on genotoxicity using 3D models of the human liver.

BACKGROUND: With the continued integration of engineered nanomaterials (ENMs) into everyday applications, it is important to understand their potential for inducing adverse human health effects. However, standard in vitro hazard characterisation approaches suffer limitations for evaluating ENM and so it is imperative to determine these potential hazards under more physiologically relevant and realistic exposure scenarios in target organ systems, to minimise the necessity for in vivo testing. The aim of this study was to determine if acute (24 h) and prolonged (120 h) exposures to five ENMs (TiO2, ZnO, Ag, BaSO4 and CeO2) would have a significantly different toxicological outcome (cytotoxicity, (pro-)inflammatory and genotoxic response) upon 3D human HepG2 liver spheroids. In addition, this study evaluated whether a more realistic, prolonged fractionated and repeated ENM dosing regime induces a significantly different toxicity outcome in liver spheroids as compared to a single, bolus prolonged exposure. RESULTS: Whilst it was found that the five ENMs did not impede liver functionality (e.g. albumin and urea production), induce cytotoxicity or an IL-8 (pro-)inflammatory response, all were found to cause significant genotoxicity following acute exposure. Most statistically significant genotoxic responses were not dose-dependent, with the exception of TiO2. Interestingly, the DNA damage effects observed following acute exposures, were not mirrored in the prolonged exposures, where only 0.2-5.0 µg/mL of ZnO ENMs were found to elicit significant (p ≤ 0.05) genotoxicity. When fractionated, repeated exposure regimes were performed with the test ENMs, no significant (p ≥ 0.05) difference was observed when compared to the single, bolus exposure regime. There was < 5.0% cytotoxicity observed across all exposures, and the mean difference in IL-8 cytokine release and genotoxicity between exposure regimes was 3.425 pg/mL and 0.181%, respectively. CONCLUSION: In conclusion, whilst there was no difference between a single, bolus or fractionated, repeated ENM prolonged exposure regimes upon the toxicological output of 3D HepG2 liver spheroids, there was a difference between acute and prolonged exposures. This study highlights the importance of evaluating more realistic ENM exposures, thereby providing a future in vitro approach to better support ENM hazard assessment in a routine and easily accessible manner.

Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer patients.

BACKGROUND: The tumor microenvironment (TME) is a critical player in tumor progression, metastasis and therapy outcomes. Tumor-associated macrophages (TAMs) are a well-recognized core element of the TME and generally characterized as M2-like macrophages. TAMs are believed to contribute to tumor progression, but the mechanism behind this remains unclear. We aimed to investigate the clinical, angiogenic, and lymphangiogenic significance of TAMs in non-small cell lung cancer (NSCLC). METHODS: Utilizing combined immunohistochemistry and digital image analysis, we assessed CD68, CD163, VEGF-A, and VEGF-C expression in 349 patients with NSCLC. Subsequently, the potential association between M2 TAMs and angiogenic VEGF-A and/or lymphangiogenic VEGF-C was evaluated for its prognostic value. Furthermore, the effects of M2 TAMs on angiogenesis and lymphangiogenesis were explored via an in vitro co-culture system. RESULTS: CD68 and CD163 expression were found to directly correlate with VEGF-A and/or VEGF-C expression (all p < 0.001). Furthermore, elevated M2 ratio (CD163+/CD68+) was significantly associated with poor overall survival (p = 0.023). Dual expression of M2 ratiohigh and VEGF-Chigh (M2 ratiohighVEGF-Chigh) was correlated with worse overall survival (p = 0.033). Multivariate analysis revealed that M2 ratiohigh [HR (95% CI) = 1.53 (1.01-2.33), p = 0.046] and combined M2 ratiohighVEGF-Chigh expression [HR (95% CI) = 2.01 (1.28-3.16), p = 0.003] were independent predictors of poor overall survival. Notably, we confirmed that M2 macrophages significantly enhanced the protein and mRNA expression of both VEGF-A and VEGF-C, while M1 macrophages induced only mRNA expression of VEGF-A in A549 cells. CONCLUSIONS: This study suggests that TAMs are significantly associated with angiogenesis and lymphangiogenesis, contributing to the progression of NSCLC. Furthermore, elevated M2 ratio, similar to combined high M2 ratio and high VEGF-C expression, is a strong indicator of poor prognosis in patients with NSCLC, providing insight for future TAM-based immunotherapy strategies.

Correlation Between Total Repair Timing and Late Aortic Root Dilatation in Repaired Tetralogy of Fallot.

Aortic root dilatation is frequently encountered in adults with repaired Tetralogy of Fallot (TOF). The timing of total repair is known to have a significant correlation with late aortic root dilatation, but it is not well established. The objective of this study was to investigate the risk factors and correlation with timing of total repair for aortic root dilatation in adults with repaired TOF. An observational retrospective cohort study was conducted in 314 adults (≥ 18 years) with repaired TOF. Aortic root dilatation was defined when the absolute diameter of Sinus of Valsalva (SoV) was over 40 mm. SoV was measured by echocardiography in 110 patients, computed tomography angiography in 168 patients, and magnetic resonance image in 36 patients. Aortic root dilatation was observed in 65 patients (20.7%). Among them, 3 patients underwent Bentall operation due to acute aortic dissection or aortic root aneurysm. On multivariate logistic regression analysis, age at total repair was a significant risk factor for late aortic root dilatation (OR = 3.14; 95% CI 1.62-6.08; p = 0.001) and the cutoff value of age was 1.9 years. However, late aortic root dilatation was also observed in 10% of patients (10/91) who operated before 1 year of age. Late total repair was a significant risk factor for late aortic root dilatation in repaired TOF. However, early total repair did not always prevent late aortic root dilatation. These results suggest that congenital aortic pathology may also be a possible cause of aortic root dilatation along with longstanding hemodynamic stress.

Comparative global metabolite profiling of xylose-fermenting Saccharomyces cerevisiae SR8 and Scheffersomyces stipitis.

Bioconversion of lignocellulosic biomass into ethanol requires efficient xylose fermentation. Previously, we developed an engineered Saccharomyces cerevisiae strain, named SR8, through rational and inverse metabolic engineering strategies, thereby improving its xylose fermentation and ethanol production. However, its fermentation characteristics have not yet been fully evaluated. In this study, we investigated the xylose fermentation and metabolic profiles for ethanol production in the SR8 strain compared with native Scheffersomyces stipitis. The SR8 strain showed a higher maximum ethanol titer and xylose consumption rate when cultured with a high concentration of xylose, mixed sugars, and under anaerobic conditions than Sch. stipitis. However, its ethanol productivity was less on 40 g/L xylose as the sole carbon source, mainly due to the formation of xylitol and glycerol. Global metabolite profiling indicated different intracellular production rates of xylulose and glycerol-3-phosphate in the two strains. In addition, compared with Sch. stipitis, SR8 had increased abundances of metabolites from sugar metabolism and decreased abundances of metabolites from energy metabolism and free fatty acids. These results provide insights into how to control and balance redox cofactors for the production of fuels and chemicals from xylose by the engineered S. cerevisiae.

Poorly Differentiated Clusters in Colorectal Adenocarcinomas Share Biological Similarities with Micropapillary Patterns as well as Tumor Buds.

In colorectal carcinoma, poorly differentiated clusters (PDCs) are a poor prognostic indicator and show morphological continuity and behavioral similarities to micropapillary patterns (MPPs) as well as tumor buds (TBs). Epithelial-mesenchymal transition (EMT) and inhibition of cancer-stromal interactions may contribute to the development of PDCs. To clarify the biological nature of PDCs, we examined immunohistochemical stainings for ß-catenin, Ki-67, E-cadherin, epithelial cell adhesion molecule (EpCAM), MUC1, and epithelial membrane antigen (EMA), which are associated with EMT and cancer-stromal interactions. The expression frequencies and patterns of PDCs, TBs, and differentiated neoplastic glands from the tumor center (TC) were compared. In the study group (117 cases), the nuclear ß-catenin staining index was higher in PDCs (37.3%) and TBs (43.3%) than in neoplastic glands from TC (8.9%, P < 0.001). The mean Ki-67 labeling index in TC was 71.5%, whereas it was decreased in PDCs (31.2%) and TBs (10.2%, P < 0.001). E-cadherin and EpCAM displayed a tendency to be found along the cell membrane in TC samples (91.5% and 92.3%, respectively), whereas they showed loss of membranous staining in PDC (44.4% and 36.8%, respectively) and TB samples (60.7% and 68.4%, respectively). An inside-out pattern for MUC1 and EMA was frequently observed in PDC (48.7% and 45.3%, respectively) and TB samples (46.2% and 45.3%, respectively), but not in TC samples. Our data demonstrate that there is a pathogenetic overlap among PDCs, TBs, and MPPs and suggest that they might represent sequential growth patterns that branch from common biological processes such as dedifferentiation and alteration in cancer-stromal interactions.

Osteonevus of Nanta Presenting as Flesh-Colored Papule of Cheek Following Laser Ablation.

Osteonevus of Nanta is a melanocytic nevus displaying secondary ossification and carrying a potential for malignancy. A solitary occurrence is reported herein, presenting as a flesh-colored papule following laser ablation.A 56-year-old woman sought treatment for a minor papular growth of the cheek. This lesion had developed at the site of prior CO2 laser ablation done elsewhere to eradicate a pigmented nevus. The patient's medical records and histopathology report were obtained after surgical excision.Histologically, a completely excised osteonevus of Nanta was evident, marked by an intradermal nevus with subjacent osseous metaplasia. Clinical presentations of these lesions may vary, but the potential for malignancy remains.

Synthesis of Monodisperse Bi-Compartmentalized Amphiphilic Janus Microparticles for Tailored Assembly at the Oil-Water Interface.

Janus particles endowed with controlled anisotropies represent promising building blocks and assembly materials because of their asymmetric functionalities. Herein, we show that using the seeded monomer swelling and polymerization technique allows us to obtain bi-compartmentalized Janus microparticles that are generated depending on the phase miscibility of the poly (alkyl acrylate) chains against the polystyrene seed, thus minimizing the interfacial free energy. When tetradecyl acrylate is used, complete compartmentalization into two distinct bulbs can be achieved, while tuning the relative dimension ratio of compartmented bulb against the whole particle. Finally, we have demonstrated that selectively patching the silica nanoparticles onto one of the bulb surfaces gives amphiphilicity to the particles that can assemble at the oil-water interface with a designated level of adhesion, thus leading to development of a highly stable Pickering emulsion system.

Influence of halide precursor type and its composition on the electronic properties of vacuum deposited perovskite films.

We fabricate mixed halide perovskite films through dual-source vacuum deposition of PbX2 (X = Cl, Br, and I) and methyl ammonium iodide (MAI) precursors with various deposition ratios. Vacuum deposition is an optimal way for film fabrication because it gives a uniform perovskite film which is free from contamination such as metallic phase lead, residual solvent, and moisture. The ionization potential and bandgap of MAPb(I1-yBry)3 film are controlled by changing the halide composition and lattice constant. In contrast, MAPb(I1-yCly)3 film shows negligible difference from MAPbI3 in terms of structural and electronic properties, which is due to poor Cl incorporation in the film from the MACl removal during crystal formation. An excess supply of MAI is necessary to form a perovskite crystal structure. Based on the elemental stoichiometry analysis, the additional methyl ammonium cation with respect to Pb in the film plays a critical role in changing the electron affinity and energy level alignment.

Clinicopathologic impacts of poorly differentiated cluster-based grading system in colorectal carcinoma.

Differentiation-based histologic grading of colorectal carcinoma (CRC) is widely used, but its clinical impact is limited by insufficient prognostic value, interobserver disagreement, and the difficulty of its application to CRC with specific histologic types such as mucinous and medullary carcinoma. A recently proposed novel grading system based on quantifying poorly differentiated clusters (PDCs) claims to have the advantages of reproducibility and improved prognostic value, and might apply to heterogeneous CRC. We aimed to validate the clinicopathologic significance of the PDCs-based grading system and to determine the relationship between this grading system and microsatellite instability (MSI). Two hundred and one patients who had undergone radical surgery were reviewed. Based on the number of PDCs, 85, 58, and 58 tumors were classified as grade (G) 1 (42.3%), G2 (28.9%), and G3 (28.9%), respectively. PDCs-based grade was significantly associated with T, N, and M stages; lymphovascular invasion; conventional histologic grade; and frequent tumor budding (all P <0.001). In multivariate analysis, PDCs-based grade was found to be an independent prognostic factor for disease-free survival (P = 0.022; hazard ratio, 3.709 [G2], 7.461 [G3]). G3 CRC significantly correlated with high MSI (MSI-H) compared to G1 and G2 (P = 0.002; odds ratio, 5.750). In conclusion, this novel grading would provide valuable prognostic information to a greater number of patients and would require continued verification. PDCs-based grading is feasible for CRCs with heterogeneous morphology, and we propose that the association between G3 and MSI-H be further evaluated in different histological subtypes of CRC.

Endoscopic and clinical analysis of primary T-cell lymphoma of the gastrointestinal tract according to pathological subtype.

BACKGROUND AND AIM: Little is known about the clinicopathological characteristics of primary gastrointestinal T-cell lymphomas (PGITL). This study evaluated the clinical and endoscopic features of the pathological subtypes of PGITL. METHODS: Forty-two lesions in 36 patients with PGITL were assessed, including 15 enteropathy-associated T-cell lymphomas (EATL), 13 peripheral T-cell lymphomas (PTCL), 10 NK/T-cell lymphomas (NK/TL), and four anaplastic large cell lymphomas (ALCL). RESULTS: PTCL occurred more frequently in the stomach and duodenum and NK/TL more frequently in the small and large intestines (P = 0.009). The endoscopic features of the four subtypes were similar (P = 0.124). Fifteen of 41 lesions (36.6%) were Epstein-Barr virus (EBV) positive, with NK/TL more likely to be EBV positive than the other types (P < 0.001). First endoscopy and first computed tomography (CT) scan indicated that 65.4% and 51.4% of the lesions, respectively, were malignant, and that 43.2% and 42.3%, respectively, were GI lymphomas. The two modalities together correctly diagnosed about half of the lesions before biopsy. Intestinal perforation was associated with small bowel location (P < 0.001) and infiltrative type (P = 0.009), and was more common in NK/TL than in the other subtypes (P = 0.015). Multivariate analysis showed that higher international prognosis index (P = 0.008) and the presence of complications (P = 0.006) were associated with poor prognosis. Survival was poorer in patients with small bowel lesions than with lesions at other locations (P = 0.048). CONCLUSIONS: The four main pathological types of PGITL differed in clinical characteristics. As PGITL was often not diagnosed by initial endoscopic or radiological examination, a high index of suspicion is necessary to ensure its early diagnosis.

Electrochemical flow-based solution-solid growth of the Cu2O nanorod array: potential application to lithium ion batteries.

The catalyzed solution-liquid-solid (SLS) growth has been well developed to synthesize semiconductor nanowires with controlled diameters. The SLS growth occurs in the longitudinal direction of nanowires, due to the directional anisotropy driven by the metal catalysts where chemical precursors are introduced. In the present study, we report a selective, template-free, and environmentally-friendly electrochemical flow-based solution-solid (electrochemical flow-SS) growth of the Cu2O nanorod array. The anisotropy for directional growth without any catalysts is generated by the electrical field in a flowing electrolyte of ultra-dilute CuSO4. The filamentary anisotropy originates from electric field enhancement on pyramidal nanocrystals in the electrolyte of low ionic conductivity (13 µS cm(-1)). The Cu2O and Cu nanorods are able to be selectively synthesized by controlling the electrolyte pH and oxygen dissolution into the electrolyte. The synthesized Cu2O nanorod array shows excellent electrochemical properties as an anode material for lithium-ion batteries; the specific capacities increase from 323 to 1206 mA h g(-1) during 500 cycles. The capacity enhancement is due to the phase transformation from Cu2O to CuO, nano-restructuring of nanorods into fragmented nanoparticles, and the progressive generation of an electroactive polymeric gel-like layer on the surface of the nanoparticles. The electrochemical flow-SS growth of Cu2O nanorods is expected to contribute to further development of other functional nanorods.

Oral bioavailability and egg drug residue of lincomycin in laying hens after different treatment.

Lincomycin (LCM) is an antibiotic used to treat severe bacterial infections in livestock and companion animals. In this study, we aimed to investigate the oral bioavailability of LCM with PK data after IV and PO administration and to compare differences in drug residue patterns in eggs. To ensure food safety, an additional study on egg residue was conducted using 3 different commercial LCM drugs. For bioavailability study, laying hens were divided into oral and intravenous (n = 8/group) groups and received single dose (10 mg/kg) of LCM. The limits of quantification for LCM were 0.729 µg/mL and 0.009 mg/kg in plasma and eggs, respectively. The oral group exhibited a significantly lower average serum drug concentration than the IV group, with a bioavailability of 2.6%. Furthermore, the egg residue profiles confirmed reduced systemic drug exposure after oral administration. For the commercial LCM drug egg residue experiment, laying hens were divided into low- and high-dose groups (n = 12/group) for each drug and treated with the recommended dosage and administration method for each respective drug. The eggs were collected and analyzed until 14 d after the last drug treatment. Despite differences in the LCM content and formulation among commercial drugs, all the tested commercial drugs showed average concentrations below the MRL in eggs within approximately 3 d after the last drug treatment. In this study, we have confirmed that LCM has a low oral absorption rate in laying hens, and this was consistent with the findings from the egg residue profiles. Further studies are requested to elucidate the exact reasons for evidently low oral drug absorption in laying hens.

Korean red ginseng suppresses mitochondrial apoptotic pathway in denervation-induced skeletal muscle atrophy.

Background: Skeletal muscle denervation leads to motor neuron degeneration, which in turn reduces muscle fiber volumes. Recent studies have revealed that apoptosis plays a role in regulating denervation-associated pathologic muscle wasting. Korean red ginseng (KRG) has various biological activities and is currently widely consumed as a medicinal product worldwide. Among them, ginseng has protective effects against muscle atrophy in in vivo and in vitro. However, the effects of KRG on denervation-induced muscle damage have not been fully elucidated. Methods: We induced skeletal muscle atrophy in mice by dissecting the sciatic nerves, administered KRG, and then analyzed the muscles. KRG was administered to the mice once daily for 3 weeks at 100 and 400 mg/kg/day doses after operation. Results: KRG treatment significantly increased skeletal muscle weight and tibialis anterior (TA) muscle fiber volume in injured areas and reduced histological alterations in TA muscle. In addition, KRG treatment reduced denervation-induced apoptotic changes in TA muscle. KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. Also, KRG decreases protein kinase B/mammalian target of rapamycin pathway, reducing restorative myogenesis. Conclusion: Thus, KRG has potential protective role against denervation-induced muscle atrophy. The effect of KRG treatment was accompanied by reduced levels of mitochondria-associated apoptosis.

Korean Red Ginseng suppresses emphysematous lesions induced by cigarette smoke condensate through inhibition of macrophage-driven apoptosis pathways.

Background: Cigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. Methods: Mice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. Results: KRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. Conclusion: Taken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.