Prognostic Factors for Predicting Post-COVID-19 Condition in Patients With COVID-19 in an Outpatient Setting.

BACKGROUND: Although data on post-coronavirus disease 2019 (COVID-19) conditions are extensive, the prognostic factors affecting symptom duration in non-hospitalized patients with COVID-19 are currently not well known. We aimed to investigate the various prognostic factors affecting symptom duration among outpatients with COVID-19. METHODS: Data were analyzed from 257 patients who were diagnosed with mild COVID-19 and visited the 'post-COVID-19 outpatient clinic' between April and December 2022 after a mandatory isolation period. The symptom duration was measured from diagnosis to symptom resolution. Laboratory and pulmonary function test results from their first visit were collected. RESULTS: The mean age of patients was 55.7 years, and the median symptom duration was 57 days. The development of post-COVID-19 conditions (> 12 weeks) were significantly correlated with not using antiviral drugs, leukocytosis (white blood cell > 10,000/µL), lower 25(OH)D3 levels, forced vital capacity (FVC) < 90% predicted, and presence of dyspnea and anxiety/depression. Additionally, in multivariable Cox regression analysis, not using antiviral drugs, lower 25(OH)D3 levels, and having dyspnea were poor prognostic factors for longer symptom duration. Particularly, vitamin D deficiency (< 20 ng/mL) and not using antivirals during the acute phase were independent poor prognostic factors for both post-COVID-19 condition and longer symptom duration. CONCLUSION: The non-use of antivirals, lower 25(OH)D3 levels, leukocytosis, FVC < 90% predicted, and the presence of dyspnea and anxiety/depression symptoms could be useful prognostic factors for predicting post-COVID-19 condition in outpatients with COVID-19. We suggest that the use of antiviral agents during the acute phase and vitamin D supplements might help reduce COVID-19 symptom duration.

Mild magnetic hyperthermia is synergistic with an antibiotic treatment against dual species biofilms consisting of S. aureus and P. aeruginosa by enhancing metabolic activity.

OBJECTIVE: The wound biofilm infections that develop tolerance to standard-of-care antimicrobial treatment has been increasing. The objective of this study was to demonstrate a proof-of-concept of mild magnetic nanoparticle (MNP)/alternating magnetic field (AMF) hyperthermia as an anti-biofilm therapy against multispecies biofilm infections. METHODS: Using both an in vitro cell culture and in vivo murine model of wound infection, we investigated whether MNP/AMF hyperthermia applied at a mild thermal dosage would be synergistically effective against dual species biofilm infection consisting of S. aureus and P. aeruginosa when combined with a broad-spectrum antibiotic, ciprofloxacin (CIP). RESULTS: The combined treatment of MNP/AMF hyperthermia and CIP to the wounds of diabetic mice (db/db mice) significantly reduced the CFU number of S. aureus and P. aeruginosa by 2-log and 3-log, respectively, compared to the untreated control group, whereas either mild MNP/AMF hyperthermia or CIP treatment alone had little effect on the eradication of both bacteria. Our gene microarray data obtained from the culture of S. aureus biofilm suggest that mild MNP/AMF could shift the expression of genes for cellular respiration from anaerobic fermentation to an aerobic glycolytic/tricarboxylic acid cycle (TCA) pathway, implicating that the beneficial effect of mild MNP/AMF hyperthermia on the increased susceptibility of biofilm bacteria to an antibiotic treatment is associated with an increased metabolic activity. CONCLUSION: Our results support the translational potential of mild MNP/AMF as an adjunctive therapy that can be combined with a broad-spectrum antibiotic treatment for the management of wound biofilm infections associated with multispecies bacteria.

The effects of smoking habit change on the risk of depression-Analysis of data from the Korean National Health Insurance Service.

BACKGROUND: We examined the effects of smoking habit change on the risk of depression using the National Health Insurance Service-National Health Screening Cohort database of Korea. METHODS: This nationwide population-based cohort study included 88,931 men aged 40 years or older. The participants were divided into baseline heavy (≥20 cigarettes/day), moderate (10-19 cigarettes/day), and light (<10 cigarettes/day) smokers, quitters, and never smokers. Smokers were then categorized as continual smokers, reducers, quitters, and non-smokers based on the two-year change in smoking status between the first and second health examinations. The participants were followed from the index date to 2013 to assess depression status. Cox proportional models were used to examine the effects of smoking habit change on the risk of depression. RESULTS: After a median 7.7 years of follow-up, 2,833 depression cases were identified. Never smokers and long-term quitters had a lower risk of depression than heavy continual smokers (hazard ratio, HR 0.817; 95% CI, confidence interval 0.689-0.967 and HR: 0.691; 95% CI: 0.559-0.853, respectively). Short-term quitters and reducers had a lower risk of depression, but it was not significant. The influence of smoking on depression was prominent among men in their 50 s (HR: 0.585; 95% CI: 0.419-0.820 in long-term quitters, HR:.0.738; 95% CI: 0.570-0.954 in never smokers). LIMITATIONS: The information about smoking habits was based on self-reported questionnaires. This study examined only men because the smoking rate among women in Korea is very low. CONCLUSIONS: This population-based study found that never smokers and long-term quitters have lower risk of depression. The risk of depression decreased when the amount of smoking decreased, but the difference was not statistically significant. Furthermore, more attention should be paid to middle-aged men when formulating smoking cessation policies.

An aluminum lining to the dark cloud of silver resistance: harnessing the power of potent antimicrobial activity of γ-alumina nanoparticles.

Although a biologically nonessential element in living organisms, aluminum is notably nontoxic to eukaryotic cells and has a venerable history of medicinal use. We demonstrate that polyethylene glycol-coated γ-alumina nanoparticles (Al2O3-NPs) with an average size of 15 nm prepared from a commercial bulk γ-alumina (γ-Al2O3) via the top-down sonication technique exhibit antibacterial activity that is comparable to that of AgNPs against both the Gram-negative drug-susceptible Pseudomonas aeruginosa (DSPA) and multidrug-resistant Pseudomonas aeruginosa (DRPA) bacteria, while the antibacterial activity of such Al2O3-NPs considerably surpasses that of AgNPs against both the Gram-positive methicillin-susceptible Staphylococcus aureus (DSSA) and methicillin-resistant Staphylococcus aureus (MRSA) bacteria. We also demonstrate that the DSPA bacteria sequentially exposed to Al2O3-NPs for 30 days show no indication of resistance development. Furthermore, such Al2O3-NPs can completely overcome the drug resistance developed in the conventional antibiotic ciprofloxacin-resistant and AgNP-resistant mutants without developing Al resistance.

Mild magnetic nanoparticle hyperthermia promotes the disaggregation and microglia-mediated clearance of beta-amyloid plaques.

The formation of beta-amyloid (Aß) plaques is a classical hallmark of Alzheimer's disease (AD) that is associated with the promotion of neuroinflammation and subsequent neurotoxicity. Given the limited therapeutic options for targeting and clearing Aß plaques in AD, there is an urgent need to develop effective approaches to reduce plaque accumulation. The objective of this study was to validate mild magnetic nanoparticle (MNP) hyperthermia technology as a strategy to clear Aß deposits and determine the impact on microglia functionality. Our results demonstrated that the heating of MNPs localized to Aß aggregates upon exposure to high frequency alternating magnetic field (AMF) was sufficient to disrupt Aß plaques, resulting in its fragmentation. Importantly, this could facilitate the phagocytic clearance of Aß as well as attenuate pro-inflammatory responses by human microglial cells. Our results support the feasibility of mild MNP/AMF hyperthermia as a new strategy for reducing beta-amyloid burdens in Alzheimer's disease.

A review on numerical modeling for magnetic nanoparticle hyperthermia: Progress and challenges.

Recent progress in nanotechnology has advanced the development of magnetic nanoparticle (MNP) hyperthermia as a potential therapeutic platform for treating diseases. Due to the challenges in reliably predicting the spatiotemporal distribution of temperature in the living tissue during the therapy of MNP hyperthermia, critical for ensuring the safety as well as efficacy of the therapy, the development of effective and reliable numerical models is warranted. This article provides a comprehensive review on the various mathematical methods for determining specific loss power (SLP), a parameter used to quantify the heat generation capability of MNPs, as well as bio-heat models for predicting heat transfer phenomena and temperature distribution in living tissue upon the application of MNP hyperthermia. This article also discusses potential applications of the bio-heat models of MNP hyperthermia for therapeutic purposes, particularly for cancer treatment, along with their limitations that could be overcome.

Metabolic syndrome, metabolic components, and their relation to the risk of pancreatic cancer.

BACKGROUND: Components of the metabolic syndrome (MetS), such as elevated fasting glucose levels and abdominal obesity, have been suggested as potential risk factors for pancreatic cancer. However, data are still insufficient to assure the influence of MetS on incident pancreatic cancer. The objective of the current study was to investigate the association between MetS, metabolic components, and the risk of pancreatic cancer. METHODS: In the Korea National Health Information Database, 223,138 individuals who were without pancreatic cancer in 2009 were enrolled and followed until 2013. They were categorized into 4 groups according to the number of baseline metabolic components (0, 1, 2, 3, and 4-5). A multivariate Cox proportional hazard model was used to calculate the adjusted hazard ratios (HRs) and 95% CIs for incident pancreatic cancer according to the presence of MetS and the number of metabolic components. In addition, the risk of pancreatic cancer was evaluated in individuals who had a single metabolic component. RESULTS: The presence of MetS was significantly associated with incident pancreatic cancer (adjusted HR, 1.47; 95% CI, 1.19-1.81). The group with 4 or 5 baseline metabolic components had a higher risk of pancreatic cancer than the other groups (0 components: reference category; 1 component: adjusted HR, 0.94 [95% CI, 0.61-1.45]; 2 components: adjusted HR, 1.03 [95% CI, 0.68-1.56]; 3 components: adjusted HR, 1.35 [95% CI, 0.89-2.04]; 4-5 components: adjusted HR, 1.64 [95% CI, 1.06-2.51]). Regarding associations between the individual metabolic components and pancreatic cancer, no metabolic component alone had a statistically significant association with pancreatic cancer. CONCLUSIONS: MetS is a potential risk factor for pancreatic cancer. The presence of ≥4 metabolic components leads to a higher risk of pancreatic cancer even within categories of the MetS.

Mild magnetic nanoparticle hyperthermia enhances the susceptibility of Staphylococcus aureus biofilm to antibiotics.

Objective: A critical challenge in the treatment of biofilm infection is the capacity of biofilm-grown bacteria to develop resistance to traditional antimicrobial therapies. The objective of this study was to validate the therapeutic potential of magnetic nanoparticle/alternating magnetic field (MNP/AMF) hyperthermia in combination with conventional antibiotics against biofilm infection.Materials and methods: The impact of MNP/AMF hyperthermia on the viability of S. aureus biofilm in the absence and presence of antibiotics as well as on the bactericidal activity of macrophages were evaluated at varying conditions of MNPs concentration and AMF intensity using in vitro cell culture models.Results: The application of MNP/AMF alone at a CEM43 thermal dose below the threshold for skin tissue exhibited a modest efficacy in the eradication of Staphylococcus aureus (S. aureus) biofilm (<1-log reduction). The treatment of antibiotics (ciprofloxacin, vancomycin) alone at a bactericidal concentration for planktonic S. aureus had no significant effect on the eradication of biofilm phase of S. aureus. However, when the biofilm was pre-exposed to mild MNP/AMF hyperthermia, the treatment of antibiotics could exhibit bactericidal effects against S. aureus biofilm, which was associated with increased uptake of antibiotics to the bacterial cells. Importantly, the application of MNP/AMF could promote the bactericidal activity of macrophages against intracellular bacteria via MNP-dependent generation of reactive oxygen species (ROS).Conclusion: Our results validate that the application of mild MNP/AMF hyperthermia within a safe thermal dose threshold is synergistic with conventional antibiotics as well as aids host innate immune response of macrophages for the clearance of intracellular bacteria.

Improvement of depressive behavior by Sweetme Sweet Pumpkin™ and its active compound, ß-carotene.

AIMS: Sweetme Sweet Pumpkin™ (SSP, baked Cucurbita moschata Duch.) has been used to treat patients with depression in Korea. However, the role of SSP in improving depression has not been elucidated yet. Thus, we assessed the antidepressant-like effect of SSP and its active compound, ß-carotene, with the forced swimming test (FST). MAIN METHODS: SSP and ß-carotene were orally administered once a day for 28days. The levels of brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase (pERK), and estrogen receptor-beta (ER-ß) were analyzed by Western blotting and quantitative real-time-polymerase chain reaction. KEY FINDINGS: After 28days, treatment with SSP and ß-carotene significantly decreased the immobility time during the FST. SSP significantly increased the levels of serotonin and norepinephrine in the brain. The levels of BDNF, pERK, and ER-ß were significantly increased in the SSP- and ß-carotene-administered groups compared with the control group. In addition, the groups treated with SSP and ß-carotene showed significantly reduced levels of tumor necrosis factor-alpha and interleukin-6 compared with the control group. SIGNIFICANCE: In conclusion, these findings suggest the potential of SSP and ß-carotene as a novel therapeutic agent for the treatment of depression.

Estrogen-like osteoprotective effects of glycine in in vitro and in vivo models of menopause.

Recently, the placenta mesotherapy has been widely used to treat menopause. Placenta contains amino acids, peptides, minerals, and estrogen. Here, we investigated the estrogen-like osteoprotective effects of glycine (a main ingredient of placenta) in in vitro and in vivo models of menopause. We assessed the effect of glycine on MG-63 osteoblast cell line, MCF-7 estrogen-dependent cell line, and ovariectomized (OVX) mice. Glycine significantly increased the MG-63 cell proliferation in a dose-dependent manner. Activity of alkaline phosphatase (ALP) and phosphorylation of extracellular-signal-regulated kinase were increased by glycine in MG-63 cells. Glycine also increased the BrdU-incorporation and Ki-67 mRNA expression in MCF-7 cells. Glycine induced the up-regulation of estrogen receptor-ß mRNA expression and estrogen-response element-luciferase activity in MG-63 and MCF-7 cells. In OVX mice, glycine was administered orally at a daily dose of 10 mg/kg per day for 8 weeks. Glycine resulted in the greatest decrease in weight gain caused by ovariectomy. Meanwhile, vaginal weight reduced by ovariectomy was increased by glycine. Glycine significantly increased the ALP activity in OVX mice. MicroCT-analysis showed that glycine significantly enhanced bone mineral density, trabecular number, and connectivity density in OVX mice. Moreover, glycine significantly increased the serum 17ß-estradiol levels reduced by ovariectomy. Glycine has an estrogen-like osteoprotective effect in menopause models. Therefore, we suggest that glycine may be useful for the treatment of menopause.

Taurine, a major amino acid of oyster, enhances linear bone growth in a mouse model of protein malnutrition.

Oysters (Oys) contain various beneficial components, such as, antioxidants and amino acids. However, the effects of Oys or taurine (Tau), a major amino acid in Oys on bone growth have not been determined. In the present study, we evaluated the effects of Oys or Tau on linear bone growth in a mouse model of protein malnutrition. To make the protein malnutrition in a mouse, we used a low protein diet. Growth plate thickness was increased by Oys or Tau. Bone volume/tissue volume, trabecular thickness, trabecular number, connection density, and total porosity were also improved by Oys or Tau. Oys or Tau increased insulin-like growth factor-1 (IGF-1) levels in serum, liver, and tibia-growth plate. Phosphorylations of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) were increased by Oys and by Tau. These findings show that Oys or Tau may increase growth plate thickness by elevating IGF-1 levels and by promoting the phosphorylations of JAK2-STAT5, and suggest that Oys or Tau are growth-promoting substances of potential use in the food and pharmaceutical industries.

Comparative study on efficacy and safety of 1550 nm Er:Glass fractional laser and fractional radiofrequency microneedle device for facial atrophic acne scar.

BACKGROUND: The 1550 nm Er:Glass fractional laser is widely used for the treatment of atrophic acne scar. A novel fractional radiofrequency microneedle device has recently emerged as an alternative for treating acne scars. OBJECTIVES: To evaluate the clinical efficacy and safety of a Er:Glass fractional laser and fractional radiofrequency microneedle device in the treatment of facial atrophic acne scars and to assess the difference between the treatment modalities depending on facial compartment. METHODS: A total of 40 patients were equally randomized into two groups. Each group of 20 patients received three treatments at 4-week interval using Er:Glass fractional laser or fractional radiofrequency microneedle device. RESULTS: Scar severity scores (ECCA grading scale) improved by a mean of 25.0% and 18.6% in groups A and B, respectively (both P < 0.01). The difference in the degree of improvement was not statistically significant between the groups after three sessions of treatment. There were no significant side effects. CONCLUSION: Atrophic acne scars improved in both groups without significant side effects. Additionally, the fractional laser was a more effective treatment option for acne scars, but the fractional radiofrequency microneedle device offered good adherence and short downtime.

Bacteriology and changes in antibiotic susceptibility in adults with community-acquired perforated appendicitis.

This study evaluated bacterial etiology and antibiotic susceptibility in patients diagnosed with community-acquired perforated appendicitis over a 12-year-period. We retrospectively reviewed records of adult patients diagnosed with perforated appendicitis at an 800-bed teaching hospital between January 2000 and December 2011. In total, 415 culture-positive perforated appendicitis cases were analyzed. Escherichia coli was the most common pathogen (277/415, 66.7%), followed by Streptococcus species (61/415, 14.7%). The susceptibility of E. coli to ampicillin, piperacillin/tazobactam, ceftriaxone, cefepime, amikacin, gentamicin, and imipenem was 35.1%, 97.1%, 97.0%, 98.2%, 98.9%, 81.8%, and 100%, respectively. The overall susceptibility of E. coli to quinolones (ciprofloxacin or levofloxacin) was 78.7%. During the study period, univariate logistic regression analysis showed a significant decrease in E. coli susceptibility to quinolones (OR = 0.91, 95% CI 0.84-0.99, P = 0.040). We therefore do not recommend quinolones as empirical therapy for community-acquired perforated appendicitis.

The (2'S,7'S)-O-(2-methylbutanoyl)-columbianetin as a novel allergic rhinitis-control agent.

AIMS: The (2'S,7'S)-O-(2-methylbutanoyl)-columbianetin (OMC) is a novel secondary metabolite extracted from Corydalis heterocarpa, which has long been used as a folk medicine for various inflammatory diseases in Korea. We examined the effect of OMC on allergic rhinitis (AR). MAIN METHODS: We assessed the therapeutic effects and regulatory mechanisms of OMC on the phorbol 12-myristate 13-acetate plus A23187-stimulated mast cell line, HMC-1 cells and ovalbumin (OVA)-induced AR models. KEY FINDINGS: OMC significantly decreased the releases of histamine and tryptase from stimulated HMC-1 cells. The degranulation process, characterized by morphological extension of the filopodia on the surface and membrane ruffling, was strongly induced in the stimulated-HMC-1 cell, however OMC suppressed the morphological changes in stimulated-HMC-1 cells. OMC reduced the production and mRNA expression of inflammatory cytokines. These inhibitory actions by OMC were dependent on the regulation of mitogen-activated protein kinases, nuclear factor-κB, and caspapase-1 signaling pathways. In the AR animal model, the increased rub scores and AR biomarkers (histamine and IgE) in ovalbumin (OVA)-sensitized mice were significantly reduced by the administration of OMC. Furthermore, eosinophils and mast cell infiltrations in nasal mucosa tissue were also blocked through the regulation of macrophage-inflammatory protein and intercellular adhesion molecule-1 levels. SIGNIFICANCE: OMC showed the possibility to regulate AR in activated mast cells and OVA-induced AR models. Hence, we suggest that OMC is a powerful and feasible new agent to suppress AR.

Magnetic nanoparticle targeted hyperthermia of cutaneous Staphylococcus aureus infection.

The incidence of wound infections that do not adequately respond to standard-of-care antimicrobial treatment has been increasing. To address this challenge, a novel antimicrobial magnetic thermotherapy platform has been developed in which a high-amplitude, high-frequency, alternating magnetic field is used to rapidly heat magnetic nanoparticles that are bound to Staphylococcus aureus (S. aureus). The antimicrobial efficacy of this platform was evaluated in the treatment of both an in vitro culture model of S. aureus biofilm and a mouse model of cutaneous S. aureus infection. We demonstrated that an antibody-targeted magnetic nanoparticle bound to S. aureus was effective at thermally inactivating S. aureus and achieving accelerated wound healing without causing tissue injury.

Interleukin-32-induced thymic stromal lymphopoietin plays a critical role in macrophage differentiation through the activation of caspase-1 in vitro.

INTRODUCTION: Interleukin (IL)-32 is an inflammatory cytokine induced by Mycobacterium tuberculosis and Mycobacterium bovis in a variety of cell types and discovered in the synovial of patients with rheumatoid arthritis (RA). Thymic stromal lymphopoietin (TSLP) play several roles in the pathogenesis of RA. However, the role of IL-32 and TSLP in RA has not been elucidated. METHODS: We evaluated the specific mechanism of between IL-32 and TSLP in RA using human monocyte cell line, THP-1 cells. RESULTS: Here we documented for the first time that IL-32 highly increased TSLP production in THP-1 cells and human blood monocytes. TSLP expression was induced by IL-32 via activation of caspase-1 and nuclear factor-κB. TSLP produced by IL-32 increased differentiation of monocytes but depletion of TSLP prevented differentiation of monocytes into macrophage-like cells. Chondroprotective drugs such as chondroitin sulfate (CS) and the traditional Korean medicine, BaekJeol-Tang (BT) decrease production of TSLP and activation of caspase-1 and nuclear factor-κB. In addition, CS and BT inhibited IL-32-induced monocytes differentiation. CONCLUSIONS: Taken together, IL-32 and TSLP are important cytokines involved in the development of RA. The effects of CS and BT were associated with the downregulation of TSLP and caspase-1 through negative regulation of IL-32 pathways in RA.

C-kit binding properties of hesperidin (a major component of KMP6) as a potential anti-allergic agent.

Accumulation of mast cells can be causally related to several allergic inflammations. Stem cell factor (SCF) as a mast cell chemotaxin induces mast cell migration. To clarify a new effect of Pyeongwee-San extract (KMP6, a drug for indigestion) for the treatment of allergy, we investigated the effects of KMP6 on SCF-induced migration of rat peritoneal mast cells (RPMCs). A molecular docking simulation showed that hesperidin, a major component of KMP6, controls the SCF and c-kit binding by interaction with the active site of the c-kit. KMP6 and hesperidin significantly inhibited SCF-induced migration of RPMCs (P<0.05). The ability of the SCF to enhance morphological alteration and F-actin formation was also abolished by treatment with KMP6 or hesperidin. KMP6 and hesperidin inhibited SCF-induced p38 MAPK activation. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment with KMP6 or hesperidin (P<0.05). Our results show for the first time that KMP6 potently regulates SCF-induced migration, p38 MAPK activation and inflammatory cytokines production through hindrance of SCF and c-kit binding in RPMCs. Such modulation may have functional consequences during KMP6 treatment, especially mast cell-mediated allergic inflammation disorders.

Rosmarinic acid, active component of Dansam-Eum attenuates ototoxicity of cochlear hair cells through blockage of caspase-1 activity.

Cisplatin causes auditory impairment due to the apoptosis of auditory hair cells. There is no strategy to regulate ototoxicity by cisplatin thus far. Dansam-Eum (DSE) has been used for treating the central nerve system injury including hearing loss in Korea. However, disease-related scientific investigation by DSE has not been elucidated. Here, we demonstrated that DSE and its component rosmarinic acid (RA) were shown to inhibit apoptosis of the primary organ of Corti explants as well as the auditory cells. Administration of DSE and RA reduced the thresholds of the auditory brainstem response in cisplatin-injected mice. A molecular docking simulation and a kinetic assay show that RA controls the activity of caspase-1 by interaction with the active site of caspase-1. Pretreatment of RA inhibited caspase-1 downstream signal pathway, such as the activation of caspase-3 and 9, release of cytochrome c, translocation of apoptosis-inducing factor, up-regulation of Bax, down-regulation of Bcl-2, generation of reactive oxygen species, and activation of nuclear factor-κB. Anticancer activity by cisplatin was not affected by treatment with RA in SNU668, A549, HCT116, and HeLa cells but not B16F10 cells. These findings show that blocking a critical step by RA in apoptosis may be useful strategy to prevent harmful side effects of ototoxicity in patients with having to undergo chemotherapy.

Specific blockage of caspase-1 activation by purple bamboo-salt prevents apoptosis of auditory cell line, HEI-OC1.

Cisplatin is a highly effective chemotherapeutic agent but with significant ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell loss following exposure to an ototoxic level of cisplatin. The present study investigated the effects of purple bamboo-salt (BS) on cisplatin-induced apoptosis. We demonstrated that apoptosis induced by cisplatin was inhibited by treatment with BS in a dose-dependent manner. Activation of caspase-3, caspase-8, and caspase-9 was observed within cisplatin-treated HEI-OC1 cells. BS inhibited activation of caspase-3, caspase-8, and caspase-9. BS also inhibited release of cytochrome c and translocation of apoptosis-inducing factor. BS inhibited cisplatin-induced reactive oxygen species production. Lastly, BS suppressed cisplatin-induced caspase-1 activation. In conclusion, these findings show that BS blockage of a critical step in apoptosis may be a useful strategy to prevent harmful side effects of cisplatin ototoxicity in patients undergoing chemotherapy.

Effects of topically applied Korean red ginseng and its genuine constituents on atopic dermatitis-like skin lesions in NC/Nga mice.

Ginseng (the root of Panax ginseng C.A. Meyer, family Araliaceae) possesses various biological activities, including anti-inflammatory and anti-tumor actions. However, their topical effect on atopic dermatitis (AD) has not been studied yet. The aim of this study was to examine the therapeutic effects of topical Korean red ginseng saponin fraction (KRGS) and its genuine constituents on AD-like skin lesions in an AD mouse model. The therapeutic effect of topical KRGS and ginsenosides in 2-chloro-1,3,5-trinitrobenzene (TNCB)-treated NC/Nga mice was assessed by measuring the skin severity scores, ear thickness, histological changes of lesional skin including mast cell count, tissue tumor necrosis factor (TNF)-α, interleukin (IL)-4, and interferon (IFN)-γ mRNA expression, and total serum IgE. Topical administration of 0.1% KRGS, 0.1% Rh2 and 0.1% Rh2+0.1% Rg3 significantly reduced the clinical skin severity scores, ear thickness and mast cell infiltration in the TNCB-induced AD-like skin lesions. Topical application of KRGS and its constituents significantly reduced TNCB-induced increase in ear TNF-α and IL-4 mRNA expression, but not IFN-γ mRNA expression. There was little change of serum total IgE level by topical KRGS and its constituents. In this study, topical KRGS and ginsenosides Rh2 and Rg3 were found to exert an anti-inflammatory effect in vivo and proved to be beneficial in an animal model of AD. Our results suggest that KRGS and its ginsenosides Rh2 and Rg3 have potential as a topical agent for the treatment of AD.