Pitavastatin Induces Apoptosis of Cutaneous Squamous Cell Carcinoma Cells through Geranylgeranyl PyrophosphateDependent c-Jun N-Terminal Kinase Activation

Background@#Pitavastatin is a cholesterol-lowering drug and is widely used clinically. In addition to this effect, pitavastatin has shown the potential to induce apoptosis in cutaneous squamous cell carcinoma (SCC) cells. @*Objective@#The purpose of this study is to investigate the effects and possible action mechanisms of pitavastatin. @*Methods@#SCC cells (SCC12 and SCC13 cells) were treated with pitavastatin, and induction of apoptosis was confirmed by Western blot. To examine whether pitavastatin-induced apoptosis is related to a decrease in the amount of intermediate mediators in the cholesterol synthesis pathway, the changes in pitavastatin-induced apoptosis after supplementation with mevalonate, squalene, geranylgeranyl pyrophosphate (GGPP) and dolichol were investigated. @*Results@#Pitavastatin dose-dependently induced apoptosis of cutaneous SCC cells, but the viability of normal keratinocytes was not affected by pitavastatin at the same concentrations. In supplementation experiments, pitavastatin-induced apoptosis was inhibited by the addition of mevalonate or downstream metabolite GGPP. As a result of examining the effect on intracellular signaling, pitavastatin decreased Yes1 associated transcriptional regulator and Ras homolog family member A and increased Rac family small GTPase 1 and c-Jun Nterminal kinase (JNK) activity. All these effects of pitavastatin on signaling molecules were restored when supplemented with either mevalonate or GGPP. Furthermore, pitavastatininduced apoptosis of cutaneous SCC cells was inhibited by a JNK inhibitor. @*Conclusion@#These results suggest that pitavastatin induces apoptosis of cutaneous SCC cells through GGPP-dependent JNK activation.

Searching for Novel Candidate Small Molecules for Ameliorating Idiopathic Pulmonary Fibrosis: a Narrative Review

Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)-β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

Regulation of the Gene Expression of Airway MUC5AC Mucin through NF-κκB Signaling Pathway by Artesunate, an Antimalarial Agent

In this study, artesunate, an antimalarial agent, was investigated for its potential effect on the gene expression of airway MUC5AC mucin. The human pulmonary epithelial NCI-H292 cells were pretreated with artesunate for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of artesunate on PMA-induced nuclear factor kappa B (NFkB) signaling pathway was also examined. Artesunate inhibited the glycoprotein production and mRNA expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation.These results suggest artesunate suppresses the gene expression of mucin through regulation of NF-kB signaling pathway, in human pulmonary epithelial cells.

Meclofenamate Suppresses MUC5AC Mucin Gene Expression by Regulating the NF-kB Signaling Pathway in Human Pulmonary Mucoepidermoid NCI-H292 Cells

The current study aimed to reveal the potential effect of meclofenamate, a nonsteroidal anti-inflammatory drug, on the gene expression of airway MUC5AC mucin. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with meclofenamate for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. Thereafter, the effect of meclofenamate on the PMAinduced nuclear factor kappa B (NF-kB) signaling pathway was assessed. Meclofenamate inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA by inhibiting the degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest meclofenamate suppresses mucin gene expression by regulating NF-kB signaling pathway in human pulmonary epithelial cells.

Inhibitory Effect of Mitoxantrone on Collagen Synthesis in Dermal Fibroblasts

Background@#Fibroblasts produce collagen molecules that support the structure of the skin.The decrease and hypersynthesis of collagen causes skin problems such as skin atrophy, wrinkles and scars. @*Objective@#The purpose of this study is to investigate the mechanism of mitoxantrone on collagen synthesis in fibroblasts. @*Methods@#Cultured fibroblasts were treated with mitoxantrone, and then collagen synthesis was confirmed by reverse transcription-polymerase chain reaction and Western blot. @*Results@#Mitoxantrone inhibited the expression of type I collagen in fibroblasts at both the mRNA and protein levels. In the collagen gel contraction assay, mitoxantrone significantly inhibited gel contraction compared to the control group. Mitoxantrone inhibited transforming growth factor (TGF)-β-induced phosphorylation of SMAD3. Finally, mitoxantrone inhibited the expression of LARP6, an RNA-binding protein that regulates collagen mRNA stability. @*Conclusion@#These results suggest that mitoxantrone reduces collagen synthesis by inhibiting TGF-β/SMAD signaling and LARP6 expression in fibroblasts, which can be developed as a therapeutic agent for diseases caused by collagen hypersynthesis.

If the Lower Extremity Alignment is Corrected, Will Osteochondral Lesions of the Talus Improve? / 대한족부족관절학회지

Increased loading in a localized area is a possible cause of pain-related osteochondral lesions of the talus (OLT), but the reported effects of realignment surgery for OLT have been anecdotal. Moreover, no report of realignment surgery for OLT could be found in the English literature. This study reviewed previous articles on lower extremity alignment and OLT to determine if OLT can be treated with realignment surgery.

Corni Fructus attenuates testosterone-induced benign prostatic hyperplasia by suppressing 5α-reductase and androgen receptor expression in rats

BACKGROUND/OBJECTIVES: Benign prostatic hypertrophy (BPH) is a major cause of abnormal overgrowth of the prostate mainly in the elderly. Corni Fructus has been reported to be effective in the prevention and treatment of various diseases because of its strong antioxidant effect, but its efficacy against BPH is not yet known. This study was designed to evaluate the therapeutic efficacy of Corni Fructus water extract (CF) in testosterone-induced BPH rats. MATERIALS/METHODS: To induce BPH, rats were intraperitoneal injected with testosterone propionate (TP). Rats in the treatment group were orally administered with CF with TP injection, and finasteride, which is a selective inhibitor of 5α-reductase type 2, was used as a positive control. RESULTS: Our results showed that the increased prostate weight and histopathological changes in BPH model rats were suppressed by CF treatment. CF, similar to the finasteride-treated group, decreased the levels of testosterone and dihydrotestosterone by TP treatment in the serum, and it also reduced 5α-reductase expression and concentration in prostate tissue and serum, respectively. In addition, CF significantly blocked the expression of the androgen receptor (AR), AR co-activators, and proliferating cell nuclear antigen in BPH rats, and this blocking was associated with a decrease in prostate-specific antigen levels in serum and prostate tissue. CONCLUSIONS: These results suggest that CF may weaken the BPH status through the inactivation of at least 5α-reductase and AR activity and may be useful for the clinical treatment of BPH.

Upper Extremity Injuries in Youth Baseball Players / 대한정형외과학회잡지

The elbow and shoulder in young baseball players are prone to injuries. The internal factors of sports injuries are the fragility of the bones and joints of growing children and adolescents. The main external factors of injuries are the competition and eagerness of adolescent players and the motivation of hard-work. Baseball injuries have many causes, including fast rotation and movement of a load from the trunk to arm, repetitive incorrect placement of the arm in the throwing position, too-many throwing practices, etc. Orthopedic surgeons have generally focused on surgical procedure to cure, but it is time to consider and share the methods of injury prevention.

Risk Factors for Neck Shortening in Patients with Valgus Impacted Femoral Neck Fractures Treated with Three Parallel Screws: Is Bone Density an Affecting Factor? / 대한고관절학회지

PURPOSE: The purpose of this study is to analyze the relationship between significant femoral neck shortening (SFNS) and bone density after three parallel screw fixation in valgus impacted femoral neck fracture, and to analyze the risk factors for SFNS. MATERIALS AND METHODS: This is retrospective study of 83 patients. We performed univariate analysis for patient information, bone density, fracture configuration and screw position divided into SFNS group (n=13) and non-SFNS group (n=70) and performed multivariate analysis using logistic regression model. We also analyzed the relationship between SFNS and complications such as osteonecrosis of femoral head and nonunion. RESULTS: There was a significant difference in age, screw non-parallelism and bone mineral density of intertrochanteric and total hip area in the univariate analysis between the two groups (P < 0.05). In multivariate analysis, old age (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.03-1.21) and screw non-parallelism (OR, 2.95; 95% CI, 1.44-6.59) were significant risk factors for SFNS. The incidence of SFNS was significantly higher in the complication group (P=0.027). CONCLUSION: Bone density did not significantly affect SFNS in valgus impacted femoral neck fractures treated with three parallel screws. The risk factors of SFNS were old age and screw non-parallelism. Therefore, we recommend using other fixation method to prevent SFNS in older ages and making the screw position as parallel as possible when performing screw fixation in valgus impacted femoral neck fracture.

Expression of p53 and Epidermal Growth Factor Receptor in the Oral and Oropharyngeal Squamous Cell Carcinomas / 대한이비인후과학회지

The prognostic significance of the squamous cell carcinomas of the oral and oropharynx have been evaluated to identify those features associated with aggressive biologic behavior according to the immunologic and histologic characteristics. For determining prognostic indicators, the authors performed immunohistochemical staining of p53 and epidermal growth factor receptor(EGFR) in 29 cases of squamous cell carcinomas of the oral and oropharynx. The expression rate of p53 was 51.7%, that of EGFR was 96.6%, and overexpression rate of EGFR was 41.4%, however there were no statistical significance between the reactivity of EGFR, p53 and clinicopathological features such as primary stage, nodal stage, clinical stage, death and histologic grade.