Effects of resistance training and nutritional support on osteosarcopenia in older, community-dwelling postmenopausal Korean females (ERTO-K study): a study protocol.

BACKGROUND: Osteosarcopenia is geriatric syndrome defined as the concomitant occurrence of osteopenia/osteoporosis, and sarcopenia. Osteosarcopenia is a relatively new concept in geriatric medicine; however, it may increase the risk of fragility fractures, several morbidities and mortalities, and socioeconomic costs. Although resistance exercises and nutritional support-including protein, calcium, and vitamin D-are potential non-pharmacological management procedures, evidence is still lacking. The objective of this study was therefore to evaluate the effect of combined resistance exercise and nutritional support on the quality and quantity of bone and muscle in postmenopausal females with osteosarcopenia. METHODS: This research proposal presents the protocol for a prospective, single-center, single-blinded, two-armed randomized controlled trial. Thirty-four participants with osteosarcopenia will be recruited and randomly divided into intervention and control groups; both groups will receive nutritional supplements (protein, 40 g; vitamin D, 1600 IU; calcium, 600 mg) daily. The intervention group will undergo 24 weeks of resistance exercise of increasing intensity, achieved through a three-phase step-up process. The primary outcomes will be the changes in skeletal muscle index and bone marrow density of the lumbar spine and femoral neck between the baseline and end of intervention (24 weeks). The secondary outcomes will be the body composition, whole body phase angle, physical function assessment, quality of life, psychological assessment, and bone turnover markers of participants, surveyed at multiple time points. DISCUSSION: This randomized controlled trial may reveal the effect of resistance exercise and nutritional support on older postmenopausal women with osteosarcopenia. The results will provide evidence for developing proper non-pharmacological management guidelines for postmenopausal women. TRIAL REGISTRATION: Clinical Research Information Service of Republic of Korea, KCT0008291, Registered on 16 March 2023, https://cris.nih.go.kr/cris/search/detailSearch.do/25262 .

Distribution and Transport of CO2 in Hyperbranched Poly(ethylenimine)-Loaded MCM-41: A Molecular Dynamics Simulation Approach.

Fossil fuel use is accelerating climate change, driving the need for efficient CO2 capture technologies. Solid adsorption-based direct air capture (DAC) of CO2 has emerged as a promising mode for CO2 removal from the atmosphere due to its potential for scalability. Sorbents based on porous supports incorporating oligomeric amines in their pore spaces are widely studied. In this study, we investigate the intermolecular interactions and adsorption of CO2 and H2O molecules in hyperbranched poly(ethylenimine) (HB-PEI) functionalized MCM-41 systems to understand the distribution and transport of CO2 and H2O molecules. Density Functional Theory (DFT) is employed to compute the binding energies of CO2 and H2O molecules with HB-PEI and MCM-41 and to develop force field parameters for molecular dynamics (MD) simulations. The MD simulations are performed to examine the distribution and transport of CO2 and H2O molecules as a function of the HB-PEI content. The study finds that an HB-PEI content of approximately 34 wt % is thermodynamically favorable, with an upper limit of HB-PEI loading between 45 and 50 wt %. The distribution of CO2 and H2O molecules is primarily determined by their adsorptive binding energies, for which H2O molecules dominate the occupation of binding sites due to their strong affinity with silanol groups on MCM-41 and amine groups of HB-PEI. The HB-PEI content has a considerable impact on the diffusion of CO2 and H2O molecules. Furthermore, a larger number of water molecules (higher relative humidity) reduces the correlation of CO2 with the MCM-41 pore surface while enhancing the correlation of CO2 with the amine groups of the HB-PEI. Overall, the presence of H2O molecules increases the CO2 correlation with the amine groups and also the CO2 transport within HB-PEI-loaded MCM-41, meaning that the presence of H2O enhances the CO2 capture in the HB-PEI-loaded MCM-41. These findings are consistent with experimental observations of the impact of increasing humidity on CO2 capture while providing new, molecular-level explanations for the macroscopic experimental findings.

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)-ß-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-κB 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 (NF-kB) 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.

Pitavastatin Induces Apoptosis of Cutaneous Squamous Cell Carcinoma Cells through Geranylgeranyl Pyrophosphate-Dependent 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 N-terminal kinase (JNK) activity. All these effects of pitavastatin on signaling molecules were restored when supplemented with either mevalonate or GGPP. Furthermore, pitavastatin-induced 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.

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 PMA-induced 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.

Betulin, an Anti-Inflammatory Triterpenoid Compound, Regulates MUC5AC Mucin Gene Expression through NF-kB Signaling in Human Airway Epithelial Cells.

Betulin is a triterpenoid natural product contained in several medicinal plants including Betulae Cortex. These medicinal plants have been used for controlling diverse inflammatory diseases in folk medicine and betulin showed anti-inflammatory, antioxidative, and anticancer activities. In this study, we tried to examine whether betulin exerts a regulative effect on the gene expression of MUC5AC mucin under the status simulating a pulmonary inflammation, in human airway epithelial cells. Confluent NCI-H292 cells were pretreated with betulin for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h or the indicated periods. The MUC5AC mucin mRNA expression and mucin glycoprotein production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. To elucidate the action mechanism of betulin, effect of betulin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated by western blot analysis. The results were as follows: 1) Betulin significantly suppressed the production of MUC5AC mucin glycoprotein and down-regulated MUC5AC mRNA expression induced by PMA in NCI-H292 cells. 2) Betulin inhibited NF-κB activation stimulated by PMA. Suppression of inhibitory kappa B kinase (IKK) by betulin led to the inhibition of the phosphorylation and degradation of inhibitory kappa B alpha (IκBα), and the nuclear translocation of NF-κB p65. This, in turn, led to the down-regulation of MUC5AC glycoprotein production in NCI-H292 cells. These results suggest betulin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

Evaluation of Non-Fermented and Fermented Chinese Chive Juice as an Alternative to Antibiotic Growth Promoters of Broilers.

The present study explores the application of CC juice as a suitable feed additive and alternative to conventional antibiotics. We performed a comparative study to investigate the effects of non-fermented and fermented CC juice on broiler productivity, meat quality, blood characteristics, intestinal characteristics, and microbiota associated with intestinal characteristics. A total of 800 one-day-old Ross 308 broiler chickens were randomly assigned to one of the four dietary treatment groups: (1) basal diet (negative control; NC); (2) basal diet + 0.01% enramycin (positive control; PC); (3) basal diet + 3% non-fermented CC juice (NCC; CC juice 10%, water 90%); and (4) basal diet + 3% fermented CC juice (FCC; CC juice 10%, water 90%, Lactobacillus plantarum SK4719). Feed and water were provided ad libitum. Intriguingly, all treatments showed similar results in terms of broiler productivity and chicken meat quality. Considering organ characteristics, the FCC group showed a low spleen weight and lower (p < 0.05) blood levels of AST and total cholesterol (TCHO). Regarding intestinal characteristics, the CC feed additive (NCC and FCC) resulted in a heavier intestinal weight (p < 0.05) without affecting the length ratio of the villi or the crypt compared to the control (NC or PC). NCC and FCC lowered the growth of intestinal pathogens (p < 0.01). In summary, the addition of FCC can maintain poultry health by improving blood compositions and inhibiting the growth of intestinal pathogens, leading to a productivity comparable to that of poultry treated with growth-promoting antibiotics.

On-chip selection of adenosine aptamer using graphene oxide-coated magnetic nanoparticles.

Systematic evolution of ligands by exponential enrichment (SELEX) is a method that is generally used for developing aptamers, which have arisen the promising alternatives for antibodies. However, conventional SELEX methods have limitations, such as a limited selection of target molecules, time-consuming and complex fabrication processes, and labor-intensive processes, which result in low selection yields. Here, we used (i) graphene oxide (GO)-coated magnetic nanoparticles in the selection process for separation and label-free detection and (ii) a multilayered microfluidic device manufactured using a three-dimensionally printed mold that is equipped with automated control valves to achieve precise fluid flows. The developed on-chip aptamer selection device and GO-coated magnetic nanoparticles were used to screen aptamer candidates for adenosine in eight cycles of the selection process within approximately 2 h for each cycle. Based on results from isothermal titration calorimetry, an aptamer with a dissociation constant of 18.6 ± 1.5 µM was selected. Therefore, the on-chip platform based on GO-coated magnetic nanoparticles provides a novel label-free screening technology for biosensors and micro/nanobiotechnology for achieving high-quality aptamers.

Involvement of IKK/IkBα/NF-kB p65 Signaling into the Regulative Effect of Engeletin on MUC5AC Mucin Gene Expression in Human Airway Epithelial Cells.

In this study, we examined whether engeletin exerts an effect on the gene expression of MUC5AC mucin, in human pulmonary epithelial NCI-H292 cells. The cells were pretreated with engeletin for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of engeletin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated. Engeletin suppressed the mRNA expression and production of MUC5AC mucin, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest engeletin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

Evaluation of different non-fasting molting methods on laying performance and egg quality during molting and post molting periods.

The study evaluated different molt-inducing methods to achieve the main goal of molting in commercial layers during molting and post-molting periods. A total of 400 60-week-old Lohmann Brown layers were randomly divided into five groups (eight replicates of 10 birds for each group). Laying hens in the fasting control group received no diet from day 1 to day 10. The second group received a molt-inducing diet recommended by the breeding company. The third group received a wheat bran-based diet. The fourth group received a commercial layer diet with 8,000 ppm zinc (as zinc oxide, ZnO). The fifth group received an induced molting diet given to the second group with 8,000 ppm zinc, respectively. Egg production in the fasting control group and groups fed a diet with ZnO were significantly lower (p < 0.001) than those in groups fed the molt-inducing and wheat bran-based diets without ZnO during molting. Egg laying in the fasting control group was rapidly reduced and stopped on the 5.9th day of molting. In both groups having molt treatment with ZnO, egg production was similarly reduced and ceased on the 6.9th day and 7.0th day of molting, respectively, none of them differed significantly from the control. Layers fed molt-inducing diet or wheat bran-based diet did not reach the cessation of laying even on the 28th d of molting period. Relative weights of the ovary and growing oocytes of layers subjected to fasting or fed diets with ZnO were significantly lower than those of other groups. During the first two weeks of post molting, layers fed molt-inducing diet with ZnO showed higher egg production than the other two groups (p < 0.01). The eggshell strength in the group fed the commercial diet with ZnO was significantly higher than those fed the molt-inducing diet or wheat bran-based diets at 6 weeks of post molting (p < 0.05). These results suggest that the non-feed withdrawal molting using ZnO is more effective in inducing molting and increasing post-molt egg production and egg quality than other methods using a molt-inducing diet alone or wheat bran-based diet without ZnO.

Potential Probiotic Acceptability of a Novel Strain of Paenibacillus konkukensis SK 3146 and Its Dietary Effects on Growth Performance, Intestinal Microbiota, and Meat Quality in Broilers.

This study evaluates the in vitro probiotic characteristics of P. konkukensis sp. nov. SK-3146, which was isolated from animal feed, and its dietary effects on growth performance, intestinal characteristics, intestinal microbiota, and meat quality in broilers. In vitro experiments revealed that P. konkukensis was non-hemolytic with variable antibiotic susceptibility, and acid as well as bile tolerance. To assess the effect of P. konkukensis on broilers, a total of four hundred eighty 1-day-old Ross 308 broiler chicks were allocated to 3 treatment groups with 4 replicates of 40 birds each; the negative control group was fed a basal diet without any feed additives (NC), the positive control group was fed a basal diet containing 0.01% enramycin (PC), and the experimental group was fed a basal diet containing P. konkukensis bacterial culture (PK) at 104 CFU/g of the diet based on bacterial count. The experiment lasted for 35 days. Results indicated that there were no significant differences in any growth performance parameters among the dietary treatments (p > 0.05). In addition, the inclusion of P. konkukensis in the broilers' diet did not affect meat cooking loss, color, and pH but increased the relative weight of breast meat (p < 0.05). The PK group showed heavier intestinal weight and shorter intestinal length than the NC group (p < 0.05). The ratio of the intestinal weight to length of jejunum was the highest in the PK group (p < 0.05). The PK group showed increased counts of Streptococcus thermophilus (p < 0.05) with no adverse effects of P. konkukensis on other intestinal microbiota in the jejunum. This study implies that P. konkukensis might have the potential to be applied as a probiotic feed additive in poultry.

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)-ß-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-ß/SMAD signaling and LARP6 expression in fibroblasts, which can be developed as a therapeutic agent for diseases caused by collagen hypersynthesis.

Sorafenib induces pigmentation via the regulation of ß-catenin signalling pathway in melanoma cells.

We conducted large-scale screening test on drugs that were already approved for other diseases to find pigmentation-modulating agents. Among drugs with potential for pigmentation control, we selected sorafenib and further investigated the effect on pigmentation using HM3KO melanoma cells. As a result of treating melanoma cells with sorafenib, pigmentation was promoted in terms of melanin content and tyrosinase activity. Sorafenib increased mRNA and protein levels of pigmentation-related genes such as MITF, tyrosinase and TRP1. To uncover the action mechanism, we investigated the effect of sorafenib on the intracellular signalling pathways. Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. In addition, sorafenib significantly increased the level of active ß-catenin, together with activation of ß-catenin signalling. Mechanistic study revealed that sorafenib decreased phosphorylation of serine 9 (S9) of GSK3ß, while it increased phosphorylation of tyrosine 216 (Y216) of GSK3ß. These results suggest that sorafenib activates the ß-catenin signalling through the regulation of GSK3ß phosphorylation, thereby affecting the pigmentation process.

Feasibility of sodium long chain polyphosphate as a potential growth promoter in broilers.

The objective of this study was to evaluate in vitro antimicrobial and anti-biofilm activity of sodium long chain polyphosphate (SLCPP) and effect of dietary supplementation of SLCPP on growth performance, organ characteristics, blood metabolites, and intestinal microflora of broilers. Antimicrobial activities of SLCPP were observed against Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica ser. Pullorum, Shigella sonnei, Klebsiella pneumonia, Pseudomonas aeruginosa in agar well diffusion assay. In addition, SLCPP demonstrated good anti-biofilm activity against K. pneumonia and P. aeruginosa. Furthermore, to investigate the dietary effect of SLCPP, a total of 480 1-day-old male Ross 308 broiler chicks were randomly allotted to three dietary treatment groups (4 replicates per group, 40 birds in each replicate): an antibiotic-free corn-soybean meal basal diet (NC); basal diet + enramycin 0.01% (PC); and basal diet + 0.1% SLCPP (SPP). The experiment lasted for 35 days. Results showed that birds fed with SLCPP had higher body weight (BW) and average daily gain (ADG), and lower feed conversion ratio (FCR) during the grower phase (days 7 to 21) (p < 0.05). Except for blood urea nitrogen, all other blood biochemical parameters remained unaffected by the dietary supplementation of SLCPP. Compared to the control group, lengths of the duodenum and ileum in the SPP group were significantly shorter (p < 0.05). Moreover, counts of lactic acid bacteria (LAB), total aerobes, and Streptococcus spp. in jejunum as well as LAB in cecum were increased in the SPP group than in the PC group (p < 0.05). These results suggest that dietary supplementation of SLCPP might promote the growth of broilers in their early growth phase.

Distribution and Transport of CO2 in Hydrated Hyperbranched Poly(ethylenimine) Membranes: A Molecular Dynamics Simulation Approach.

Hyperbranched poly(ethylenimine) (HB-PEI) has been distinguished as a promising candidate for carbon dioxide (CO2) capture. In this study, we investigate the distribution and transport of CO2 molecules in a HB-PEI membrane at various hydration levels using molecular dynamics (MD) simulations. For this, model structures consisting of amorphous HB-PEI membranes with CO2 molecules are equilibrated at various hydration levels. Under dry conditions, the primary and secondary amines are highly associated with CO2, indicating that they would participate in CO2 capture via the carbamate formation mechanism. Under hydrated conditions, the pair correlations of CO2 with the primary and secondary amines are reduced. This result suggests that the carbamate formation mechanism is less prevalent compared to dry conditions, which is also supported by CO2 residence time analysis. However, in the presence of water molecules, it is found that the CO2 molecules can be associated with both amine groups and water molecules, which would enable the tertiary amine as well as the primary and secondary amines to capture CO2 molecules via the bicarbonate formation mechanism. Through our MD simulation results, the feasibilities of different CO2 capture pathways in HB-PEI membranes are demonstrated at the molecular level.

Multifunctional Heterogeneous Carbon Nanotube Nanocomposites Assembled by DNA-Binding Peptide Anchors.

Although carbon nanotubes (CNTs) are remarkable materials with many exceptional characteristics, their poor chemical functionality limits their potential applications. Herein, a strategy is proposed for functionalizing CNTs, which can be achieved with any functional group (FG) without degrading their intrinsic structure by using a deoxyribonucleic acid (DNA)-binding peptide (DBP) anchor. By employing a DBP tagged with a certain FG, such as thiol, biotin, and carboxyl acid, it is possible to introduce any FG with a controlled density on DNA-wrapped CNTs. Additionally, different types of FGs can be introduced on CNTs simultaneously, using DBPs tagged with different FGs. This method can be used to prepare CNT nanocomposites containing different types of nanoparticles (NPs), such as Au NPs, magnetic NPs, and quantum dots. The CNT nanocomposites decorated with these NPs can be used as reusable catalase-like nanocomposites with exceptional catalytic activities, owing to the synergistic effects of all the components. Additionally, the unique DBP-DNA interaction allows the on-demand detachment of the NPs attached to the CNT surface; further, it facilitates a CNT chirality-specific NP attachment and separation using the sequence-specific programmable characteristics of oligonucleotides. The proposed method provides a novel chemistry platform for constructing new functional CNTs suitable for diverse applications.

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.

Induction of pigmentation by a small molecule tyrosine kinase inhibitor nilotinib.

Skin color is determined by the melanin pigments that are produced in melanocytes then transferred to surrounding keratinocytes. Despite the growing number of commercial products claiming the pigmentation-regulatory effects, there is still a demand for the development of new materials that are safe and more efficacious. We tried to screen the pigmentation-regulatory materials using a commercially available drugs, and found that nilotinib could induce pigmentation in melanoma cells. When HM3KO melanoma cells were treated with nilotinib, melanin content was increased together with increase of tyrosinase activity. Nilotinib increased the expression of pigmentation-related genes such as MITF, tyrosinase and TRP1. Consistent with these results, the protein level for MITF, tyrosinase, and TRP1 was significantly increased by nilotinib. To delineate the action mechanism of nilotinib, we investigated the effects of nilotinib on intracellular signaling. As a result, nilotinib decreased the phosphorylation of AKT, while increased the phosphorylation of CREB. The pretreatment of PKA inhibitor H89 markedly blocked the nilotinib-induced phosphorylation of CREB. In accordance with, pretreatment of H89 significantly inhibited the nilotinib-induced pigmentation, indicating that nilotinib induces pigmentation via the activation of PKA signaling. Together, our data suggest that nilotinib can be developed for the treatment of hypopigmentary disorder such as vitiligo.

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

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.