All-Inside Arthroscopic and Open Techniques of the Modified Broström Procedure for the Treatment of Lateral Ankle Instability: Comparison of the Times to Return to Play.

Background and Objectives: Lateral ankle injuries are commonly encountered injuries, and the open modified Broström operation (OMBO) is the primary treatment option. Recently, an arthroscopic modification of the Broström operation (AMBO) was developed; many studies have shown that there are no significant differences in clinical and radiological outcomes between the two surgical methods. However, no studies have been conducted comparing the two surgical methods in terms of return to play (RTP) time. This study assesses the time to RTP and the functional clinical outcomes. Materials and Methods: Sixty patients were enrolled from January 2012 to July 2014. They were segregated into two cohorts: the AMBO group comprised 30 patients, while the OMBO group comprised another 30 patients. Each participant underwent standardized treatment and rehabilitation regimens and RTP time was measured using seven questions that explored the times to return of painless walking, running, jumping, squatting, climbing stairs, and rising up on the heels and toes. We compared the time intervals from the onset of instability to the date of surgery. Clinical outcomes were evaluated before the surgery, 6 weeks after surgery, and 6 months after surgery. The assessments included the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, the pain visual analog scale (VAS) score, subjective satisfaction with rehabilitation, and activity level. Results: In terms of RTP, AMBO was associated with a shorter interval to walking without pain (7.07 ± 2.96 weeks) relative to OMBO (11.03 ± 8.58 weeks). No disparities were observed in the time to return to play (RTP) between OMBO and AMBO. While there were no discrepancies in the 6-month postoperative AOFAS or VAS scores, the 6-week postoperative VAS score was notably lower in the AMBO group compared to the OMBO group. AMBO provided a faster RTP in terms of two of the seven questions in a group exhibiting high-level physical activity. The rate of subjective satisfaction with rehabilitation was higher for AMBO than for OMBO. Conclusions: Aside from walking, the duration to return to play and the clinical outcomes were similar between AMBO and OMBO treatments for lateral ankle instability. AMBO is a good treatment option and should be carefully considered for athletes with lateral ankle instability. AMBO demonstrated positive outcomes in a group with higher activity levels compared to others, particularly in terms of time to RTP, subjective satisfaction, and postoperative pain.

hiPSC-derived macrophages improve drug sensitivity and selectivity in a macrophage-incorporating organoid culture model.

Accurate simulation of different cell type interactions is crucial for physiological and precisein vitrodrug testing. Human tissue-resident macrophages are critical for modulating disease conditions and drug-induced injuries in various tissues; however, their limited availability has hindered their use inin vitromodeling. Therefore, this study aimed to create macrophage-containing organoid co-culture models by directly incorporating human-induced pluripotent stem cell (hiPSC)-derived pre-macrophages into organoid and scaffold cell models. The fully differentiated cells in these organoids exhibited functional characteristics of tissue-resident macrophages with enriched pan-macrophage markers and the potential for M1/M2 subtype specialization upon cytokine stimulation. In a hepatic organoid model, the integrated macrophages replicated typical intrinsic properties, including cytokine release, polarization, and phagocytosis, and the co-culture model was more responsive to drug-induced liver injury than a macrophage-free model. Furthermore, alveolar organoid models containing these hiPSC-derived macrophages also showed increased drug and chemical sensitivity to pulmonary toxicants. Moreover, 3D adipocyte scaffold models incorporating macrophages effectively simulated in vivo insulin resistance observed in adipose tissue and showed improved insulin sensitivity on exposure to anti-diabetic drugs. Overall, the findings demonstrated that incorporating hiPSC-derived macrophages into organoid culture models resulted in more physiological and sensitivein vitrodrug evaluation and screening systems.

Synthesis of Hyaluronic Acid-Conjugated Fe3O4@CeO2 Composite Nanoparticles for a Target-Oriented Multifunctional Drug Delivery System.

This study is based on the principle that superparamagnetic iron oxide nanoparticles (Fe3O4) can be used to target a specific area given that their magnetic properties emerge when an external magnetic field is applied. Cerium oxide (CeO2), which causes oxidative stress by generating reactive oxygen species (ROS) in the environment of tumor cells, was synthesized on the surface of superparamagnetic iron oxide nanoparticles to produce nanoparticles that selectively kill cancer cells. In addition, hyaluronic acid (HA) was coated on the cerium's surface to target CD44-overexpressing tumor cells, and natZr was chelated on the Fe3O4@CeO2 surface to show the usefulness of labeling the radioisotope 89Zr (T1/2 = 3.3 d). The synthesis of Fe3O4@CeO2 was confirmed by Fourier Transform-Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD) and Field Emission-Transmission Electron Microscope (FE-TEM). The coating of HA was confirmed by FT-IR, X-ray Photoelectron. Spectroscopy (XPS), FE-TEM, Energy-Dispersive X-ray Spectroscopy (EDS) and Thermogravimetric Analysis (TGA)/Differential Scanning Calorimetry (DSC). The sizes of the prepared nanoparticles were confirmed through FE-TEM and Field Emission-Scanning Electron (FE-SEM) (sizes of 15 to 30 nm), and it was confirmed that natZr was introduced onto the surface of the nanoparticles using EDS. The particle size of the dispersed material was limited through Dynamic Light Scattering (DLS) to about 148 nm in aqueous solution, which was suitable for the (enhanced permeation and retention) EPR effect. It was confirmed that the HA-coated nanoparticles have good dispersibility. Finally, a cytotoxicity evaluation confirmed the ability of CeO2 to generate ROS and target the delivery of HA. In conclusion, Fe3O4@CeO2 can effectively inhibit cancer cells through the activity of cerium oxide in the body when synthesized in nano-sized superparamagnetic coral iron that has magnetic properties. Subsequently, by labeling the radioactive isotope 89Zr, it is possible to create a theranostic drug delivery system that can be used for cancer diagnosis.

Synthesis of Zr-89-Labeled Folic Acid-Conjugated Silica (SiO2) Microwire as a Tumor Diagnostics Carrier for Positron Emission Tomography.

This study evaluated the in vivo behavior and accumulation of silica particles in the form of wires, which were actively studied as drug carriers along with spheres, using positron emission tomography (PET). Wire-shaped silicon dioxide (SiO2) was synthesized at micro-size, using anodic aluminum oxide (AAO), a template, and folic acid (FA), which specifically binds folate receptors (FR) which are overexpressed in many cancers, and which was bound to the wire's surface to confirm its possible use as a cancer diagnostic agent. In addition, for evaluation using PET, the positron-emitting nuclide 89Zr (t1/2 = 3.3 days) was directly bonded to the hydroxyl group (-OH) on the particle surface. The diameter and shape of the synthesized silica microwires (SMWs) were confirmed using SEM and TEM, the chemical bonding of FA was confirmed through FT-IR and NMR, and the labeling of 89Zr was measured by means of radio-thin-layer chromatography (TLC) measurement. Folic acid-conjugated SMWs (FA-SMWs) were found to have a low receptor-mediated uptake in cell internalization evaluation, but in PET studies, FA-SMWs stayed longer at the tumor site. In conclusion, we successfully synthesized a homogeneous silica microwire for drug delivery, we confirmed that the FA-conjugated sample remains at the tumor site for a relatively longer time, and we have reported the characteristic in vivo behavior of 89Zr-FA-SMWs.

Knotless All-Inside Arthroscopic Modified Broström Procedure for Lateral Ankle Instability.

One reported complication of the arthroscopic modified Broström operation is pain caused by the suture anchoring knot. We hypothesized that a knotless technique could reduce such pain. Therefore, in this study we evaluated the clinical and radiological outcomes after knotless all-inside arthroscopic modified Broström operation for lateral ankle instability. From July 2017 to November 2017, 28 patients were treated. Clinical and radiological features were evaluated preoperatively and 3, 6, and 12 months postoperatively using the American Orthopaedic Foot & Ankle Society ankle-hindfoot scale score, visual analogue scale score for pain, anterior talar drawer test, and talar tilt angle. The mean age of the 28 patients (14 men, 14 women) was 41.71 ± 17.19 years. Three (10.7%) complications, but no knot-associated pain, occurred. The clinical and radiological outcomes were significantly improved 12 months postoperatively compared with preoperative outcomes (all p < .05). Knotless all-inside arthroscopic modified Broström operation for lateral ankle instability avoided knot-associated pain and improved not only patient satisfaction but also clinical and radiological outcomes.

A Novel Selective 11ß-HSD1 Inhibitor, (E)-4-(2-(6-(2,6-Dichloro-4-(Trifluoromethyl)Phenyl)-4-Methyl-1,1-Dioxido-1,2,6-Thiadiazinan-2-yl)Acetamido)Adamantan-1-Carboxamide (KR-67607), Prevents BAC-Induced Dry Eye Syndrome.

Dry eye syndrome is the most common eye disease and it is caused by various reasons. As the balance of the tear film that protects the eyes is broken due to various causes, it becomes impossible to properly protect the eyes. In this study, the protective effects and underlying mechanisms of topical (E)-4-(2-(6-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamido)adamantan-1-carboxamide (KR-67607), a novel selective 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) inhibitor, were investigated in benzalkonium chloride (BAC)-induced dry eye syndrome. BAC-treated rat eyes induced significant increases in ocular surface damage, decreased corneal thickness, corneal basement membrane destruction in the conjunctival epithelium, and expression of pro-inflammatory cytokines tumor necrosis factor-α and 11ß-HSD1. These effects of BAC were reversed by topical KR-67607 treatment. Furthermore, KR-67607 decreased 4-hydroxynonenal expression and increased antioxidant and mucus secretion in BAC-treated rat eyes. Taken together, a novel selective 11ß-HSD1 inhibitor can prevent BAC-induced dry eye syndrome by inhibiting pro-inflammatory cytokine and reactive oxygen species expression via the inhibition of both 11ß-HSD1 activity and expression.

Development and structure-activity relationship study of SHP2 inhibitor containing 3,4,6-trihydroxy-5-oxo-5H-benzo[7]annulene.

SHP2, a non-receptor protein tyrosine phosphatase encoded by PTPN11 gene, plays an important role in the cell growth and proliferation. Activating mutations of SHP2 have been reported as a cause of various human diseases such as solid tumors, leukemia, and Noonan syndrome. The discovery of SHP2 inhibitor can be a potent candidate for the treatment of cancers and SHP2 related human diseases. Several reports on a small molecule targeting SHP2 have published, however, there are limitations on the discovery of SHP2 phosphatase inhibitors due to the polar catalytic site environment. Allosteric inhibitor can be an alternative to catalytic site inhibitors. 3,4,6-Trihydroxy-5-oxo-5H-benzo[7]annulene 1 was obtained as an initial hit with a 0.097 µM of IC50 from high-throughput screening (HTS) study. After the structure-activity relationship (SAR) study, compound 1 still showed the most potent activity against SHP2. Moreover, compound 1 exerted good potency against SHP2 expressing 2D and 3D MDA-MB-468.

Properties of differentiated SH-SY5Y grown on carbon-based materials.

Neural cell differentiation has been extensively studied in two-dimensional (2D) cell culture plates. However, the cellular microenvironment and extracellular matrix (ECM) are much more complex and flat 2D surfaces are hard to mimic in ECM. Carbon nanotubes (CNTs) and graphenes are multidimensional carbon-based nanomaterials and may be able to provide extra dimensions on cell growth and differentiation. To determine the effect of CNTs and graphene surfaces on the growth, gene expression, differentiation and functionality of neuroblastoma to a neural cell, SH-SY5Y cells were grown on a 2D (control) surface, a CNT network and a graphene film. The data suggest that SH-SY5Y cells grown on CNT surfaces show an average 20.2% increase in cell viability; 5.7% decrease in the ratio of cells undergoing apoptosis; 78.3, 43.4 and 38.1% increases in SOX2, GFAP and NeuN expression, respectively; and a 29.7% increase in mean firing rate on a multi-electrode array. SH-SY5Y cells grown on graphene film show little or no changes in cell properties compared to cells grown in 2D. The data indicate that the three-dimensional (3D) surface of CNTs provides a favorable environment for SH-SY5Y cells to proliferate and differentiate to neurons.

iTRAQ-Based Quantitative Proteomic Comparison of 2D and 3D Adipocyte Cell Models Co-cultured with Macrophages Using Online 2D-nanoLC-ESI-MS/MS.

The demand for novel three-dimensional (3D) cell culture models of adipose tissue has been increasing, and proteomic investigations are important for determining the underlying causes of obesity, type II diabetes, and metabolic disorders. In this study, we performed global quantitative proteomic profiling of three 3D-cultured 3T3-L1 cells (preadipocytes, adipocytes and co-cultured adipocytes with macrophages) and their 2D-cultured counterparts using 2D-nanoLC-ESI-MS/MS with iTRAQ labelling. A total of 2,885 shared proteins from six types of adipose cells were identified and quantified in four replicates. Among them, 48 proteins involved in carbohydrate metabolism (e.g., PDHα, MDH1/2, FH) and the mitochondrial fatty acid beta oxidation pathway (e.g., VLCAD, ACADM, ECHDC1, ALDH6A1) were relatively up-regulated in the 3D co-culture model compared to those in 2D and 3D mono-cultured cells. Conversely, 12 proteins implicated in cellular component organisation (e.g., ANXA1, ANXA2) and the cell cycle (e.g., MCM family proteins) were down-regulated. These quantitative assessments showed that the 3D co-culture system of adipocytes and macrophages led to the development of insulin resistance, thereby providing a promising in vitro obesity model that is more equivalent to the in vivo conditions with respect to the mechanisms underpinning metabolic syndromes and the effect of new medical treatments for metabolic disorders.

Characterization of the Anti-Cancer Activity of the Probiotic Bacterium Lactobacillus fermentum Using 2D vs. 3D Culture in Colorectal Cancer Cells.

The aim of this study was to investigate the potential anti-cancer effects of probiotic cell-free supernatant (CFS) treatment using Lactobacillusfermentum for colorectal cancer (CRC) in 3D culture systems. Cell viability was assessed using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assays, whereas apoptosis was monitored through RT-qPCR analysis of Bax, Bak, Noxa, and Bid mRNA expressions in addition to flow cytometry analysis of Lactobacillus cell-free supernatant (LCFS) treatment. Our results showed that the anti-cancer effect of LCFS on cell viability was pronouncedly enhanced in 3D-cultured HCT-116 cells, which was linked to the increased level of cleaved caspase 3. Additionally, upregulation of apoptotic marker gene mRNA transcription was dramatically increased in 3D cultured cells compared to 2D systems. In conclusion, this study suggests that LCFS enhances the activation of intrinsic apoptosis in HCT-116 cells and the potential anti-cancer effects of Lactobacilli mixtures in 3D culture systems. All in all, our study highlights the benefits of 3D culture models over 2D culture modeling in studying the anti-cancer effects of probiotics.

αVß3-Targeted Delivery of Camptothecin-Encapsulated Carbon Nanotube-Cyclic RGD in 2D and 3D Cancer Cell Culture.

Integrin αvß3 is widely expressed in various types of human cancer lines and plays a key role in angiogenesis for tumor growth and metastasis. Delivery of therapeutics to αvß3-expressing tumors can thus be a promising approach for treating cancer. For targeted delivery of anticancer therapeutics to αvß3-expressing tumor cells, cyclic arginylglycylaspartic acid (RGD) peptide was covalently conjugated to the surface of carboxylic acid-functionalized carbon nanotubes (fCNTs), and the topoisomerase I inhibitor camptothecin (CPT) was encapsulated in the fCNTs (CPT@fCNT-RGD). CPT@fCNT-RGD was successfully delivered to αvß3-expressing A375 cells, and compared with nontargeted CPT@fCNT, it provided 3.78- and 3.02-fold increases in the anticancer effect in 2D and 3D culture. Analysis of apoptosis-related gene expression shows that the expression levels of Bax, cleaved caspase-3, and nuclear factor kappa-light-chain-enhancer of activated B cells were significantly increased in A375 cells incubated with CPT@fCNT-RGD compared with those incubated with CPT@fCNT. These results suggest that cyclic RGD-conjugated CNTs encapsulating an anticancer therapeutic can be a promising platform for treating cancer.

Development of a parallel microbore hollow fiber enzyme reactor platform for online 18O-labeling: Application to lectin-specific lung cancer N-glycoproteome.

We introduce a simple online 18O-labeling protocol for protein samples that uses a parallelizing microbore hollow fiber enzyme reactor (mHFER) as an alternative tool for online proteolytic digestion. Online 18O-labeling is performed by separately attaching two mHFERs in parallel to a 10-port switching valve with a high-pressure syringe pump and two syringes containing 16O- or 18O-water. 16O-/18O-labeled peptides are formed in this manner and simultaneously analyzed online using nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS/MS) without any residual trypsin activity. The usefulness of a parallel mHFER platform (P-mHFER) in 18O-labeling was tested using both cytochrome C and alpha-1-acid-glycoprotein to verify the incorporation level of two 18O atoms into tryptic peptides and to provide a quantitative assessment with varied mixing ratios. Additionally, our 18O-labeling approach was used to study the serum N-glycoproteome from lung cancer patients and controls to evaluate the applicability of lectin-based quantitative N-glycoproteomics. We successfully quantified 76 peptides (from 62 N-glycoproteins). Nineteen of these peptides from lung cancer serum were up-/down-regulated at least 2.5-fold compared to controls. As a result, the P-mHFER-based online 18O-labeling platform presented here can be a simple and reproducible way to allow quantitative proteomic analysis of diverse proteome samples.

Protective effects of carbenoxolone, an 11ß-HSD1 inhibitor, against chemical induced dry eye syndrome.

Dry eye syndrome (DES) is a disorder of the eye due to tear deficiency or excessive evaporation that causes damage to the eye and is associated with discomfort and dryness. 11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) is an enzyme that converts inactive cortisone to active cortisol. Recently, 11ß-HSD1 has been expressed in human and rodent eyes and has been recognized as a target of glaucoma. In this study, the therapeutic effects and underlying mechanisms of topical carbenoxolone, an 11ß-HSD1 inhibitor, were investigated in benzalkonium chloride (BAC)-treated human conjunctival epithelial cells and a rat DES model. In the in vitro study, carbenoxolone dose-dependently inhibited cell death and 11ß-HSD1 activity in BAC-treated human conjunctival epithelial cells. For the in vivo study, carbenoxolone or a solvent was administered to the BAC-induced DES model twice daily. BAC-treated rat eyes showed significant increases in ocular surface damage, a reduction of tears, decrease corneal thickness, corneal basement membrane destruction, apoptosis in the conjunctival epithelium, and expression of pro-inflammatory cytokines (TNF-α and IL-6) and 11ß-HSD1. These effects of BAC were reversed by topical carbenoxolone treatment. These results demonstrate that carbenoxolone can prevent DES by inhibiting pro-inflammatory cytokine expression and cell death of the corneal and conjunctival epithelium via inhibition of both 11ß-HSD1 activity and expression in the eyes of BAC-treated rats. It is suggested that topical 11ß-HSD1 inhibitors may provide a new therapeutic window in the prevention and/or treatment of DES.

Carbenoxolone prevents chemical eye ischemia-reperfusion-induced cell death via 11ß-hydroxysteroid dehydrogenase type 1 inhibition.

Glaucoma is one of the leading causes of preventable blindness diseases, affecting more than 2 million people in the United States. Recently, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors were found to exert preventive effects against glaucoma. Therefore, we investigated whether carbenoxolone (CBX), an 11ß-HSD1 inhibitor, prevents chemical ischemia-reperfusion-induced cell death in human trabecular meshwork (HTM) cells. The present study demonstrated that CBX inhibited cell death caused by iodoacetic acid (IAA)-induced ischemia-reperfusion, and its effect was associated with the inhibition of 11ß-HSD1 expression and activity. Furthermore, CBX reversed the IAA-induced structural damage on filamentous actin in HTM cells. In IAA-treated cells, the levels of 11ß-HSD1 and the apoptosis-related factors Bax and FASL were increased throughout the reperfusion period, and CBX was able to attenuate the expression of 11ß-HSD1 and the apoptosis-related factors. CBX also effectively suppressed IAA-induced intracellular ROS formation and cytochrome c release, which are involved in the mitochondrial apoptosis pathway. In addition, IAA-induced chemical ischemia-reperfusion stimulated TNF-α expression and NF-κB p65 phosphorylation, and these effects were attenuated by CBX. 11ß-HSD1 RNAi also suppressed IAA-induced cell apoptosis via reduction of oxidative stress and inhibition of the pro-inflammatory pathway. Taken together, the present study demonstrated that the inhibition of 11ß-HSD1 protected the TM against chemical ischemia-reperfusion injury, suggesting that the use of 11ß-HSD1 inhibitors could be a useful strategy for glaucoma therapy.

Characteristics of Adenovirus Pneumonia in Korean Military Personnel, 2012-2016.

Adenovirus (AdV) can cause severe pneumonia in non-immunocompromised host, but limited data exist on the distinctive characteristics of AdV pneumonia in non-immunocompromised patients. We evaluated distinctive clinico-laboratory and radiological characteristics and outcomes of AdV pneumonia (n = 179), compared with non-AdV pneumonia (n = 188) in Korean military personnel between 2012 and 2016. AdV pneumonia patients had a higher rate of consolidation with ground-glass opacity (101/152) in lobar distribution (89/152) on computed tomography (CT) (P < 0.001). Laboratory findings showed a higher incidence of unusual blood profiles such as leukopenia (55/179, P < 0.001) or thrombocytopenia (100/179, P < 0.001). The patients had more systemic symptoms such as myalgia (82/179, P = 0.001) or diarrhea (23/179, P < 0.001), compared with non-AdV pneumonia patients. Bacterial co-infection was identified in 28.5% of AdV pneumonia. Most of the AdV isolates typed (69/72, 95.8%) were AdV-55. Patients with a pneumonia severity index ≥ class III were more commonly observed in AdV pneumonia patients compared with non-AdV pneumonia patients (11.2% vs. 2.1%, P < 0.001), and time to clinical stabilization from admission was longer in the AdV pneumonia patients compared with the non-AdV pneumonia patients (3.8 vs. 2.6 days, P < 0.001). Mechanical ventilation (n = 6) was only required in AdV pneumonia patients, one of whom died due to AdV-55. Our data showed that AdV pneumonia in non-immunocompromised patients had distinct characteristics and most of the isolates typed in our study were AdV-55. It is suggested that AdV-55 is an important pathogen of pneumonia in Korean military personnel.

Anti-inflammatory effect of a selective 11ß-hydroxysteroid dehydrogenase type 1 inhibitor via the stimulation of heme oxygenase-1 in LPS-activated mice and J774.1 murine macrophages.

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) converts inactive cortisone to the active cortisol. 11ß-HSD1 may be involved in the resolution of inflammation. In the present study, we investigate the anti-inflammatory effects of 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344), a selective 11ß-HSD1 inhibitor, in lipopolysaccharide (LPS)-activated C57BL/6J mice and macrophages. LPS increased 11ß-HSD1 activity and expression in macrophages, which was inhibited by KR-66344. In addition, KR-66344 increased survival rate in LPS treated C57BL/6J mice. HO-1 mRNA expression level was increased by KR-66344, and this effect was reversed by the HO competitive inhibitor, ZnPP, in macrophages. Moreover, ZnPP reversed the suppression of ROS formation and cell death induced by KR-66344. ZnPP also suppressed animal survival rate in LPS plus KR-66344 treated C57BL/6J mice. In the spleen of LPS-treated mice, KR-66344 prevented cell death via suppression of inflammation, followed by inhibition of ROS, iNOS and COX-2 expression. Furthermore, LPS increased NFκB-p65 and MAPK phosphorylation, and these effects were abolished by pretreatment with KR-66344. Taken together, KR-66344 protects against LPS-induced animal death and spleen injury by inhibition of inflammation via induction of HO-1 and inhibition of 11ß-HSD1 activity. Thus, we concluded that the selective 11ß-HSD1 inhibitor may provide a novel strategy in the prevention/treatment of inflammatory disorders in patients.

Roots extracts of Adenophora triphylla var. japonica improve obesity in 3T3-L1 adipocytes and high-fat diet-induced obese mice.

OBJECTIVE: To investigate the anti-obesity activity and the action mechanism of the roots of Adenophora triphylla var. japonica extract (ATE) in high-fat diet (HFD)-induced obese mice and 3T3-L1 adipocytes. METHODS: The roots of Adenophora triphylla were extracted with 70% ethanol. To demonstrate the compounds, linoleic acid was analyzed by using gas chromatography; and the anti-obesity effects and possible mechanisms of ATE were examined in 3T3-L1 adipocytes and HFD-induced obese mice. RESULTS: Treatment with ATE inhibited the lipid accumulation without cytotoxicity in 3T3-L1 adipocytes. Furthermore, 200 and 400 mg/kg ATE treatment significantly decreased the body weight gain, white adipose tissues (WATs) weight and plasma triglyceride level, while 100 and 200 mg/kg ATE treatment increased the plasma high-density lipoprotein cholesterol level in the HFD-induced obese mice, as compared with the HFD group. Treatment with 200 and 400 mg/kg ATE also lowered the size of adipocytes in adipose tissue and reduced the lipid accumulation in liver. ATE treatment showed significantly lower expression level of adipogenesis-related proteins, such as peroxisome proliferator-activated receptor γ, fatty acid binding protein (aP2), fatty acid synthase in 3T3-L1 adipocytes; and furthermore, decreased peroxisome proliferator-activated receptor γ, aP2, fatty acid synthase, sterol regulatory element binding protein-1c, and lipoprotein lipase mRNA expression levels in WAT of the HFD-induced obese mice. CONCLUSIONS: These results suggested that the ATE has an anti-obesity effect, which may be elicited by regulating the expression of adipogenesis and lipogenesis-related genes and proteins in adipocytes and WAT of the HFD-induced obese mice.

Outcomes of early administration of cidofovir in non-immunocompromised patients with severe adenovirus pneumonia.

The benefits of treatment with antiviral therapy for severe adenovirus (AdV) pneumonia are not well established. We described the clinical characteristics and treatment outcomes of early cidofovir treatment of severe AdV pneumonia in non-immunocompromised patients. We retrospectively reviewed the medical records of all patients diagnosed with severe AdV pneumonia between 2012 and 2014. A total of seven non-immunocompromised patients with severe AdV pneumonia were identified, and all isolates typed (n = 6) were human AdV-B55. All patients had progressive respiratory failure with lobar consolidation with or without patchy ground glass opacity. Three patients required vasopressors and mechanical ventilation. All patients had abnormal laboratory findings including: leukopenia, thrombocytopenia, or elevated liver enzymes. After admission, all patients received antiviral therapy with cidofovir, and the median time from admission to cidofovir administration was 48 h and median the time from onset of symptoms to cidofovir administration was 7.1 days. After cidofovir administration, complete symptomatic improvement occurred after a median of 12 days and radiographic resolution occurred after a median of 21 days. Consequently, all patients completely improved without complications. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection.

Biodegradation-tunable mesoporous silica nanorods for controlled drug delivery.

Mesoporous silica in the forms of micro- or nanoparticles showed great potentials in the field of controlled drug delivery. However, for precision control of drug release from mesoporous silica-based delivery systems, it is critical to control the rate of biodegradation. Thus, in this study, we demonstrate a simple and robust method to fabricate "biodegradation-tunable" mesoporous silica nanorods based on capillary wetting of anodic aluminum oxide (AAO) template with an aqueous alkoxide precursor solution. The porosity and nanostructure of silica nanorods were conveniently controlled by adjusting the water/alkoxide molar ratio of precursor solutions, heat-treatment temperature, and Na addition. The porosity and biodegradation kinetics of the fabricated mesoporous nanorods were analyzed using N2 adsorption/desorption isotherm, TGA, DTA, and XRD. Finally, the performance of the mesoporous silica nanorods as drug delivery carrier was demonstrated with initial burst and subsequent "zero-order" release of anti-cancer drug, doxorubicin.

Sex-related differences in outcomes after hallux valgus surgery.

PURPOSE: With differences between the sexes in foot bone anatomy and ligamentous laxity, there is the possibility that the results of hallux valgus surgery may also differ between the sexes. We aimed to compare the results of hallux valgus surgery between the sexes. MATERIALS AND METHODS: The authors retrospectively reviewed 60 males (66 feet) and 70 females (82 feet) who underwent distal or proximal chevron osteotomy for the treatment of hallux valgus deformity between June 2005 and December 2011. We compared the clinical and radiologic outcomes between the sexes. RESULTS: There were no statistically significant differences in demographics between the sexes. The mean American Orthopedic Foot and Ankle Society score, visual analogue scale for pain, and patient satisfaction at the last follow-up did not differ significantly between the sexes. The mean preoperative hallux valgus angle (HVA) and inter-metatarsal angle (IMA) were not significantly different between the sexes. At the last follow-up, the mean HVA was significantly greater in females (p=0.003) than in males; mean IMA was not significantly different between the sexes. The mean correction of HVA in males was significantly greater than that in females (p=0.014). CONCLUSION: There were no significant differences between the sexes regarding clinical outcomes after distal and proximal chevron osteotomy. However, male patients achieved greater correction of HVA than female patients. There is a possibility that sexual dimorphism of the foot may affect postoperative HVA.