Assessment of Escherichia coli-derived Recombinant Human Bone Morphogenic Protein-2 on Fertilization and Early Embryonic Development in Rats.

OBJECTIVE: Bone morphogenetic protein-2 (BMP-2) impacts fertility in women by affecting the menstrual cycle and embryonic development. We aimed to determine the reproductive toxicity of Escherichia coli (E. coli)-derived recombinant human BMP-2 (rhBMP-2) by measuring changes in the reproductive performance and organs in rhBMP-2-treated rats. METHODS: Overall, 88 male and female rats each were categorized into one control and three experimental groups. rhBMP-2 was intravenously administered to the experimental groups at 0.05, 0.15, and 0.50 mg/kg/day, respectively. The male rats were administered rhBMP-2 daily, starting from 28 days before mating until the day of necropsy (48 days), after which they were euthanized and necropsied. The female rats were administered rhBMP-2 daily, starting from 14 days before mating until 7 days after fertilization (22-36 days), after which they were necropsied 13 days after fertilization. RESULTS: No rhBMP-2-related death occurred throughout the study period. All rhBMP-2-treated groups showed swelling in the tail at the site of rhBMP-2 administration. In the high-dose rhBMP-2 group, the male rats showed a slight reduction in body weight and food consumption, whereas the female rats showed a reduction in the weights of the ovary and oviduct. Examining the fertilization status and necropsy showed no effect of rhBMP-2 on fertility and early embryonic development. The no-observed-adverse-effect level of rhBMP-2 was 0.50 mg/kg/day in all rats. CONCLUSION: rhBMP-2 had no reproductive toxicity on the reproductive performance and organs in female and male rats. Therefore, these results provide new toxicology information on E. coli-derived rhBMP-2 as a therapeutic protein.

Anti-inflammatory effects of methanol extracts from the Antarctic lichen, Amandinea sp. in LPS-stimulated raw 264.7 macrophages and zebrafish.

The aim of the present study was to determine the anti-inflammatory effect of an extracts isolated from the lichen. Amandinea sp. was collected from the Antarctic and extracted with methanol. The basic screening of the anti-inflammatory property of the extracts was done using the NO assay. The extracts showed very little cytotoxicity, and reduced NO production in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. Furthermore, the extracts inhibited LPS-induced release of pro-inflammatory cytokines such as interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α), and inflammatory mediators inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The extracts also reduced the cytosolic p-IκB-α level and the level of the nuclear factor p65. We examined the anti-inflammatory effects of the extracts using zebrafish in vivo. The extracts reduced the amount of reactive oxygen species (ROS) in LPS-induced zebrafish larvae and inhibited the mRNA expression of inflammatory cytokines and mediators in a tail-cutting induced model. These results are similar to those obtained in vitro with RAW 264.7 cells. Collectively, the data suggest that the extracts may contain one of more compounds with anti-inflammatory effects. Further studies are required to identify the candidate compound/s and to understand the mechanism of action of the extract.

A novel diagnostic method to predict subscapularis tendon tear with sagittal oblique view magnetic resonance imaging.

PURPOSE: To find novel measurement guidelines correlating with known tear size on two sagittal oblique views (en-face view and Y-view). METHODS: From a series of arthroscopic rotator cuff repair cases between 2012 and 2015, 50 patients were randomly selected from each of six subscapularis tear classifications. Due to rarity of type IV lesions, 272 shoulders were included. En-face view and Y-view in sagittal plane MRI were selected. Image evaluation was retrospectively performed by two researchers independently. In en-face view, anatomical line connecting the coracoid tip to the glenoid base designated as the base-to-tip line was used for thickness measurement and classification. Grading according to base-to-tip line, overlapped segment of base-to-tip line, thickness of subscapularis, and fluid accumulation were measured. In Y-view, a tangent line was drawn through the scapular spine and the coracoid. Parallel lines were then made. Grading according to tangent line, vertical length, cephalic width, caudal width, and fluid accumulation was measured. RESULTS: In en-face view, grading according to base-to-tip line and overlapped segment of base-to-tip line showed differences in subscapularis tendon tear types IIB, III, and IV compared to the normal group. Thickness of subscapularis showed differences in types III and IV. No significant difference was observed in fluid accumulation. In Y-view, grading according to tangent line, vertical length, cephalic width, and fluid accumulation showed significant differences in types III and IV. Caudal width in Y-view was significantly different only in type IV. CONCLUSION: Several measurement parameters in two additional views in sagittal-oblique MRI (en-face view and Y-view) showed different degrees of subscapularis tendon tears. Grading of base-to-tip line is easy to use and helps diagnose partial subscapularis tear. LEVEL OF EVIDENCE: III.

Cystatin C is a good predictor of hepatorenal syndrome and survival in patients with cirrhosis who have normal serum creatinine levels.

BACKGROUND/AIMS: We evaluated the usefulness of cystatin C as a prognostic marker in patients with liver cirrhosis and normal serum creatinine. METHODOLOGY: We retrospectively analyzed prospectively enrolled patients with liver cirrhosis and normal serum creatinine from February 2007 to March 2008. We checked liver function and kidney variables including serum creatinine, cystatin C and glomerular filtration rate from 51Cr-EDTA on the same day for all patients. The endpoints of the study were either development of hepatorenal syndrome or mortality. RESULTS: In total, 112 patients with liver cirrhosis were enrolled in the study (87 men and 25 women, age 52 ± 12 years). Twelve (11%), 59 (53%) and 41 (36%) patients were in Child-Pugh class A, B and C, respectively. Cystatin C was better correlated with glomerular filtration rate from 51Cr-EDTA than creatinine. The 1-year cumulative incidence of hepatorenal syndrome and the 1-year survival rate of patients were 20.5% and 79.5%, respectively. Cystatin C, Model for End-Stage Liver Disease and serum sodium were the independent predictive factors for hepatorenal syndrome. Cystatin C, serum sodium and prothrombin time were the independent factors for predicting survival. CONCLUSIONS: In patients with liver cirrhosis and normal creatinine levels, cystatin C is a useful marker for predicting hepatorenal syndrome and survival.

Anchoring of a fully covered self-expandable metal stent with a 5F double-pigtail plastic stent to prevent migration in the management of benign biliary strictures.

OBJECTIVES: Fully covered self-expandable metal stents (FCSEMSs) can be effectively placed in patients with benign biliary stricture (BBS). However, stent migration is an inherent problem of FCSEMSs. We evaluated the efficacy of anchoring with a 5F double-pigtail plastic stent (anchoring stent) to prevent migration of an FCSEMS in patients with BBS. METHODS: Between January 2007 and December 2009, 33 of 37 consecutive patients with BBS who had experienced treatment failure of at least one plastic stent placement were prospectively enrolled in this study. The patients with BBS were randomly assigned to undergo FCSEMS placement with or without an anchoring stent (anchoring group: 16 patients; non-anchoring group: 17 patients). The main outcome measures were the stent migration rate and success rates. RESULTS: The technical success rate was 100% in both groups. Significantly less stent migration occurred in the anchoring group (6.3%, 1/16) than in the non-anchoring group (41.2%, 7/17; P=0.024). The median indwelling time was significantly longer in the anchoring group (154 days; range, 86-176 days) than in the non-anchoring group (114 days; range, 19-162 days; P=0.010). Improvement or resolution of the BBS was confirmed in 15 of 16 patients (93.8%) in the anchoring group, and in 12 of 17 patients (70.6%) in the non-anchoring group (P=0.101). CONCLUSIONS: The placement of an anchoring stent appears to be a simple and effective method of preventing premature migration of FCSEMSs in patients with BBS. Appropriately powered studies are needed to confirm this finding.

Clinical feasibility of direct peroral cholangioscopy-guided photodynamic therapy for inoperable cholangiocarcinoma performed by using an ultra-slim upper endoscope (with videos).

BACKGROUND: Photodynamic therapy (PDT) has emerged as a promising palliative treatment for inoperable cholangiocarcinoma. Cholangioscopy-guided PDT can be useful for identification of tumor margins, determination of the appropriate location for placement of the diffuser, and evaluation of the patient's response to therapy. OBJECTIVE: To evaluate the feasibility of PDT under direct peroral cholangioscopy (POC) by using an ultra-slim upper endoscope in patients with inoperable cholangiocarcinoma. DESIGN: Prospective, observational, pilot study. SETTING: Single tertiary-care referral center. PATIENTS: This study involved 9 patients with inoperable extrahepatic cholangiocarcinoma. INTERVENTION: Photofrin II was administered intravenously 48 hours before PDT. Additional PDT was performed up to 48 hours after the initial application of therapy. A successful direct POC-guided PDT was defined as advancement of the endoscope into the distal margin of the tumor and maintenance of endoscope position until PDT was completed. MAIN OUTCOME MEASUREMENTS: The clinical feasibility, usefulness, and complications of direct POC for PDT. RESULTS: Seventeen sessions of direct POC for PDT were performed in 9 patients. PDT was performed successfully in 15 of 17 sessions (88.2%) and 7 of 9 patients (77.8%). Biliary drainage under direct POC, if necessary after PDT, was possible in 100% of patients (7/7). Follow-up direct POC confirmed significant tumor ablation after PDT in 5 patients. One patient reported mild skin redness; no major procedure-related complications were observed. LIMITATIONS: Small sample size, pilot study. CONCLUSION: Direct POC-guided PDT by using an ultra-slim upper endoscope seems to be both feasible and safe in select patients with inoperable extrahepatic cholangiocarcinoma.

Anti-Inflammatory Effects of Antarctic Lichen Umbilicaria antarctica Methanol Extract in Lipopolysaccharide-Stimulated RAW 264.7 Macrophage Cells and Zebrafish Model.

Umbilicaria antarctica (UA) is a member of the family Umbilicariaceae. To the best of our knowledge, no studies on its anti-inflammatory effects have been reported yet. In the present study, we examined its ability to suppress inflammatory responses and the molecular mechanisms underlying these abilities using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells and a zebrafish model of inflammation. We investigated the effects of UA on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated RAW 264.7 cells. To explore the anti-inflammatory mechanisms of UA, we measured the mRNA and protein expression of proinflammatory mediators in LPS-stimulated RAW 264.7 cells using quantitative RT-PCR and western blot analyses, respectively. UA significantly inhibited the production of NO, PGE2, interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α in the LPS-stimulated RAW 264.7 cells. It also suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor- (NF-) κB activation in LPS-stimulated RAW 264.7 cells and tail pin-cutting-induced zebrafish model. Collectively, these findings indicate that UA significantly inhibits LPS-stimulated inflammatory responses. These effects were considered to be strongly associated with the suppression of NF-κB activation. Overall, our results demonstrate that UA extract exerts strong anti-inflammatory activities in in vitro and in vivo models and suggest that UA may be an effective novel therapeutic agent for the treatment of inflammatory diseases.

Compartmental culture of embryonic stem cell-derived neurons in microfluidic devices for use in axonal biology.

Axonal pathology has been clearly implicated in neurodegenerative diseases making the compartmental culture of neurons a useful research tool. Primary neurons have already been cultured in compartmental microfluidic devices but their derivation from an animal is a time-consuming and difficult work and has a limit in their sources. Embryonic stem cell (ESC)-derived neurons (ESC_Ns) overcome this limit, since ESCs can be renewed without limit and can be differentiated into ESC_Ns by robust and reproducible protocols. In this research, ESC_Ns were derived from mouse ESCs in compartmental microfluidic devices, and their axons were isolated from the somal cell bodies. Once embryoid bodies (EBs) were localized in the microfluidic culture chamber, ESC_Ns spread out from the EBs and occupied the cell culture chamber. Their axons traversed the microchannels and finally were isolated from the somata, providing an arrangement comparable to dissociated primary neurons. This ESC_N compartmental microfluidic culture system not only offers a substitute for the primary neuron counterpart system but also makes it possible to make comparisons between the two systems.

Does Combining a Suprascapular Nerve Block With an Intra-articular Corticosteroid Injection Have an Additive Effect in the Treatment of Adhesive Capsulitis? A Comparison of Functional Outcomes After Short-term and Minimum 1-Year Follow-up.

BACKGROUND: No therapeutic intervention is universally accepted as the most effective treatment for adhesive capsulitis. An intra-articular corticosteroid injection (IAI) with a suprascapular nerve block (SSNB), a common treatment for this disease, is a safe and effective method for the resolution of pain and restoration of shoulder range of motion (ROM). PURPOSE: To compare the efficacy of combined SSNB and IAI with that of IAI alone in the treatment of adhesive capsulitis. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We performed a retrospective review of 102 patients with adhesive capsulitis who were treated at an outpatient clinic from July 2016 to January 2017. A combined SSNB with IAI was performed in 48 patients (SSNB + IAI group), and an IAI alone was performed in 54 patients (IAI group). Patients were assessed before the intervention and at 2 weeks and 2 months after the intervention. ROM and pain and function visual analog scales (PVAS and FVAS, respectively), the American Shoulder and Elbow Surgeons (ASES) score, the Korean Shoulder Scoring System (KSS), the Constant score, the Simple Shoulder Test (SST), and the Shoulder Pain and Disability Index (SPADI) were used for clinical assessments. PVAS, FVAS, and ASES scores at a minimum of 1 year after the intervention were assessed for 82 patients. RESULTS: At the 2-month assessment, all parameters significantly improved in both the SSNB + IAI and IAI groups (P < .05), however, improvements in forward flexion (FF) and abduction (ABD) between the 2-week and 2-month assessments were better in the SSNB + IAI group. At the 2-month assessment, improvements in the FVAS, ASES, SST, and SPADI scores and FF and ABD values were statistically significantly greater in the SSNB + IAI group compared with the IAI group. Improvements in FVAS and ASES scores were significantly greater in the SSNB + IAI group at a minimum of 1 year. CONCLUSION: Both a combined SSNB and IAI and an IAI alone significantly improved pain and functional outcomes in patients with adhesive capsulitis. The use of an SSNB with an IAI further increased treatment efficacy, as per the FVAS, ASES, SST, and SPADI scores and FF and ABD values. Patients who underwent SSNB combined with an IAI showed better improvements in the FVAS and ASES scores compared with IAI alone at a minimum of 1 year after the intervention. Therefore, an SSNB combined with an IAI may be a good treatment choice for adhesive capsulitis.

Location of Rotator Cuff Tear Initiation: A Magnetic Resonance Imaging Study of 191 Shoulders.

BACKGROUND: Degenerative rotator cuff tears (RCTs) are generally thought to originate at the anterior margin of the supraspinatus tendon. However, a recent ultrasonography study suggested that they might originate more posteriorly than originally thought, perhaps even from the isolated infraspinatus (ISP) tendon, and propagate toward the anterior supraspinatus. Hypothesis/Purpose: It was hypothesized that this finding could be reproduced with magnetic resonance imaging (MRI). The purpose was to determine the most common location of degenerative RCTs by using 3-dimensional multiplanar MRI reconstruction. It was assumed that the location of the partial-thickness tears would identify the area of the initiation of full-thickness tears. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A retrospective analysis was conducted including 245 patients who had RCTs (nearly full- or partial-thickness tears) at the outpatient department between January 2011 and December 2013. RCTs were measured on 3-dimensional multiplanar reconstruction MRI with OsiriX software. The width and distance from the biceps tendon to the anterior margin of the tear were measured on T2-weighted sagittal images. In a spreadsheet, columns of consecutive numbers represented the size of each tear (anteroposterior width) and their locations with respect to the biceps brachii tendon. Data were pooled to graphically represent the width and location of all tears. Frequency histograms of the columns were made to visualize the distribution of tears. The tears were divided into 2 groups based on width (group A, <10 mm; group B, <20 and ≥10 mm) and analyzed for any differences in location related to size. RESULTS: The mean width of all RCTs was 11.9 ± 4.1 mm, and the mean length was 11.1 ± 5.0 mm. Histograms showed the most common location of origin to be 9 to 10 mm posterior to the biceps tendon. The histograms of groups A and B showed similar tear location distributions, indicating that the region approximately 10 mm posterior to the biceps tendon is the most common site of tear initiation. CONCLUSION: These results demonstrate that degenerative RCTs most commonly originate from approximately 9 to 10 mm posterior to the biceps tendon.

Chitosan-coated C-phycocyanin Liposome for Extending the Neuroprotective Time Window Against Ischemic Brain Stroke.

The time window for neuroprotection during ischemic brain stroke is short, and hence, development of neuroprotectants is critical to extend this time window. This study sought to verify if muco-adhesive chitosan coating improves the neuroprotective potential of the pre-proven C-Phycocyanin-pertaining liposome (C-Pc liposome). The use of chitosan-coated liposomes extended the neuroprotective time window by 6 h after occlusion, and further improved the neuroprotection efficiency of the C-Pc liposome in a rat Middle Cerebral Artery Occlusion (MCAO) model. Beneficial changes in mRNA expressions of antioxidants, inflammatory cytokines and glia scar proteoglycans were evident in the C-Pc liposomes. In addition, in the cultured astrocytes, the chitosan- coated C-Pc liposome expressed anti-oxidative activity without cytotoxicity.

Nasal Delivery of Antioxidants by Cholesterol-incorporated Liposomes Extends the Neuroprotective Time Window in Cerebral Ischemia.

Antioxidants have the potential to prevent cerebral ischemia-reperfusion (IR)-associated secondary damage induced by reactive oxygen species (ROS); however, the short therapeutic time window of IR is a considerable obstacle. Nano-sized nasal delivery systems provide an effective means of delivering drugs through the BBB, but few such systems have been developed to extend the treatment time window in IR. In this work, a nanosized nasal delivery system for antioxidants was found to have the potential to extend the neuroprotective time window. The authors chose to use the antioxidant C-phycocyanin (C-Pc) to design a neuroprotective liposome with a long life, controllable release, and high neuronal uptake rate. Liposomes formulated with various cholesterol to phospholipid ratios were assessed thermodynamically, kinetically, and biologically. Thermodynamically stable, monodispersive, and release-controllable C-Pc liposomes were more effectively taken up by Neuro2a cells than free C-Pc and were biocompatible, maintaining the anti-oxidative properties of C-Pc. When optimal C-Pc liposomes were administered to middle cerebral artery occlusion (MCAO) rats 2 h after onset, infarct sizes were smaller and behavioral activities improved compared with the same metrics in free C-Pc-treated rats. Liposomal delivery still reduced infarct sizes and improved behavioral activity 6 h after onset, whereas free C-Pc did not.

Assessment of Neuronal Cell-Based Cytotoxicity of Neurotoxins from an Estuarine Nemertean in the Han River Estuary.

A heteronemertean, Yininemertes pratensis, was collected in Han River Estuary, South Korea. This estuarine nemertean has been known by the local fishermen for harmful effects to the glass eels, juveniles of Japanese eel Anguilla japonica, migrating to fresh water. The present study confirmed the neurotoxic effects of this heteronemertean ribbon worm at the cellular level. Derivative types of neurotoxic tetrodotoxin (TTX), 5,11-dideoxy TTX (m/z 288) and 11-norTTX-6(S)-01 (m/z 305.97), were identified through HPLC and MALDI-TOF MS. However, significant neurotoxicity was confirmed in the fraction containing an undefined molecule corresponding to the 291.1 (m/z) peak, when tested in rat primary astrocytes and dorsal ganglion cells. This study is the first to report neurotoxins of the estuarine nemertean, fairly abundant in the Han River estuary, and suggests the long-term monitoring of population dynamics and surveillance of the toxicity in this river estuary.

[Two cases of acute hepatitis E in patients with hyperthyroidism].

Acute hepatitis E occur commonly as outbreaks in endemic areas, but can occur sporadically in other part of the world. Acute hepatitis E has been reported rarely in Korea. A case of concurrent acute hepatitis E virus (HEV) infection and hyperthyroidism was reported in an inactive hepatitis B surface antigen carrier. We experienced two cases of concomitant acute HEV infection in patients with hyperthyroidism. The first case had acute HEV infection with subclinical hyperthyroidism while taking propylthiouracil. The second case suffered from acute HEV infection in a patient with Graves' disease intractable to propylthiouracil. Herein, we suggest the possible association between HEV infection and hyperthyroidism.

Nanocellulose size regulates microalgal flocculation and lipid metabolism.

Harvesting of microalgae is a cost-consuming step for biodiesel production. Cellulose has recently been studied as a biocompatible and inexpensive flocculant for harvesting microalgae via surface modifications such as cation-modifications. In this study, we demonstrated that cellulose nanofibrils (CNF) played a role as a microalgal flocculant via its network geometry without cation modification. Sulfur acid-treated tunicate CNF flocculated microalgae, but cellulose nanocrystals (CNC) did not. In addition, desulfurization did not significantly influence the flocculation efficiency of CNF. This mechanism is likely related to encapsulation of microalgae by nanofibrous structure formation, which is derived from nanofibrils entanglement and intra-hydrogen bonding. Moreover, flocculated microalgae were subject to mechanical stress resulting in changes in metabolism induced by calcium ion influx, leading to upregulated lipid synthesis. CNF do not require surface modifications such as cation modified CNC and flocculation is derived from network geometry related to nanocellulose size; accordingly, CNF is one of the least expensive cellulose-based flocculants ever identified. If this flocculant is applied to the biodiesel process, it could decrease the cost of harvest, which is one of the most expensive steps, while increasing lipid production.

Do Anterior Cervical Osteophytes Prevent Dynamization of Cervical Dynamic Plates?

STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate radiographic changes of patients with osteophytes at the anterior border of the caudal vertebral body who were treated with anterior cervical discectomy and fusion using dynamic rotational plates. SUMMARY OF BACKGROUND DATA: Dynamic cervical plates are widely used in surgeries of the anterior cervical spine. One concern in using dynamic plates is that the subjacent anterior osteophytes might act as a bony block and prevent dynamization of the plate. To our knowledge, there are no studies that have investigated the validity of this concern. MATERIALS AND METHODS: Twenty-eight patients were selected for the study out of patients who had undergone 1-level anterior cervical discectomy and fusion using a dynamic rotational plate. They were divided into 2 groups on the basis of the presence of osteophytes located at the anterior border of the subjacent vertebrae. Thirteen patients had osteophytes and 15 control patients did not. The mean follow-up period was 10.8±8.4 months (range, 6-36 mo). Lateral radiographs were taken preoperatively, immediately postoperatively, and at the final follow-ups to assess changes in the following radiographic parameters: Cobb angle of the adjacent segments and fused segment, horizontal distance between C2 and C7 plumb lines, height of the bone graft, vertebral heights of the operated segment, and migration distance of the plate. RESULTS: No statistical significance was found in the Cobb angles of the adjacent segments and fused segment, distance between the C2-C7 plumb lines, height of the graft, height of vertebral bodies of the operated segment, and migration distance of the plate through the preoperative, postoperative, and final follow-ups between the 2 groups. CONCLUSION: Osteophytes did not appear to affect the dynamization of plates in any of the measured radiographic parameters.

Assessment of C-phycocyanin effect on astrocytes-mediated neuroprotection against oxidative brain injury using 2D and 3D astrocyte tissue model.

Drugs are currently being developed to attenuate oxidative stress as a treatment for brain injuries. C-phycocyanin (C-Pc) is an antioxidant protein of green microalgae known to exert neuroprotective effects against oxidative brain injury. Astrocytes, which compose many portions of the brain, exert various functions to overcome oxidative stress; however, little is known about how C-Pc mediates the antioxidative effects of astrocytes. In this study, we revealed that C-Pc intranasal administration to the middle cerebral artery occlusion (MCAO) rats ensures neuroprotection of ischemic brain by reducing infarct size and improving behavioral deficits. C-Pc also enhanced viability and proliferation but attenuated apoptosis and reactive oxygen species (ROS) of oxidized astrocytes, without cytotoxicity to normal astrocytes and neurons. To elucidate how C-Pc leads astrocytes to enhance neuroprotection and repair of ischemia brain, we firstly developed 3D oxidized astrocyte model. C-Pc had astrocytes upregulate antioxidant enzymes such as SOD and catalase and neurotrophic factors BDNF and NGF, while alleviating inflammatory factors IL-6 and IL-1ß and glial scar. Additionally, C-Pc improved viability of 3D oxidized neurons. In summary, C-Pc was concluded to activate oxidized astrocytes to protect and repair the ischemic brain with the combinatorial effects of improved antioxidative, neurotrophic, and anti-inflammatory mechanisms.

Regulation of astrocyte activity via control over stiffness of cellulose acetate electrospun nanofiber.

Astrocytes are involved in neuron protection following central nervous system (CNS) injury; accordingly, engineered astrocytes have been investigated for their usefulness in cell therapy for CNS injury. Nanofibers have attracted a great deal of attention in neural tissue engineering, but their mechanical properties greatly influence physiology. Cellulose acetate (CA) has been studied for use in scaffolds owing to its biocompatibility, biodegradability, and good thermal stability. In this study, stiffness of CA nanofibers controlled by heat treatment was shown to regulate astrocyte activity. Adhesion and viability increased in culture as substrate became stiffer but showed saturation at greater than 2 MPa of tensile strength. Astrocytes became more active in terms of increasing intermediate filament glial fibrillary acidic protein (GFAP). The results of this study demonstrate the effects of stiffness alone on cellular behaviors in a three-dimensional culture and highlight the efficacy of heat-treated CA for astrocyte culture in that the simple treatment enables control of astrocyte activity.

Thermodynamic Insights and Conceptual Design of Skin-Sensitive Chitosan Coated Ceramide/PLGA Nanodrug for Regeneration of Stratum Corneum on Atopic Dermatitis.

Atopic dermatitis (AD) is a complex skin disease primarily characterized by psoriasis of the stratum corneum. AD drugs have usually been used in acidic and hydrophilic solvents to supply moisture and prevent lipid defects. Ceramide is a typical treatment agent to regenerate the stratum corneum and relieve symptoms of AD. However, ceramide has limitation on direct use for skin because of its low dispersion properties in hydrophilic phase and side effects at excessive treatment. In this study, ceramide imbedded PLGA nanoparticles were developed with chitosan coating (Chi-PLGA/Cer) to overcome this problem. The chitosan coating enhanced initial adherence to the skin and prevented the initial burst of ceramide, but was degraded by the weakly acidic nature of skin, resulting in controlled release of ceramide with additional driving force of the squeezed PLGA nanoparticles. Additionally, the coating kinetics of chitosan were controlled by manipulating the reaction conditions and then mathematically modeled. The Chi-PLGA/Cer was not found to be cytotoxic and ceramide release was controlled by pH, temperature, and chitosan coating. Finally, Chi-PLGA/Cer was demonstrated to be effective at stratum corneum regeneration in a rat AD model. Overall, the results presented herein indicated that Chi-PLGA/Cer is a novel nanodrug for treatment of AD.