Efficacy of the erector spinae plane block with sedation for unilateral biportal endoscopic spine surgery and comparison with other anesthetic methods.

BACKGROUND: Erector spinae plane block (ESPB) is a new regional anesthesia. Unilateral biportal endoscopic (UBE) spine surgery, a minimal invasive technique, has been performed under not only general anesthesia (GA) but regional anesthesia including spinal anesthesia (SA). The aims of this study were to evaluate the efficacy of ESPB with sedation for UBE lumbar decompression and compare it with GA and SA. METHOD: A retrospective age matched case-control study design was performed. Three groups (20 patients in each group) of patients who underwent UBE lumbar decompressions under each anesthetic method (GA, SA, or ESPB) were formed. The total anesthesia time excluding operation time, postoperative analgesia effects, hospital days, and complications related to anesthetic methods were evaluated. RESULTS: In the ESPB group, all the operations were performed without change of anesthetic methods and without anesthetic complications. But there were no anesthetic effects in the epidural space, which resulted in additional intravenous fentanyl usage. The mean of time from initiation of anesthesia to completion of surgical preparation was 23.3 ± 4.7 min in the ESPB group, which was shorter than 32.3 ± 10.8 min in the GA (p value = 0.001) or 33.3 ± 6.7 min in the SA group (p < 0.001). The proportion of patients requiring first rescue analgesia within 30 min was 30% in the ESPB group, which was lower than 85% in the GA (p < 0.001), but no significant different with 10% in the SA (p = 0.11). The mean of total hospital days in the ESPB was 3.0 ± 0.8, shorter than 3.7 ± 1.8 in the GA (p = 0.02) or 3.8 ± 1.1 in the SA group (p = 0.01). There was no case of postoperative nausea and vomiting in the ESBB even without prophylactic antiemesis. CONCLUSION: ESPB with sedation is a viable anesthetic option for UBE lumbar decompression.

Enhanced oral bioavailability of valsartan in rats using a supersaturable self-microemulsifying drug delivery system with P-glycoprotein inhibitors.

Valsartan (VST) is a poorly water-soluble drug and a P-glycoprotein (P-gp) substrate. To enhance the dissolution and oral absorption of VST, a novel supersaturable self-microemulsifying drug delivery system (Su-SMEDDS) was formulated. Based on the previously reported Su-SMEDDS composed of Capmul® MCM (oil), Tween® 20 (T20; surfactant), Transcutol® P (cosurfactant), and Poloxamer 407 (supersaturating agent), P-gp inhibitory surfactants including Tween® 80 (T80) and Cremophor® EL (CR) were newly introduced to replace T20. All Su-SMEDDS formulations had a droplet size of <200 nm and showed rapid (>90% within 5 min) and pH-independent dissolution characteristics. The effective permeability coefficient (Peff) in rat jejunum was obtained using an in situ single-pass intestinal perfusion study: Peff values of Su-SMEDDS-T20, Su-SMEDDS-T80, and Su-SMEDDS-CR were 2.3, 4.1, and 3.4 times greater, respectively, than that of the VST solution. After oral administration of various formulations to rats (equivalent dose of VST 10 mg/kg), plasma drug levels were measured by liquid chromatography-tandem mass spectrometry. The relative bioavailabilities of Su-SMEDDS-T20, Su-SMEDDS-T80, and Su-SMEDDS-CR were 262%, 470%, and 458%, respectively, compared with the VST suspension. Thus, we propose that the Su-SMEDDS-T80 formulation is a good candidate for improving the oral absorption of poorly water-soluble and P-gp substrate drugs such as VST.

Room Temperature Compressive Property and Deformation Behavior of Microporous STS 316L Stainless Steel Tube Manufactured with Powder Sintering Process.

This study investigated the room-temperature compressive property and deformation behavior of microporous STS 316L stainless steel tube for catalyst manufactured with powder sintering after two-way compression molding. The microporous tube was manufactured using STS 316L powder stocks with an outer diameter of 30 mm, inner diameter of 25 mm and length of 120 mm. In initial microstructure observed from different directions and locations, the porosity was measured as 32%, and the relative density obtained using micro-computed tomography was 0.54. Phase analysis did not identify phases other than γ-Fe. In a room temperature compression test, compressive yield strength measured 32 MPa. Observation of fractpgraphy after compression test revealed that dimples were formed at the powder-powder interface during the process where necks were disconnected. Based on the above findings, this study attempted to identify the deformation behavior of microporous STS 316L material manufactured with powder sintering after two-way compression molding and powder sintering process.

Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type.

Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL), leptodactylic (lepto-SEMDJL) or Hall type, is an autosomal-dominant skeletal dysplasia manifesting with short stature, joint laxity with dislocation(s), limb malalignment, and spinal deformity. Its causative gene mutation has not yet been discovered. We captured and sequenced the exomes of eight affected individuals in six unrelated kindreds (three individuals in a family and five simplex individuals). Five novel sequence variants in KIF22, which encodes a member of the kinesin-like protein family, were identified in seven individuals. Sanger sequencing of KIF22 confirmed that c.443C>T (p.Pro148Ser) cosegregated with the phenotype in the affected individuals in the family; c.442C>T (p.Pro148Leu) or c.446G>A (p.Arg149Gln) was present in four of five simplex individuals, but was absent in unaffected individuals in their family and 505 normal cohorts. KIF22 mRNA was detected in human bone, cartilage, joint capsule, ligament, skin, and primary cultured chondrocytes. In silico analysis of KIF22 protein structure indicates that Pro148 and Arg149 are important in maintaining hydrogen bonds in the ATP binding and motor domains of KIF22. We conclude that these mutations in KIF22 cause lepto-SEMDJL.

Physicochemical Stability and Compatibility of Mixtures of Ropivacaine with Dexamethasone or Betamethasone for Epidural Steroid Injections: An In Vitro Study.

BACKGROUND: Epidural steroid injections are widely used to treat spinal and radiating pain. However, crystal formation has recently been reported in mixtures of ropivacaine and nonparticulate steroids, commonly used in epidural steroid injections. OBJECTIVES: Our study assessed the physicochemical stability of mixtures of different nonparticulate steroids and ropivacaine and aimed to propose a safe regimen for epidural steroid injections. STUDY DESIGN: An in vitro protocol was used to examine the physicochemical stability of epidural steroid injection mixtures most commonly used at our institution. SETTING: In vitro laboratory study. METHODS: Twelve solutions were prepared by mixing 0.75% or 0.2% ropivacaine with dexamethasone or betamethasone at volume ratios of 1:1, 2:1, and 3:1 in propylene syringes at 24°C. The physical properties of the mixtures were observed with the naked eye and under a microscope, and their pH was measured. The concentration of each drug in the mixture was evaluated using high-performance liquid chromatography. RESULTS: None of the ropivacaine and dexamethasone mixtures showed macroscopic or microscopic crystal formation after 2 hours, and there were no significant changes in pH. The concentrations of the 2 drugs remained stable for up to 2 hours. In contrast, at least 10 mu-m crystals were observed microscopically and macroscopically in all mixtures of ropivacaine and betamethasone; the ropivacaine concentration was reduced by > 10% after one hour. LIMITATIONS: Confirming the stability of drugs in vitro does not ensure that their pharmacokinetics and pharmacodynamics remain unaltered in vivo. CONCLUSION: The combination of ropivacaine and betamethasone should be avoided because of their physicochemical instability. Combinations of ropivacaine and dexamethasone should be administered cautiously because they are more physicochemically stable than combinations of ropivacaine and betamethasone.

Biomimetic Marine-Sponge-Derived Spicule-Microparticle-Mediated Biomineralization and YAP/TAZ Pathway for Bone Regeneration In Vivo.

Marine-sponge-derived spicule microparticles (SPMs) possess unique structural and compositional features suitable for bone tissue engineering. However, significant challenges remain in establishing their osteogenic mechanism and practical application in animal models. This study explores the biomimetic potential of SPM in orchestrating biomineralization behavior and modulating the Yes-associated protein 1/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) pathway both in vitro and in vivo. Characterization of SPM revealed a structure comprising amorphous silica oxide mixed with collagen and trace amounts of calcium and phosphate ions, which have the potential to facilitate biomineralization. Structural analysis indicated dynamic biomineralization from SPM to hydroxyapatite, contributing to both in vitro and in vivo osteoconductions. In vitro assessment demonstrated dose-dependent increases in osteogenic gene expression and bone morphogenetic protein-2 protein in response to SPM. In addition, focal adhesion mediated by silica diatoms induced cell spreading on the surface of SPM, leading to cell alignment in the direction of SPM. Mechanical signals from SPM subsequently increased the expression of YAP/TAZ, thereby inducing osteogenic mechanotransduction. The osteogenic activity of SPM-reinforced injectable hydrogel was evaluated in a mouse calvaria defect model, demonstrating rapid vascularized bone regeneration. These findings suggest that biomimetic SPM holds significant promise for regenerating bone tissue.

Ankle sprain bracing solutions and future design consideration for civilian and military use.

INTRODUCTION: Ankle sprains are common injuries within the civilian and military populations, with lingering symptoms that include pain, swelling, giving-way, and a high likelihood for recurrence. Numerous bracing systems are available to stabilize the ankle joint following sprains, with new design iterations frequently entering the market. Currently available braces generally include sleeve, lace-up, and stirrup designs. Sleeves provide mild compression and warmth but limited stability for the ankle, while lace-ups and stirrups appear to be more effective at preventing and treating lateral ankle sprains. AREAS COVERED: This review summarizes the use of various brace options in practice. Their major clinical benefits, and limitations are highlighted, followed by an overview of emerging concepts in brace design. Current advancements in biomechanical simulation, multifunctional material fabrication, and wearable, field-deployed devices for human injury surveillance are discussed, providing possibilities for conceiving new design concepts for next-generation smart ankle braces. EXPERT OPINION: Performance of the commercially available braces are limited by their current design concepts. Suggestions on future brace design include: (1) incorporating high-performance materials suitable for extreme environments, (2) leveraging modeling and simulation techniques to predict mechanical support requirements, and (3) implementing adaptive, customizable componentry material to meet the needs of each unique patient.

Synaptic connections of calbindin-immunoreactive cone bipolar cells in the inner plexiform layer of rabbit retina.

In the mammalian retina, information concerning various aspects of an image is transferred in parallel, and cone bipolar cells are thought to play a major role in this parallel processing. We have examined the synaptic connections of calbindin-immunoreactive (IR) ON cone bipolar cells in the inner plexiform layer (IPL) of rabbit retina and have compared these synaptic connections with those that we have previously described for neurokinin 1 (NK1) receptor-IR cone bipolar cells. A total of 325 synapses made by calbindin-IR bipolar axon terminals have been identified in sublamina b of the IPL. The axons of calbindin-IR bipolar cells receive synaptic inputs from amacrine cells through conventional synapses and are coupled to putative AII amacrine cells via gap junctions. The major output from calbindin-IR bipolar cells is to amacrine cell processes. These data resemble our findings for NK1 receptor-IR bipolar cells. However, the incidences of output synapses to ganglion cell dendrites of calbindin-IR bipolar cells are higher compared with the NK1-receptor-IR bipolar cells. On the basis of stratification level and synaptic connections, calbindin-IR ON cone bipolar cells might thus play an important role in the processing of various visual aspects, such as contrast, orientation, and approach sensing, and in transferring rod signals to the ON cone pathway.

Enhanced docetaxel delivery using sterically stabilized RIPL peptide-conjugated nanostructured lipid carriers: In vitro and in vivo antitumor efficacy against SKOV3 ovarian cancer cells.

Docetaxel (DTX) has poor solubility, low specificity, and severe side effects. For efficient targeting of DTX to hepsin-overexpressing SKOV3 ovarian cancer cells, PEGylated and RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated nanostructured lipid carriers (PEG-RIPL-NLCs) were examined for in vitro and in vivo antitumor efficacy. DTX-loaded plain NLCs (DTX-pNLCs), RIPL-NLCs (DTX-RIPL-NLCs), and PEG-RIPL-NLCs (DTX-PEG-RIPL-NLCs) were prepared using a solvent emulsification-evaporation technique. DTX was successfully loaded with high encapsulation efficiency (>93%), and all NLCs showed homogeneous dispersion with zeta potentials varying from -17 to 15 mV. Drug release was biphasic: initial rapid release, then gradual release. In vitro cytotoxicity was time- and dose-dependent: DTX-RIPL-NLCs and DTX-PEG-RIPL-NLCs exhibited greater cytotoxicity, enhanced cell apoptosis owing to the cell cycle arrest in the G2/M phase, and increased activation of the mitochondria-related intrinsic apoptosis pathway compared to DTX-pNLCs. Pharmacokinetic experiments in male Sprague-Dawley rats revealed that DTX-PEG-RIPL-NLCs increased the mean residence time of DTX but reduced total body clearance and volume of distribution. In a SKOV3-bearing xenograft Balb/c athymic mouse model, DTX-PEG-RIPL-NLCs suppressed tumors, evidenced by tumor volume change and histopathological examination. Thus, we conclude that PEG-RIPL-NLCs have an advantage of high payload of poorly water-soluble drugs and are a good candidate for drug targeting to SKOV3-derived ovarian cancer.

Intravesical delivery of rapamycin via folate-modified liposomes dispersed in thermo-reversible hydrogel.

PURPOSE: To develop an intravesical instillation system for the treatment of bladder cancer, rapamycin (Rap) was encapsulated into liposomes and then homogeneously dispersed throughout a poloxamer 407 (P407)-based hydrogel. METHODS: Rap-loaded conventional liposomes (R-CL) and folate-modified liposomes (R-FL) were prepared using a film hydration method and pre-loading technique, and characterized by particle size, drug entrapment efficiency, and drug loading. The cellular uptake behavior in folate receptor-expressing bladder cancer cells was observed by flow cytometry and confocal laser scanning microscopy using a fluorescent probe. In vitro cytotoxic effects were evaluated using MTT assay, colony forming assay, and Western blot. For in vivo intravesical instillation, Rap-loaded liposomes were dispersed in P407-gel, generating R-CL/P407 and R-FL/P407. Gel-forming capacities and drug release were evaluated. Using the MBT2/Luc orthotopic bladder cancer mouse model, in vivo antitumor efficacy was evaluated according to regions of interest (ROI) measurement. RESULTS: R-CL and R-FL were successfully prepared, at approximately <160 nm, 42% entrapment efficiency, and 57 µg/mg drug loading. FL cellular uptake was enhanced over 2-fold than that of CL; folate receptor-mediated endocytosis was confirmed using a competitive assay with folic acid pretreatment. In vitro cytotoxic effects increased dose-dependently. Rap-loaded liposomes inhibited mTOR signaling and induced autophagy in urothelial carcinoma cells. With gelation time of <30 seconds and gel duration of >12 hrs, both R-CL/P407 and R-FL/P407 preparations transformed into gel immediately after instillation into the mouse bladder. Drug release from the liposomal gel was erosion controlled. In orthotopic bladder cancer mouse model, statistically significant differences in ROI values were found between R-CL/P407 and R-FL/P407 groups at day 11 (P=0.0273) and day 14 (P=0.0088), indicating the highest tumor growth inhibition by R-FL/P407. CONCLUSION: Intravesical instillation of R-FL/P407 might represent a good candidate for bladder cancer treatment, owing to its enhanced retention and FR-targeting.

pH-sensitive PEGylation of RIPL peptide-conjugated nanostructured lipid carriers: design and in vitro evaluation.

BACKGROUND: RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated nanostructured lipid carriers (RIPL-NLCs) can facilitate selective drug delivery to hepsin (Hpn)-expressing cancer cells, but they exhibit low stability in the blood. Generally, biocompatible and nontoxic poly(ethylene glycol) surface modification (PEGylation) can enhance NLC stability, although this may impair drug delivery and NLC clearance. To attain RIPL-NLC steric stabilization without impairing function, pH-sensitive cleavable PEG (cPEG) was grafted onto RIPL-NLCs (cPEG-RIPL-NLCs). METHODS: Various types of NLC formulations including RIPL-NLCs, PEG-RIPL-NLCs, and cPEG-RIPL-NLCs were prepared using the solvent emulsification-evaporation method and characterized for particle size, zeta potential (ZP), and cytotoxicity. The steric stabilization effect was evaluated by plasma protein adsorption and phagocytosis inhibition studies. pH-sensitive cleavage was investigated using the dialysis method under different pH conditions. Employing a fluorescent probe (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiI]), in vitro drug delivery capacity of the cPEG-RIPL-NLCs under different pH conditions was also performed on Hpn-expressing SKOV3 cells and 3D-tumor spheroids. RESULTS: All prepared NLCs showed homogenous dispersion (<220 nm in size) with a negative ZP (-18 to -22 mV), except for positively charged RIPL-NLCs (~10 mV), revealing no significant cytotoxicity in either SKOV3 or RAW 264.7 cell lines. cPEG-RIPL-NLC protein adsorption was 1.75-fold less than that of RIPL-NLCs, and PEGylation significantly reduced the macrophage uptake. PEG detachment from the cPEG-RIPL-NLCs was pH-sensitive and time dependent. At 2 hours incubation, cPEG-RIPL-NLCs and PEG-RIPL-NLCs exhibited comparable cellular uptake at pH 7.4, whereas cPEG-RIPL-NLC uptake was increased over 2-fold at pH 6.5. 3D-spheroid penetration also demonstrated pH-sensitivity: at pH 7.4, cPEG-RIPL-NLCs could not penetrate deep into the spheroid core region during 2 hours, whereas at pH 6.5, high fluorescence intensity in the core region was observed for both cPEG-RIPL-NLC-and RIPL-NLC-treated groups. CONCLUSION: cPEG-RIPL-NLCs are good candidates for Hpn-selective drug targeting in conjunction with pH-responsive PEG cleavage.

Association of miR-149 polymorphism with onset age and severity in Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by 1.5-fold increased dosage of the PMP22; however, onset age and severity vary considerably among patients. The exact reason behind these phenotypic heterogeneities has rarely been discovered yet. Because miRNAs are the key regulators of gene expression, we speculated that variants of miRNAs might be the genetic modifiers for CMT1A. This study noticed a common single nucleotide polymorphism (n.86T > C, rs2292832) in the miR-149 which was predicted to target several CMT causing genes including PMP22. The rs2292832 was located near the 3' end of the precursor microRNA of the miR-149. We performed an association study between the rs2292832 polymorphism and clinical phenotypes of CMT1A in subjects consisting of 176 unrelated Korean CMT1A patients and 176 controls. From this study, we observed that rs2292832 was closely associated to the onset age and severity of CMT1A. Particularly, the TC and CC genotypes were significantly associated with late onset and mild symptom. Therefore, we suggest that the rs2292832 variant in the miR-149 is a potential candidate as a genetic modifier which affects the phenotypic heterogeneity of CMT1A. This study may provide the first evidence that polymorphism in the miR gene is associated with the CMT1A phenotype.

Optimization of self-microemulsifying drug delivery system for phospholipid complex of telmisartan using D-optimal mixture design.

To improve the dissolution behavior of telmisartan (TMS), a poorly water-soluble angiotensin II receptor blocker, TMS-phospholipid complex (TPC) was prepared by solvent evaporation method and characterized by differential scanning calorimetry and powder X-ray diffractometry. The crystalline structure of TMS was transited into an amorphous state by TPC formation. The equilibrium solubility of TPC (1.3-6.1 mg/mL) in various vehicles was about 100 times higher than that of TMS (0.009-0.058 mg/mL). TPC-loaded self-microemulsifying drug delivery system (SMEDDS) formulation was optimized using the D-optimal mixture design with the composition of 14% Capryol 90 (oil; X1), 59.9% tween 80 (surfactant; X2), and 26.1% tetraglycol (cosurfactant; X3) as independent variables, which resulted in a droplet size of 22.17 nm (Y1), TMS solubilization of 4.06 mg/mL (Y2), and 99.4% drug release in 15 min (Y3) as response factors. The desirability function value was 0.854, indicating the reliability and accuracy of optimization; in addition, good agreement was found between the model prediction and experimental values of Y1, Y2, and Y3. Dissolution of raw TMS was poor and pH-dependent, where it had extremely low dissolution (< 1% for 2 h) in water, pH 4, and pH 6.8 media; however, it showed fast and high dissolution (> 90% in 5 min) in pH 1.2 medium. In contrast, the dissolution of the optimized TPC-loaded SMEDDS was pH-independent and reached over 90% within 5 min in all the media tested. Thus, we suggested that phospholipid complex formation and SMEDDS formulation using the experimental design method might be a promising approach to enhance the dissolution of poorly soluble drugs.

Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution.

As a platform for hepsin-specific drug delivery, we previously prepared IPLVVPLRRRRRRRRC peptide (RIPL)-conjugated nanostructured lipid carriers (RIPL-NLCs) composed of Labrafil® M 1944 CS (liquid oil) and Precirol® ATO 5 (solid lipid). In this study, to prevent the recognition by the mononuclear phagocyte system, polyethylene glycol (PEG)-modified RIPL-NLCs (PEG-RIPL-NLCs) were prepared using PEG3000 at different grafting ratios (1, 5, and 10 mole %). All prepared NLCs showed a homogeneous dispersion (130⁻280 nm), with zeta potentials varying from -18 to 10 mV. Docetaxel (DTX) was successfully encapsulated in NLCs: encapsulation efficiency (93⁻95%); drug-loading capacity (102⁻109 µg/mg). PEG-RIPL-NLCs with a grafting ratio of 5% PEG or higher showed significantly reduced protein adsorption and macrophage phagocytosis. The uptake of PEG(5%)-RIPL-NLCs by cancer cell lines was somewhat lower than that of RIPL-NLCs because of the PEG-induced steric hindrance; however, the uptake level of PEG-RIPL-NLCs was still greater than that of plain NLCs. In vivo biodistribution was evaluated after tail vein injection of NLCs to normal mice. Compared to RIPL-NLCs, PEG(5%)-RIPL-NLCs showed lower accumulation in the liver, spleen, and lung. In conclusion, we found that PEG(5%)-RIPL-NLCs could be a promising nanocarrier for selective drug targeting with a high payload of poorly water-soluble drugs.

Antifungal Activities of Dimeric Sesquiterpenes, Shizukaols C and F, Isolated from Chloranthus japonicus Sieb.

Two dimeric sesquiterpenes were separated from Chloranthus japonicus Sieb. and identified as shizukaols C and F. They exhibited potent antifungal activities (MICs = 4-16 µg/ml) in vitro against various plant pathogenic fungi (Pythium ultimum, Phytophthora infestans, Botrytis cinerea, Colletotrichum lagenarium, Alternaria kikuchiana, and Magnaporthe grisea). Shizukaol C showed 88% and 91% protective activities in the greenhouse against Puccinia recondita (wheat leaf rust) and Phytophthora infestans (tomato late blight), respectively, at 100 µg/ml; shizukaol F exhibited 93% antifungal activity against Puccinia recondita at the same concentration. Therefore, these compounds might serve as interesting candidates for effective antifungal agents.

Identification and characterization of an aquaporin 1 immunoreactive amacrine-type cell of the mouse retina.

Using immunocytochemistry, a type of amacrine cell that is immunoreactive for aquaporin 1 was identified in the mouse retina. AQP1 immunoreactivity was found in photoreceptor cells of the outer nuclear layer (ONL) and in a distinct type of amacrine cells of the inner nuclear layer (INL). AQP1-immunoreactive (IR) amacrine cell somata were located in the INL and their processes extended through strata 3 and 4 of the inner plexiform layer (IPL) with thin varicosities. The density of the AQP1-IR amacrine cells increased from 100/mm(2) in the peripheral retina to 350/mm(2) in the central retina. The AQP1-IR amacrine cells comprise 0.5% of the total amacrine cells. The AQP1-IR amacrine cell bodies formed a regular mosaic, which suggested that they represent a single type of amacrine cell. Double labeling with AQP1 and glycine, gamma-aminobutyric acid (GABA) or GAD(65) antiserum demonstrated that the AQP1-IR amacrine cells expressed GABA or GAD(65) but not glycine. Their synaptic input was primarily from other amacrine cell processes. They also received synaptic inputs from a few cone bipolar cells. The primary synaptic targets were ganglion cells, followed by other amacrine cells and cone bipolar cells. In addition, gap junctions between an AQP1-IR amacrine process and another amacrine process were rarely observed. In summary, a GABAergic amacrine cell type labeled by an antibody against AQP1 was identified in the mouse retina and was found to play a possible role in transferring a certain type of visual information from other amacrine or a few cone bipolar cells primarily to ganglion cells.

Inhibitory effects of Saururus chinensis and its components on stomach cancer cells.

Saururus chinensis (SC) Baill. (Saururaceae), a perennial herb commonly called Chinese lizard's tail or Sam-baekcho in Korea, has been used in the treatment of edema, gonorrhea, jaundice, and inflammatory diseases. Recently, several reports have been commissioned to examine the anti-cancer activities of this plant. In this study, we evaluated the inhibitory activity and mechanism of action on SC and its components against stomach cancer cells. SC extracts displayed cytotoxic effects on AGS cells in a dose-dependent manner. Moreover, SC increased the number of annexin V-positive apoptotic bodies and phosphorylated JNK and p38 in AGS cells. SC also down-regulated anti-apoptotic (Bcl-2) genes and up-regulated apoptotic (Bax) genes in AGS cells. We further confirmed that caspase activation plays an important role in SC-induced apoptosis in AGS cells. Furthermore, we examined erythro-Austrobailignan-6 and meso-dihydroguaiaretic acid, major active constituents of SC, which induced apoptosis in both the AGS and NCI-N87 stomach cancer cell lines. Taken together, our data provide the evidence that SC and its components induce apoptosis in stomach cancer cells, making it a potential candidate as a chemotherapeutic drug.

A Phenylpropanoid Glycoside as a Calcineurin Inhibitor Isolated from Magnolia obovata Thunb.

To identify plant-derived cell signaling inhibitors with antifungal properties, a twocomponent screening system using both wild-type Cryptococcus neoformans and a calcineurin mutant was employed owing to their counter-regulatory actions on the Hog1 mitogenactivated protein kinase and calcineurin pathways. Of the 2,000 plant extracts evaluated, a single bioactive compound from M. obovata Thunb. was found to act specifically on the calcineurin pathway of C. neoformans. This compound was identified as magnoloside A, and had potent antifungal activities against various Cryptococcus strains with minimum inhibitory concentration values ranging from 1.0 to 4.0 µg/ml.

Meso-dihydroguaiaretic acid induces apoptosis and inhibits cell migration via p38 activation and EGFR/Src/intergrin ß3 downregulation in breast cancer cells.

AIMS: Meso-dihydroguaiaretic acid (MDA) is known for its anti-inflammatory, anti-oxidant, anti-bacterial, and anti-tumor activity. However, the anti-breast cancer effect and the mechanism of MDA remain undefined. MAIN METHODS: In this study, we examined the anti-cancer activity and the mechanisms of action of MDA in breast cancer cell lines, 4T-1 and MCF-7 cells; and 4T-1 bearing mouse model. KEY FINDINGS: MDA showed cytotoxic effects on 4T-1 and MCF-7 cells in a dose-dependent manner. Moreover, MDA increased the amount of Annexin V-positive apoptotic bodies, phosphorylated JNK and p38 in 4T-1 cells. MDA also down-regulated cell-cycle dependent proteins, CDK-4 and cyclin D1; and induced cleaved caspase-3 in MDA-treated 4T-1 cells. We further verified that MDA-induced apoptosis is mediated by p38 and caspase-3 activation in 4T-1 cells. Next, we studied the effect of MDA treatment on cell migration and found that MDA significantly reduced cell migration. Moreover, MDA reduced EGFR and intergrin ß3 expression, and dephosphorylated Src in a dose-dependent manner in 4T-1 cells. Furthermore, we observed in vivo effect of MDA in 4T-1 cell inoculated mice. MDA (20mg/kg/day) significantly suppressed mammary tumor volume and activated caspase-3 in tumor tissues. SIGNIFICANCE: These results suggest novel targets of MDA in breast cancer in vitro and in vivo, making it a potential candidate as a chemotherapeutic drug.

Apios americana Medik Extract Alleviates Lung Inflammation in Influenza Virus H1N1- and Endotoxin-Induced Acute Lung Injury.

Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.