Development of a Nucleic Acid Lateral Flow Immunoassay for the Detection of Human Polyomavirus BK.

The BK virus (BKV) is an emerging pathogen in immunocompromised individuals and widespread in the human population. Polymerase chain reaction is a simple and highly sensitive method for detecting BKV, but it is time consuming and requires expensive instruments and expert judgment. The lateral flow assay, a rapid, low-cost, minimal-labor, and easy-to-use diagnostic method, was successfully applied for pathogen detection. In this study, we used oligonucleotide probes to develop a simple and rapid sandwich-type lateral flow immunoassay for detecting BKV DNA within 45 minutes. The detection limit for the synthetic single-stranded DNA was 5 nM. The specificity study showed no cross-reactivity with other polyomaviruses, such as JC virus and simian virus 40. For the Escherichia coli containing BKV plasmid cultured samples, the sensitivity was determined to be 107 copies/mL. The approach offers great potential for BKV detection of various target analytes in point-of-care settings.

Risk of suicide within 1 year of cancer diagnosis.

The association of the risk of suicide with cancer at different time points after a new cancer diagnosis is unclear. This study explored the suicide hazard at different time points after a first cancer diagnosis during the 1-year period before suicide. This case-crossover study included 2,907 suicide cases from 2002 to 2012 in Taiwan and compared the odds of suicide risk at different time points during one year after any cancer diagnosis with self-matched periods. The 13th month preceding the suicide date was used as the control period, and the hazard period was the duration from the 1st to 12th month in the conditional logistic regression for case-crossover comparisons. Among major groups of cancers, group of lip, oral cavity and pharynx cancers tended to have higher risk of suicide than other groups of cancers. The first month of cancer diagnosis was associated with the highest risk of suicide compared with the 13th month before suicide. The odds ratio (OR) of suicide were significantly in the first six months after cancer diagnosis but declined afterwards. For example, the adjusted OR was 3.47 [95% confidence interval (CI) = 2.60-4.62] in the first month and 1.53 (95% CI = 1.11-2.12) in the sixth month following cancer diagnosis. These findings provide clinicians with a vital reference period during which sufficient support and necessary referral to mental health support should be provided to reduce the risk of suicide among patients with newly diagnosed cancer morbidity.

Inappropriate self-medication among adolescents and its association with lower medication literacy and substance use.

BACKGROUND: While self-medication is common, inappropriate self-medication has potential risks. This study assesses inappropriate self-medication among adolescents and examines the relationships among medication literacy, substance use, and inappropriate self-medication. METHOD: In 2016, a national representative sample of 6,226 students from 99 primary, middle, and high schools completed an online self-administered questionnaire. Multiple logistic regression analysis was used to examine factors related to inappropriate self-medication. RESULTS: The prevalence of self-medication in the past year among the adolescents surveyed was 45.8%, and the most frequently reported drugs for self-medication included nonsteroidal anti-inflammatory drugs or pain relievers (prevalence = 31.1%), cold or cough medicines (prevalence = 21.6%), analgesics (prevalence = 19.3%), and antacids (prevalence = 17.3%). Of the participants who practiced self-medication, the prevalence of inappropriate self-medication behaviors included not reading drug labels or instructions (10.1%), using excessive dosages (21.6%), and using prescription and nonprescription medicine simultaneously without advice from a health provider (polypharmacy) (30.3%). The results of multiple logistic regression analysis showed that after controlling for school level, gender, and chronic diseases, the participants with lower medication knowledge, lower self-efficacy, lower medication literacy, and who consumed tobacco or alcohol were more likely to engage in inappropriate self-medication. CONCLUSION: Lower medication literacy and substance use were associated with inappropriate self-medication among adolescents.

Cross-sectional investigation of drug-related problems among adults in a medical center outpatient clinic: application of virtual medicine records in the cloud.

PURPOSE: To analyze and characterize data regarding the prevalence and types of outpatient drug-related problems (DRPs) found by clinical pharmacists after implementation of the Virtual Medicine Record in Cloud System (VMRCS). METHODS: A cross-sectional study regarding outpatient pharmaceutical care was conducted at a medical center in Taiwan. Patients aged >20 years old with multiple chronic diseases and polypharmacy were enrolled. In Stage I (1 October-31 December 2014), patients received pharmaceutical care according to prescription data accessed online in the VMRCS. In Stage II (1 June-31 August 2015), the VMRCS were pre-download and arranged to the institute's required format, facilitated DRP detection. Clinical pharmacists then reviewed and evaluated the prescription data through pre-downloaded VMRCS. Overall, 1539 and 1600 prescriptions were evaluated in these two stages, respectively. DRPs were recorded using the Pharmaceutical Care Network Europe (PCNE)-DRP. RESULTS: DRPs were found for 50.2% of patients in Stage I and 55.2% in Stage II (p < 0.05) and were most frequently encountered for "Drugs for the cardiovascular system" and caused by "Inappropriate duplication of therapeutic group or active ingredient." In terms of problems, incidence of "Unnecessary drug treatment" was highest. Duplicate medications were most frequently seen for "Drugs for acid-related disorders." The efficiency to identify DRPs was at least 2.4 times higher with pre-downloaded prescription data than with real-time online queries. CONCLUSIONS: With VMRCS, DRPs were more easily identified whether patients received medical care in the same hospital or not. DRPs could be efficiently prevented through the use of pre-downloaded patient prescription data. Copyright © 2016 John Wiley & Sons, Ltd.

Efficacy of Combined Ultrasound-and-Microbubbles-Mediated Diclofenac Gel Delivery to Enhance Transdermal Permeation in Adjuvant-Induced Rheumatoid Arthritis in the Rat.

A previous study that investigated the effect of ultrasound (US) on the transdermal permeation of the non-steroidal anti-inflammatory drug diclofenac found that therapeutic US can increase circulation in an inflamed joint and decrease arthritic pain. Transdermal drug delivery has recently been demonstrated by US combined with microbubbles (MB) contrast agent (henceforth referred to as "US-MB"). The present study evaluated the efficacy of US-MB-mediated diclofenac delivery for treating adjuvant-induced rheumatoid arthritis (RA) in rats. RA was induced by injecting 100 µL of complete Freund's adjuvant into the ankle joint of male Sprague-Dawley rats (250-300 g) that were randomly divided into five treatment groups: (i) carbopol gel alone (the control [group C]), (ii) diclofenac-carbopol gel (group D), (iii) US plus carbopol gel (group U), (iv) US plus diclofenac-carbopol gel (group DU) and (v) US-MB plus diclofenac-carbopol gel (group DUB). The ankle width was measured over 10 d using high-frequency (40-MHz) US B-mode and color Doppler-mode imaging, covering the period before and after treatment. Longitudinal US images of the induced RA showed synovitis and neovascularity. Only a small amount of neovascularity was observed after treatment. The recovery rate on day 10 was significantly higher in group DUB (97.7% ± 2.7%, mean ± standard deviation [SD]) than in groups C (1.0% ± 2.7%), D (37.5% ± 4.6%), U (75.5% ± 4.2%) and DU (87.3% ± 5.2%) (p < 0.05). The results obtained indicate that combining US and MB can increase the skin permeability and thereby enhance the delivery of diclofenac sodium gel and thereby inhibit inflammation of the tissues surrounding the arthritic ankle. Color Doppler-mode imaging revealed that US-MB treatment induced a rapid reduction in synovial neoangiogenesis in the arthritic area.

Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹8F]-ADAM/small-animal PET study.

The misuse of 3,4-methylenedioxymethamphetamine (MDMA) has drawn a growing concern worldwide for its psychophysiological impacts on humans. MDMA abusers are often accompanied by long-term serotonergic neurotoxicity, which is associated with reduced density of cerebral serotonin transporters (SERT) and depressive disorders. Resveratrol (RSV) is a natural polyphenolic phytoalexin that has been known for its antidepressant and neuroprotective effects. However, biological targets of RSV as well as its neuroprotective effects against MDMA remained largely unknown. In this study, we examined binding potency of RSV and MDMA to SERT using small-animal positron emission tomography (PET) with the SERT radioligand, N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) and investigated the protection of RSV against the acute and long-term adverse effects of MDMA. We found that RSV exhibit binding potentials to SERT in vivo in a dose-dependent manner with variation among brain regions. When the MDMA-treated rats (10mg/kg, s.c.) were co-injected with RSV (20mg/kg, i.p.) twice daily for 4 consecutive days, MDMA-induced acute elevation in plasma corticosterone was significantly reduced. Further, 4-[(18)F]-ADAM PET imaging revealed that RSV protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus 2 weeks following the co-treatment. The PET data were comparable to the observation from the forced swim test that RSV sufficiently ameliorated the depressive-like behaviors of the MDMA-treated rats. Together, these findings suggest that RSV is a potential antidepressant and may confer protection against neurobiological and behavioral changes induced by MDMA.

Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases.

Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits.

Pre-medication to improve esophagogastroduodenoscopic visibility: a meta-analysis and systemic review.

BACKGROUND/AIMS: The use of pre-medication to improve visibility in gastrointestinal endoscopy has not been well addressed and remains controversial. The aim is to evaluate the effects of current pre-medication on endoscopic visualization. METHODOLOGY: We made the overall strategies to search the different databases and assessed the quality of included studies according to the included and excluded standard. 1541 patients were treated with pre-medication. RESULT: Ten prospective studies involving 1541 patients were included. There was improved visibility in patients treated with Simethicone (weighted mean difference -4.3; 95% confidence interval (CI), -4.94 to -3.67), compared to those who did not use Simethicone. In the Simethicone based regiment, administration of Pronase was noted with significantly improved visibility in the location of antrum and fundus, compared to those who did not use; however, administration of N-acetyl-L-cysteine could not lead to significantly improved visibility. Simethicone offered better visibility than N-acetyl-L-cysteine and Pronase alone. CONCLUSIONS: There is improved visibility with pre-medication using Simethicone before esophagogastroduodenoscopy. In the Simethicone based regimen, administration of Pronase or N-acetyl-Lcysteine may be of little use in improving visibility. Based on the literature review, Simethicone dissolved in the water with the acceptably lowest ratio of 0.7 can still offer the good visibility but 30 mL of water should be avoided.

Improving anticancer efficacy of (-)-epigallocatechin-3-gallate gold nanoparticles in murine B16F10 melanoma cells.

(-)-Epigallocatechin-3-gallate (EGCG), the major bioactive constituent in green tea, has been reported to effectively inhibit the formation and development of tumors. To maximize the effectiveness of EGCG, we attached it to nanogold particles (EGCG-pNG) in various ratios to examine in vitro cytotoxicity and in vivo anti-cancer activity. EGCG-pNG showed improved anti-cancer efficacy in B16F10 murine melanoma cells; the cytotoxic effect in the melanoma cells treated with EGCG-pNG was 4.91 times higher than those treated with EGCG. The enhancement is achieved through mitochondrial pathway-mediated apoptosis as determined by annexin V assay, JC-10 staining, and caspase-3, -8, -9 activity assay. Moreover, EGCG-pNG was 1.66 times more potent than EGCG for inhibition of tumor growth in a murine melanoma model. In the hemolysis assay, the pNG surface conjugated with EGCG is most likely the key factor that contributes to the decreased release of hemoglobin from human red blood cells.

Efficacy of simethicone and N-acetylcysteine as premedication in improving visibility during upper endoscopy.

BACKGROUND: Simethicone and N-acetylcysteine have been widely used in improving endoscopic visibility. However, the optimal dose, volume, and dosing time for the premedication regimen are still unclear. AIM: Our aim was to assess the efficacy of premedication in improving endoscopic visibility and determine the contributions of dose, volume, and premedication time. METHODS: A total of 1849 patients were prospectively treated in three groups: group A: 100-mg simethicone suspension in 5 mL water; group B: 100-mg simethicone suspension in 100 mL water; and group C: 100-mg simethicone suspension in 100 mL water containing 200 mg N-acetylcysteine. Mucosa visibility was assessed at seven sites of upper gastrointestinal tract. The sum of scores was considered as total mucosal visibility score (TMVS). RESULTS: The upper body of stomach had the worst visibility score for all groups. TMVS of groups B and C were significantly lower than those of group A. Group C had a significantly fewer patients requiring endoscopic flushing than groups A and B. The TMVS for groups B and C were significantly lower than for group A within 30 min of beginning premedication. Beyond 30 min of premedication, there was no significant difference in the TMVS among groups. CONCLUSIONS: Premedication using 100 mg simethicone in 100 mL of water improves endoscopic visibility. Addition of N-acetylcysteine to simethicone in 100 mL of water reduces the need for endoscopic flushing. For patients unable to tolerate a large fluid volume, a 5-mL simethicone suspension administered more than 30 min prior to upper endoscopy is suggested.

Efficient downregulation of VEGF in retinal pigment epithelial cells by integrin ligand-labeled liposome-mediated siRNA delivery.

BACKGROUND: The purpose of this study was to demonstrate the effectiveness of an integrin peptide ligand-labeled liposomal delivery system loaded with vascular endothelial growth factor (VEGF)-siRNA in a model study of gene therapy for retinopathy using human retinal pigment epithelial cells. METHODS: Arg(R)-Gly(G)-Asp(D) motif peptide conjugating polyethylene glycol modified (RGD-PEGylated) liposomes were prepared using a thin-film hydration method and optimized for surface charge, particle size, small interfering RNA (siRNA) load, and entrapment efficiency. Reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine VEGF levels in retinal pigment epithelial cells. Cytotoxicity was determined using the 3-[4, 5-dimethylthiazol-2-yl]-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and flow cytometry. RESULTS: Physicochemical properties, including particle size, zeta potential, and siRNA load, of the prepared RGD-PEGylated liposomes and their entrapment efficiency were determined to be within the following ranges: 123.8-234.1 nm, 17.31-40.09 m V, 5.27%-6.33%, and >97%, respectively. RGD-PEGylated liposome-mediated fluorescent-labeled siRNA delivery demonstrated significantly enhanced cellular uptake, and 3 mol% RGD-PEGylated liposomes (having 3ß-[N-(N', N'-dimethylaminoethane) carbamoyl] cholesterol (DC-cholesterol) DSPE and DSPE-PEG(2000)-RGD with molar ratio of 50/47/3) were shown to have better efficacy with regard to specificity for retinal pigment epithelial cells, reduced cytotoxicity, and knockdown of the target molecule. CONCLUSION: By integrin receptor-mediated endocytosis, 3 mol% RGD-PEGylated liposomes were shown to be a suitable vector when loaded with VEGF-siRNA for efficient downregulation of VEGF in retinal pigment epithelial cells at both the protein and gene levels. This integrin ligand-modified liposomal delivery system has therapeutic potential for ocular gene therapy.

Erythropoietin protects adult retinal ganglion cells against NMDA-, trophic factor withdrawal-, and TNF-α-induced damage.

PURPOSE: This study aimed to evaluate the neuroprotective effect of EPO in the presence of N-methyl-d-aspartate (NMDA)-, trophic factor withdrawal (TFW)-, and tumor necrosis factor-alpha (TNF-α)-induced toxicity on total, small, and large retinal ganglion cells (RGCs). METHODS: Retinal cells from adult rats were cultured in a medium containing brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF), and forskolin. Expression of RGC markers and EPOR was examined using immunocytochemistry. RGCs were classified according to their morphological properties. Cytotoxicity was induced by NMDA, TFW, or TNF-α. RGC survival was assessed by counting thy-1 and neurofilament-l double-positive cells. RESULTS: EPO offered dose-dependent (EC50 = 5.7 ng/mL) protection against NMDA toxicity for small RGCs; protection was not significant for large RGCs. Time-course analysis showed that the presence of EPO either before or after NMDA exposure gave effective protection. For both small and large RGCs undergoing trophic factor withdrawal, EPO at concentrations of 1, 10, or 100 ng/mL improved survival. However, EPO had to be administered soon after the onset of injury to provide effective protection. For TNF-α-induced toxicity, survival of small RGCs was seen only for the highest examined concentration (100 ng/mL) of EPO, whereas large RGCs were protected at concentrations of 1, 10, or 100 ng/mL of EPO. Time-course analysis showed that pretreatment with EPO provided protection only for large RGCs; early post-treatment with EPO protected both small and large RGCs. Inhibitors of signal transduction and activators of transcription such as (STAT)-5, mitogen-activated protein kinases (MAPK)/extracellular-regulated kinase (ERK), and phosphatidyl inositol-3 kinase (PI3K)/Akt impaired the protective effect of EPO on RGCs exposed to different insults. CONCLUSION: EPO provided neuroprotection to cultured adult rat RGCs; however, the degree of protection varied with the type of toxic insult, RGC subtype, and timing of EPO treatment.

Influence of charge on FITC-BSA-loaded chondroitin sulfate-chitosan nanoparticles upon cell uptake in human Caco-2 cell monolayers.

BACKGROUND AND METHODS: Chondroitin sulfate-chitosan (ChS-CS) nanoparticles and positively and negatively charged fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA)-loaded ChS-CS nanoparticles were prepared and characterized. The properties of ChS-CS nanoparticles, including cellular uptake, cytotoxicity, and transepithelial transport, as well as findings on field emission-scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy were evaluated in human epithelial colorectal adenocarcinoma (Caco-2) fibroblasts. ChS-CS nanoparticles with a mean particle size of 250 nm and zeta potentials ranging from -30 to +18 mV were prepared using an ionic gelation method. RESULTS: Standard cell viability assays demonstrated that cells incubated with ChS-CS and FITC-BSA-loaded ChS-CS nanoparticles remained more than 95% viable at particle concentrations up to 0.1 mg/mL. Endocytosis of nanoparticles was confirmed by confocal laser scanning microscopy and measured by flow cytometry. Ex vivo transepithelial transport studies using Caco-2 cells indicated that the nanoparticles were effectively transported into Caco-2 cells via endocytosis. The uptake of positively charged FITC-BSA-loaded ChS-CS nanoparticles across the epithelial membrane was more efficient than that of the negatively charged nanoparticles. CONCLUSION: The ChS-CS nanoparticles fabricated in this study were effectively endocytosed by Caco-2 fibroblasts without significant cytotoxicity at high nanoparticle concentrations. ChS-CS nanoparticles represent a potential novel delivery system for the transport of hydrophilic macromolecules.

The preparation and characterization of gold-conjugated polyphenol nanoparticles as a novel delivery system.

Nanogold particles are commonly used in nanomedicine. We generated physical nanogold (pNG) conjugated with different ratios of epigallocatechin-3-gallate (EGCG) and evaluated its physicochemical properties, antioxidant activity, and cytotoxicity in vitro as well as anticancer activity in vivo. Results showed that the EGCG-pNG conjugates were successfully prepared at ratios between 23:1 and 23:5, with the percentage of EGCG content increasing with the EGCG:pNG ratio from 23:1 (2.0% ± 0.02%) to 23:5 (28% ± 0.3%). EGCG-pNG particles at ratios of 23:1 and 23:5 demonstrated significantly decreased size from 500 to 20 nm and decreasing zeta potentials of 21 mV to -22 mV, respectively. At a ratio of 23:2.5, the EGCG-pNG particles (27% EGCG, 50 nm in size, zeta potential of -8 mV) showed longer EGCG activity half-life (110 days vs 5 hours), controlled release (2 hours vs 30 minutes), and higher antioxidant activity (four times), as well as inhibition of tumor cell growth, than controls. The present study indicated that EGCG-pNG possesses promising therapeutic potential, based on its strong free-radical scavenging and anticancer activities.

Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy.

Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of current clinically approved liposome-based drugs with free drugs, and to also determine the clinical effect via liposomal variations in lipid composition. Furthermore, the major preclinical and clinical data related to the principal liposomal formulations are also summarized.

Doctor pharmaceutical utilization behaviour changed by the global budget programme strategies on hypertensive outpatient prescription.

RATIONALE, AIMS AND OBJECTIVES: This study was to examine changes in doctor pharmaceutical utilization behaviour in response to Taiwan's newly implemented National Health Insurance individual hospital global budget (GB) programme and the changes in health care costs and prescription trends for hypertensive (HT) patients. METHOD: We analysed hospital outpatient prescription utilization with a pre-post individual hospital GB group and comparison group (the hospitals who did not join the programme) to evaluate the impact of GB strategies on hypertensive expenditure. Descriptive analyses were performed based on the average daily medication expenditure for each prescription, and average number of items per prescription. RESULTS: This study reviewed 16,770,057 outpatient records and prescription records of 213,568 hypertensive patients. The average total medication expense (+17.6%), HT medication expense (+8.8%), daily medication expense (+16.3%), and daily HT medication expense (+6.3%) significantly increased after the action. After the individual hospital GB action, hospital doctors participating in action switched their patients' prescription drugs to other less expensive drugs such as rennin-angiotensin-aldosterone system inhibitors (-1.1%). The increase in volume of medications prescribed for control group were significantly larger for both alfa- and beta-adrenergic blocking agents (1.5%), and calcium channel blocking agents (3.9%). CONCLUSION: The individual hospital GB programme slowed down the trend of prescription drug cost increasing rate and reduced the prescription drug volume in hospitals.

The treatment of bladder cancer in a mouse model by epigallocatechin-3-gallate-gold nanoparticles.

(--)-Epigallocatechin-3-gallate (EGCG), an active ingredient in green tea, was known to effectively inhibit formation and development of tumors. However, excessive uptake of EGCG was also known to cause cytotoxicity to normal cells. In this study, EGCGs that were physically attached onto the surface of nanogold particles (pNG) was confirmed by scanning electron microscopy. The anticancer activity of the EGCG-adsorbed pNG was investigated in C3H/HeN mice subcutaneously implanted with MBT-2 murine bladder tumor cells. EGCG-pNG was confirmed to inhibit tumor cell growing by means of cell apoptosis. The mechanism that EGCG-pNG mediates tumor apoptosis was uncovered to activate the caspase cascade through the Bcl-family proteins in the mitochondrial pathway. Additionally, the mechanism that tumors were suppressed by injecting EGCG-pNG directly into the tumor site was determined to be through downregulation of VEGF, whereas that by oral administration of EGCG was through reversing immune suppression upon cancer progression. In this assessment, the prepared EGCG-pNG was confirmed to be more effective than free EGCG in inhibiting bladder tumor in model mice.

Erythropoiesis-stimulating protein delivery in providing erythropoiesis and neuroprotection.

Erythropoietin (EPO), a glycoprotein, plays an important role in erythropoiesis and neuroprotection. EPO therapies for anemia or neurodegenerative diseases require frequent injections or high-dose systemic administration which may cause unwanted side effects. Various strategies for EPO delivery have been investigated for increasing EPO bioavailability and decreasing side effects, including nano/micro particles, PEGylation of EPO and transport-mediated delivery systems. Nano/micro particles provide EPO with long-term effect and protect EPO against proteolytic cleavage. PEGylated EPO prolong circulating time and reduce injection frequency of anemia treatment. A transport-mediated delivery system enables protein to cross biological barriers. Presently, there is no report about an effective delivery system of EPO for neuroprotection. This review focuses on EPO delivery systems for erythropoiesis or neuroprotection with prolonged duration and enhanced bioavailability.

Association of cortactin and fascin-1 expression in gastric adenocarcinoma: correlation with clinicopathological parameters.

Cortactin and fascin-1 are important factors in tumor progression. We tested the hypothesis that cortactin and fascin-1 expression correlates with clinicopathological parameters of gastric adenocarcinoma. Immunohistochemical analysis of cortactin and fascin-1 was done using tissue microarrays of 100 surgical specimens, including 20 well-differentiated, 20 moderately differentiated, and 60 poorly differentiated gastric adenocarcinomas. Among the 20 well-differentiated gastric adenocarcinomas, 15 cases (75%) showed negative or weak staining (1+); 5 cases (25%) had moderate (2+) or strong (3+) cortactin expression. Among the 60 poorly differentiated gastric adenocarcinomas, more than three-quarters of the cases (76.7%) had moderate or strong cortactin expression; 14 cases (23.3%) had weak staining. Of 20 well-differentiated gastric adenocarcinoma cases, 14 (70%) showed negative or weak staining of fascin-1, whereas nearly one-third (30%) had moderate or strong expression. Among the 60 poorly differentiated gastric adenocarcinomas, 32 (53.3%) exhibited moderate or strong fascin-1 expression; fewer than half of the cases showed negative or weak staining. Higher intensity of cortactin and fascin-1 staining correlated directly with more-advanced cancer stages (TNM) and inversely with survival rates. Our findings suggest the possibility that pharmacological inhibitors of cortactin and fascin-1 activity may slow down tumor progression and prolong survival time in patients with gastric adenocarcinomas.

Contribution of poly(amino acids) to advances in pharmaceutical biotechnology.

Recently, protein biotechnology generates tremendous impacts in therapeutic products. These products include enzymes, antibodies, hormones, blood factors, growth factors and regulatory factors. Protein, vaccine and gene therapy drugs could be formulated with suitable biomaterials to deliver active agents to their target sites at the right time and maintain therapeutic effects for proper durations. In this review article, we focus on poly(amino acids) or polymerized amino acids for their applications in drug delivery systems, vaccines, and gene therapy. The nomenclatures of poly(amino acids) are briefly introduced to systematically express synthetic polypeptides. In drug delivery systems, we introduce two applications of poly(amino acids) in pharmaceutical biotechnology, either as carriers to facilitate drug delivery, or as biomaterials to be formulated as suitable delivery systems for application in tissue engineering. Many short polypeptides are mapped from antigen motifs and used for vaccination. These poly(amino acids) provide protective effects in animal challenge tests and potential application in vaccine development to be briefly introduced. Finally, some reports related to new developed poly(amino acids) as DNA carriers for achieving gene delivery are also described in the text.