Showing papers by "Fu Jen Catholic University published in 2018"

Current Mechanistic Concepts in Ischemia and Reperfusion Injury.

Abstract: Ischemia-reperfusion injury is associated with serious clinical manifestations, including myocardial hibernation, acute heart failure, cerebral dysfunction, gastrointestinal dysfunction, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Ischemia-reperfusion injury is a critical medical condition that poses an important therapeutic challenge for physicians. In this review article, we present recent advances focusing on the basic pathophysiology of ischemia-reperfusion injury, especially the involvement of reactive oxygen species and cell death pathways. The involvement of the NADPH oxidase system, nitric oxide synthase system, and xanthine oxidase system are also described. When the blood supply is re-established after prolonged ischemia, local inflammation and ROS production increase, leading to secondary injury. Cell damage induced by prolonged ischemia-reperfusion injury may lead to apoptosis, autophagy, necrosis, and necroptosis. We highlight the latest mechanistic insights into reperfusion-injury-induced cell death via these different processes. The interlinked signaling pathways of cell death could offer new targets for therapeutic approaches. Treatment approaches for ischemia-reperfusion injury are also reviewed. We believe that understanding the pathophysiology ischemia-reperfusion injury will enable the development of novel treatment interventions.

Which students benefit most from a flipped classroom approach to language learning

Abstract: Research has shown that the potential benefits of a flipped classroom could be diminished by the way students perceive and prepare information prior to class. This study aims to explore individual characteristics, such as learner motivation, self-efficacy and epistemology beliefs, that might have an impact on learning outcomes in a flipped classroom. Data were collected using four instruments during a 7-week flipped classroom conducted from mid-September 2014 to mid-November 2014 with a total enrolment of 85 students (10 females and 75 males) in the required course, Applied English for Vocational Education. After controlling for pre-test and other covariates (eg, gender, grade and experience), an analysis based on structural equation modeling showed a positive and significant (β = 0.12, p < 0.05) indirect effect of instrumentality (promotion) on the change in test scores through averaged quiz scores. Beliefs had a significant positive effect on change in scores between pre- and post-tests (β = 0.20, p < 0.05). Findings revealed that language learners with a high level of motivation in instrumentality (promotion) followed quiz mechanisms closely and thus benefited most from the flipped classroom. Learners with high beliefs exhibited improvement in the post-tests without doing well in quizzes. The implications for a flipped language learning classroom are discussed, including multiple strategies for regulating learners of different personal traits to preview the online course content before class.

Fecal microbiota transplantation confers beneficial metabolic effects of diet and exercise on diet-induced obese mice

Abstract: Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity.

Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120.

Abstract: Uremic toxins, such as indoxyl sulfate (IS) and p-cresol, or p-cresyl sulfate (PCS), are markedly accumulated in the organs of chronic kidney disease (CKD) patients These toxins can induce inflammatory reactions and enhance oxidative stress, prompting glomerular sclerosis and interstitial fibrosis, to aggravate the decline of renal function Consequently, uremic toxins play an important role in the worsening of renal and cardiovascular functions Furthermore, they destroy the quantity and quality of bone Oral sorbent AST-120 reduces serum levels of uremic toxins in CKD patients by adsorbing the precursors of IS and PCS generated by amino acid metabolism in the intestine Accordingly, AST-120 decreases the serum IS levels and reduces the production of reactive oxygen species by endothelial cells, to impede the subsequent oxidative stress This slows the progression of cardiovascular and renal diseases and improves bone metabolism in CKD patients Although large-scale studies showed no obvious benefits from adding AST-120 to the standard therapy for CKD patients, subsequent sporadic studies may support its use This article summarizes the mechanisms of the uremic toxins, IS, and PCS, and discusses the multiple effects of AST-120 in CKD patients

Management of gout and hyperuricemia: Multidisciplinary consensus in Taiwan.

Abstract: Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long-term urate-lowering treatment. Urate-lowering drugs should be used during the inter-critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate-lowering therapy should aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi, the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi dissolution. The goal of this consensus paper was to improve gout and hyperuricemia management at a more comprehensive level. The content of this consensus paper was developed based on local epidemiology and current clinical practice, as well as consensuses from two multidisciplinary meetings and recommendations from Taiwan Guideline for the Management of Gout and Hyperuricemia.

The interplay of reactive oxygen species and the epidermal growth factor receptor in tumor progression and drug resistance.

Abstract: The epidermal growth factor receptor (EGFR) plays important roles in cell survival, growth, differentiation, and tumorigenesis. Dysregulation of the EGFR is a common mechanism in cancer progression especially in non-small cell lung cancer (NSCLC). Suppression of the EGFR-mediated signaling pathway is used in cancer treatment. Furthermore, reactive oxygen species (ROS)-induced oxidative stress from mitochondrial dysfunction or NADPH oxidase (NOX) overactivation and ectopic expression of antioxidative enzymes were also indicated to be involved in EGFR-mediated tumor progression (proliferation, differentiation, migration, and invasion) and drug resistance (EGFR tyrosine kinase inhibitor (TKI)). The products of NOX, superoxide and hydrogen peroxide, are considered to be major types of ROS. ROS are not only toxic materials to cells but also signaling regulators of tumor progression. Oxidation of both the EGFR and downstream phosphatases by ROS enhances EGFR-mediated signaling and promotes tumor progression. This review primarily focuses on the recent literature with respect to the roles of the EGFR and ROS and correlations between ROS and the EGFR in tumor progression and EGFR TKI resistance. The evidence discussed in this article can serve as a basis for basic and clinical research to understand how to modulate ROS levels to control the development and drug resistance of cancers.

Revisiting the Advances in Isolation, Characterization and Secretome of Adipose-Derived Stromal/Stem Cells.

Abstract: Adipose-derived stromal/stem cells (ASCs) seems to be a promising regenerative therapeutic agent due to the minimally invasive approach of their harvest and multi-lineage differentiation potential. The harvested adipose tissues are further digested to extract stromal vascular fraction (SVF), which is cultured, and the anchorage-dependent cells are isolated in order to characterize their stemness, surface markers, and multi-differentiation potential. The differentiation potential of ASCs is directed through manipulating culture medium composition with an introduction of growth factors to obtain the desired cell type. ASCs have been widely studied for its regenerative therapeutic solution to neurologic, skin, wound, muscle, bone, and other disorders. These therapeutic outcomes of ASCs are achieved possibly via autocrine and paracrine effects of their secretome comprising of cytokines, extracellular proteins and RNAs. Therefore, secretome-derivatives might offer huge advantages over cells through their synthesis and storage for long-term use. When considering the therapeutic significance and future prospects of ASCs, this review summarizes the recent developments made in harvesting, isolation, and characterization. Furthermore, this article also provides a deeper insight into secretome of ASCs mediating regenerative efficacy.

Drivers of consumers’ behavioral intention toward green hotels

Abstract: Purpose This study explores the relationships among consumers’ environmental value, low-carbon knowledge, perceived value of green hotels, and behavioral intention to stay in green hotels as well as willingness to cooperate with green hotels’ environmentally friendly practices. Design/methodology/approach Structural equation modeling and indirect effect estimation through bootstrapping technique were performed using 415 valid questionnaires collected from customers who had green hotel stay experiences in Taiwan. Findings The analytical results indicate that environmental value and low-carbon knowledge positively affect perceived value of green hotels, which in turn positively affect consumers’ behavioral intention to stay in green hotels and willingness to cooperate with green hotels’ environmentally friendly practices. Perceived value of green hotels also partially mediates the effects of environmental value and low-carbon knowledge on two behavioral intention variables. Practical implications This study...

Antrodia cinnamomea reduces obesity and modulates the gut microbiota in high-fat diet-fed mice

Abstract: Obesity is associated with gut microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Given the high and increasing prevalence of obesity worldwide, anti-obesity treatments that are safe, effective and widely available would be beneficial. We examined whether the medicinal mushroom Antrodia cinnamomea may reduce obesity in mice fed with a high-fat diet (HFD). Male C57BL/6J mice were fed a HFD for 8 weeks to induce obesity and chronic inflammation. The mice were treated with a water extract of A. cinnamomea (WEAC), and body weight, fat accumulation, inflammation markers, insulin sensitivity and the gut microbiota were monitored. After 8 weeks, the mean body weight of HFD-fed mice was 39.8±1.2 g compared with 35.8±1.3 g for the HFD+1% WEAC group, corresponding to a reduction of 4 g or 10% of body weight (P<0.0001). WEAC supplementation reduced fat accumulation and serum triglycerides in a statistically significant manner in HFD-fed mice. WEAC also reversed the effects of HFD on inflammation markers (interleukin-1β, interleukin-6, tumor necrosis factor-α), insulin resistance and adipokine production (leptin and adiponectin). Notably, WEAC increased the expression of intestinal tight junctions (zonula occludens-1 and occludin) and antimicrobial proteins (Reg3g and lysozyme C) in the small intestine, leading to reduced blood endotoxemia. Finally, WEAC modulated the composition of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio and increasing the level of Akkermansia muciniphila and other bacterial species associated with anti-inflammatory properties. Supplementation with A. cinnamomea produces anti-obesogenic, anti-inflammatory and antidiabetic effects in HFD-fed mice by maintaining intestinal integrity and modulating the gut microbiota.

Drug survival of biologics in treating psoriasis: a meta-analysis of real-world evidence.

Abstract: Drug survival of biologics represents their real-world effectiveness and safety. We conducted a meta-analysis of real-world evidence on the drug survival of biologics in treating psoriasis. We searched the PubMed, CENTRAL, and EMBASE databases from inception to 7th October 2017 for studies reporting the annual drug survival for at least 1 year. Two authors independently screened and selected relevant studies, and assessed their risk of bias. A third author was available for arbitrating discrepancies. We conducted a random-effects model meta-analysis to obtain the respective pooled drug survival from year 1 to 4. We conducted subgroup analysis on biologic-naive subjects, discontinuation for loss of efficacy and adverse effects. We included 37 studies with 32,631 subjects. The drug survival for all biologics decreased with time, dropping from 66% at year 1 to 41% at year 4 for etanercept, from 69% to 47% for adalimumab, from 61% to 42% for infliximab, and from 82% to 56% for ustekinumab. Ustekinumab was associated with the highest drug survival in all and biologic-naive subjects. Etanercept was associated with the lowest drug survival and was most commonly discontinued for loss of efficacy. Infliximab was most frequently associated with discontinuation for adverse effects. Clinicians may use this study as a reference in treating psoriasis.

A Contract Game for Direct Energy Trading in Smart Grid

Abstract: Direct trading is a promising approach to simultaneously achieve trading benefits and reduce transmission line losses in smart grid However, due to the selfish nature, small-scale electricity suppliers (SESs) and electricity consumers (ECs) will not participate direct trading if the trading does not bring them benefits Therefore, how to provide proper economic incentives for these two parties to take part in direct trading is an essential issue Nevertheless, the asymmetry trading information between them makes the problem challenging In this paper, we propose a contract-based direct trading framework to tackle this challenge, in which the decision making process of ECs and SESs in the presence of asymmetric information is modeled as a contract game In the proposed game, the EC designs a contract which contains its trading strategies toward all types of SESs Through the contract, the EC not only attracts SESs to sell electricity but also maximizes its own revenue The SESs, on the other hand, get maximal benefits if they truthfully select the contract items of their own types We derive theoretically the optimal contract for the short-term market where the supply of SESs is deterministic Then we extend our study to the long-term market where the supply of SESs is encountering significant uncertainty Finally, simulation results are shown to verify the effectiveness of the proposed scheme

First-line Helicobacter pylori eradication therapies in countries with high and low clarithromycin resistance: a systematic review and network meta-analysis.

Abstract: Objective To determine the optimal regimen of different first-line Helicobacter pylori eradication therapies according to the clarithromycin resistance rate. Design Electronic search for articles published between January 2005 and April 2016. Randomised, controlled trials that reported the effectiveness of first-line eradication therapies in treatment-naive adults were included. Two independent reviewers performed articles screening and data extraction. Network and traditional meta-analyses were conducted using the random effect model. Subgroup analyses were performed to determine the ranking of regimens in countries with high (>15%) and low ( Results 117 trials (totally 32 852 patients) for 17 H. pylori eradication regimens were eligible for inclusion. Compared with 7-day clarithromycin-based triple therapy, sequential therapy (ST) for 14 days had the highest effectiveness (OR=3.74, 95% CrI 2.37 to 5.96). ST-14 (OR=6.53, 95% CrI 3.23 to 13.63) and hybrid therapy (HY) for 10 days or more (OR=2.85, 95% CrI 1.58 to 5.37) represented the most effective regimen in areas with high and low clarithromycin resistance, respectively. The effectiveness of standard triple therapy was below therapeutic eradication rate in most of the countries. Longer duration was associated with higher eradication rate, but with a higher risk of events that lead to discontinuation. Conclusions ST and HY appeared to be the most effective therapies in countries with high and low clarithromycin resistance, respectively. The clinical decision for optimal regimen can be supported by referring to the rank ordering of relative efficacies stratified by local eradication rates, antibiotic resistance and safety profile. Trial registration number CRD42015025445.

Mineral bone disorders in chronic kidney disease.

Abstract: As the GFR loss aggravates, the disturbed mineral metabolism worsens the bone microstructure and remodelling - scenario, which is known as CKD-mineral bone disease (MBD). CKD-MBD is characterized by : (i) abnormal metabolism of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; (ii) abnormalities in bone turnover, mineralization, volume linear growth or strength; (iii) soft-tissue calcifications, either vascular or extra-osseous. Uremic vascular calcification and osteoporosis are the most common complications related to CKD-MBD. Disregulated bone turnover by uremic toxin or secondary hyperparathyroidism disturbed bone mineralization and makes it difficult for calcium and inorganic phosphate to enter into bone, resulting in increased serum calcium and inorganic phosphate. Vascular calcification worsens by hyperphosphatemia and systemic inflammation. Since vitamin D deficiency plays an important role in renal osteodystrophy, supplement of nutritional vitamin D is important in treating uremic osteoporosis and vascular calcification at the same time. Its pleotropic effect improves the bone remodeling initiated by osteoblast and alleviates the risk factors for vascular calcification with less hypercalcemia than vitamin D receptor analogs. Therefore, nutritional vitamin D should be considered in managing CKDMBD.

Depolying Tunable Metal-Shell/Dielectric Core Nanorod Arrays as the Virtually Perfect Absorber in the Near-Infrared Regime.

Abstract: In this paper, the coupled Ag-shell/dielectric-core nanorod for sensor application is investigated and the different dielectric core plasmonic metamaterial is adopted in our design. The operational principle is based on the concept of combining the lattice resonance, localized surface plasmon resonance (SPR), and cavity plasmon resonance modes within the nanostructure. The underlying mechanisms are investigated numerically by using the three-dimensional finite element method and the numerical results of coupled solid Ag nanorods are included for comparison. The characteristic absorptance/reflectance peaks/dips have been demonstrated to be induced by different plasmonic modes that could lead to different responses required for plasmonic sensors. A nearly perfect absorptance and an approximate zero reflectance with a sharp band linewidth are obtained from the proposed system, when operated as an SPR sensor with the sensitivity and figure of merit of 757.58 nm/RIU (RIU is the refractive index unit) and 50.51...

Face Liveness Detection Using a Flash Against 2D Spoofing Attack

Abstract: Face recognition technique has been widely applied to personal identification systems due to its satisfying performance. However, its security may be a crucial issue, since many studies have shown that face recognition systems may be vulnerable in an adversarial environment, in which an adversary can camouflage as a legitimate user in order to mislead the system. Although face liveness detection methods have been proposed to distinguish real and fake faces, they are either time-consuming, costly, or sensitive to noise and illumination. This paper proposes a face liveness detection method with flash against 2D spoofing attack. Flash not only can enhance the differentiation between legitimate and illegitimate users, but it also reduces the influence of environmental factors. Two images are taken from a subject, one with flash and another without flash. Four texture and 2D structure descriptors with low computational complexity are used to capture information of the two images in our model. Advantages of our method include low installation cost of flash and no user cooperation required. A data set of 50 subjects collected under different scenarios is used in the experiments to evaluate the proposed method. The experimental results indicate that the proposed model performs better than existing liveness detection methods in different environmental scenarios. This paper confirms that the use of flash successfully improves face liveness detection in terms of accuracy, robustness, and running time.

Resource Allocation for 5G Heterogeneous Cloud Radio Access Networks With D2D Communication: A Matching and Coalition Approach

Abstract: Device-to-Device (D2D) communication is a promising technology toward the fifth generation mobile communication. However, when D2D communication is incorporated into heterogeneous cloud radio access network (H-CRAN), the interference management between the D2D users and current users is a challenge. In this paper, we study how to assign the sub-channels of different bandwidth to multiple D2D pairs and the remote radio head users. In such a way, the sub-channels that have been pre-allocated to macro-cell users can be reused, the system performance can be maximized while the quality of service of all users can be guaranteed. Such a resource allocation problem is formulated as a mixed integer nonlinear programming (MINLP) problem which is NP-hard. To obtain the solution, the proposed problem is reformulated into a many-to-one matching sub-game with externality followed by a coalition sub-game. Then, a constrained deferred acceptance algorithm and a coalition formation algorithm are proposed to find solutions to these two sequential sub-games, respectively. Finally, we prove theoretically that both the proposed algorithms can convergent with a low computational complexity. Numerical results demonstrate that compared with existing resource allocation schemes, our proposed scheme can significantly improve the system performance in terms of overall throughput, the total number of admitted users and fairness.

Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells.

Abstract: Quercetin is one of the natural components from natural plant and it induces cell apoptosis in many human cancer cell lines. However, no available reports show that quercetin induces apoptosis and altered associated gene expressions in human gastric cancer cells, thus, we investigated the effect of quercetin on the apoptotic cell death and associated gene expression in human gastric cancer AGS cells. Results indicated that quercetin induced cell morphological changes and reduced total viability via apoptotic cell death in AGS cells. Furthermore, results from flow cytometric assay indicated that quercetin increased reactive oxygen species (ROS) production, decreased the levels of mitochondrial membrane potential (ΔΨm ), and increased the apoptotic cell number in AGS cells. Results from western blotting showed that quercetin decreased anti-apoptotic protein of Mcl-1, Bcl-2, and Bcl-x but increased pro-apoptotic protein of Bad, Bax, and Bid. Furthermore, quercetin increased the gene expressions of TNFRSF10D (Tumor necrosis factor receptor superfamily, member 10d, decoy with truncated death domain), TP53INP1 (tumor protein p53 inducible nuclear protein 1), and JUNB (jun B proto-oncogene) but decreased the gene expression of VEGFB (vascular endothelial growth factor B), CDK10 (cyclin-dependent kinase 10), and KDELC2 (KDEL [Lys-Asp-Glu-Leu] containing 2) that are associated with apoptosis pathways. Thus, those findings may offer more information regarding the molecular, gene expression, and signaling pathway for quercetin induced apoptotic cell death in human gastric cancer cells.

Boosting employee retention through CSR: A configurational analysis

Abstract: Internal stakeholders' perception of corporate social responsibility (CSR) plays a crucial role for organizations in pursuing innovative, sustainability‐based business models. The majority of research on CSR has examined its effects on organizations' financial performance or external stakeholders' behavior toward CSR. However, little attention has been devoted to employees' behavior toward CSR. The current study investigated how organizations' CSR initiatives and the fulfillment of employee job needs (existence, relatedness and growth, or ERG) affect employees' job satisfaction and retention intention. Methodologically, the study applied the fuzzy‐set qualitative comparative analysis method to capture the integrative effects of explanatory factors on the outcomes by examining the case of a leading chain department store in Asia. The results revealed that an organization's efforts on CSR could enhance the fulfillment of employees' ERG needs. Moreover, the perceived CSR initiatives could generate positive effects on employees' satisfaction and retention intention by fulfilling employees' ERG needs.

ECG Data Encryption Then Compression Using Singular Value Decomposition

Abstract: Electrocardiogram (ECG) monitoring systems are widely used in healthcare. ECG data must be compressed for transmission and storage. Furthermore, there is a need to be able to directly process biomedical signals in encrypted domains to ensure the protection of patients’ privacy. Existing encryption-then-compression (ETC) approaches for multimedia using the state-of-the-art encryption techniques inevitably sacrifice the compression efficiency or signal quality. This paper presents the first ETC approach for processing ECG data. The proposed approach not only can protect data privacy but also provide the same quality of the reconstructed signals without sacrificing the compression efficiency relative to unencrypted compressions. Specifically, the singular value decomposition technique is used to compress the data such that the proposed system can provide quality-control compressed data, even though the data has been encrypted. Experimental results prove the proposed system to be an effective technique for assuring data security as well as compression performance for ECG data.

Plasmonic effects in composite metal nanostructures for sensing applications

Abstract: We have investigated numerically the plasmonic effect on a two-dimensional periodic array of metallic nanostructures. The unit cell of the array has an Ag nanosphere and nanorod pair formed in a single structure. Three-dimensional finite element method is used for the study on the sensing performance within the optical spectra. The study takes into account the influences of the structural and material parameters, the rotational angle of the metal nanostructure, the number of metal nanostructure per unit cell, and the localized surface plasmon resonances. The proposed nanostructures function as a refractive index sensor with a sensitivity of 400 nm/RIU (RIU is the refractive index unit), showing the characteristics of low transmittance (T = 3.90%), high absorptance (A = 94.5%), and near-zero reflectance (R = 0.15%), could be achieved by a triangular arrangement of nanostructures within a unit cell. We also show how the tailoring of the structural parameters relates to the specific sensing schematics of the sensor.

Post-treatment with PT302, a long-acting Exendin-4 sustained release formulation, reduces dopaminergic neurodegeneration in a 6-Hydroxydopamine rat model of Parkinson's disease.

Abstract: We previously demonstrated that pretreatment with Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) –mediated dopaminergic neurodegeneration. The use of GLP-1 or Exendin-4 for Parkinson’s disease (PD) patients is limited by their short half-lives. The purpose of this study was to evaluate a new extended release Exendin-4 formulation, PT302, in a rat model of PD. Subcutaneous administration of PT302 resulted in sustained elevations of Exendin-4 in plasma for >20 days in adult rats. To define an efficacious dose within this range, rats were administered PT302 once every 2 weeks either before or following the unilaterally 6-hydroxydopamine lesioning. Pre- and post-treatment with PT302 significantly reduced methamphetamine–induced rotation after lesioning. For animals given PT302 post lesion, blood and brain samples were collected on day 47 for measurements of plasma Exendin-4 levels and brain tyrosine hydroxylase immunoreactivity (TH-IR). PT302 significantly increased TH-IR in the lesioned substantia nigra and striatum. There was a significant correlation between plasma Exendin-4 levels and TH-IR in the substantia nigra and striatum on the lesioned side. Our data suggest that post-treatment with PT302 provides long-lasting Exendin-4 release and reduces neurodegeneration of nigrostriatal dopaminergic neurons in a 6-hydroxydopamine rat model of PD at a clinically relevant dose.