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Kaohsiung City is the largest harbor city in Taiwan. The Linhai Special Industrial Complex (LSIC), which is the largest heavy industrial zone in Taiwan, and other industrial zones and storage station of petrochemicals are adjacent to the Kaohsiung Port. Volatile organic compounds (VOCs), which are discharged from industrial processes in this large industrial area, are likely to cause the poor ambient air quality and atmospheric visibility in Kaohsiung City. This study uses the continuous monitoring data of 54 VOCs during 2018-2020 at eight air quality monitoring stations in the industrialized city to evaluate the spatiotemporal distributions and seasonal variations of VOC concentrations. Principal component analysis and ratios of benzene, toluene, ethylbenzene and xylenes (BTEX) are used to track the potential sources of VOCs for different stations. The highest average concentration of total volatile organic compounds (TVOC) was observed in winter (32.54 ppb), while the lowest TVOC concentration was observed in summer (25.84 ppb), which is related to the prevailing wind directions of monsoons. Kaohsiung is located in the weak monsoon wake area, and air pollutants are easily accumulated in the winter. The southwest wind prevailing in summer results in good diffusion and frequent rainfalls. However, the Qijin station close to the seashore has the highest average TVOC concentration among the eight stations. The seasonal prevailing winds caused the average TVOC concentrations in summer (41.3 ppb) to be higher than that in winter (31.62 ppb) at the Qijin station. It was attributed to the fact that the Qijin Peninsula is vulnerable to VOC emissions from ship sailing in the Taiwan Strait, the processing and export zone, and the shipbuilding yards nearby the Kaohsiung Harbor. Comparing the BTEX ratios of Kaohsiung City with the data of Hong Kong, we found that VOCs were mainly from industrial emissions in Kaohsiung City, which were significantly different from Hong Kong that VOCs were mainly emitted from traffic emissions. Overall, VOCs in Kaohsiung City have been decreased from 2018 to 2020; however, according to the analytical results of ozone formation potential, toluene and m,p-xylenes are the most potential photochemical precursors for ozone formation. The government should enforce and regulate aromatic hydrocarbons from industrial emission sources to reduce the potential formation of ozone.

We aimed to evaluate factors influencing the outcomes of patients with platinum-sensitive recurrent epithelial ovarian carcinoma (EOC). Patients with advanced-stage EOC, who received debulking surgery and adjuvant chemotherapy for recurrence, were obtained from the National Health Insurance Research database of Taiwan between 2000 and 2013. A total of 1038 patients with recurrent advanced-stage EOC were recruited. The platinum + paclitaxel (PT) group had the best five-year overall survival (OS) compared with the other three groups (p &lt, 0.001). The hazard ratios (HRs) of five-year OS for the platinum + liposomal doxorubicin (PD), topotecan (TOP), and pegylated liposomal doxorubicin (PLD) groups were 1.21 (p = 0.07), 1.35 (p = 0.016), and 1.80 (p &lt, 0.001), respectively, compared with the PT group. The PT group also had lower hazard ratios of five-year OS for patients with platinum therapy-free interval (TFIp) between 6 and 12 months compared with the other three groups (p &lt, 0.0001). However, the HRs of five-year OS did not differ between the PT and PD groups in patients with TFIp &gt, 12 months. Patients with TFIp &gt, 12 months had lower HRs of five-year OS compared with those with TFIp of 6–12 months, regardless of whether they were treated with platinum-based (p = 0.001) or non-platinum-based (p = 0.003) regimens. Chemotherapeutic regimens and TFIp influenced the outcomes of patients with recurrent EOC. For patients with TFIp of 6–12 months, the PT regimen is the first choice based on their best overall survival result. For patients with TFIp &gt, 12 months, either platinum-based or non-platinum regimens could be used because of their similar excellent overall survival.

Polyethylene glycol (PEG) coating of gold nanoparticles (AuNPs) improves AuNP distribution via blood circulation. The use of PEG-coated AuNPs was shown to result in acute injuries to the liver, kidney, and spleen, but long-term toxicity has not been well studied. In this study, we investigated reporter induction for up to 90 days in NF-&kappa, B transgenic reporter mice following intravenous injection of PEG-coated AuNPs. The results of different doses (1 and 4 &mu, g AuNPs per gram of body weight), particle sizes (13 nm and 30 nm), and PEG surfaces (methoxyl- or carboxymethyl-PEG 5 kDa) were compared. The data showed up to 7-fold NF-&kappa, B reporter induction in mouse liver from 3 h to 7 d post PEG-AuNP injection compared to saline-injected control mice, and gradual reduction to a level similar to control by 90 days. Agglomerates of PEG-AuNPs were detected in liver Kupffer cells, but neither gross pathological abnormality in liver sections nor increased activity of liver enzymes were found at 90 days. Injection of PEG-AuNPs led to an increase in collagen in liver sections and elevated total serum cholesterol, although still within the normal range, suggesting that inflammation resulted in mild fibrosis and affected hepatic function. Administrating PEG-AuNPs inevitably results in nanoparticles entrapped in the liver, thus, further investigation is required to fully assess the long-term impacts by PEG-AuNPs on liver health.

Additional file 1: Table S1. A list of animals used for the assays indicated in figures and supplementary figures; Figure S1. Anatomical diagram; Figure S2. Examination of myelin structure in the hypothalamus of mice receiving Chow and HFD feeding for 3 months; Figure S3. Examination of the body weight, water intake, food intake and calorie intake of mice receiving Chow and HFD; Figure S4. Microglia activation induced by HFD feeding in hypothalamic arcuate nucleus at 2 month after feeding; Figure S5. Exposure to IL-33 hinders the maturation of rat oligodendrocytes.

Lymphoid T-zone fibroblastic reticular cells (FRCs) actively promote T-cell trafficking, homeostasis, and expansion but can also attenuate excessive T-cell responses via inducible nitric oxide (NO) and constitutive prostanoid release. It remains unclear how these FRC-derived mediators dampen T-cell responses and whether this occurs in vivo. Here, we confirm that murine lymph node (LN) FRCs produce prostaglandin E2 (PGE2) in a cyclooxygenase-2 (COX2)-dependent and inflammation-independent fashion. We show that this COX2/PGE2 pathway is active during both strong and weak T-cell responses, in contrast to NO, which only comes into play during strong T-cell responses. During chronic infections in vivo, PGE2-receptor signaling in virus-specific cluster of differentiation (CD)8 cytotoxic T cells was shown by others to suppress T-cell survival and function. Using COX2flox/flox mice crossed to mice expressing Cre recombinase expression under control of the CC chemokine ligand (CCL19) promoter (CCL19cre), we now identify CCL19+ FRC as the critical source of this COX2-dependent suppressive factor, suggesting PGE2-expressing FRCs within lymphoid tissues are an interesting therapeutic target to improve T-cell–mediated pathogen control during chronic infection., Fibroblasts in secondary lymphoid organs can be active participants in adaptive immunity, often enhancing T-cell responses. This study shows how these fibroblasts dampen T-cell responses via the constitutive production of the COX2-dependent prostaglandin PGE2, including during persistent viral infection.

Antibody-secreting plasma cells (PCs) arise rapidly during adaptive immunity to control infections. The early PCs are retained within the reactive lymphoid organ where their localization and homeostasis rely on extrinsic factors, presumably produced by local niche cells. While myeloid cells have been proposed to form those niches, the contribution by colocalizing stromal cells has remained unclear. Here, we characterized a subset of fibroblastic reticular cells (FRCs) that forms a dense meshwork throughout medullary cords of lymph nodes (LNs) where PCs reside. This medullary FRC type is shown to be anatomically, phenotypically, and functionally distinct from T zone FRCs, both in mice and humans. By using static and dynamic imaging approaches, we provide evidence that medullary FRCs are the main cell type in contact with PCs guiding them in their migration. Medullary FRCs also represent a major local source of the PC survival factors IL-6, BAFF, and CXCL12, besides also producing APRIL. In vitro, medullary FRCs alone or in combination with macrophages promote PC survival while other LN cell types do not have this property. Thus, we propose that this FRC subset, together with medullary macrophages, forms PC survival niches within the LN medulla, and thereby helps in promoting the rapid development of humoral immunity, which is critical in limiting early pathogen spread.

本研究目的旨在發展大學生基本素養測驗並進行信度與效度評估。藉由分析國內大專院校的通識教育目標和核心素養，並參考ATC21S 提出的21世紀現代學生需具備的10 項基本素養，歸納出大學生基本素養測驗的九項素養，分別為：溝通合作、美感素養、科學思辨、資訊素養、終身學習、創新領導、問題解決、公民社會及生涯發展。測驗形式為線上多媒體情境式題型，每個題本均包含九項素養的內容，每項素養皆有二至三個題組。研究對象為全國大專校院一至四年級學生，研究樣本來自20 校10,958名大學生。由效度評估結果可知，大學生基本素養測驗的題組效果不大，可以忽略，並採用部分計分模式來估計，幾乎所有試題與模式都能適配，顯示建構效度良好。試題發展過程均歷經嚴謹修審題程序，取得良好專家效度證據。此外，不同性別和年級的學生在各素養的表現上差異不大，和過去的文獻相符合，具有良好的效標關聯效度。信度證據方面，各素養能力估計誤差約在 .20～ .60 logit 之間，單一題本的信度高於 .69，顯示本測驗題數雖少，但信度大致良好。整體而言，大學生基本素養測驗具良好的信度與效度。 This study evaluated the psychometric properties of the General Literacy Test for University Students. To develop the assessment framework, the educational objectives of general literacy courses of universities in Taiwan as well as the core competencies of Assessment and Teaching of 21st Century Skills were all reviewed and considered. The general literacy test is composed of nine literacy domains: communication and collaboration, esthetics, information, lifelong learning, career, leadership, problem solving, social concerns and citizenship, and scientific thinking. The items of the general literacy test were developed into a multimedia assessment. In addition, booklets including two to three testlets on each of the nine literacy domains were organized. Overall, 10,958 students from 20 universities participated. The results demonstrated that testlet effect could be ignored and the partial credit model could be used to analyze data. In addition, the items fit the partial credit model closely and the test demonstrated favorable construct validity. In addition, small differences existed between gender and grades. The results were consistent with those of previous studies and showed that the test’s criterion-related validity was acceptable. Furthermore, the standard error of ability ranged from .20 to .60 logit and the reliabilities of the booklets were more than .69 in the nine literacy domains. The evidence supports the high degree of reliability and validity of basic literacy assessment.

Micelles are self-assembled nanoscaled aggregates from amphiphilic unimers and can be used to encapsulate hydrophobic drugs. However, the dynamic exchanging of unimers between micelles and bulk solution often leads to micelle destabilization and subsequent leaking of the encapsulated substances. Thus, we incorporated a hydrophobic polymer into the micellar core for interlacing the unimers and stabilizing the micelle structure. The polymer-stabilized and non-polymer-stabilized micelles have similar physicochemical properties including small sizes (~35 nm), negative surface charges (~−35 mV), and high drug contents (~15%). Drugs encapsulated in polymer-stabilized micelles are released in a slower rate than are non-polymer-stabilized micelles. From in vivo pharmacokinetic studies, drugs loaded in polymer-stabilized micelles have lower clearance and higher plasma concentration and lower volume distribution than non-polymer-stabilized micelles have. In conclusion, polymer-stabilized micelles can reduce rapid drug clearance via strengthening of the micellar structure and increase in the available drug amount in plasma, thus broadening pharmaceutical applications of micelles.

IntroductionAnxiety and depression have become a focus of concern in mood changes among childbearing women. However, less is known regarding how anxiety and depressive symptom changes over time in women underwent an elective cesarean section. This study is aimed to (1) characterize the joint trajectories of anxiety and depressive symptoms, and (2) investigate the effect of the anxiety and depression courses on the subsequent body weight.MethodsA prospective longitudinal study of childbearing women (N = 139) who underwent an elective cesarean section was conducted. Anxiety and depressive symptoms were assessed using the State Anxiety Inventory (SAI) and the Edinburgh Postnatal Depression Scale, respectively, in the third trimester and 1 day, 1 week, and 1 and 6 months postpartum. The structured questionnaires on demographic features, health status, and body mass index (BMI) were completed. Trajectory analyses were conducted using semiparametric group-based modeling. Analysis of covariance and the trend test were applied.ResultsThe mean age of participants was 33.6 years. Most study participants were multiparas (61.9%) and had at least some college education (73.4%). We identified four distinctive joint trajectories of anxiety and depressive symptoms: class 1 (low, 24.9%), class 2 (mild, 42.9%), class 3 (high, 23%), and class 4 (very high, 6.9%). After adjustment for age and parity, the BMIs were significantly different among the trajectories classes (p

This study aims to evaluate the relationships between chromosome 20q13.2 zinc finger protein 217 (ZNF217) locus amplification, ZNF217 expression, E-cadherin expression, and PI3K-Akt pathway alterations (activating PIK3CA mutations or loss of phosphatase and tensin homolog [PTEN] expression), and whether these molecular alterations can predict the clinical survival data in ovarian clear cell carcinoma (OCCC) patients. Samples and clinical data of 72 OCCC patients were collected. Chromosome 20q13.2 ZNF217 locus amplification was detected by fluorescence in situ hybridization. ZNF217, E-cadherin and PTEN expression were assessed using immunohistochemical stain. PIK3CA mutation was identified by PCR-amplified gene sequencing. Cox proportional hazard regression model was used to estimate the adjusted hazard ratios of survival. Chromosome 20q13.2 ZNF217 locus amplification was detected in 31% (22/72) of cases, and ZNF217 expression was increased in 40% (27/68) of cases. E-cadherin and PTEN expressions were decreased or lost in 44% (32/72) and 14% (10/72) of cases, respectively. Activating PIK3CA mutations were present in 35% (25/72) of cases. Thirty-three OCCC patients (46%) showed activating PI3K-Akt pathway alterations. Chromosome 20q13.2 ZNF217 locus amplification was significantly associated with decreased E-cadherin expression (P = .001). In contrast, ZNF217 expression was not related to ZNF217 amplification or E-cadherin expression. In OCCC patients with activating PI3k-Akt pathway, decreased E-cadherin expression (P = .033) and advanced Federation of Gynecology and Obstetrics stage (P = .014) predicted shorter overall survival. Two conclusions were raised in our study. First, ZNF217 plays a role in down-regulating E-cadherin expression and is a potential therapeutic target for OCCC patients. Second, E-cadherin expression is a prognostic marker for OCCC patients with activating PI3K-Akt pathway.

Adaptive immunity is initiated in T-cell zones of secondary lymphoid organs. These zones are organized in a rigid 3D network of fibroblastic reticular cells (FRCs) that are a rich cytokine source. In response to lymph-borne antigens, draining lymph nodes (LNs) expand several folds in size, but the fate and role of the FRC network during immune response is not fully understood. Here we show that T-cell responses are accompanied by the rapid activation and growth of FRCs, leading to an expanded but similarly organized network of T-zone FRCs that maintains its vital function for lymphocyte trafficking and survival. In addition, new FRC-rich environments were observed in the expanded medullary cords. FRCs are activated within hours after the onset of inflammation in the periphery. Surprisingly, FRC expansion depends mainly on trapping of naïve lymphocytes that is induced by both migratory and resident dendritic cells. Inflammatory signals are not required as homeostatic T-cell proliferation was sufficient to trigger FRC expansion. Activated lymphocytes are also dispensable for this process, but can enhance the later growth phase. Thus, this study documents the surprising plasticity as well as the complex regulation of FRC networks allowing the rapid LN hyperplasia that is critical for mounting efficient adaptive immunity.

Fasnacht et al. now show that fibroblasts in secondary lymphoid organs are responsible for the production of Notch ligands regulating the differentiation of immune cells, Fibroblast-like cells of secondary lymphoid organs (SLO) are important for tissue architecture. In addition, they regulate lymphocyte compartmentalization through the secretion of chemokines, and participate in the orchestration of appropriate cell–cell interactions required for adaptive immunity. Here, we provide data demonstrating the functional importance of SLO fibroblasts during Notch-mediated lineage specification and immune response. Genetic ablation of the Notch ligand Delta-like (DL)1 identified splenic fibroblasts rather than hematopoietic or endothelial cells as niche cells, allowing Notch 2–driven differentiation of marginal zone B cells and of Esam+ dendritic cells. Moreover, conditional inactivation of DL4 in lymph node fibroblasts resulted in impaired follicular helper T cell differentiation and, consequently, in reduced numbers of germinal center B cells and absence of high-affinity antibodies. Our data demonstrate previously unknown roles for DL ligand-expressing fibroblasts in SLO niches as drivers of multiple Notch-mediated immune differentiation processes.

Interleukin-7 (IL-7) is known since many years as stromal-cell derived cytokine that plays a key role for the adaptive immune system. It promotes lymphocyte development in the bone marrow and thymus as well as naive and memory T cell homeostasis in the periphery. More recently, IL-7 reporter mice and other approaches have led to the further characterization of the various stromal cell sources of IL-7 in secondary lymphoid organs (SLO) and other tissues. We will review these advances along with a discussion of the regulation of IL-7 and its receptor, and compare the biological effects IL-7 has on adaptive as well as innate immune cells in SLO. Finally, we will review the role of IL-7 in development of SLO and tertiary lymphoid tissues that frequently are associated with sites of chronic inflammation.

The bactericidal properties of myristic acid and curcumin were revealed in a number of studies. However, whether curcumin-loaded myristic acid microemulsions can be used to inhibit Staphylococcus epidermidis, which causes nosocomial infections, has not been reported. Our aim was to develop curcumin-loaded myristic acid microemulsions to inhibit S. epidermidis on the skin. The interfacial tension, size distribution, and viscosity data of the microemulsions were characterized to elucidate the physicochemical properties of the curcumin microemulsions. Curcumin distribution in neonate pig skin was visualized using confocal laser scanning microscopy. Dermal curcumin accumulation (326 µg/g skin) and transdermal curcumin penetration (87 µg/cm(2)/d) were obtained with the microemulsions developed herein. Curcumin at the concentration of 0.86 µg/mL in the myristic acid microemulsion could inhibit 50% of the bacterial growth, which was 12 times more effective than curcumin dissolved in dimethyl sulfoxide (DMSO). The cocktail combination of myristic acid and curcumin in the microemulsion carrier synergistically inhibited the growth of S. epidermidis. The results we obtained highlight the potential of using curcumin-loaded microemulsions as an alternative treatment for S. epidermidis-associated diseases and acne vulgaris.

Glial cell line derived neurotrophic factor (GDNF) induces neuronal survival and tissue repair after spinal cord injury (SCI). A continuous GDNF supply is believed to gain greater efficacy in the neural restoration of the injured spinal cord. Accordingly, nanovehicle formulation for their efficient delivery and sustained release in injured spinal cord was examined. We first used fluorescence-labeled bovine serum albumin (FBSA) loaded in biodegradable poly(lactic acid-co-glycolic acid) (PLGA) for intraspinal administration after SCI and for in vitro study. Our results showed that the preservation of PLGA-FBSA was observed in the injured spinal cord at 24h, and PLGA-FBSA nanoparticles were well absorbed by neurons and glia, indicating that PLGA as a considerable nanovehicle for the delivery of neuroprotective polypeptide into injured spinal cord. Furthermore, intraspinal injection of GDNF encapsulated in PLGA (PLGA-GDNF) nanoparticles into the injured spinal cord proximal to the lesion center had no effect on gliosis when compared to that observed in SCI rats receiving PLGA injection. However, local administration of PLGA-GDNF effectively preserved neuronal fibers and led to the hindlimb locomotor recovery in rats with SCI, providing a potential strategy for the use of PLGA-GDNF in the treatment of SCI.

GATA-3 is the key transcriptional factor for Th2 commitment in T cells and is strongly associated with asthma and allergic disease. We studied the silencing of the GATA-3 gene expression using RNA interference (RNAi) delivered by a lentiviral vector, to evaluate the therapeutic role of GATA-3 short hairpin RNAs (shRNAs) in a murine model of asthma. Mice were sensitized with OVA and instilled intratracheally (IT) with GATA-3 shRNAs lentiviral vector (Lenti-si-GATA-3) once, 48 hours before challenge. After three challenges with the OVA antigen, the mice were assessed for airway hyperresponsiveness (AHR) and inflammation. With infection of Lenti-si-GATA-3 in EL-4 cells, GATA-3 gene expression was abrogated and downstream Th2 cytokines, such as interleukin-4 (IL-4) and IL-5, were also significantly inhibited. IT delivery of Lenti-si-GATA-3 in OVA-immunized mice resulted in a strong inhibition of local GATA-3 gene expression. Treatment with Lenti-si-GATA-3 successfully alleviated OVA-induced airway eosinophilia and Th2 cytokine release. While evaluating AHR by means of enhanced pause (Penh) and pulmonary resistance (R(L)) using body plethysmography, it was found that the administration of Lenti-si-GATA-3 had significantly decreased AHR in OVA-immunized mice. These results suggest that inhibition of GATA-3 gene expression by shRNAs lentiviral vectors strongly attenuates antigen-induced airway inflammation and hyper-responsiveness in mice.

In this study, the event-specific primers for insecticide-resistant maize, MON810, and herbicide-tolerance maize, NK603, have been designed. Simplex PCR and multiplex PCR detection method have been developed. The detection limit of the multiplex PCR is 0.5% for MON810 and NK603 in 50 ng of the template for one reaction. Quantitative methods based on real-time quantitative PCR were developed for MON810 and NK603. Plasmid pMulM2 as reference molecules for the detection of MON810 and NK603 was constructed. Quantification range was from 0.5 to 100% in 100 ng of the DNA template for one reaction. The precision of real-time Q-PCR detection methods, expressed as coefficient of variation for MON810 and NK603 varied from 1.97 to 8.01% and from 3.45 to 10.94%, respectively. The range agreed with European interlaboratories test results (25%). According to the results, the methods for quantitative detection of genetically modified maize were acceptable.

Microglia activated after many neurological degeneration of the central nervous system (CNS) act as important regulators for neuropathogenesis in the injured CNS via producing proinflammatory mediators, such as nitric oxide (NO), TNF-alpha, and IL-1beta. Neurotrophin-3 (NT-3) is a well-known trophic factor for neural survival, development, and plasticity. Activated microglia are NT-3-producing cells in the injured CNS, and express its receptor-TrkC. However, little is known about the effect of NT-3 on activated microglia. In this study, pre-treatment of a mouse microglial cell line, BV2, with NT-3 for 24 h indicated that NT-3 reduced the inducible form of NO synthase (iNOS), NO, and TNF-alpha in BV2 stimulated with lipopolysaccharide (LPS). NT-3 exerted less effect on the reduction of these proinflammatory mediators when it was added to BV2 cultures either simultaneously with LPS or post LPS treatment. These findings indicate that NT-3 may serve as an anti-inflammatory factor to suppress microglial activation.

Aims To understand the role of and differences in molecular alterations between endometrial and ovarian endometrioid adenocarcinomas. Methods and results We investigated the microsatellite status of 26 ovarian endometrioid adenocarcinomas (OVEMs), 42 endometrial endometrioid adenocarcinomas (EMCAs), and 19 concurrent (endometrial and ovarian) endometrioid adenocarcinomas. We evaluated the expression of the mismatch repair proteins, PTEN and ARID1A, and mutations of PTEN, KRAS, CTNNB1, and PIK3CA. High levels of microsatellite instability (MSI-H) were present in one of 26 OVEMs, 12 of 42 EMCAs, and four of 19 concurrent endometrioid adenocarcinomas. Only four of 19 concurrent endometrioid adenocarcinomas showed identical molecular alterations in their endometrial and ovarian components. Loss of ARID1A or loss of PTEN expression, and MSI-H, were more common in EMCAs than OVEMs (P = 0.044, P = 0.004, and P = 0.012, respectively). MSI-H in endometrial endometrioid adenocarcinomas was also related to loss of ARID1A expression (P

This paper addresses the stabilization design problem for the continuous perturbed systems subjected to a time delay. By using the Riccati equation approach associated with the upper bound of the solution of the Riccati equation, a new stabilizability criterion is proposed. This criterion is easy to be tested. According to the above criterion, a simple stabilization controller is developed. This controller is very simple and hence is easy to be implemented.

Propionibacterium acnes acts a critical role in the development of inflammatory acne when it overgrows in pilosebaceous units. The spread of multiple drug resistance bacteria indicates a growing need for new antimicrobial agents. The objective of this study is to develop lipid vehicles to deliver curcumin and inhibit P. acnes in the skin. The inhibitory activities of the curcumin containing vehicles against P. acnes were studied by the bioluminescence assay. Curcumin accumulation patterns in neonate pig skin were studied using Franz diffusion cells and confocal laser scanning microscopy. The physicochemical properties of the curcumin containing vehicles including interfacial tension, size distribution and viscosity were analyzed. Significant curcumin accumulation (362±8 µg/g skin) was observed with the lipid vehicles developed herein. Curcumin (0.43 µg/mL) in the vehicles significantly inhibited the growth of P. acnes. Confocal laser scanning microscopy confirmed the formation of curcumin reservoir in the skin by the curcumin-loaded vehicles. Curcumin-loaded vehicles could efficiently accumulate in the skin and inhibit P. acnes in vitro. Our results highlight the potential of using vehicles containing lauric acid and curcumin as an alternative treatment for acne vulgaris.

ZnO nanoparticles with controlled sizes produced by a sol-gel method are studied by means of time-integrated as well as time-resolved photoluminescence (TRPL) spectroscopy. Room-temperature photoluminescence spectra show a blueshift of the excitonic emission with the decreasing particle size, which is attributed to the quantum confinement effect. The temperature dependence of the exciton lifetimes deduced from the TRPL results contains two components: the fast decay is attributed to surface trapping of exciton and the slow decay is mainly representative of the radiative processes involving the bound or free excitons. Funding Agencies|National Science Council of Taiwan|NSC-100-2112-M-006-002-MY3|Headquarters of University Advancement at the National Cheng Kung University||Ministry of Education, Taiwan

An Annular Denuder System (ADS) was used to study sampling errors of total PM{sub 10} and soluble ionic species concentrations determined by the high volume PM{sub 10} (HVPM{sub 10}) sampler. Experimental results show that in the HVPM{sub 10} sampler, more alkaline glass fiber filters collect more sulfate and nitrate but less ammonium ion than quartz filters. However, total PM{sub 10} concentrations do not seem to depend on the types of filters. Artifact sulfate concentrations in glass fiber filters of the HVPM{sub 10} sampler are found to exceed those predicted by the Coutant`s model. It is suggested that artifact sulfate and nitrate not only occur within filters but also in particle deposits. Chloride ion concentrations in the filters of the HVPM{sub 10} sampler are underestimated significantly due to evaporative loss of ammonium chloride. 17 refs., 8 figs., 1 tab.

The bactericidal properties of myristic acid and curcumin were revealed in a number of studies. However, whether curcumin-loaded myristic acid microemulsions can be used to inhibit Staphylococcus epidermidis, which causes nosocomial infections, has not been reported. Our aim was to develop curcumin-loaded myristic acid microemulsions to inhibit S. epidermidis on the skin. The interfacial tension, size distribution, and viscosity data of the microemulsions were characterized to elucidate the physicochemical properties of the curcumin microemulsions. Curcumin distribution in neonate pig skin was visualized using confocal laser scanning microscopy. Dermal curcumin accumulation (326 µg/g skin) and transdermal curcumin penetration (87 µg/cm(2)/d) were obtained with the microemulsions developed herein. Curcumin at the concentration of 0.86 µg/mL in the myristic acid microemulsion could inhibit 50% of the bacterial growth, which was 12 times more effective than curcumin dissolved in dimethyl sulfoxide (DMSO). The cocktail combination of myristic acid and curcumin in the microemulsion carrier synergistically inhibited the growth of S. epidermidis. The results we obtained highlight the potential of using curcumin-loaded microemulsions as an alternative treatment for S. epidermidis-associated diseases and acne vulgaris.

Nanoparticles were designed to encapsulate drugs to alter their pharmacological behaviors, therefore, it is very essential to monitor the pharmacokinetic profile of drug encapsulated in nanoparticles in order to clarify and predict their efficacy and side effects. In this paper, we reported a simple, rapid μ-elution 96-well solid phase extraction (μSPE) method combining with ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for determination of nanoformulated drug in rat plasma. This method presented satisfactory results in terms of sensitivity, precision, accuracy, and recovery, for the first time, of quantitatively analyzing clarithromycin (CLA) in rat plasma after intravenous administration CLA-loaded ultrafine PLGA nanoparticles for pharmacokinetic study. This method has been proved to be fast, reliable and reproducible to accurately analyze drug encapsulated in polymeric nanoparticles sample for a pharmacokinetic study.

A novel method was developed for the one-pot synthesis of ultrafine poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), using an emulsion solvent evaporation formulation method. Using either cetyltrimethylammonium bromide (CTAB) or poly(ethylene glycol)-distearyl phosphoethanolamine (PEGPE) as an oily emulsifier during the emulsion process, produced PLGA particle sizes of less than 50 nm, constituting a breakthrough in emulsion formulation methods. The yield of ultrafine PLGA NPs increased with PEGPE/PLGA ratio, reaching a plateau at around 85%, when the PEGPE/PLGA ratio reached 3:1. The PEGPE-PLGA NPs exhibited high drug loading content, reduced burst release, good serum stability, and enhanced cell uptake rate compared with traditional PLGA NPs. Sub-50 nm diameter PEG-coated ultrafine PLGA NPs show great potential for in vivo drug delivery systems.

Interleukin (IL)-4 and IL-13 are two key cytokines released from activated T helper type 2 (Th2) cells and strongly associated with asthma and allergic disease. We applied silencing of the IL-4 and IL-13 gene expression by RNA interference delivered by a lentiviral vector to evaluate the therapeutic role of IL-4 and IL13 short hairpin RNAs (shRNAs) in a murine model of asthma. Mice were sensitized with ovalbumin (OVA), and one treatment of IL-4 and IL-13 shRNA lentiviral vector (Lenti-si-IL-4 and Lenti-si-IL-13) was instilled intratracheally 48 hr before challenge. After three challenges of OVA antigen, mice were assessed for airway inflammation and hyperresponsiveness. With infection of Lenti-si-IL-4 and Lenti-si-IL-13 in EL-4 cells, both RNA and protein expressions of IL-4 and IL-13 were obviously abrogated. Furthermore, intratracheal instillation of Lenti-si-IL-4 and Lenti-si-IL-13 in OVA-immunized mice resulted in a strong inhibition of local IL-4 and IL-13 cytokine release. Treatment with Lenti-si-IL-4 and Lenti-si-IL-13 successfully alleviated OVA-induced airway eosinophilia and Th2 cell cytokine release. Finally, to determine airway hyperresponsiveness by enhanced pause and pulmonary resistance in noninvasive and invasive body plethysmography, we found that administration of Lenti-si-IL-4 and Lenti-si-IL-13 markedly decreased airway hyperresponsiveness in OVA-immunized mice. These results suggest that inhibition of IL-4 and IL-13 gene expression by shRNA lentiviral vector markedly inhibits antigen-induced airway inflammation and hyperresponsiveness in mice.

Adaptive immune responses are initiated when T cells encounter antigen on dendritic cells (DC) in T zones of secondary lymphoid organs. T zones contain a 3-dimensional scaffold of fibroblastic reticular cells (FRC) but currently it is unclear how FRC influence T cell activation. Here we report that FRC lines and ex vivo FRC inhibit T cell proliferation but not differentiation. FRC share this feature with fibroblasts from non-lymphoid tissues as well as mesenchymal stromal cells. We identified FRC as strong source of nitric oxide (NO) thereby directly dampening T cell expansion as well as reducing the T cell priming capacity of DC. The expression of inducible nitric oxide synthase (iNOS) was up-regulated in a subset of FRC by both DC-signals as well as interferon-γ produced by primed CD8+ T cells. Importantly, iNOS expression was induced during viral infection in vivo in both LN FRC and DC. As a consequence, the primary T cell response was found to be exaggerated in Inos(-/-) mice. Our findings highlight that in addition to their established positive roles in T cell responses FRC and DC cooperate in a negative feedback loop to attenuate T cell expansion during acute inflammation

RNAi is the process of sequence-specific, post-transcriptional/transcriptional gene silencing through siRNA. RNAi is a popular method of controlling gene expression and has potential in the development of drugs for several diseases, such as various types of cancer and viral infections. Gene therapy for asthma has already been developed and has demonstrated promising results in animal models. Recent progress in delivering siRNA to the respiratory system has also improved the therapeutic feasibility of RNAi for asthma. In this review, the mechanism, as well as the general strategies and problems associated with the application of RNAi in vivo, are discussed, focusing on the possibility of applying RNAi to alleviate airway inflammation in allergic asthma. Data from studies with siRNA against molecules involved in allergic responses are summarized, and the potential and limitations of RNAi as a novel therapeutic approach are discussed.

Therapeutic proteins or polypeptides can be formulated into various particulate delivery systems including the polymeric carriers to avoid rapid degradation and to maintain the sustained release for better therapeutic effects (1). Poly(lactic/glycolic) acid (PLGA) micro/nanoparticle is a widely used formulation agent because of its good biodegradability, biocompatibility, and approved clinical usage, which have been available in the market to treat prostate cancer, acromegaly, periodontal disease, and pediatric growth hormone deficiency (2). The sustaining and complete release of proteins in their native or active forms from the PLGA micro/nanoparticles is often a challenging task (3). Proteins are generally formulated into PLGA nanoparticles by water/oil/water double-emulsion–solvent evaporation method, which generates hydrophilic/hydrophobic interface that may result in the unfolding or denaturing of protein molecules (4). Thus, polymeric surfactants are usually used to lower surface tension of protein solutions and to prevent aggregation of protein molecules at hydrophobic surface (1). Polyvinyl alcohol (PVA) is a widely used polymeric surfactant in the exterior aqueous phase as an emulsifier. However, the safety of PVA still appears to be a concern from the previous literature reports (5,6). Following repeated subcutaneous or intravenous administrations of PVA, various organ lesions and hypertension have been reported in rats, and central nervous system depression and anemia followed by renal damage have also been reported in beagle dogs; whereas, orally administered PVA is relatively harmless in mice or rat (5,6). Therefore, residual PVA was always removed by washing procedures such as repetitive centrifugation (7) or filtration (8), which removes not only the PVA but also the unencapsulated proteins or polypeptides, which might be often valuable or hard to collect. Hence, a few substituting emulsifiers have been studied. For example, poly(ethylene glycol) (PEG) was used successfully as the stabilizer to prepare enzyme-loaded PLGA microparticles (9). Besides, surfactant-free formulation was achieved by nanoprecipitation/solvent-displacement method that would not alter surface properties of PLGA nanoparticles, but this method may suffer the low encapsulation efficiency when low protein concentration solution is to be used (10). In the present study, we introduced another surfactant-free method to prepare PLGA nanoparticles encapsulating polypeptides by double-emulsion–solvent evaporation method. We used sucrose as the stabilizer of the exterior aqueous phase to prevent aggregation of PLGA nanoparticles during formulation process. Nerve growth factor (NGF), a small secreted protein which can induce the differentiation and survival of particular target neurons, was used as the model protein. As sucrose is a nontoxic material, additional washing procedures are not necessarily needed for NGF-loaded PLGA nanoparticles, and thus, the valuable NGF loss can be minimized. The release of functional NGF molecules from these nanoparticles was verified by either the antibody recognition in enzyme-linked immunosorbent assay (ELISA) method or the induction on the neurite outgrowth of PC-12 cells.

Background Eosinophilia plays the major role in the pathogenesis of asthma and correlates with the up-regulation of eotaxin, which, together with interleukin (IL)-5, is important for differentiation, chemo-attraction, degranulation, and survival of eosinophils in local tissue. In a previous study, we found that administration of lentivirus-delivered short hairpin RNA (shRNA) to suppress the expression of IL-5 inhibited airway inflammation. The present study aimed to investigate the role of eotaxin shRNA and the synergistic effect of eotaxin and IL-5 shRNAs on airway inflammation in an ovalbumin (OVA)-induced murine model of asthma. Methods Lentivirus-delivered shRNAs were used to suppress the expression of eotaxin and/or IL-5 in local tissue in an OVA-induced murine asthma model. Results Intra-tracheal administration of lentivirus containing eotaxin shRNA expressing cassette (eoSEC3.3) efficiently moderated the characteristics of asthma, including airway hyper-responsiveness, cellular infiltration of lung tissues, and eotaxin and IL-5 levels in bronchio-alveolar lavage fluid. Administration of lentiviruses expressing IL-5 or eotaxin shRNAs (IL5SEC4 + eoSEC3.3) also moderated the symptoms of asthma in a mouse model. Conclusions Local delivery of lentiviruses expressing IL-5 and eotaxin shRNAs provides a potential tool in moderating airway inflammation and also has the potential for developing clinical therapy based on the application of shRNAs of chemokines and cytokines involved in T helper 2 cell inflammation and eosinophilia. Copyright © 2008 John Wiley & Sons, Ltd.

Interleukin-5 (IL-5) has been suggested to be involved in the development of airway hyper-responsiveness (AHR). Both clinical and experimental investigations have shown strong correlation between the presence of eosinophils and AHR. In this study, we used small interfering RNA (siRNA) as an approach to inhibiting the expression of IL-5 and reducing AHR. siRNAs targeting IL-5 were characterized in vitro, and siRNA-expressing lentiviruses were administered intratracheally to OVA-sensitized BALB/c mice. AHR, cytokine levels, serum levels of OVA-specific antibodies and infiltration of inflammatory cells were analyzed to investigate the effects of siRNA in an OVA-induced murine model of asthma. Lentivirus-delivered siRNA targeting IL-5 efficiently moderated the characteristics of asthma, including AHR, cellular infiltration of lung tissues, eotaxin levels in the bronchoalveolar lavage fluid and IL-5 mRNA levels in lungs in the mouse model of asthma. However, there was no effect on OVA-specific IgE level. These data demonstrate that siRNA delivered by the lentiviral system is an efficacious therapeutic strategy for asthma.

Microglia activated by neural injuries produce proinflammatory mediators, but activated microglia also appear in developing neural tissue to phagocytose cell debris resulting from programmed cell death without inducing tissue damage. Thus, factors associated with the developing CNS may modulate microglial activities. Previously we reported that pretreatment with neurotrophin-3 (NT-3), a factor known to regulate neural development, inhibits the production of proinflammatory mediators, nitric oxide (NO), tumor necrosis factor-alpha, and interleukin-1beta, in BV2 activated by inflammagen lipopolysaccharide (LPS). In this study, the inhibition of proinflammatory mediators by NT-3 pretreatment (preNT-3) in primary microglia with LPS stimulation was corroborated. Moreover, pretreatment of LPS-activated microglia with NT-3 induced a trend of reduction in phagocytotic ability. By using LPS-activated BV2 cells, we further found that reduced expression of inducible NO synthetase by preNT-3 was mediated by MAP kinase and PI3 kinase signaling pathways. Moreover, pretreatment of BV2 cells with NT-3 led to reduced levels of the p65 subunit of nucleus factor-kappaB (NFkappaB) and its DNA binding activity. Accordingly, our results indicate that preexposure of microglia to NT-3 leads to a reduced production of proinflammatory mediators in activated microglia by the induction of MAP kinase and PI3 kinase signaling, which in turn may reduce NFkappaB DNA binding activity. This suggests that an NT-enriched microenvironment may be favorable for preventing the inflammatory reaction of microglia.