Highly efficient prevention of radiation dermatitis using a PEGylated superoxide dismutase dissolving microneedle patch.

PEGylated superoxide dismutase (PEG-SOD) is commonly used as a cytoprotective agent in radiotherapy. However, its effectiveness in preventing radiation dermatitis is limited owing to its poor skin permeability. To address this issue, a PEG-SOD-loaded dissolving microneedle (PSMN) patch was developed to effectively prevent radiation dermatitis. Initially, PSMN patches were fabricated using a template mold method with polyvinylpyrrolidone K90 as the matrix material. PSMNs exhibited a conical shape with adequate mechanical strength to penetrate the stratum corneum. More than 90 % of PEG-SOD was released from the PSMN patches within 30 min. Notably, the PSMN patches showed a significantly higher drug skin permeation than the PEG-SOD solutions, with a 500-fold increase. In silico simulations and experiments on skin pharmacokinetics confirmed that PSMN patches enhanced drug permeation and skin absorption, in contrast to PEG-SOD solutions. More importantly, PSMN patches efficiently mitigated ionizing radiation-induced skin damage, accelerated the healing process of radiation-affected skin tissues, and exhibited highly effective radioprotective activity for DNA in the skin tissue. Therefore, PSMN patches are promising topical remedy for the prevention of radiation dermatitis.

Pharmacokinetics and Bioequivalence of Two Formulations of Azithromycin Tablets: A Randomized, Single-Dose, Three-Period, Crossover Study in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

BACKGROUND AND OBJECTIVE: Azithromycin is the first azalide antibiotic that is related to the macrolide family of antibiotics. Bioequivalence studies in China are initiated by the National Medical Products Administration (NMPA), which supports a generic consistency evaluation program for ensuring that generic products manufactured in China meet the required standards and provide equivalent therapeutic effects to their reference products. This study aimed to assess the bioequivalence of two azithromycin tablets under both fasting and fed conditions in healthy Chinese volunteers. METHODS: This was a single-center, open-label, single-dose, randomized, three-way crossover trial with two independent groups (fasting group and fed group). A total of 72 healthy Chinese subjects (36 subjects in the fasting state and 36 subjects in the fed state) were enrolled and randomized to treatment. Blood samples were collected from 0 to 120 h after a single oral dose of a 250-mg generic azithromycin tablet (test, T) or branded azithromycin tablet (reference, R). The plasma concentrations of azithromycin were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC‒MS/MS). A non-compartmental analysis method was used to estimate the pharmacokinetic parameters. Adverse events were documented. RESULTS: In a fasting state, the bioequivalence of maximum plasma concentration (Cmax) was evaluated using the reference-scaled average bioequivalence (RSABE) approach (within-subject standard deviation, SWR > 0.294), and the bioequivalence of area under the concentration-time curve from time 0 to the time of the last measurable plasma concentration (AUC0-t) and area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) were evaluated by the average bioequivalence (ABE) method (SWR <  0.294). The geometric mean ratio (GMR) of T/R for Cmax was 106.49%, while the 95% upper confidence bound was <  0. The GMRs of AUC0-t and AUC0-∞ were 103.34% and 101.28%, and the 90% confidence intervals (CIs) of the test/reference were 95.90-111.35%/94.85-108.15%, respectively. In the fed state, the RSABE approach was applied to estimate the bioequivalence of Cmax (SWR >0.294), and the ABE approach was applied to estimate the bioequivalence of AUC0-t and AUC0-∞ (SWR <  0.294). The GMR for Cmax was 99.80%, while the 95% upper confidence bound value was <  0. The GMRs of AUC0-t and AUC0-∞ were 97.07% and 98.15%, and the 90% CIs of the T/R were 90.02-104.68% and 90.66-106.25%, respectively. All adverse events were mild and transient. CONCLUSIONS: The trial indicated that the test and the reference azithromycin tablets were bioequivalent and well tolerated in healthy Chinese volunteers under both fasting and fed conditions. TRIAL REGISTRATION: Clinicaltrials, ChiCTR2300071630 (retrospectively registered in 19/05/2023).

Rapid Correction of the Hypoglycemia State in Nonhuman Primates Using a Glucagon Long-Dissolving Microneedle Patch.

The timely administration of glucagon is a standard clinical practice for the treatment of severe hypoglycemia. However, the process involves cumbersome steps, including the reconstitution of labile glucagon and filling of the syringe, which cause considerable delays in emergency situations. Moreover, multiple dosages are often required to prevent the recurrence of the hypoglycemic episode because of the short half-life of glucagon in plasma. Herein, we develop a glucagon-loaded long-dissolving microneedle (GLMN) patch that exhibits the properties of fast onset and sustained activity for the effective treatment of severe hypoglycemia. Three types of MN patches were fabricated with different dimensions (long, medium, and short). The longer MN patch packaged a higher dosage of glucagon and exhibited supreme mechanical strength compared to the shorter one. Additionally, the longer MN patch could insert more deeply into the skin, resulting in higher permeability of glucagon across the skin tissue and more rapid systemic absorption as compared with the shorter MN patch. The GLMN patch was observed to reverse the effects of hypoglycemia within 15 min of application in animal models (specifically, rat and rhesus monkey models) and maintained long-term glycemic control, owing to highly efficient drug permeation and the drug reservoir effect of the MN base. The current study presents a promising strategy for the rapid reversal of severe hypoglycemia that exhibits the desirable properties of easy use, high efficiency, and sustained action.

Effect of genetic polymorphisms on the pharmacokinetics of gefitinib in healthy Chinese volunteers.

Gefitinib is the first-generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolised by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were administered a single dose of gefitinib and the blood samples were used for quantifying the concentration of gefitinib and genotyping fifteen single-nucleotide polymorphisms of cytochrome P450 enzymes (CYP3A4, CYP3A5, CYP2D6, CYP2C9 and CYP2C19) and drug transporters (ABCB1 and ABCG2).CYP3A5*3 (rs776746) polymorphism showed a significant influence, with higher gefitinib AUC0-t in carrier of CC genotype than in CT/TT genotype (BH-adjusted p value <0.05). For CYP2C9*3 (rs1057910), significant differences in pharmacokinetics of gefitinib were detected between carriers of AA and AC genotypes, with higher AUC0-t, AUC0-∞ and Cmax in carrier of AC genotype than in AA gen-otype (BH-adjusted p value <0.05). No associations were found between SNPs in CYP3A4, CYP2D6, CYP2C19, ABCB1, ABCG2 and the pharmacokinetics of gefitinib.The SNPs in CYP3A5*3 (rs776746) and CYP2C9*3 (rs1057910) were found to be associated with altered gefitinib pharmacokinetics in healthy Chinese volunteers.

Eight Hypotheses on Technology Use and Psychosocial Wellbeing: A Bicultural Phenomenological Study of Gaming during the COVID-19 Pandemic.

In this nonconfirmatory qualitative study, we pursued a range of hypotheses regarding how gaming operates in the lives and psychosocial wellbeing of those who actively play videogames during a crisis, such as the COVID-19 pandemic in 2020. Informed by an explorative survey (N = 793), interpretive phenomenological analysis was applied to interview data from actively gaming Chinese (n = 10) and Finnish (n = 10) participants. Our findings demonstrate how the general increase of pandemic-time gaming did not manifest in all player groups, but in some life contexts gaming activity rather decreased along with reformations in subjective meaning hierarchies and values. Ultimately, eight subordinate themes were refined into testable hypotheses. The study encourages policies that promote socially supportive gaming during pandemic-like situations to consider including personally meaningful solitary play in their recommendations and highlighting context-specificity over generalization. Finally, as almost all our data points echoing experiences of decreasing gaming activity came from China, we stress the importance of culturally diverse samples in the psychological study of global phenomena. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03586-x.

Pharmacokinetics and Bioequivalence of 2 Oral Formulations of Domperidone After Single-Dose Administration in Healthy Chinese Subjects.

To evaluate the pharmacokinetic properties and bioequivalence of 2 oral formulations of domperidone in healthy Chinese subjects, a randomized, open-label, 2-way crossover study was conducted under fasting and fed states. All 96 healthy subjects were randomized to receive a single oral dose of a 10-mg generic domperidone tablet (test) or branded domperidone tablet (reference). Blood samples were collected at specified time intervals and analyzed for domperidone using liquid chromatography-tandem mass spectrometry. In the fasting test, 90% CIs of geometric mean ratios were 86.7% to 105.8% for maximum concentration, 96.7% to 106.1% for area under the concentration-time curve (AUC) from time 0 to the time of the last measurable plasma concentration, and 97.1% to 106.1% for AUC from time 0 extrapolated to infinity. In the fed test, the 90% CIs were 90.8% to 121.1%, 99.7% to 109.4%, and 99.4% to 109.1%, respectively. All 90% CIs were within the bioequivalence range of 80% to 125%, indicating that the 2 formulations were bioequivalent. In addition, the values of time to maximum concentration, terminal-phase elimination half-life, and AUC were significantly higher in the fed group than in the fasting group, suggesting that a high-fat meal slowed down the absorption and elimination of domperidone and significantly increased domperidone exposure.

The Influence of Green Brand Affect on Green Purchase Intentions: The Mediation Effects of Green Brand Associations and Green Brand Attitude.

This study investigates the impact of green brand affect on green purchase intentions and explores the mediation effects of green brand attitude and green brand associations by means of the structural equation model (SEM). There is no previous literature discussing the relationship between brand affect and purchase intentions from the perspective of green marketing. Therefore, this article establishes a green purchase intention framework to fill in the research gap. The research object of this study focuses on Taiwanese consumers who have the purchase experience of information and electronics products in Taiwan. A total of 1000 consumers were randomly selected and 365 valid responses were received. In addition, this research conducted an empirical study using a questionnaire survey and structural equation model (SEM) to verify the research framework. The results show that green brand affect has no direct influence on green purchase intentions. Besides, this study indicates that green brand associations and green brand attitude fully mediate the relationship between green brand affect and green purchase intentions. It implies that green brand affect indirectly influences green purchase intentions via green brand attitude and green brand associations. While companies tend to raise their customers' green purchase intentions, they need to increase their green brand affect, green brand associations, and green brand attitude.

Long-term monitoring reveals invariant clutch size and unequal reproductive costs between sexes in a subtropical lacertid lizard.

Based on 20,000 records representing c. 11,000 individuals from an 8-year capture-mark-recapture (CMR) study, we tested and confirmed a new case of invariant clutch size (ICS) in a sexually dichromatic lacertid lizard, Takydromus viridipunctatus. In the grassland habitat of the early succession stage, females showed strictly low and invariant clutch size, multiple clutches in a breeding season, high reproductive potential, and annual breeding cycles that correspond to the emergence of male courtship coloration. The hatchlings mature quickly, and join the adult cohort for breeding within a few months, whereas adults show low survival rates and a short lifespan, such that most die within one year. Mortality increased in both sexes during the breeding season, especially in females, indicating an unequal cost of reproduction in survival. These life history characters may be explained by two non-exclusive hypotheses of ICS-arboreal hypothesis and predation hypothesis-within the ecological context of their habitat. Our study highlights a confirmed case of ICS, which adapts well to this r-selected grassland habitat that experiences seasonal fluctuation and frequent disturbance.

Serum Lipidomics Profiling to Identify Biomarkers for Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, which ranks top in both incidence and mortality. To broaden our understanding of the lipid metabolic alterations in NSCLC and to identify potential biomarkers for early diagnosis, we performed nontargeted lipidomics analysis in serum from 66 early-stage NSCLC, 40 lung benign disease patients (LBD), and 40 healthy controls (HC) using Ultrahigh Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-Q-TOF/MS). The identified biomarker candidates of phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) were further externally validated in a cohort including 30 early-stage NSCLC, 30 LBD, and 30 HC by a targeted lipidomic analysis. We observed a significantly altered lipid metabolic profile in early-stage NSCLC and identified panels of PCs and PEs to distinguish NSCLC patients and HC. The levels of PCs and PEs were found to be dysregulated in glycerophospholipid metabolism, which was the top altered pathway in early-stage NSCLC. Receiver operating characteristic (ROC) curve analysis revealed that panels of PCs and PEs exhibited good performance in differentiating early-stage NSCLC and HC. The levels of PE(16:0/16:1), PE(16:0/18:3), PE(16:0/18:2), PE(18:0/16:0), PE(17:0/18:2), PE(18:0/17:1), PE(17:0/18:1), PE(20:5/16:0), PE(18:0/18:1), PE(18:1/20:4), PE(18:0/20:3), PC(15:0/18:1), PC(16:1/20:5), and PC(18:0/20:1) in early-stage NSCLC were significantly increased compared with HC (p<0.05). Overall, our study has thus highlighted the power of using comprehensive lipidomic approaches to identify biomarkers and underlying mechanisms in NSCLC.

Simultaneous quantification of serum monounsaturated and polyunsaturated phosphatidylcholines as potential biomarkers for diagnosing non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide. In this study, we investigated Ultrahigh Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry and Gas Chromatography Time-of-Flight/Mass Spectrometry-based non-targeted metabolomic profiles of serum samples obtained from early-stage NSCLC patients and healthy controls (HC). Metabolic pathways and the biological relevance of potential biomarkers were extensively studied to gain insights into dysregulated metabolism in NSCLC. The identified biomarker candidates were further externally validated via a targeted metabolomics analysis. The global metabolomics profiles could clearly distinguish NSCLC patients from HC. Phosphatidylcholine (PC) levels were found to be dysregulated in glycerophospholipid (GPL) metabolism, which was the top altered pathway in early-stage NSCLC. Compared with those in HC, significant increases in the levels of saturated and monounsaturated PCs such as PC (15:0/18:1), PC (18:0/16:0) and PC (18:0/20:1) were observed in NSCLC. Additionally, relative to those in HC, the levels of 9 polyunsaturated PCs, namely, PC (17:2/2:0), PC (18:4/3:0), and PC (15:0/18:2), and so on were significantly decreased in NSCLC patients. A panel of 12 altered PCs had good diagnostic performance in differentiating early-stage NSCLC patients from HC, and these PCs may thus be used as serum biomarkers for the early diagnosis of NSCLC.

MiR-1260b promotes the migration and invasion in non-small cell lung cancer via targeting PTPRK.

OBJECTIVE: Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases which cause most of cancer-related deaths globally. As our previous study discovered miR-1260b can be regarded as a specific signature for metastasis in NSCLC patients. However, the molecular mechanisms of miR-1260b underlying NSCLC progression and metastasis remain dismal. METHODS: The expression of miR-1260b in NSCLC tissues and cell lines were examined by real-time PCR, the effects of miR-1260b on cell migration, invasion and proliferation were evaluated in vitro. Furthermore, luciferase reporter assay was performed to identify the targets of miR-1260b, and the association between miR-1260b and its target gene was determined by real-time PCR and western blot assay. RESULTS: The results showed that miR-1260b was significantly upregulated in NSCLC cell lines. The inhibition of miR-1260b expression decreased the migratory and invasive rates in A549 cells while miR-1260b overexpression had the opposite effect. Furthermore, PTPRK was identified as a direct target of miR-1260b, and PTPRK expression was inversely correlated with miR-1260b in NSCLC cell lines and clinical tissues. CONCLUSIONS: These results suggested that miR-1260b may play an important role in NSCLC metastasis progression and could serve as a putative target for diagnosis and treatment of NSCLC.

Astrocyte elevated gene-1 is overexpressed in non-small-cell lung cancer and associated with increased tumour angiogenesis.

OBJECTIVES: Astrocyte elevated gene-1 (AEG-1) functions to mediate angiogenesis, and its upregulation is responsible for tumour angiogenesis during cancer development. This study analysed AEG-1 expression in non-small-cell lung cancer (NSCLC) for association with NSCLC clinicopathological features and tumour angiogenesis. METHODS: The expression of AEG-1, vascular endothelial growth factor and intratumoural microvessel density (assessed using the expression of CD105) was detected by immunohistochemistry in 88 paired tumour tissue and adjacent normal tissue specimens obtained from NSCLC patients. The Kaplan-Meier curves were used for survival analysis through an online tool (http://kmplot.com/analysis/). RESULTS: AEG-1 was overexpressed in 61.3% of NSCLC tissues vs 6.8% (6/88) of normal tissues (P < 0.001). AEG-1 expression in NSCLC was significantly associated with advanced pTNM stage (P = 0.021), tumour dedifferentiation (P = 0.034), vascular invasion (P = 0.035), lymph node metastasis (P < 0.001) and poor overall survival (P = 0.024). Moreover, the expression of AEG-1 in NSCLC was associated with tumour angiogenesis; that is, vascular endothelial growth factor overexpression (P < 0.001) and intratumoural microvessel density (P < 0.001). CONCLUSIONS: This study demonstrates that AEG-1 expression is associated with NSCLC development, angiogenesis, progression and poor prognosis, indicating that the adjuvant therapy with antiangiogenic agent be adopted for the early postoperative period before the start of conventional chemotherapy in patients with AEG-1 overexpressed NSCLC.

AEG-1 mRNA expression in non-small cell lung cancer is associated with increased tumor angiogenesis.

Astrocyte-elevated gene-1 (AEG-1) is implicated in the oncogenesis and angiogenesis of various types of human malignant disease. However, the angiogenesis roles of AEG-1 in non-small cell lung cancer (NSCLC) remain to be further elucidated. In the present study, the expression level of AEG-1 mRNA in seven human lung cell lines and 89 paired tissue samples (tumor tissues (TTs) and pair-matched normal adjacent tissues (PMNATs)) from NSCLC patients was detected by real-time PCR. Staining of vascular endothelial growth factor (VEGF) and intratumoral microvessel density (iMVD, labeled by CD105) were assessed by immunohistochemistry. Furthermore, cell migration and invasion were evaluated by wound healing assay and transwell assays. AEG-1 mRNA level was significantly higher in human lung cancer cells and TTs than that in human normal bronchial epithelial cell line 16HBE and PMNATs, respectively (P<0.001). Higher AEG-1 mRNA level in patients with NSCLC was correlated with clinical stages (P=0.028), differentiation (P=0.042), and lymph node metastasis (P=0.004). Moreover, Upregulated AEG-1 mRNA expression level was associated with higher tumor angiogenesis, reflected by the increase of VEGF expression and iMVD counting (P=0.021, P<0.001). However, 95D cell line transfected with AEG-1 siRNA oligos (siAEG-1) exhibited no significant decrease of cell invasion or migration capacities when compared with the control cells (P>0.05).These results suggested that AEG-1 may play important roles at the transcription level in malignant transformation and tumor angiogenesis in NSCLC, and anti-AEG-1 mRNA expression may be a novel potential strategy for anti-angiogenic therapy of NSCLC.

Metabolic Profiling of Plasma in Gestational Diabetes Mellitus Using Liquid Chromatography and Q-TOF Mass Spectrometry.

BACKGROUND: To delineate the metabolomic profiling and identify early diagnostic biomarkers in maternal plasma from the pregnant women who subsequently developed gestational diabetes mellitus (GDM) using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-Q-TOF MS). METHODS: Plasma samples were collected from GDM pregnant women (n = 30) and healthy controls (n = 30) at the 20th gestational week in Huzhou Central Hospital and Huzhou Maternal and Child Health Hospital. The principle component analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and orthogonal PLS (OPLS) were sequentially applied to discover the differential metabolites for GDM diagnosis. Further, we analyzed the identified biomarkers in the MetPA database in order to reveal the key relevant metabolism in GDM. RESULTS: Twenty-four out of 975 aligned metabolites were distinguished among GDM plasma and healthy controls. In particular, the level of linolenic acid and arachidonic acid was significantly elevated in GDM. CONCLUSIONS: The linolenic acid and arachidonic acid could be selected as new potent biomarkers for GDM diagnosis and prognosis in early pregnancy; however, they still need to be confirmed from large samples in future.

Tail regeneration after autotomy revives survival: a case from a long-term monitored lizard population under avian predation.

Caudal autotomy in lizards has intrigued scientists for more than 100 years. Because of the relative lack of literature under natural conditions, the complicated association among field autotomy rate, real predation pressure, the long-term cost of tail loss, and the benefit of regeneration remains equivocal. In this study, we conducted a 7-year capture-mark-recapture (CMR) programme with a wild population of a sexually dichromatic lizard, Takydromus viridipunctatus We used autotomy indexes and a contemporary bird census mega-dataset of four predatory birds as predictors to examine the association between tail loss and predation pressure. We further estimated the survival cost of tail loss and alleviation by regeneration under natural conditions through CMR modelling. We found that large and small avian predators affect lizard survival through the following two routes: the larger-sized cattle egret causes direct mortality while the smaller shrikes and kestrels are the major causes of autotomy. Following autotomy, the survival rate of tailless individuals over the next month was significantly lower than that of tailed individuals, especially males during the breeding season, which showed a decline of greater than 30%. This sex-related difference further demonstrated the importance of reproductive costs for males in this sexually dichromatic species. However, the risk of mortality returned to baseline after the tails were fully grown. This study indicates the benefit of tail regeneration under natural conditions, which increases our understanding of the cost-benefit dynamics of caudal autotomy and further explains the maintenance of this trait as an evolutionarily beneficial adaption to long-term predator-prey interactions.

Augmented miR-10b expression associated with depressed expression of its target gene KLF4 involved in gastric carcinoma.

Previous studies have revealed several targets of miR-10b, such as syndecan-1, HOXD10, TBX5, and E-cadherin. In this study, we aimed to assess whether Krüppel-like factor 4 (KLF4) is a target gene of miR-10b in gastric cancer (GC). Targeting of KLF4 by miR-10b was confirmed by dual-luciferase reporter assays. The expression levels of miR-10b and KLF4 mRNA in 5 different gastric cancer cell lines and 65 pairs of gastric cancer tissues were detected by Real-time PCR. In addition, KLF4 protein in gastric cancer cell lines and 30 GC tissues was measured by western blotting and immunochemistry, respectively. KLF4 is a direct target gene of miR-10b in GC, and its expression is reduced by miR-10b at both mRNA and protein levels. In addition, the expression level of miR-10b was tendentiously upregulated in GC tissues while the expression levels of KLF4 mRNA and protein were decreased in gastric cancer tissues compared with normal adjacent tissue. There was a dramatically inverse correlation between the expression levels of miR-10b and KLF4 mRNA in GC (r=-0.339, P=0.006). These findings indicate that miR-10b was upregulated in GC and may have a key role in GC pathogenesis and development through the downregulation of its target gene KLF4.

Biomarker identification and pathway analysis by serum metabolomics of lung cancer.

Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC) curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA) and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.

Metabolomic profiling of human serum in lung cancer patients using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry and gas chromatography/mass spectrometry.

PURPOSE: Lung cancer is one of the most common causes of death from cancer. Serum markers that enable diagnosis of the disease in the early stage have not been found. METHODS: Serum samples were collected from 30 healthy volunteers and from 30 lung cancer patients preoperatively and postoperatively. Samples were subjected to metabolomic analysis using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry and gas chromatography/mass spectrometry. Differences in metabolomic profiles among the three groups were characterized by multivariate statistical techniques such as principal components analysis and partial least squares discriminant analysis (PLS-DA). An independent t test was used to determine whether levels of biomarker candidates identified using PLS-DA modeling were significantly different among groups at the univariate analysis level (p < 0.05). RESULTS: Based on pattern recognition results and univariate analysis, we showed that levels of ten potential biomarkers in serum were significantly different in the preoperative lung cancer patients compared with healthy volunteers and/or the postoperative lung cancer patients. The levels of sphingosine, phosphorylcholine, glycerophospho-N-arachidonoyl ethanolamine, γ-linolenic acid, 9,12-octadecadienoic acid, oleic acid, and serine were significantly different in preoperative lung cancer patients compared to healthy volunteers and to postoperative lung cancer patients. For prasterone sulfate, α-hydroxyisobutyric acid, 2,3,4-trihydroxybutyric acid, the levels were statistically different in preoperative and postoperative lung cancer patients compared with the healthy volunteers. CONCLUSIONS: Our study identified potential metabolic biomarkers for diagnosis of lung cancer.

Pharmacokinetic study of multiple active constituents after oral gavage of Guizhi decoction in rats using a LC-MS/MS method.

Guizhi decoction (GZD) is a classic traditional Chinese medicine formula, clinically used for the treatment of influenza, common cold, and other pyretic conditions. A sensitive, specific, and validated liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed to investigate the pharmacokinetic properties of cinnamic acid, hippuric acid, paeoniflorin, and glycyrrhetic acid in rat. After single dose oral administration of 7.9 g extract/kg body weight GZD in rats, plasma concentrations of cinnamic acid, hippuric acid, paeoniflorin, and glycyrrhetic acid were measured by LC-MS/MS. Pharmacokinetic parameters were calculated from the plasma concentration-time data. The values of AUC0-t, half-life (t 1/2), and C max were 7.2 ± 2.3 µg h/mL, 1.2 ± 0.3 h, and 9.2 ± 5.2 µg/mL for cinnamic acid, 53 ± 31 µg h/mL, 2.8 ± 2.0 h, and 17 ± 3 µg/mL for hippuric acid, 1.1 ± 0.5 µg h/mL, 1.9 ± 1.1 h, and 0.6 ± 0.3 µg/mL for paeoniflorin, and 11 ± 6 µg h/mL, 6.6 ± 2.5 h, and 0.9 ± 0.6 µg/mL for glycyrrhetic acid, respectively. The results would offer useful information for effective components of GZD in vivo.

Strict consistency between genetic and topographic landscapes of the brown tree frog (Buergeria robusta) in Taiwan.

Taiwan presents an excellent opportunity to build a phylogeographic paradigm for fine-scaled differentiation occurring within short distances on an single island. Due to the limitation of habitat availability on the island, demographic histories of species in Taiwan were strongly influenced by glacial-interglacial cycles. Nevertheless, there are relatively few studies demonstrating such phylogeographic patterns for islands, especially in subtropical Asia. In this study, we aim to construct the genetic landscape of a philopatric stream frog Buergeria robusta by an intense and fine-scaled collection throughout the island. The deduced genetic landscape of B. robusta presented extremely high congruence with the actual topography of Taiwan. Two major lineages were found on the eastern and the western sides of Taiwan with a non-overlapping distribution, indicating the importance of the Central Mountain Range as the major biogeographic barrier. Both clades showed a strong and congruent tendency of demographic or distributional expansion in recent history based on different analyses. Population expansion of such a subtropical lowland species might be a result from a release of available habitat in post-glacial periods.