Association between tea drinking and disability levels in older Chinese adults: a longitudinal analysis.

Objective: As the global population ages, disability among the elderly presents unprecedented challenges for healthcare systems. However, limited research has examined whether dietary interventions like tea consumption may alleviate and prevent disability in older adults. As an important dietary therapy, the health benefits of tea drinking have gained recognition across research disciplines. Therefore, this study aimed to investigate the association between tea drinking habits and disability levels in the elderly Chinese population. Methods: Leveraging data from the 2008 to 2018 waves of the Chinese Longitudinal Healthy Longevity Survey, we disaggregated tea drinking frequency and activities of daily living (ADL) measures and deployed fixed-effect ordered logit models to examine the tea-disability association for the first time. We statistically adjusted for potential confounders and conducted stratified analyses to assess heterogeneity across subpopulations. Results: Multivariable fixed-effect ordered logistic regression suggested tea drinking has protective effects against ADL disability. However, only daily tea drinking was associated with lower risks of basic activities of daily living (BADL) disability [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.41-0.92] and lower levels of instrumental activities of daily living (IADL) disability (OR = 0.78; 95% CI, 0.64-0.95). Stratified analyses indicated heterogeneous effects across age and income groups. Daily tea drinking protected against BADL (OR = 0.26 and OR = 0.28) and IADL disability (OR = 0.48 and OR = 0.45) for adults over 83 years old and high-income households, respectively. Conclusion: We found that drinking tea almost daily was protective against disability in elderly people, warranting further research into optimal dosages. Future studies should utilize more rigorous causal inference methods and control for confounders.

A survey of potential acceptance of 9-valent HPV vaccine among Chinese male college students.

Human papillomavirus (HPV) has a great impact on world health. Vaccination is among the most important methods of preventing HPV infection. This study investigated Chinese male college students' knowledge of, attitude toward, and acceptance of the 9vHPV vaccine and the independent predictors. An online cross-sectional study was conducted among male college students at Chinese colleges and universities from March 12 to March 23, 2022. Based on a literature review of similar studies, a self-questionnaire was designed to investigate the students' knowledge of, attitude toward, and acceptance of the 9vHPV vaccine. Multivariate logistic regression analysis was performed to identify factors influencing their willingness to be vaccinated. In addition, the structural equation model was constructed. A total of 1,547 male college students completed the survey. Of all the students, 54.95% were unwilling to receive a 9vHPV vaccination, while only 45.05% expressed willingness. Multivariate logistic regression analysis revealed that the male college students willing to receive the vaccine included medical students, those in a romantic relationship, those whose relatives and friends had cervical cancer, those whose relatives and friends had received the 9vHPV vaccine, those supportive of promoting the vaccine for men, and those who would recommend the vaccine to their relatives and friends. Male college students exhibited high hesitancy toward the 9vHPV vaccine. Acceptance of the 9vHPV vaccine by male college students can be improved by deepening their accurate understanding of the vaccine and enhancing their positive attitude toward it.

Tissue distribution and integrated pharmacokinetic properties of major effective constituents of oral Gegen-Qinlian decoction in mice.

Gegen-Qinlian decoction (GQD) is a classic traditional Chinese medicine (TCM) formula. GQD is effective against colon or liver-related diseases including ulcerative colitis, non-alcoholic fatty liver, and type 2 diabetes. In this study, a liquid chromatography-tandem mass spectrometry method was developed, validated, and then applied to reveal the tissue distribution and integrated pharmacokinetic properties of major effective constituents of oral GQD in mice. The established method was quick, sensitive, and accurate enough to analyze GQD constituents in plasma and tissue homogenate samples quantitatively. According to their concentrations in the portal vein, systemic circulation, liver and colon samples of the mice after oral administration of GQD, the concentration-time curves of the constituents were respectively plotted. The results showed that daidzein, baicalin, and baicalein had relatively high exposure levels in the livers, while puerarin, berberine, epiberberine, coptisine, palmatine, jatrorrhizine, magnoflorine, glycyrrhizic acid, and glycyrrhetinic acid were enriched in the colons. Given that these constituents have significant biological activity, they could be regarded as the major effective constituents of GQD in treating colon or liver-related diseases, respectively. In addition, the integrated pharmacokinetic properties of GQD were studied. The GQD "integrated constituent" reached peak concentration at 4.0 h in the portal vein, the systemic circulation, the livers, and the colons, with half-lives of 1.5-4.1 h and mean retention time of 4.5-6.3 h, respectively. Furthermore, the concentration of the GQD "integrated constituent" in the colons was approximately 10 times higher than that in the livers, both of which were much higher than that in the systemic circulation, indicating its accumulation in these tissues, especially in the colons. In conclusion, the tissue distribution and integrated pharmacokinetic properties of oral GQD were revealed in the study. The results of the tissue distribution study would contribute to identifying the major target tissues and effective constituents of GQD, while the results of the integrated pharmacokinetic study would help to explain the pharmacokinetic properties of oral GQD as a whole.

The distinct role of orbitofrontal and medial prefrontal cortex in encoding impulsive choices in an animal model of attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder affecting up to 5% of children worldwide. The lack of understanding of ADHD etiology prevented the development of effective treatment for the disease. Here, using in vivo electrophysiology recordings, we have recorded and analyzed the neuronal encoding of delay discounting behavior in prefrontal and orbitofrontal cortex of spontaneously hypertensive rat (SHR). We found that in the presence of rewards, neurons in the orbitofrontal cortex (OFC) were activated regardless to the value of the rewards and OFC neurons in SHR exhibited significantly higher rates of neuronal discharging towards the presence of rewards. While in the medial prefrontal cortex (mPFC), neurons of SHR responded similarly in the presence of large rewards compared with control rats whereas they displayed higher firing rates towards smaller rewards. In addition, the reward-predicting neurons in the OFC encodes for value of rewards in control animals and they were strongly activated upon receiving a small immediate reinforcer in the SHR whereas the reward-predicting neurons in the mPFC neurons generally did not respond to the value of the rewards. Our study characterized the neuronal discharging patterns of OFC and mPFC neurons in the SHR and the control animals and provided novel insights for further understanding the neuronal basis of ADHD pathology.

Antimicrobial Peptides-Loaded Hydroxyapatite Microsphere With Different Hierarchical Structures for Enhanced Drug Loading, Sustained Release and Antibacterial Activity.

Antimicrobial peptides (AMPs) have great potential for clinical treatment of bacterial infection due to the broad-spectrum and highly effective antibacterial activity. However, the easy degradation and inactivation in vivo has been a major obstacle for their application and an effective delivery system is demanding. The surface physicochemical properties of the carrier, including surface potential, surface polarity, pore structure and morphology, have exerted great effects on the adsorption and release behavior of AMPs. This study investigated the influence of micro/nano carriers with different hierarchical structures on the loading, release and biological behavior of AMPs. Three types of AMPs-loaded hydroxyapatite microspheres (HA/AMPs MSs) with different hierarchical structures (needle-like, rod-like, and flake-like) were developed, which was investigated by the surface morphology, chemical composition and surface potential in detail. The different hierarchical structures of hydroxyapatite microspheres (HA MSs) had noticeable impact on the loading and release behavior of AMPs, and the flake-like HA MSs with hierarchical structure showed the highest loading efficiency and long-lasting release over 9 days. Meanwhile, the stability of AMPs released from HA MSs was effectively maintained. Moreover, the antibacterial test indicated that the flake-like HA/AMPs MSs showed more sustained antibacterial properties among three composites. In view of the excellent biocompatibility and osteogenic property, high loading efficiency and the long-term release properties of HA MSs with hierarchical structure, the HA/AMPs MSs have a great potential in bone tissue engineering.

m6A RNA methylation regulators were associated with the malignancy and prognosis of ovarian cancer.

N6-methyladenosine (m6A) RNA methylation regulators play a regulatory role in tumor pathogenesis and development. However, the role of m6A regulator genes in ovarian cancer (OC) has not been fully elucidated. This study aims to investigate the mRNA expressions, clinicopathological features, and prognostic values of m6A regulators in OC. Here, we demonstrate that the 17 m6A RNA methylation regulators are differentially expressed in ovarian cancer and normal tissues. By using consensus clustering, all ovarian cancer patients can be divided into two subgroups (cluster 1 and 2) based on the expression of 17 m6A RNA methylation regulators. Using Gene Set Enrichment Analysis, we identified that cluster 1 was most connected to oxidative phosphorylation pathways. Regression models identified that prognosis is associated with HNRNPA2B1, KIAA1429, and WTAP. qRT-PCR result show that the expression trends of HNRNPA2B1 and KIAA1429 are consistent with the predicted results. Multivariate Cox regression analysis results show that the risk score was an independent predictive factor in OV. The overall survival of high-risk patients was significantly shorter than that of low-risk patients. ROC curve analysis showed that the prognostic signature precisely predicted the 5-year survival of OV patients. A nomogram was developed to predict each patient's survival probability and well calibrated and showed a satisfactory discrimination. Dendritic fraction, macrophage fraction, and neutrophil fraction showed higher fraction in high-risk patients. In conclusion, m6A RNA methylation regulators are vital participants in ovarian cancer pathology, and three-gene mRNA levels are valuable factors for prognosis predictions.

Acute Mitral Valve Injury Following Percutaneous Left Atrial Appendage Occlusion: A Case Report and Literature Review.

Acute mitral valve injury following percutaneous left atrial appendage (LAA) occlusion is a rare, but potentially life-threatening complication. This report presents a case of severe mitral valve injury following left atrial appendage occlusion (LAAO) that required mitral valve replacement. The LAAO device successfully was removed, and the LAA was closed with a double-running polypropylene suture. In addition, the mitral valve was replaced with an artificial valve. The patient had an uneventful clinical evolution and was discharged 10 days after emergency surgery.

Several critical genes and microRNAs associated with the development of polycystic ovary syndrome.

BACKGROUND: We aimed to identify key genes and microRNAs (miRNAs) associated with the development of polycystic ovary syndrome (PCOS). METHODS: GSE84376 mRNA microarray data (15 PCOS granulosa cells and 13 control granulosa cells) and GSE34526 mRNA microarray data (7 PCOS granulosa cells and 3 control granulosa cells) were downloaded from the Gene Expression Omnibus (GEO) database. First, differentially expressed gene (DEG) analysis, gene set enrichment analysis (GSEA) for differentially expressed mRNAs, and protein-protein interaction (PPI) network analysis were conducted. Next, miRNA-target genes were analyzed and functions predicted, and a competing endogenous RNA (ceRNA) network was constructed. Finally, the relationship between miR-486-5p and PRELID2 was experimentally validated. RESULTS: Spleen tyrosine kinase (SYK), major histocompatibility complex, class II, DR alpha (HLA-DRA), and interleukin 10 (IL-10) were important nodes in the PPI network. Interestingly, HLA-DRA was significantly enriched in phagosomes mediated by Staphylococcus aureus infection, and in IL-10 enriched during S. aureus infection. One miRNA (miR-486-5p) and a single target gene (PRELID2) were obtained from the ceRNA network. Further experiments showed that miR-486-5p is upregulated and PRELID2 is downregulated in PCOS patient granulosa cells, and that miR-486-5p targets the PRELID2 3'UTR. Topological property analysis showed that hsa-miR-4687-5p downregulation and hsa-miR-4651 upregulation determined the levels of most mRNAs. Levels of the hsa-miR-4651 target gene were significantly enriched in the leukocyte transendothelial migration pathway. CONCLUSIONS: Our results suggest that HLA-DRA and IL-10 may contribute to PCOS progression via phagosome enriched by S. aureus infection, while miR-486-5p may be implicated in follicular development in PCOS by targeting PRELID2. Besides, miR-4651 may be involved in inflammation via leukocyte transendothelial migration, by regulating its target gene. These findings may indicate new directions and constitute a breakthrough in studying the pathophysiology of PCOS.

Controlling magnesium corrosion and degradation-regulating mineralization using matrix GLA protein.

Magnesium (Mg) alloys are embraced for their biodegradability and biocompatibility. However, Mg degrades spontaneously in the biological environment in vivo and in vitro, triggering deposition of calcium phosphate on the metal. Upon complete metal absorption, minerals remain in the tissue, which could lead to pathogenic calcification. Hence, our aims are to test the feasibility of matrix GLA protein (MGP) to locally inhibit Mg mineralization that is induced by metal alloy degradation. MGP is a small secretory protein that has been shown to inhibit soft tissue calcification. We exposed Mg to MGP, stably transfected into mammalian cells. Results showed that less calcium and phosphorous deposition on the Mg surface when MGP was present relative to when it was not. In the in vivo mouse intramuscular model conducted for 4 and 6 weeks, Mg rods were embedded in collagen scaffolds, seeded with cells overexpressing MGP. Microtomography, electron dispersive x-ray spectroscopy, and histology assessments revealed lower deposited mineral volume around Mg rods from the MGP group. Compared to other groups, higher volume loss after implantation was observed from the MGP group at both time points, indicating a higher corrosion rate without the protective mineral layer. This study is the first to our knowledge to demonstrate that local exposure to a biomolecule, such as MGP, can modulate the corrosion of Mg-based implants. These findings may have important implications for the future design of endovascular stents and orthopedic devices.

An in vitro model of foam cell formation induced by a stretchable microfluidic device.

Although a variety of animal models of atherosclerosis have been developed, these models are time-consuming and costly. Here, we describe an in vitro model to induce foam cell formation in the early stage of atherosclerosis. This model is based on a three-dimension co-culture system in a stretchable microfluidic device. An elastic membrane embedded in the microfluidic device is capable of delivering nonuniform strain to vascular smooth muscle cells, endothelial cells and monocytes adhering thereto, which are intended to mimic the biological environment of blood vessels. Under low-density lipoprotein and stretch treatment, foam cell formation was successfully induced in co-culture with changes in mRNA and protein expression of some related key factors. Subsequently, the model was used to assess the inhibitory effect of atorvastatin on foam cell formation. The results obtained indicate that atorvastatin has a significantly dose-dependent inhibition of foam cell formation, which can be explained by the changes in mRNA and protein expression of the related factors. In principle, the model can be used to study the role of different types of cells in the formation of foam cells, as well as the evaluation of anti-atherosclerotic drugs.

Neurons in rat orbitofrontal cortex and medial prefrontal cortex exhibit distinct responses in reward and strategy-update in a risk-based decision-making task.

The orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC) are known to participate in risk-based decision-making. However, whether neuronal activities of these two brain regions play similar or differential roles during different stages of risk-based decision-making process remains unknown. Here we conducted multi-channel in vivo recordings in the OFC and mPFC simultaneously when rats were performing a gambling task. Rats were trained to update strategy as the task was shifted in two stages. Behavioral testing suggests that rats exhibited different risk preferences and response latencies to food rewards during stage-1 and stage-2. Indeed, the firing patterns and numbers of non-specific neurons and nosepoking-predicting neurons were similar in OFC and mPFC. However, there were no reward-expecting neurons and significantly more reward-excitatory neurons (fired as rats received rewards) in the mPFC. Further analyses suggested that nosepoking-predicting neurons may encode the overall value of reward and strategy, whereas reward-expecting neurons show more intensive firing to a big food reward in the OFC. Nosepoking-predicting neurons in mPFC showed no correlation with decision-making strategy updating, whereas the response of reward-excitatory neurons in mPFC, which were barely observed in OFC, were inhibited during nosepoking, but were enhanced in the post-nosepoking period. These findings indicate that neurons in the OFC and mPFC exhibit distinct responses in decision-making process during reward consumption and strategy updating. Specifically, OFC encodes the overall value of a choice and is thus important for learning and strategy updating, whereas mPFC plays a key role in monitoring and execution of a strategy.

Anticorrosive Self-Assembled Hybrid Alkylsilane Coatings for Resorbable Magnesium Metal Devices.

Magnesium (Mg) and its alloys are promising candidates for use as resorbable materials for biomedical devices that can degrade in situ following healing of the defect, eliminating the need for a second surgery to remove the device. Hydrogen gas is the main product of magnesium corrosion, and one of the limitations for use of Mg devices in clinic is the formation of gas pockets around them. One potential solution to this problem is reducing the rate of corrosion to the levels at which H2 can diffuse through the body fluids. The study's aim was to evaluate the potential of hybrid alkylsilane self-assembled multilayer coatings to reduce Mg corrosion and to modify physicochemical properties of the coatings using surface functionalization. The coating was made by copolymerization of n-Decyltriethoxysilane and Tetramethoxysilane followed by dip coating of metal discs. This resulted in a formation of homogeneous, micron thick, and defect free coating. The coated surface was more hydrophobic than bare Mg, however functionalization of the coating with 3-aminopropyltriethoxysilane reduced the hydrophobicity of the coating. The coatings reduced several fold the rate of Mg corrosion based on the H2 evolution and other assessment methods, and effectively prevented the initial corrosion burst over the first 24 h. In vitro tissue culture studies demonstrated cytocompatibility of the coatings. These results reveal excellent anticorrosive properties and good cytocompatibility of the hybrid alkylsilane coatings and suggest great potential for use of these coatings on resorbable Mg devices.

Repetitive and Prolonged Omega-3 Fatty Acid Treatment After Traumatic Brain Injury Enhances Long-Term Tissue Restoration and Cognitive Recovery.

Traumatic brain injury (TBI) is one of the most disabling clinical conditions that could lead to neurocognitive disorders in survivors. Our group and others previously reported that prophylactic enrichment of dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) markedly ameliorate cognitive deficits after TBI. However, it remains unclear whether a clinically relevant therapeutic regimen with n-3 PUFAs administered after TBI would still offer significant improvement of long-term cognitive recovery. In the present study, we employed the decline of spatial cognitive function as a main outcome after TBI to investigate the therapeutic efficacy of post-TBI n-3 PUFA treatment and the underlying mechanisms. Mice were subjected to sham operation or controlled cortical impact, followed by random assignment to receive the following four treatments: (1) vehicle control; (2) daily intraperitoneal injections of n-3 PUFAs for 2 weeks, beginning 2 h after TBI; (3) fish oil dietary supplementation throughout the study, beginning 1 day after TBI; or (4) combination of treatments (2) and (3). Spatial cognitive deficits and chronic brain tissue loss, as well as endogenous brain repair processes such as neurogenesis, angiogenesis, and oligodendrogenesis, were evaluated up to 35 days after TBI. The results revealed prominent spatial cognitive deficits and massive tissue loss caused by TBI. Among all mice receiving post-TBI n-3 PUFA treatments, the combined treatment of fish oil dietary supplement and n-3 PUFA injections demonstrated a reproducible beneficial effect in attenuating cognitive deficits although without reducing gross tissue loss. Mechanistically, the combined treatment promoted post-TBI restorative processes in the brain, including generation of immature neurons, microvessels, and oligodendrocytes, each of which was significantly correlated with the improved cognitive recovery. These results indicated that repetitive and prolonged n-3 PUFA treatments after TBI are capable of enhancing brain remodeling and could be developed as a potential therapy to treat TBI victims in the clinic.

A Post-stroke Therapeutic Regimen with Omega-3 Polyunsaturated Fatty Acids that Promotes White Matter Integrity and Beneficial Microglial Responses after Cerebral Ischemia.

White matter injury induced by ischemic stroke elicits sensorimotor impairments, which can be further deteriorated by persistent proinflammatory responses. We previously reported that delayed and repeated treatments with omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve spatial cognitive functions and hippocampal integrity after ischemic stroke. In the present study, we report a post-stroke n-3 PUFA therapeutic regimen that not only confers protection against neuronal loss in the gray matter but also promotes white matter integrity. Beginning 2 h after 60 min of middle cerebral artery occlusion (MCAO), mice were randomly assigned to receive intraperitoneal docosahexaenoic acid (DHA) injections (10 mg/kg, daily for 14 days), alone or in combination with dietary fish oil (FO) supplements starting 5 days after MCAO. Sensorimotor functions, gray and white matter injury, and microglial responses were examined up to 28 days after MCAO. Our results showed that DHA and FO combined treatment-facilitated long-term sensorimotor recovery and demonstrated greater beneficial effect than DHA injections alone. Mechanistically, n-3 PUFAs not only offered direct protection on white matter components, such as oligodendrocytes, but also potentiated microglial M2 polarization, which may be important for white matter repair. Notably, the improved white matter integrity and increased M2 microglia were strongly linked to the mitigation of sensorimotor deficits after stroke upon n-3 PUFA treatments. Together, our results suggest that post-stroke DHA injections in combination with FO dietary supplement benefit white matter restoration and microglial responses, thereby dictating long-term functional improvements.

Delayed Docosahexaenoic Acid Treatment Combined with Dietary Supplementation of Omega-3 Fatty Acids Promotes Long-Term Neurovascular Restoration After Ischemic Stroke.

Prophylactic dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been shown to remarkably ameliorate ischemic brain injury. However, the therapeutic efficacy of n-3 PUFA administration post-stroke, especially its impact on neurovascular remodeling and long-term neurological recovery, has not been fully characterized thus far. In this study, we investigated the effect of n-3 PUFA supplementation, as well as in combination with docosahexaenoic acid (DHA) injections, on long-term stroke outcomes. Mice were subjected to transient middle cerebral artery occlusion (MCAO) before randomly assigned to four groups to receive the following: (1) low dose of n-3 PUFAs as the vehicle control, (2) intraperitoneal DHA injections, (3) n-3 PUFA dietary supplement, or (4) combined treatment of (2) and (3). Neurological deficits and brain atrophy, neurogenesis, angiogenesis, and glial scar formation were assessed up to 28 days after MCAO. Results revealed that groups 2 and 3 showed only marginal reduction in post-stroke tissue loss and attenuation of cognitive deficits. Interestingly, group 4 exhibited significantly reduced tissue atrophy and improved cognitive functions compared to groups 2 and 3 with just a single treatment. Mechanistically, the combined treatment promoted post-stroke neurogenesis and angiogenesis, as well as reduced glial scar formation, all of which significantly correlated with the improved spatial memory in the Morris water maze. These results demonstrate an effective therapeutic regimen to enhance neurovascular restoration and long-term cognitive recovery in the mouse model of MCAO. Combined post-stroke DHA treatment and n-3 PUFA dietary supplementation thus may be a potential clinically translatable therapy for stroke or related brain disorders.

Severity-Dependent Long-Term Spatial Learning-Memory Impairment in a Mouse Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major cause of death and disability in young adults. Long-term mental disability often occurs in patients suffering moderate and severe TBI while not as frequent in the victims of mild TBI. To explore the potential mechanism underlying this severity-dependent cognitive deficit, we subjected C57/BL6 mice to different severities of controlled cortical impact (CCI) and assessed their learning-memory functions. The mice subjected to moderate and severe TBI exhibited significantly impaired long-term spatial learning-memory ability, which was accompanied by marked white matter injury and hippocampus damage. In contrast, long-term learning-memory deficits or structural abnormalities within the hippocampus or white matter were not significant in the case of mild TBI. According to a correlation analysis, the hippocampus or white matter injury severity was more relevant to Morris water maze outcome than tissue volume. This study revealed that long-term spatial learning-memory deficits are dependent on the severity of destruction in the white matter and hippocampus. Therapeutic strategies targeting both the white matter and hippocampus may be needed to improve the neurological functions in TBI victims.

White matter injury in ischemic stroke.

Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions.

Mechanistic studies of the transport of peimine in the Caco-2 cell model.

Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of the liver and cervix. Although the alkaloid, peimine, is largely responsible for these pharmacological effects, it has very low oral bioavailability. The aim of this study was to investigate the intestinal absorption of peimine in Caco-2 cell monolayers. Having demonstrated that peimine is non-toxic to Caco-2 cells at concentrations <200 µmol/L, the effect of peimine concentration, pH, temperature, efflux transport protein inhibitors and EDTA-Na2 on peimine transport were studied. The results show that peimine transport is concentration-dependent; that at pH 6.0 and 7.4, the P app(AP-BL) of peimine is not significantly different but the P app(BL-AP)) is; that both P app(AP-BL) and P app(BL-AP) at 4 °C are significantly higher than their corresponding values at 37 °C; that the P-glycoprotein (P-gp) inhibitors, verapamil and cyclosporin A, increase absorption of peimine; and that EDTA-Na2 has no discernible effect. In summary, the results demonstrate that the intestinal absorption of peimine across Caco-2 cell monolayers involves active transport and that peimine is a substrate of P-gp.