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Yi Lu

Publications and source records attributed to Yi Lu.

At least 19 recordsLinked to original sources
PubMed2026

Genomic meta-analyses of binge-eating behavior and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes.

Eating disorders-including anorexia nervosa (AN), bulimia nervosa and binge-eating disorder-are clinically distinct but exhibit symptom overlap and diagnostic crossover. Genomic analyses have mostly examined AN. Here we conducted a genomic meta-analysis of case-control studies of binge-eating behavior (BE; 39,279 cases, 1,227,436 controls), alongside analyses of AN (24,223 cases, 1,243,971 controls) and its subtypes (all European ancestries). We identified six BE-associated loci, including loci associated with a higher body mass index and impulse-control behaviors. AN genome-wide association studies yielded eight loci, validating six loci. Subsequent polygenic risk score analysis demonstrated an association with AN in two East Asian ancestry studies. BE and AN exhibited similar positive genetic correlations with psychiatric disorders but opposing genetic correlations with anthropometric traits. Most of the genetic signal in BE and AN was not shared with body mass index. We have extended eating disorder genomics beyond AN; future work will incorporate multiple diagnoses and global ancestries.

Behavioural genetics↗
PubMed2026

TPMM: three-component posterior mixture model enables robust inverton detection in low-depth metagenomes and suggests potential viral invertons.

SUMMARY: Bacterial phase variation enables reversible, locus-specific phenotypic switching, often driven by DNA inversion (invertons). To identify these events, researchers commonly rely on sequencing reads that provide orientation-specific support. Metagenomic sequencing, which captures total genetic material independent of cultivation, offers a powerful platform for the comprehensive study of invertons. However, computational inverton calling from metagenomic data is difficult at low sequencing depth: hard read-support cutoffs can miss true events, while sequence-only predictors lack read-backed interpretability and uncertainty quantification. To address this, we present TPMM, a three-component posterior mixture model for inverton calling in metagenomic data. TPMM explicitly incorporates sequencing depth to formulate inverton detection as a probabilistic mixture problem. Starting from candidates flanked by inverted repeats, the model classifies the candidates into noise, low-probability, or high-probability inversion signals using read evidence. Finally, TPMM assigns posterior probabilities as soft labels and applies cumulative Bayesian False Discovery Rate control to robustly identify true invertons. On two real gut metagenomic datasets, TPMM agrees well with PhaseFinder at high depth but recovers substantially more invertons under systematic downsampling, demonstrating superior performance in sparse-data regimes. We further examine potential reversible inversion elements in viral genomes and provide supporting analyses, suggesting a broader scope for inversion-mediated regulation. AVAILABILITY: The source code of TPMM is available via: https://github.com/KennyxxD/TPMM.

Metagenomics↗
PubMed2026

Risk of subsequent self-harm, suicide attempts and suicide following a first hospital-treated self-harm episode among young people: a population-based cohort study.

BACKGROUND: Self-harm in young people is associated with elevated risks for subsequent self-harm, suicide attempts and suicide, particularly during the first year. Yet the trajectory across sex, age and self-harm methods remains poorly understood. OBJECTIVE: To estimate risk for subsequent self-harm, suicide attempts and suicide following a first hospital-treated self-harm event in young people. METHODS: This study included 77 647 individuals (57.0% female) whose first hospital-treated (ie, within inpatient or outpatient specialised healthcare) self-harm episode occurred between ages 10-24 years during 1973-2019. We estimated cumulative incidence and incidence rate for subsequent self-harm, suicide attempts and suicide at 1 month, 3 months and 1 year following the initial episode. FINDINGS: Within 1 year, the cumulative incidence was 17.3% (95% CI 17.0 to17.5) for subsequent self-harm, 8.3% (8.1 to 8.5) for suicide attempt and 0.3% (0.2 to 0.3) for suicide. The highest risks occurred in the first month: 8.4% (8.2 to 8.6) for self-harm, 2.9% (2.8 to 3.0) for suicide attempt and 0.04% (0.03 to 0.05) for suicide. In the first month, the incidence rate of self-harm was 2.97 per 1000 person-days (2.90 to 3.05), falling to 0.55 (0.54 to 0.56) over the year. The suicide attempt rate declined from 0.98 (0.94 to 1.02) to 0.24 (0.24 to 0.25) and the suicide rate from 0.013 (0.009 to 0.019) to 0.007 (0.006 to 0.008). Males exhibited the highest suicide risk and females the highest attempts risk. First-month self-harm risk was greatest among males and children aged 10-12. CONCLUSIONS: The month following a self-harm episode is marked by an elevated risk of subsequent self-harm, suicide attempts and suicide, yet risk remains elevated over the full year. CLINICAL IMPLICATIONS: These findings underscore the need for both acute and sustained prevention efforts. Special attention should be given to males and children aged 10-12 presenting with self-harm of ambiguous intent, as their risk of repetition may otherwise go unrecognised.

Humans↗
PubMed2025

Genome-wide association study of adolescent-onset depression.

Adolescent depression is a heritable psychiatric condition with rising global prevalence and severe long-term outcomes, yet its biological underpinnings remain poorly understood. We conducted the first genome-wide association study of adolescent-onset depression, comprising 102,428 cases (diagnosis or clinical symptom thresholds) and 286,911 controls, including diverse ancestries. Cross-ancestry meta-analysis identified 52 independent variants across 17 loci; European-only analysis found 61 variants at 29 loci, with a SNP-based heritability of 9.8%. Comparative analyses revealed two genes unique to adolescent-onset versus lifetime depression, enriched in neuronal subtypes, and two genes as potential drug repurposing targets. Polygenic scores were associated with adolescent-onset depression across ancestries, persistent depression trajectories, more severe outcomes, as well as reduced cortical volume, surface area and white matter integrity. Genetic correlation and Mendelian randomisation analyses support shared genetic liability and causal links with early puberty and modifiable health and behavioural risk factors. These findings uncover novel genetic loci and refine biological pathways underlying adolescent-onset depression, revealing age-specific mechanisms and early intervention opportunities.

Journal Article↗
PubMed2025

Associations of Genetic Liability to Six Psychiatric Disorders With Cardiometabolic Diseases.

IMPORTANCE: Individuals with psychiatric disorders have increased risk of cardiometabolic diseases (CMDs). Evaluating how psychiatric genetic liability relates to CMD may clarify mechanisms. OBJECTIVE: Identify genetic overlap between psychiatric disorders and CMDs independent of cross-disorder pleiotropy, BMI, and smoking. DESIGN SETTING AND PARTICIPANTS: Three Northern European cohorts (the Swedish Twin Registry, the Estonian Biobank, and the Norwegian Mother, Father and Child Cohort Study [MoBa]) totaling 355,159 individuals. Associations with CMDs were estimated as adjusted odds ratios (AORs) from logistic models mutually adjusted for all psychiatric PRSs and in models additionally adjusting for body mass index (BMI) and smoking. Cohort-specific AORs were pooled by inverse-variance weighting. MAIN OUTCOMES AND MEASURES: Exposures were PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), anxiety disorder, posttraumatic stress disorder (PTSD), bipolar disorder, and schizophrenia. Outcomes were diagnoses of CMDs (hyperlipidemia, obesity, type 2 diabetes, hypertensive diseases, arteriosclerosis, ischemic heart disease, heart failure, thromboembolic disease, cerebrovascular disease, and arrhythmias), ascertained from electronic health records. RESULTS: The MDD PRS was associated with increased risk of all CMDs across analyses (AORs ranged from 1.13 [95% CI, 1.10-1.15] for heart failure to 1.02 [95% CI, 1.00-1.05] for arrhythmias). The ADHD PRS was associated with increased risk of all CMDs (AOR ranged from 1.11 [95% CI, 1.09-1.12] for obesity to 1.02 [95% CI, 1.01-1.03] for hyperlipidemia), however associations where attenuated when adjusting for BMI and smoking (lifestyle adjusted AOR for obesity: 1.03 [95% CI, 1.02-1.05]). When not mutually adjusting for all psychiatric PRSs, anxiety disorder and PTSD PRSs were associated with all CMDs; these associations diminished after adjustment. The bipolar and schizophrenia PRSs were inversely associated with most CMDs (AOR for schizophrenia PRS and obesity, 0.93 [95% CI, 0.92-0.94]). CONCLUSIONS AND RELEVANCE: Associations between psychiatric PRSs and CMDs diverged: ADHD, MDD, anxiety disorder, and PTSD PRSs were positively associated with CMDs, whereas bipolar and schizophrenia PRSs were inversely associated. Genetic liability to MDD showed robust associations with CMDs independent of cross-disorder pleiotropy, BMI, and smoking status, whereas associations between the ADHD PRS and CMDs were largely attenuated after adjustment for BMI and smoking.

Journal Article↗
PubMed2025

Genome-wide association studies of binge eating behaviour and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes.

Eating disorders -including anorexia nervosa (AN), bulimia nervosa, and binge eating disorder-are clinically distinct but exhibit symptom overlap and diagnostic crossover. Genomic analyses have mostly examined AN. We conducted the first genomic meta-analysis of binge eating behaviour (BE; 39,279 cases, 1,227,436 controls), alongside new analyses of AN (24,223 cases, 1,243,971 controls) and its subtypes (all European ancestries). We identified six loci associated with BE, including loci associated with higher body mass index (BMI) and impulse-control behaviours. AN GWAS yielded eight loci, validating six loci. Subsequent polygenic risk score analysis demonstrated an association with AN in two East Asian ancestry cohorts. BE and AN exhibited similar positive genetic correlations with psychiatric disorders, but opposing genetic correlations with anthropometric traits. Most of the genetic signal in BE and AN was not shared with BMI. We have extended eating disorder genomics beyond AN; future work will incorporate multiple diagnoses and global ancestries.

Journal Article↗
PubMed2024

Leisure television watching exerts a causal effect on gastroesophageal reflux disease: evidence from a two-step mendelian randomization study.

BACKGROUND: Previous studies have shown that physical activity (PA) and leisure sedentary behaviors (LSB, including leisure television watching) are linked to gastroesophageal reflux disease (GERD). However, the associations between PA/LSB and GERD remain controversial. In this study, we aimed to reveal whether these associations reflect causal relationships and reveal the potential mechanisms of these relationships using bidirectional and two-step Mendelian randomization (MR) analyses. METHODS: We obtained genome-wide association study (GWAS) summary statistics for PA/LSB, four common risk factors (including cigarettes smoked per day, alcoholic drinks per week, triglycerides, total cholesterol) and GERD from published GWASs. A bidirectional MR analysis was performed to identify causal relationships between PA/LSB and GERD. Then, a series of sensitivity analyses were performed to verify the robustness of the results. Finally, a mediation analysis via two-step MR was conducted to investigate any effects explained by common risk factors in these relationships. RESULTS: Genetically predicted per 1-SD increase in leisure time television watching significantly increased the risk of GERD in the bidirectional MR analysis (OR = 1.33; 95% CI: 1.14-1.56; P = 2.71 × 10- 4). Sensitivity analyses successfully verified the robustness of the causal relationship. Further mediation analysis showed that this effect was partly mediated by increasing cigarettes smoked per day, with mediated proportions of 18.37% (95% CI: 11.94-39.79%). CONCLUSION: Our findings revealed a causal relationship between leisure television watching and an increased risk of GERD, notably, the causal effect was partially mediated by cigarettes smoked per day. These findings may inform prevention and management strategies directed toward GERD.

Humans↗
PubMed2024

Polygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis.

OBJECTIVE: Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2-item scale polygenic score with anxiety in MS. METHODS: Using a case-control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview-diagnosed, and lifetime self-report physician-diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome-wide association study and was tested using regression. RESULTS: A total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta-analyses identified that in MS, each 1-SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09-1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease. INTERPRETATION: Higher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS.

Humans↗
PubMed2007

CCR2 expression correlates with prostate cancer progression.

Although the primary role of chemokines and their receptors is controlling the trafficking of leukocytes during inflammatory responses, they also play pleoitropic roles in cancer development. There is emerging evidence that cancer cells produce chemokines that induce tumor cell proliferation or chemotaxis in various cancer types. We have previously reported that MCP-1 acts as a paracrine and autocrine factor for prostate cancer (PCa) growth and invasion. As the cellular effects of MCP-1 are mediated by CC chemokine receptor 2 (CCR2), we hypothesized that CCR2 may contribute PCa progression. Accordingly, we first determined CCR2 mRNA and protein expression in various cancer cell lines, including PCa and other cancer types. All cells expressed CCR2 mRNA and protein, but in PCa, more aggressive cancer cells such as C4-2B, DU145, and PC3 expressed a higher amount of CCR2 compared with the less aggressive cancer cells such as LNCaP or non-neoplastic PrEC and RWPE-1 cells. Further, we found a positive correlation between CCR2 expression and PCa progression by analyzing an ONCOMINE gene array database. We confirmed that CCR2 mRNA was highly expressed in PCa metastatic tissues compared with the localized PCa or benign prostate tissues by real-time RT-PCR. Finally, CCR2 protein expression was examined by immunohistochemical staining on tissue microarray specimens from 96 PCa patients and 31 benign tissue controls. We found that CCR2 expression correlated with Gleason score and clinical pathologic stages, whereas lower levels of CCR2 were expressed in normal prostate tissues. These results suggest that CCR2 may contribute to PCa development.

Cell Line↗
PubMed2007

Apoptosis induced by all-trans retinoic acid in N-acetylglucosaminyltransferase V repressed human hepatocarcinoma cells is mediated through endoplasmic reticulum stress.

We previously demonstrated that endoplasmic reticulum (ER) stress was triggered in human hepatocarcinoma 7721 cells transfected with antisense cDNA of N-acetylglucosaminyltransferase V (GnT-V-AS/7721) which were more susceptible to apoptosis induced by all-trans retinoic acid (ATRA). In the present study, we report that ATRA-induced apoptosis in GnT-V-AS/7721 cells is mediated through ER stress. We show here that ER stress is enhanced in GnT-V-AS/7721 cells with 80 microM ATRA treatment for 24 h, which is evidenced by the increase of GRP78/Bip, C/EBP-homologous protein-10 (CHOP, also known as GADD153) and spliced XBP1. Additionally, activation of caspase-12, caspase-9, and -3 was detected, and apoptosis morphology was observed in GnT-V-AS/7721 cells with ATRA treatment. These results suggest that ATRA enhances the ER stress triggered in GnT-V-AS/7721 cells, which represents a novel mechanism of ATRA to induce apoptosis. We further observed that GnT-V was significantly repressed and the structure of N-glycans was changed in GnT-V-AS/7721 cells with 80 microM ATRA treatment for 24 h, suggesting that repression of GnT-V by ATRA causes the enhanced ER stress and ER stress-mediated apoptosis in GnT-V-AS/7721 cells.

Apoptosis↗
PubMed2006

Interleukin-1 (IL-1)-induced TAK1-dependent Versus MEKK3-dependent NFkappaB activation pathways bifurcate at IL-1 receptor-associated kinase modification.

Interleukin-1 (IL-1) receptor-associated kinase (IRAK) is phosphorylated after it is recruited to the receptor, subsequently ubiquitinated, and eventually degraded upon IL-1 stimulation. Although a point mutation changing lysine 134 to arginine (K134R) in IRAK abolished IL-1-induced IRAK ubiquitination and degradation, mutations of serines and threonines adjacent to lysine 134 to alanines ((S/T)A (131-144)) reduced IL-1-induced IRAK phosphorylation and abolished IRAK ubiquitination. Through the study of these IRAK modification mutants, we uncovered two parallel IL-1-mediated signaling pathways for NFkappaB activation, TAK1-dependent and MEKK3-dependent, respectively. These two pathways bifurcate at the level of IRAK modification. The TAK1-dependent pathway leads to IKKalpha/beta phosphorylation and IKKbeta activation, resulting in classical NFkappaB activation through IkappaBalpha phosphorylation and degradation. The TAK1-independent MEKK3-dependent pathway involves IKKgamma phosphorylation and IKKalpha activation, resulting in NFkappaB activation through IkappaBalpha phosphorylation and subsequent dissociation from NFkappaB but without IkappaBalpha degradation. These results provide significant insight to our further understanding of NFkappaB activation pathways.

Animals↗
PubMed2006

Transplantation of human amniotic epithelial cells improves hindlimb function in rats with spinal cord injury.

BACKGROUND: Human amniotic epithelial cells (HAECs), which have several characteristics similar to stem cells, therefore could possibly be used in cell therapy without creating legal or ethical problems. In this study, we transplanted HEACs into the injured spinal cord of rats to investigate if the cells can improve the rats' hindlimb motor function. METHODS: HAECs were obtained from a piece of fresh amnion, labeled with Hoechst33342, and transplanted into the site of complete midthoracic spinal transections in adult rats. The rats (n = 21) were randomly divided into three groups: Sham-operation group (n = 7), cells-graft group (n = 7), and PBS group (n = 7). One rat of each group was killed for histological analysis at the second week after the transplantation. The other six rats of each group were killed for histological analysis after an 8-week behavioral testing. Hindlimb motor function was assessed by using the open-field BBB scoring system. Survival rate of the graft cells was observed at second and eighth weeks after the transplantation. We also detected the myelin sheath fibers around the lesions and the size of the axotomized red nucleus. A one-way ANOVA was used to compare the means among the groups. The significance level was set at P < 0.05. RESULTS: The graft HAECs survived for a long time (8 weeks) and integrated into the host spinal cord without immune rejection. Compared with the control group, HAECs can promote the regeneration and sprouting of the axons, improve the hindlimb motor function of the rats (BBB score: cells-graft group 9.0 +/- 0.89 vs PBS group 3.7 +/- 1.03, P < 0.01), and inhibit the atrophy of axotomized red nucleus [cells-graft group (526.47 +/- 148.42) microm(2) vs PBS group (473.69 +/- 164.73) microm(2), P < 0.01]. CONCLUSION: Transplantation of HAECs can improve the hindlimb motor function of rats with spinal cord injury.

Amnion↗
PubMed2006

Reduction potential tuning of the blue copper center in Pseudomonas aeruginosa azurin by the axial methionine as probed by unnatural amino acids.

The conserved axial ligand methionine 121 from Pseudomonas aeruginosa azurin (Az) has been replaced by isostructural unnatural amino acid analogues, oxomethionine (OxM), difluoromethionine (DFM), trifluoromethionine (TFM), selenomethionine (SeM), and norleucine (Nle) using expressed protein ligation. The replacements resulted in < 6 nm shifts in the S(Cys)-Cu charge transfer (CT) band in the electronic absorption spectra and < 8 gauss changes in the copper hyperfine coupling constants (AII) in the X-band electron paramagnetic resonance spectra, suggesting that isostructural replacement of Met resulted in minimal structural perturbation of the copper center. The slight blue shifts of the CT band follow the trend of stronger electronegativity of the ligands. This trend is supported by 19F NMR studies of the fluorinated methionine analogues. However, the order of AII differs, suggesting additional factors influencing AII. In contrast to the small changes in the UV-vis and EPR spectra, a large variation of > 227 mV in reduction potential was observed for the series of variants reported here. Additionally, a linear correlation was established between the reduction potentials and hydrophobicity of the variants. Extension of this analysis to other type 1 copper-containing proteins reveals a linear correlation between change in hydrophobicity and change in reduction potential, independent of the protein scaffold, experimental conditions, measurement techniques, and steric modifications. This analysis has also revealed for the first time high and low potential states for type 1 centers, and the difference may be attributable to destabilization of the protein fold by disruption of hydrophobic or hydrogen bonding interactions that stabilize the type 1 center.

Amino Acids↗
PubMed2006

FM-test: a fuzzy-set-theory-based approach to differential gene expression data analysis.

BACKGROUND: Microarray techniques have revolutionized genomic research by making it possible to monitor the expression of thousands of genes in parallel. As the amount of microarray data being produced is increasing at an exponential rate, there is a great demand for efficient and effective expression data analysis tools. Comparison of gene expression profiles of patients against those of normal counterpart people will enhance our understanding of a disease and identify leads for therapeutic intervention. RESULTS: In this paper, we propose an innovative approach, fuzzy membership test (FM-test), based on fuzzy set theory to identify disease associated genes from microarray gene expression profiles. A new concept of FM d-value is defined to quantify the divergence of two sets of values. We further analyze the asymptotic property of FM-test, and then establish the relationship between FM d-value and p-value. We applied FM-test to a diabetes expression dataset and a lung cancer expression dataset, respectively. Within the 10 significant genes identified in diabetes dataset, six of them have been confirmed to be associated with diabetes in the literature and one has been suggested by other researchers. Within the 10 significantly overexpressed genes identified in lung cancer data, most (eight) of them have been confirmed by the literatures which are related to the lung cancer. CONCLUSION: Our experiments on synthetic datasets show that FM-test is effective and robust. The results in diabetes and lung cancer datasets validated the effectiveness of FM-test. FM-test is implemented as a Web-based application and is available for free at http://database.cs.wayne.edu/bioinformatics.

Algorithms↗
PubMed2006

Metalloprotein and metallo-DNA/RNAzyme design: current approaches, success measures, and future challenges.

Specific metal-binding sites have been found in not only proteins but also DNA and RNA molecules. Together these metalloenzymes consist of a major portion of the enzyme family and can catalyze some of the most difficult biological reactions. Designing these metalloenzymes can be both challenging and rewarding because it can provide deeper insights into the structure and function of proteins and cheaper and more stable alternatives for biochemical and biotechnological applications. Toward this goal, both rational and combinatorial approaches have been used. The rational approach is good for designing metalloenzymes that are well characterized, such as heme proteins, while the combinatorial approach is better at designing those whose structures are poorly understood, such as metallo-DNA/RNAzymes. Among the rational approaches, de novo design is at its best when metal-binding sites reside in a scaffold whose structure has been designed de novo (e.g., alpha-helical bundles). Otherwise, design using native scaffolds can be equally effective, allowing more choices of scaffolds whose structural stability is often more resistant to multiple mutations. In addition, computational and empirical designs have both enjoyed successes. Because of the limitation in defining structural parameters for metal-binding sites, a computational approach is restricted to mostly metal-binding sites that are well defined, such as mono- or homonuclear centers. An empirical approach, even though it is less restrictive in the metal-binding sites to be designed, depends heavily on one's knowledge and choice of templates and targets. An emerging approach is a combination of both computational and empirical approaches. The success of these approaches can be measured not only by three-dimensional structural comparison between the designed and target enzymes but also by the total amount of insight obtained from the design process and studies of the designed enzymes. One of the biggest advantages of designed metalloenzymes is the potential of placing two different metal-binding sites in the same protein framework for comparison. A final measure of success is how one can utilize the insight gained from the intellectual exercise to design new metalloenzymes, including those with unprecedented structures and functions. Future challenges include designing more complex metalloenzymes such as heteronuclear metal centers with strong nanomolar or better affinities. A key to meeting this challenge is to focus on the design of not only primary but also secondary coordination spheres using a combination of improved computer programs, experimental design, and high-resolution crystallography.

Amino Acid Sequence↗
PubMed2006

Synchronized and sustained release of multiple components in silymarin from erodible glyceryl monostearate matrix system.

Development of sustained delivery systems for herbal medicines was very difficult because of their complexity in composition. The concept of synchronized release from sustained release systems, which is characterized by release of multiple components in their original ratio that defines a herbal medicine, served as the basis for keeping the original pharmacological activity. In this study, erodible matrix systems based on glyceryl monostearate and polyethylene glycol 6000 or poloxamer 188 were prepared to perform strict control on synchronized release of the five active components of silymarin, i.e. taxifolin, silychrystin, silydianin, isosilybin and silybin. The matrix system was prepared by a melt fusion method. Synchronized release was achieved with high similarity factor f(2) values between each two of the five components. Erosion profiles of the matrix were in good correlation with release profiles of the five components, showing erosion-controlled release mechanisms. Through tuning some of the formulation variables, the system can be adjusted for synchronized and sustained release of silymarin for oral administration. In vitro hemolysis study indicated that the synchronized release samples showed a much better stabilizing effect on erythrocyte membrane.

Animals↗