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11
result(s) for
"Kao, I-Fang"
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The Preparation and Characterization of Chitosan/Calcium Phosphate Composite Microspheres for Biomedical Applications
2024
In this study, we successfully prepared porous composite microspheres composed of hydroxyapatite (HAp), di-calcium phosphate di-hydrated (DCPD), and chitosan through the hydrothermal method. The chitosan played a crucial role as a chelating agent to facilitate the growth of related calcium phosphates. The synthesized porous composite microspheres exhibit a specific surface area of 38.16 m2/g and a pore volume of 0.24 cm3/g, with the pore size ranging from 4 to 100 nm. Given the unique properties of chitosan and the exceptional porosity of these composite microspheres, they may serve as carriers for pharmaceuticals. After being annealed, the chitosan transforms into a condensed form and the DCPD transforms into Ca2P2O7 at 300 °C. Then, the Ca2P2O7 initially combines with HAp to transform into β tricalcium phosphate (β-TCP) at 500 °C where the chitosan is also completely combusted. Finally, the microspheres are composed of Ca2P2O7, β-TCP, and HAp, also making them suitable for applications such as injectable bone graft materials.
Journal Article
Effects of Chitosan on Drug Load and Release for Cisplatin–Hydroxyapatite–Gelatin Composite Microspheres
by
Yen, Shiow-Kang
,
Kao, I-Fang
,
Wu, Meng-Ying
in
Aqueous solutions
,
Bioavailability
,
Biocompatibility
2025
Cisplatin, a widely used chemotherapeutic agent, is limited by its poor bioavailability, rapid systemic clearance, and severe side effects. To overcome these limitations, hydroxyapatite–gelatin composite microspheres were developed to improve drug entrapment efficiency (DEE) and provide sustained drug release. Various formulations were prepared by incorporating chitosan either by mixing once or through a sequential coating strategy. By adjusting the loading procedure, the DEE increased from 58% to 99%. The composite microsphere effectively controlled the total drug release duration, extending it from one month to over 5 months. Moreover, the MTT assay demonstrated that all samples effectively inhibited cell growth, with cell viability reduced to less than 20% after 2 weeks of experimentation. These findings demonstrate that the sequential chitosan coating method offers superior drug entrapment and prolonged release compared to mixing chitosan once, exhibiting its potential as a sustained drug delivery system for cancer treatment.
Journal Article
Effects of Adding Chitosan on Drug Entrapment Efficiency and Release Duration for Paclitaxel-Loaded Hydroxyapatite—Gelatin Composite Microspheres
2023
Hydroxyapatite—gelatin microspheres with cone-like pores were synthesized via the wet-chemical method using ammonium dihydrogen phosphate ((NH4)H2PO4) and calcium nitrate (Ca(NO3)2·4H2O) as a source of calcium and phosphate ions with the addition of gelatin, which proved to be more osteoconductive than commercial products, such as fibrin glue and Osteoset® Bone Graft Substitute. Following the method of the previous study for loading paclitaxel (PTX), a drug entrapment efficiency of around 58% was achieved, which is much lower than that of the doxorubicin (DOX)-loaded one. Since PTX is hydrophobic while DOX is hydrophilic, the order of chitosan processing and addition of the solvent were tuned in this study, finally leading to an increase in drug entrapment efficiency of 94%. Additionally, the release duration of PTX exceeded six months. The MTT assay indicated that the effect of drug release on the suppression of cancer cells reached more than 40% after one week, thereby showcasing PTX’s capacity to carry out its medicinal functions without being affected by the loading procedures.
Journal Article
Porous Chitosan/Hydroxyapatite Composite Microspheres for Vancomycin Loading and Releasing
2024
Porous chitosan/hydroxyapatite (Chi-HAp) composite microspheres were prepared in an aqueous solution containing chitosan, calcium nitrate, and ammonium dihydrogen phosphate by using a hydrothermal method at various temperatures. The investigation indicated that temperature significantly impacted the final product’s appearance. Hydroxyapatite (HAp) coupled with dicalcium phosphate dihydrate (DCPD) flakes were obviously found at 65 and 70 °C, while the latter gradually disappeared at higher temperatures. Conversely, synthesis at 90 °C led to smaller particle sizes due to the broken chitosan chains. The microspheres synthesized at 75 °C were selected for further analysis, revealing porous structures with specific surface areas of 36.66 m2/g, pores ranging from 3 to 100 nm, and pore volumes of 0.58 cm3/g. Vancomycin (VCM), an antibiotic, was then absorbed on and released from the microspheres derived at 75 °C, with a drug entrapment efficiency of 20% and a release duration exceeding 20 days. The bacteriostatic activity of the VCM/composite microspheres against Staphylococcus aureus increased with the VCM concentration and immersion time, revealing a stable inhibition zone diameter of approximately 4.3 mm from 24 to 96 h, and this indicated the retained stability and efficacy of the VCM during the encapsulating process.
Journal Article
Inhibiting Effects of Antibiotic-Loaded Porous Gelatin-Hydroxyapatite Microspheres on Staphylococcus aureus
by
Yen, Chao-Chun
,
Yen, Shiow-Kang
,
Wang, Ming-Jia
in
antibacterial
,
Antibiotics
,
Biocompatibility
2025
Due to their biocompatibility and bone-like composition, calcium phosphate materials-especially hydroxyapatite (HAp)-have emerged as promising carriers for localized antibiotic delivery in bone regeneration. Here, we developed Hap-based composite microspheres using a simple wet-chemical method and incorporated multiple antibiotics to evaluate their release profiles and antibacterial potential for treating bone infections.
In this study, uniform and porous composite microspheres composed of Hap and gelatin were synthesized via a simple wet-chemical method using a mixed calcium phosphate-gelatin solution.
The resulting gelatin-Hap microspheres (G-HAM) were systematically characterized to verify their crystalline structure, morphology, composition, and thermal stability. G-HAM exhibited a highly porous structure, making them well-suited for use as drug carriers. Four clinically relevant antibiotics-gentamicin, vancomycin, teicoplanin, and zyvox-were incorporated into the microspheres and evaluated for their release behavior and antibacterial performance against
. The release profiles revealed an initial burst release within the first hour that exceeded the minimum inhibitory concentrations of all tested antibiotics, followed by a sustained release phase. Antibiotics containing carboxylic groups, such as vancomycin and teicoplanin, demonstrated stronger interactions with Hap, resulting in a more prolonged release. Antibacterial testing confirmed that the released antibiotics maintained their chemical stability and bioactivity. Furthermore, the combination of bioactive Hap and peptide-rich gelatin promoted osteoblast-like cell adhesion and proliferation, while cytotoxicity assays verified excellent biocompatibility.
Overall, these G-HAM provide a promising platform that integrates controlled antibiotic release with osteoconductive potential for bone infection treatment and tissue regeneration.
Journal Article
integrated map of Oryza sativa L. chromosome 5
by
Cheng, C.H
,
Chen, H.H
,
Liu, S.M
in
Bacterial artificial chromosomes
,
Biological and medical sciences
,
Chromatin
2006
The developments of molecular marker-based genetic linkage maps are now routine. Physical maps based on contigs of large insert genomic clones have been established in several plant species. However, integration of genetic, physical, and cytological maps is still a challenge for most plant species. Here we present an integrated map of rice (Oryza sativa L.) chromosome 5, developed by fluorescence in situ hybridization mapping of 18 bacterial artificial chromosome (BAC) clones or PI-derived artificial chromosome (PAC) clones on meiotic pachytene chromosomes. Each BAC/PAC clone was anchored by a restriction fragment length polymorphism marker mapped to the rice genetic linkage map. This molecular cytogenetic map shows the genetic recombination and sequence information of a physical map, correlated to the cytological features of rice chromosome 5. Detailed comparisons of the distances between markers on genetic, cytological, and physical maps, revealed the distributions of recombination events and molecular organization of the chromosomal features of rice chromosome 5 at the pachytene stage. Discordance of distances between the markers was found among the different maps. Our results revealed that neither the recombination events nor the degree of chromatin condensation were evenly distributed along the entire length of chromosome 5. Detailed comparisons of the correlative positions of markers on the genetic, cytological, and physical maps of rice chromosome 5 provide insight into the molecular architecture of rice chromosome 5, in relation to its cytological features and recombination events on the genetic map. The prospective applications of such an integrated cytogenetic map are discussed.
Journal Article
miRNA-34c Overexpression Causes Dendritic Loss and Memory Decline
by
Wang, I-Fang
,
Tsai, Kuen-Jer
,
Kao, Yu-Chia
in
Alzheimer Disease - genetics
,
Alzheimer Disease - pathology
,
Animals
2018
Microribonucleic acids (miRNAs) play a pivotal role in numerous aspects of the nervous system and are increasingly recognized as key regulators in neurodegenerative diseases. This study hypothesized that miR-34c, a miRNA expressed in mammalian hippocampi whose expression level can alter the hippocampal dendritic spine density, could induce memory impairment akin to that of patients with Alzheimer’s disease (AD) in mice. In this study, we showed that miR-34c overexpression in hippocampal neurons negatively regulated dendritic length and spine density. Hippocampal neurons transfected with miR-34c had shorter dendrites on average and fewer filopodia and spines than those not transfected with miR-34c (control mice). Because dendrites and synapses are key sites for signal transduction and fundamental structures for memory formation and storage, disrupted dendrites can contribute to AD. Therefore, we supposed that miR-34c, through its effects on dendritic spine density, influences synaptic plasticity and plays a key role in AD pathogenesis.
Journal Article
Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients
2012
Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1).
A case-control study was conducted on 305 young ischemic stroke subjects aged = 50 years and 309 age-matched healthy controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454-397 T/C and c.454-351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models.
COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174).
Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects.
Journal Article
Purine analogue ENERGI-F706 induces apoptosis of 786-O renal carcinoma cells via 5′-adenosine monophosphate-activated protein kinase activation
by
CHENG, YI-FANG
,
CHEN, HAN-MIN
,
LIN, CHUN-HSIANG
in
5′-adenosine monophosphate-activated protein kinase
,
Adenosine kinase
,
Adenylic acid
2015
Purine compounds are known to activate 5′-adenosine monophosphate-activated protein kinase (AMPK), which has important roles in treatments for renal cell carcinoma. The present study was aimed to investigate the effects of the purine analogue ENERGI-F706 on the human renal carcinoma cell line 786-O and the underlying mechanisms. The results revealed that ENERGI-F706 (0.2-0.6 mg/ml) significantly decreased the cell viability to up to 36.4±2.4% of that of the control. Compared to 786-O cells, ENERGI-F706 exerted less suppressive effects on the viability of the human non-tumorigenic renal cell line HK-2. Flow cytometric analysis showed that ENERGI-F706 contributed to cell cycle arrest at S-phase and triggered apoptosis of 786-O cells. Immunoblot analysis revealed that anti-apoptotic B-cell lymphoma 2 (Bcl-2) levels were reduced and pro-apoptotic Bcl-2-associated X protein levels were diminished. In addition, activation of caspase-9, caspase-3 and poly(adenosine diphosphate ribose) polymerase (PARP) was promoted in 786-O cells in response to ENERGI-F706. Effects of ENERGI-F706 on AMPK cascades were investigated and the results showed that ENERGI-F706 enhanced phosphorylation of AMPKα (T172) and p53 (S15), a downstream target of AMPK. In addition, the AMPK activation, p53 (S15) phosphorylation, reduction of Bcl-2, cleavage of caspase-3 and PARP as well as suppressed cell viability induced by ENERGI-F706 were reversed in the presence of AMPK inhibitor compound C (dorsomorphin). In conclusion, the findings of the present study revealed that ENERGI-F706 significantly suppressed the viability of 786-O cells via induction of cell cycle arrest and apoptosis, attributing to AMPK and p53 activation and subsequent cell cycle regulatory and apoptotic signaling. It was therefore indicated that ENERGI-F706 may be suitable for the treatment of renal cell carcinoma.
Journal Article
High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated steatotic liver disease
by
Tung-hung Su
,
Mei-hsuan Lee
,
Jia-horng Kao
in
Alcohol-related liver disease
,
Cirrhosis
,
Hepatitis B
2025
Background/Aims: There are no hepatocellular carcinoma (HCC) surveillance recommendations for non-viral chronic liver diseases (CLD), such as metabolic dysfunction-associated steatotic liver disease (MASLD). We explored the Steatosis-Associated Fibrosis Estimator (SAFE) score to predict HCC in MASLD and other CLD etiologies.
Methods: Patients with various CLDs were included from medical centers in Taiwan. The SAFE score, consisting of age, body mass index, diabetes, and laboratory data, was calculated at baseline, and patients were traced for new development of HCC. The predictability of the SAFE score for HCC was analyzed using the sub-distribution hazard model with adjustments for competing risks.
Results: Among 12,963 CLD patients with a median follow-up of 4 years, 258 developed HCC. The SAFE score classifies 1-, 3-, and 5-year HCC risk regardless of CLD etiologies. High (≥100) and intermediate (0-100) SAFE scores increased 11 and 2 folds HCC risks compared to low (<0) SAFE scores. Combining two lower risk tiers (SAFE<100), a high SAFE score (≥100) was associated with a 7.5-fold risk of HCC (adjusted sub-distributional hazard ratio [aSHR] 7.54; 95% confidence interval (CI) 5.38-10.60). A high SAFE score increased the risks of HCC in subgroups of viral hepatitis, non-viral hepatitis (aSHR 11.10; 95% CI 3.97-31.30) and MASLD (aSHR 4.23; 95% CI 1.43-12.50). A hospital cohort (n=8,103) and a community MASLD cohort (n=120,166) validated the high SAFE score (≥100) for HCC risk prediction.
Conclusions: The SAFE score stratifies high risks for HCC in CLD patients regardless of etiologies and helps to select at-risk candidates for HCC surveillance. (Clin Mol Hepatol 2025;31:796-809)
Journal Article