Effects of polymer molecular weight on relative oral bioavailability of curcumin

Yin-Meng Tsai,1 Wan-Ling Chang-Liao,1 Chao-Feng Chien,1 Lie-Chwen Lin,1,2 Tung-Hu Tsai,1,31Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 2National Research Institute of Chinese Medicine, 3Department of Education and Research, Taipei City Hospital, Taipei, TaiwanBackground: Polylactic-co-glycolic acid (PLGA) nanoparticles have been used to increase the relative oral bioavailability of hydrophobic compounds and polyphenols in recent years, but the effects of the molecular weight of PLGA on bioavailability are still unknown. This study investigated the influence of polymer molecular weight on the relative oral bioavailability of curcumin, and explored the possible mechanism accounting for the outcome.Methods: Curcumin encapsulated in low (5000–15,000) and high (40,000–75,000) molecular weight PLGA (LMw-NPC and HMw-NPC, respectively) were prepared using an emulsification-solvent evaporation method. Curcumin alone and in the nanoformulations was administered orally to freely mobile rats, and blood samples were collected to evaluate the bioavailability of curcumin, LMw-NPC, and HMw-NPC. An ex vivo experimental gut absorption model was used to investigate the effects of different molecular weights of PLGA formulation on absorption of curcumin. High-performance liquid chromatography with diode array detection was used for quantification of curcumin in biosamples.Results: There were no significant differences in particle properties between LMw-NPC and HMw-NPC, but the relative bioavailability of HMw-NPC was 1.67-fold and 40-fold higher than that of LMw-NPC and conventional curcumin, respectively. In addition, the mean peak concentration (Cmax) of conventional curcumin, LMw-NPC, and HMw-NPC was 0.028, 0.042, and 0.057 µg/mL, respectively. The gut absorption study further revealed that the HMw-PLGA formulation markedly increased the absorption rate of curcumin in the duodenum and resulted in excellent bioavailability compared with conventional curcumin and LMw-NPC.Conclusion: Our findings demonstrate that different molecular weights of PLGA have varying bioavailability, contributing to changes in the absorption rate at the duodenum. The results of this study provide the rationale for design of a nanomedicine delivery system to enhance the bioavailability of water-insoluble pharmaceutical compounds and functional foods.Keywords: absorption, duodenum, molecular weight, poly(lactic-co-glycolic acid), PLGA, relative oral bioavailabilit

The Pharmacological Effects and Pharmacokinetics of Active Compounds of Artemisia capillaris.

Artemisia capillaris Thunb. (A.capillaris, Yin-Chen in Chinese) is a traditional medicinal herb with a wide spectrum of pharmacological properties ranging from effects against liver dysfunction to treatments of severe cirrhosis and cancer. We used relevant keywords to search electronic databases, including PubMed, Medline, and Google Scholar, for scientific contributions related to this medicinal herb and the pharmacokinetics of its components. The pharmaceutical effects of A.capillaris contribute to the treatment not only of viral hepatitis, cirrhosis, and hepatocellular hepatoma, but also metabolic syndrome, psoriasis, and enterovirus in the clinic. The bioactive compounds, including scoparone, capillarisin, scopoletin, and chlorogenic acid, exhibit antioxidant, anti-inflammatory, antisteatotic, antiviral, and antitumor properties, reflecting the pharmacological effects of A.capillaris. The pharmacokinetics of the main bioactive compounds in A. capillaris can achieve a maximum concentration within 1 hour, but only chlorogenic acid has a relatively long half-life. Regarding the use of the A. capillaris herb by health professionals to treat various diseases, the dosing schedule of this herb should be carefully considered to maximize therapeutic outcomes while lessening possible side effects

Association between copy number variation of complement component C4 and Graves' disease

<p>Abstract</p> <p>Background</p> <p>Gene copy number of complement component <it>C4</it>, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effecter in peptide-mediated inflammation and phagocytosis, we hypothesized that <it>C4 </it>genetic diversity may partially explain the development of Graves' disease (GD) and the variation in its outcomes.</p> <p>Methods</p> <p>A case-control study including 624 patients with GD and 160 healthy individuals were enrolled. CNV of <it>C4 </it>isotypes (<it>C4A </it>and <it>C4B</it>) genes were performed by quantitative real-time polymerase chain reaction analysis. Statistical comparison and identification of CNV of total <it>C4, C4 </it>isotypes (<it>C4A </it>and <it>C4B</it>) and <it>C4 </it>polymorphisms were estimated according to the occurrence of GD and its associated clinical features.</p> <p>Results</p> <p>Individuals with 4, 2, and 2 copies of <it>C4</it>, <it>C4A </it>and <it>C4B </it>genes, especially those with A2B2 polymorphism may associate with the development of GD (p = 0.001, OR = 10.994, 95% CI: 6.277-19.255; p = 0.008, OR = 1.732, 95% CI: 1.190-2.520; p = 2.420 × 10-5, OR = 2.621, 95% CI: 1.791-3.835; and <it>p </it>= 1.395 × 10^-4, OR = 2.671, 95% CI: 1.761-4.052, respectively). Although the distribution of copy number for total <it>C4</it>, <it>C4 </it>isotypes as well as <it>C4 </it>polymorphisms did not associate with the occurrence of goiter, nodular hyperplasia, GO and myxedema, <2 copies of <it>C4A </it>may associate with high risk toward vitiligo in patients with GD (<it>p </it>= 0.001, OR = 5.579, 95% CI: 1.659-18.763).</p> <p>Conclusions</p> <p>These results may be further estimated for its clinical application on GD and the vitiligo in patients with GD.</p

Anticancer Effects of Salvia miltiorrhiza

Researchers have reported significant effects from Danshen (Salvia miltiorrhiza) in terms of inhibiting tumor cell proliferation and promoting apoptosis in breast cancer, hepatocellular carcinomas, promyelocytic leukemia, and clear cell ovary carcinomas. Here we report our data indicating that Danshen extracts, especially alcohol extract, significantly inhibited the proliferation of the human oral squamous carcinoma (OSCC) cell lines HSC-3 and OC-2. We also observed that Danshen alcohol extract activated the caspase-3 apoptosis executor by impeding members of the inhibitor of apoptosis (IAP) family, but not by regulating the Bcl-2-triggered mitochondrial pathway in OSCC cells. Our data also indicate that the extract exerted promising effects in vivo, with HSC-3 tumor xenograft growth being suppressed by 40% and 69% following treatment with Danshen alcohol extract at 50 and 100 mg/kg, respectively, for 34 days. Combined, our results indicate appreciable anticancer activity and significant potential for Danshen alcohol extract as a natural antioxidant and herbal human oral cancer chemopreventive drug

Utilized mass spectrometry-based protein profiling system to identify potential biomarkers of hepatocellular carcinoma

AbstractHepatocellular carcinoma (HCC) is the most common malignant liver tumor. The purpose of this study is to characterize proteins secreted from the HepG2 cells, which may relate to cell differentiation and tumor metastasis. In the proteomic analysis, the secretome was identified by nano-high–performance liquid chromatography/electrospray ionization tandem mass spectrometry (nano-HPLC/ESIMS/MS) followed by peptide fragmentation pattern analysis. In this study, three proteins, p130Cas-associated protein (p130Cas/BCAR1), TAR DNA-binding protein 43 (TDP43/TARDBP) and translationally controlled tumor protein (TCTP/TPT1), were identified and confirmed by Western blotting, which showed significantly differential expression compared with the normal liver cells. Analyzing differential protein expressions in HepG2 cell by proteomic approaches suggests that p130Cas/BCAR1, TDP43/TARDBP and TCTP/TPT1 as key proteins and may serve as biomarkers for HCC

Corrigendum to “Anticancer Effects of Salvia miltiorrhiza

Researchers have reported significant effects from Danshen (Salvia miltiorrhiza) in terms of inhibiting tumor cell proliferation and promoting apoptosis in breast cancer, hepatocellular carcinomas, promyelocytic leukemia, and clear cell ovary carcinomas. Here we report our data indicating that Danshen extracts, especially alcohol extract, significantly inhibited the proliferation of the human oral squamous carcinoma (OSCC) cell lines HSC-3 and OC-2. We also observed that Danshen alcohol extract activated the caspase-3 apoptosis executor by impeding members of the inhibitor of apoptosis (IAP) family, but not by regulating the Bcl-2-triggered mitochondrial pathway in OSCC cells. Our data also indicate that the extract exerted promising effects in vivo, with HSC-3 tumor xenograft growth being suppressed by 40% and 69% following treatment with Danshen alcohol extract at 50 and 100 mg/kg, respectively, for 34 days. Combined, our results indicate appreciable anticancer activity and significant potential for Danshen alcohol extract as a natural antioxidant and herbal human oral cancer chemopreventive drug

REG3A overexpression functions as a negative predictive and prognostic biomarker in rectal cancer patients receiving CCRT

Background. Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patientspecific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. Methods. A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. Results. Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. Conclusion. In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decisionmaking more accurately for those patients

Improved Breath Phase and Continuous Adventitious Sound Detection in Lung and Tracheal Sound Using Mixed Set Training and Domain Adaptation

Previously, we established a lung sound database, HF_Lung_V2 and proposed convolutional bidirectional gated recurrent unit (CNN-BiGRU) models with adequate ability for inhalation, exhalation, continuous adventitious sound (CAS), and discontinuous adventitious sound detection in the lung sound. In this study, we proceeded to build a tracheal sound database, HF_Tracheal_V1, containing 11107 of 15-second tracheal sound recordings, 23087 inhalation labels, 16728 exhalation labels, and 6874 CAS labels. The tracheal sound in HF_Tracheal_V1 and the lung sound in HF_Lung_V2 were either combined or used alone to train the CNN-BiGRU models for respective lung and tracheal sound analysis. Different training strategies were investigated and compared: (1) using full training (training from scratch) to train the lung sound models using lung sound alone and train the tracheal sound models using tracheal sound alone, (2) using a mixed set that contains both the lung and tracheal sound to train the models, and (3) using domain adaptation that finetuned the pre-trained lung sound models with the tracheal sound data and vice versa. Results showed that the models trained only by lung sound performed poorly in the tracheal sound analysis and vice versa. However, the mixed set training and domain adaptation can improve the performance of exhalation and CAS detection in the lung sound, and inhalation, exhalation, and CAS detection in the tracheal sound compared to positive controls (lung models trained only by lung sound and vice versa). Especially, a model derived from the mixed set training prevails in the situation of killing two birds with one stone.Comment: To be submitted, 31 pages, 6 figures, 5 table