Response surface methodology for aqueous two-phase system extraction: An unprecedented approach for the specific flavonoid-rich extraction of Houttuynia cordata Thunb. leaves towards acne treatment.

Background: Houttuynia cordata Thunb. has long been widely used as a daily vegetable and traditional medicine. The flavonoid component of H. cordata has plenty of pharmacological effects, such as antibacterial, anti-inflammatory, and antioxidant. In this study, we applied the aqueous two-phase system (ATPS) combined with ultrasonic extraction for extracting H. cordata leaves. Methods: We optimized the extraction process to improve the extraction efficiency of the two flavonoids, hyperin and quercitrin, by Surface Method Response - Central Composite Design (RSM-CCD). Next, we investigated the antibacterial ability of H. cordata ATPS extract from optimal conditions against two bacterial strains, Cutibacterium acnes and Staphylococcus epidermidis. Results: The results showed that using 10% (NH4)2SO4 and 35% ethanol for ATPS extraction resulted in the highest hyperin and quercitrin contents. From the RSM-CCD results, the optimal extraction conditions were determined to be ultrasonic extraction at 50 °C for 30 min, giving results consistent with the predicted model and obtaining hyperin and quercitrin contents at 1.5681 ± 0.0114 and 4.6225 ± 0.0327 mg/g, respectively.Furthermore, ATPS extract has excellent antibacterial activity with a minimum inhibitory concentration (MIC) value of 250 µg/mL on both C. acnes and S. epidermidis. This MIC is significantly lower than the H. cordata ultrasound-assisted (UA) extract, with MICs of 1500.00 and 156.25 µg/mL on C. acnes and S. epidermidis, respectively. In addition, the results from the disk diffusion assay also showed that ATPS extraction has superior internal antibacterial activity with a zone of inhibition diameter at 250 µg/mL of 8.67 ± 1.15 and 5.00 ± 2.00 mm. Meanwhile, those of UA extract on C. acnes is 5.67 ± 1.53 mm (at 1500 µg/mL), and on S. epidermidis is 1.34 ± 0.58 mm (at 156.25 µg/mL). Conclusion: To sum up, our research highlights the potential of H. cordata ATPS extracts as the starting material for topical preparations for effectively treating acne.

Integrative modeling uncovers p21-driven drug resistance and prioritizes therapies for PIK3CA-mutant breast cancer.

Utility of PI3Kα inhibitors like BYL719 is limited by the acquisition of genetic and non-genetic mechanisms of resistance which cause disease recurrence. Several combination therapies based on PI3K inhibition have been proposed, but a way to systematically prioritize them for breast cancer treatment is still missing. By integrating published and in-house studies, we have developed in silico models that quantitatively capture dynamics of PI3K signaling at the network-level under a BYL719-sensitive versus BYL719 resistant-cell state. Computational predictions show that signal rewiring to alternative components of the PI3K pathway promote resistance to BYL719 and identify PDK1 as the most effective co-target with PI3Kα rescuing sensitivity of resistant cells to BYL719. To explore whether PI3K pathway-independent mechanisms further contribute to BYL719 resistance, we performed phosphoproteomics and found that selection of high levels of the cell cycle regulator p21 unexpectedly promoted drug resistance in T47D cells. Functionally, high p21 levels favored repair of BYL719-induced DNA damage and bypass of the associated cellular senescence. Importantly, targeted inhibition of the check-point inhibitor CHK1 with MK-8776 effectively caused death of p21-high T47D cells, thus establishing a new vulnerability of BYL719-resistant breast cancer cells. Together, our integrated studies uncover hidden molecular mediators causing resistance to PI3Kα inhibition and provide a framework to prioritize combination therapies for PI3K-mutant breast cancer.

Investigate the anaerobic degradation of high-acetone latex wastewater with magnetite supplement.

This study evaluated the effects of acetone on the anaerobic degradation of synthetic latex wastewater, which was simulated from the wastewater of the deproteinized natural rubber production process, including latex, acetate, propionate, and acetone as the main carbon sources, at a batch scale in 5 cycles of a total of 60 days. Fe3O4 was applied to accelerate the treatment performance from cycle 3. Acetone was added in concentration ranges of 0%, 0.05%, 0.1%, 0.15%-included latex, and 0.15%-free latex (w/v). In the Fe3O4-free cycles, for latex-added vials, soluble chemical oxygen demand (sCOD) was removed at 43.20%, 43.20%, and 12.65%, corresponding to the input acetone concentrations varying from 0.05% to 0.15%, indicating the interference of acetone for COD reduction. After adding Fe3O4, all flasks reported a significant increase in COD removal efficiency, especially for acetone-only and latex-only vials, from 36.9% to 14.30%-42.95% and 83.20%, respectively. Other highlighted results of COD balance showed that Fe3O4 involvement improved the degradation process of acetate, propionate, acetone, and the other COD parts, including the intermediate products of latex reduction. Besides, during the whole batch process, the order of reduction priority of the carbon sources in the synthetic wastewater was acetate, propionate and acetone. We also found that the acetate concentration appeared to be strongly related to reducing other carbon sources in natural rubber wastewater. Microbial community analysis revealed that protein-degrading bacteria Bacteroidetes vadinHA17 and Proteinniphilum and methylotrophic methanogens might play key roles in treating simulated deproteinized-natural-rubber wastewater.

The influence of childhood abuse and prenatal intimate partner violence on childbirth experiences and breastfeeding outcomes.

BACKGROUND: Despite the detrimental effects and life-course health consequences of violence exposure, relatively few studies have adequate capacity to investigate the evolution of violence from childhood to motherhood. OBJECTIVE: This study aims to examine the cyclical nature of childhood abuse and prenatal inter-partner violent victimization (p-IPV) and its adverse impact on childbirth trauma and exclusive breastfeeding (EBF) practice in Vietnam. METHOD: Using a prospective birth cohort, 150 pregnant women were recruited in the third trimester of pregnancy in Hue city in central Vietnam (Wave 1-Baseline) and re-interviewed approximately three months after delivery (Wave 2-Follow-up). The direct and indirect effects of violent victimization on subsequent childbirth experience (measured by Birth Memories and Recall Questionnaire) and EBF practice were estimated by using augmented-inverse-probability-weighted models, sensitivity analysis, and structural equation model. RESULTS: Detrimental and prolonged effects of the inter-generational cycle of violence transverse childhood to motherhood. Women who experienced either childhood abuse or p-IPV violence were more likely to experience negative emotional childbirth memories [ARR 1.21, 95 % CI (1.04, 1.39)]. Evidence also suggested that not continuing to exclusively breastfeed at 3 months post-partum was strongly associated with prenatal depression, young age, and perceived low social status during pregnancy. Perceived strong connectedness among extended family members and social networks (i.e. nexus among family, friends, and neighborhood) provided a buffering effect by preventing EBF termination. CONCLUSION: This research provides insights into the protective role of social connectedness in improving breastfeeding practice. It is vital to establish wholistic antenatal care and social service system to offer specialized support and response for victims of violence and mitigate the long-term sequelae of traumatic events.

Reutilization of Fe-containing tailings ore enriched by iron(iii) chloride as a heterogeneous Fenton catalyst for decolorization of organic dyes.

In this study, the Fe-containing tailings (Fe-TO) ore was reutilized and enriched with FeCl3 as a heterogeneous catalyst for the Fenton process to degrade the organic dyes from aqueous solution. The determinants of the heterogeneous catalytic Fenton system which included iron modification ratio, solution pH, catalyst dosage, H2O2 dosage and initial concentration of organic dyes were systematically investigated. The modification ratio of 15% (w/w of iron), pH of 3, MFe-TO15 dosage of 0.5 g L-1 and H2O2 dosage of 840 mg L-1 were chosen as the best operational conditions for Fenton oxidation of organic dyes. The decolorization efficiency of both MB and RhB by MFe-TO15/H2O2 was higher than that of Fe-TO/H2O2 by about two times. The kinetic study showed the degradation of organic dyes well fitted the pseudo-first-order kinetic model with apparent constant rate values (K d) following the same sequence as the degradation efficiency of organic dyes. The degradation mechanism of dyes could be attributed to adsorption due to the good-development in textural properties of the iron modified catalyst (MFe-TO) with an increase in BET surface area, pore volume and pore diameter of, respectively, 2, 5 and 5 times and leaching iron through homogeneous Fenton reaction. However, the oxidation process occurring on the MFe-TO15's surface by heterogeneous Fenton reaction which enhanced decomposition of H2O2 for continuous generation of hydroxyl radicals was the main mechanism. The key role of *OH radical in oxidation of organic dyes was further ascertained by the remarkable drop in the decolorization of both organic dyes when the various radical-scavengers, including tert-butanol and chloride were supplemented into Fenton systems. A good stability of the catalyst was obtained through leaching test with low leaching iron ratio. The applied modified catalyst remained stable through three consecutive runs. From these findings, it can be concluded that the modified material can be applied as a feasible, inexpensive and highly effective catalyst for removal of persistent organic compounds from wastewater.

Feasibility, benefits, and cost-effectiveness of adding universal hepatitis B and syphilis testing to routine antenatal care services in Thai Nguyen province, Vietnam.

Pregnant women in Vietnam have a high prevalence of hepatitis B virus (HBV) and low prevalence of human immunodeficiency virus (HIV) and syphilis. This study aims to assess the feasibility and benefit of universal testing for HIV, HBV and syphilis in antenatal care (ANC) services. A pilot project was conducted in the Thai Nguyen province of Vietnam between 2012 and 2014. HIV, HBV and syphilis testing were offered to pregnant women. Interventions to eliminate mother-to child-transmission (MTCT) of the three pathogens were provided to infected mothers and their infants. Descriptive analysis was conducted, and the number of infections averted from integrating hepatitis B tests into ANC was estimated. Testing coverage for HIV, HBV and syphilis for the cohort of pregnant women during the pilot project was 98%. Prevalence of HIV, HBV and syphilis infections in this cohort was 0.14%, 7.8%, and 0.03%, respectively. No infant was infected with HIV or syphilis, while HBV infection was diagnosed in 27 infants (13.9%). An estimated 23 mother to child HBV infections were prevented by integrated interventions. The triple prevention of mother-to-child transmission of HIV, HBV and syphilis is feasible. Investment in the expansion of the integrated approach is required to achieve the goal of eliminating MTCT.

Alignment of a wavefront-guided scleral lens correction in the presence of a lens capsulotomy.

PURPOSE: To demonstrate the necessity of aligning a wavefront-guided scleral lens (WGSL) optical correction to the eye's effective pupil, with misalignments leading to reduced performance. CASE REPORT: A 34 year old subject with a history of failed LASIK in the left eye, leading to penetrating keratoplasty, extracapsular extraction of the crystalline lens and neodymium:yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy, enrolled in a study examining WGSL performance. Habitual logMAR acuity OS (aided with a scleral lens) was +0.04. Residual higher order root mean square (HORMS) wavefront error (WFE) was 0.28 µm (Φ =4.75 mm, mean age-matched norm =0.17 µm), and objective over-refraction was -0.30 -0.54 × 008. When a WGSL (targeting aberrations up to the 5 th radial order) was manufactured with the wavefront-guided optics aligned to the center of the dilated pupil, logMAR acuity worsened to +0.15, residual HORMS WFE worsened to 0.44 µm (Φ =4.75 mm), and objective over-refraction increased to +1.19 -0.30 × 122. Slit lamp imagery revealed that the effective pupil was no longer defined by the iris of the eye, but rather the capsular opening created by the capsulotomy. When the WGSL was redesigned to align the wavefront-guided optics to the center of the capsular opening, logMAR acuity improved to -0.14, residual HORMS WFE reduced to 0.17 µm (Φ =4.75 mm) and objective over-refraction reduced to +0.20 -0.15 × 111. CONCLUSION: WGSLs are an emerging option for patients with highly aberrated, ectatic and post-surgical corneas whose visual symptoms cannot be alleviated with conventional corrections. However, alignment of the optics of the WGSL to the underlying optics of the eye over the effective pupil is critical in achieving good optical and visual performance.

Transferrin-conjugated pH-sensitive platform for effective delivery of porous palladium nanoparticles and paclitaxel in cancer treatment.

Porous palladium (Pd) nanoparticles have garnered great research attention due to their potential anticancer activity and photothermal effect. In this study, a transferrin-conjugated pH-sensitive platform (Tf-PPP), comprising porous Pd nanoparticles (PdNPs) and paclitaxel (PTX), was successfully developed for combined chemo-phototherapy. Tf-PPPs have a small size of 164.6 ± 8.7 nm, PDI of 0.278 ± 0.029, and negative charge (-13.2 ± 1.8 mV). Poly(acrylic acid)-poly(ethylene oxide) (PAA-PEO), a pH sensitive polymer, was used to achieve pH-dependent drug release from nanoparticles. Transferrin (Tf) conjugated on the surface of nanoplatforms could enhance the cellular uptake and prolong nanoparticle accumulation in the tumor site. The combination of phototherapy induced by PdNPs and chemotherapeutic agent (PTX) could exhibit synergistic anticancer activities. Consistent findings were observed in both in vitro experiments including cytotoxicity, live/dead assay, and assessment of apoptotic protein levels, and in vivo antitumor study in MCF-7 tumor-bearing mice, with results decreasing in the following order: Tf-PPPs + NIR > Tf-PPPs > PPPs + NIR > PPPs > PTX > PdNPs. These findings suggest that the administration of Tf-PPPs, followed by NIR irradiation could be a promising strategy in the treatment of cancer.

Targeting of PYK2 Synergizes with EGFR Antagonists in Basal-like TNBC and Circumvents HER3-Associated Resistance via the NEDD4-NDRG1 Axis.

Triple-negative breast cancer (TNBC) is a highly aggressive, heterogeneous disease with poor prognosis and no effective targeted therapies. EGFR is highly expressed in basal-like TNBC and is considered as a potential therapeutic target. However, EGFR targeting exerts only marginal clinical benefits, possibly due to activation of compensatory signaling pathways, which are frequently associated with HER3 upregulation. Here we show that concomitant targeting of EGFR and the nonreceptor tyrosine kinases PYK2/FAK synergistically inhibits the proliferation of basal-like TNBC cells in vitro and attenuates tumor growth in a mouse xenograft model. Dual targeting of EGFR and PYK2/FAK inhibited complementary key growth and survival pathways mediated by AKT, S6K, STAT3, and ERK1/2 activation. PYK2 inhibition also abrogated HER3 upregulation in response to EGFR antagonists, thereby circumventing HER3-associated drug resistance. Mechanistically, PYK2 inhibition facilitated the proteasomal degradation of HER3 while inducing upregulation of NDRG1 (N-myc downstream regulated 1 gene). NDRG1 enhanced the interaction of HER3 with the ubiquitin ligase NEDD4, while PYK2, which interacts with NEDD4 and HER3, interfered with NEDD4-HER3 binding, suggesting that the PYK2-NDRG1-NEDD4 circuit has a critical role in receptor degradation, drug response, and resistance mechanism. Our studies offer a preclinical proof of concept for a strategy of cotargeting the EGFR and PYK2/FAK kinases to improve TNBC therapy. Cancer Res; 77(1); 86-99. ©2016 AACR.

Nanostructured Aptamer-Functionalized Black Phosphorus Sensing Platform for Label-Free Detection of Myoglobin, a Cardiovascular Disease Biomarker.

We report the electrochemical detection of the redox active cardiac biomarker myoglobin (Mb) using aptamer-functionalized black phosphorus nanostructured electrodes by measuring direct electron transfer. The as-synthesized few-layer black phosphorus nanosheets have been functionalized with poly-l-lysine (PLL) to facilitate binding with generated anti-Mb DNA aptamers on nanostructured electrodes. This aptasensor platform has a record-low detection limit (∼0.524 pg mL(-1)) and sensitivity (36 µA pg(-1) mL cm(-2)) toward Mb with a dynamic response range from 1 pg mL(-1) to 16 µg mL(-1) for Mb in serum samples. This strategy opens up avenues to bedside technologies for multiplexed diagnosis of cardiovascular diseases in complex human samples.

Preference and willingness to pay for traditional medicine services in rural ethnic minority community in Vietnam.

BACKGROUND: Traditional medicine (TM) still plays an important role in a number of health care systems around the world, especially across Asian and African countries. In Vietnam, however, little is known about preference for traditional medicine use. This study assessed the prevalence of use, preference, satisfaction, and willingness to pay for TM services amongst rural ethnic minority community. METHODS: A cross-sectional survey in three provinces in the North and South of Vietnam. RESULTS: The results showed a high level of satisfaction with TM services, with more than 90 % of respondents reporting improved health status given the use of TM. Indicators for preference of TM over modern medicine are a longer distance to health station; being in an ethnic minority; being female; and having had higher service satisfaction. Although we did not have a comparison group, the high level of satisfaction with TM services is likely the result of a project targeting community health workers and the public regarding TM education and access promotion. Indeed, the community health workers are credited with relaying the information about TM more than any other sources. This suggests the importance of community health workers and community health centers in the promotion of TM use. CONCLUSIONS: Ethnic minority people prefer the use of traditional medicine services that supports the expansion of national programs and promotion of traditional medications.

The importance of assessment and management of morning stiffness in Asian patients with rheumatoid arthritis: Recommendations from an expert panel.

OBJECTIVE: In patients with rheumatoid arthritis (RA), morning stiffness is linked more to functional disability and pain than disease activity, as assessed by joint counts and markers of inflammation. As part of the Asia Pacific Morning Stiffness in Rheumatoid Arthritis Expert Panel, a group of eight rheumatologists met to formulate consensus points and develop recommendations for the assessment and management of morning stiffness in RA. METHODS: On the basis of a systematic literature review and expert opinion, a panel of Asian rheumatologists formulated recommendations for the assessment and medical treatment of RA. RESULTS: The panel agreed upon 10 consensus statements on morning stiffness, its assessment and treatment. Specifically, the panel recommended that morning stiffness, pain and impaired morning function should be routinely assessed in clinical practice. Although there are currently no validated tools for these parameters, they should be assessed as part of the patients' reported outcomes in RA. The panel also agreed on the benefits of low-dose glucocorticoids in RA, particularly for the improvement of morning stiffness. CONCLUSIONS: These recommendations serve to guide rheumatologists and other stakeholders on the assessment and management of morning stiffness, and help implement the treat-to-target principle in the management of RA.

Conditions for supplemental biogenic substrates to enhance activated sludge degradation of xenobiotic.

The effects of biogenic presence on the degradation of xenobiotic organics by natural microbial populations have been reported as either advantageous or disadvantageous. The inconsistency of the reports implies there could be a turning point from disadvantageous to advantageous outcomes so that conditions may exist that could bring an optimum advantage. This study tested the supplementations of varying concentrations of sucrose and peptone, separately and combined, to acclimated activated sludge degradation of xenobiotic 2,4-D, while other operational and microbiological conditions were held constant. Our test results showed that biogenic may indeed enhance or slow down xenobiotic degradation rates. The highest enhancements exist at concentrations of 50 and 80 mg/L, respectively, for sucrose and peptone when supplemented separately, and 20 mg/L sucrose and 40 mg/L peptone combined. Conditions for advantageous biogenic supplementation were identified for activated sludge degradation of a xenobiotic; specifically, the highest degradation rate enhancements occurred when biogenic supplementation was approximately 0.5 to 0.7 the concentration of 2,4-D base on chemical oxygen demand (COD), which brought a biomass yield of approximately double that yielded by 2,4-D. Kinetics analyses provided clues for the possible causes of advantageous and disadvantageous effects due to biogenic supplementation.

The role of thiamine in cancer: possible genetic and cellular signaling mechanisms.

The relationship between supplemental vitamins and various types of cancer has been the focus of recent investigation, and supplemental vitamins have been reported to modulate cancer rates. A significant association has been demonstrated between cancer and low levels of thiamine in the serum. Genetic studies have helped identify a number of factors that link thiamine to cancer, including the solute carrier transporter (SLC19) gene, transketolase, transcription factor p53, poly(ADP-ribose) polymerase-1 gene, and the reduced form of nicotinamide adenine dinucleotide phosphate. Thiamine supplementation may contribute to a high rate of tumor cell survival, proliferation and chemotherapy resistance. Thiamine has also been implicated in cancer through its effects on matrix metalloproteinases, prostaglandins, cyclooxygenase-2, reactive oxygen species, and nitric oxide synthase. However, some studies have suggested that thiamine may exhibit some antitumor effects. The role of thiamine in cancer is controversial. However, thiamine deficiency may occur in patients with cancer and cause serious disorders, including Wernicke's encephalopathy, that require parenteral thiamine supplementation. A very high dose of thiamine produces a growth-inhibitory effect in cancer. Therefore, further investigations of thiamine in cancer are needed to clarify this relationship.

Roles of vitamin D in amyotrophic lateral sclerosis: possible genetic and cellular signaling mechanisms.

Evidence suggests that there are aberrations in the vitamin D-endocrine system in subjects with amyotrophic lateral sclerosis (ALS). Here, we review the relationship between vitamin D and ALS. Vitamin D deficiency was reported in patients with ALS. Dietary vitamin D(3) supplementation improves functional capacity in the G93A transgenic mouse model of ALS. Genetic studies have provided an opportunity to identify the proteins that link vitamin D to ALS pathology, including major histocompatibility complex (MHC) class II molecules, toll-like receptors, poly(ADP-ribose) polymerase-1, heme oxygenase-1, and calcium-binding proteins, as well as the reduced form of nicotinamide adenine dinucleotide phosphate. Vitamin D also exerts its effect on ALS through cell-signaling mechanisms, including glutamate, matrix metalloproteinases, mitogen-activated protein kinase pathways, the Wnt/ß-catenin signaling pathway, prostaglandins, reactive oxygen species, and nitric oxide synthase. In conclusion, vitamin D may have a role in ALS. Further investigation of vitamin D in ALS patients is needed.

The beneficial role of thiamine in Parkinson disease.

Parkinson disease (PD) is the second most common form of neurodegeneration among elderly individuals. PD is clinically characterized by tremors, rigidity, slowness of movement, and postural imbalance. In this paper, we review the evidence for an association between PD and thiamine. Interestingly, a significant association has been demonstrated between PD and low levels of serum thiamine, and thiamine supplements appear to have beneficial clinical effects against PD. Multiple studies have evaluated the connection between thiamine and PD pathology, and candidate pathways involve the transcription factor Sp1, p53, Bcl-2, caspase-3, tyrosine hydroxylase, glycogen synthase kinase-3ß, vascular endothelial growth factor, advanced glycation end products, nuclear factor kappa B, mitogen-activated protein kinase, and the reduced form of nicotinamide adenine dinucleotide phosphate. Thus, a review of the literature suggests that thiamine plays a role in PD, although further investigation into the effects of thiamine in PD is needed.

The role of vitamin D in Alzheimer's disease: possible genetic and cell signaling mechanisms.

Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals and is associated with progressive memory loss and cognitive dysfunction. A significant association between AD and low levels of vitamin D has been demonstrated. Furthermore, vitamin D supplements appear to have a beneficial clinical effect on AD by regulating micro-RNA, enhancing toll-like receptors, modulating vascular endothelial factor expression, modulating angiogenin, and advanced glycation end products. Vitamin D also exerts its effects on AD by regulating calcium-sensing receptor expression, enhancing amyloid-ß peptides clearance, interleukin 10, downregulating matrix metalloproteinases, upregulating heme oxygenase 1, and suppressing the reduced form of nicotinamide adenine dinucleotide phosphate expression. In conclusion, vitamin D may play a beneficial role in AD. Calcitriol is the best vitamin D supplement for AD, because it is the active form of the vitamin D3 metabolite and modulates inflammatory cytokine expression. Therefore, further investigation of the role of calcitriol in AD is needed.

EpicCapo: epitope prediction using combined information of amino acid pairwise contact potentials and HLA-peptide contact site information.

BACKGROUND: Epitope identification is an essential step toward synthetic vaccine development since epitopes play an important role in activating immune response. Classical experimental approaches are laborious and time-consuming, and therefore computational methods for generating epitope candidates have been actively studied. Most of these methods, however, are based on sophisticated nonlinear techniques for achieving higher predictive performance. The use of these techniques tend to diminish their interpretability with respect to binding potential: that is, they do not provide much insight into binding mechanisms. RESULTS: We have developed a novel epitope prediction method named EpicCapo and its variants, EpicCapo(+) and EpicCapo(+REF). Nonapeptides were encoded numerically using a novel peptide-encoding scheme for machine learning algorithms by utilizing 40 amino acid pairwise contact potentials (referred to as AAPPs throughout this paper). The predictive performances of EpicCapo(+) and EpicCapo(+REF) outperformed other state-of-the-art methods without losing interpretability. Interestingly, the most informative AAPPs estimated by our study were those developed by Micheletti and Simons while previous studies utilized two AAPPs developed by Miyazawa & Jernigan and Betancourt & Thirumalai. In addition, we found that all amino acid positions in nonapeptides could effect on performances of the predictive models including non-anchor positions. Finally, EpicCapo(+REF) was applied to identify candidates of promiscuous epitopes. As a result, 67.1% of the predicted nonapeptides epitopes were consistent with preceding studies based on immunological experiments. CONCLUSIONS: Our method achieved high performance in testing with benchmark datasets. In addition, our study identified a number of candidates of promiscuous CTL epitopes consistent with previously reported immunological experiments. We speculate that our techniques may be useful in the development of new vaccines. The R implementation of EpicCapo(+REF) is available at http://pirun.ku.ac.th/~fsciiok/EpicCapoREF.zip. Datasets are available at http://pirun.ku.ac.th/~fsciiok/Datasets.zip.

Vitamin D and Parkinson's disease.

Parkinson's disease (PD) is the second most common form of neurodegeneration among the elderly population. PD is clinically characterized by tremors, rigidity, slowness of movement, and postural imbalance. Interestingly, a significant association has been demonstrated between PD and low levels of vitamin D in the serum, and vitamin D supplement appears to have a beneficial clinical effect on PD. Genetic studies have provided the opportunity to determine which proteins link vitamin D to PD pathology, e.g., Nurr1 gene, toll-like receptor, gene related to lipid disorders, vascular endothelial factor, tyrosine hydroxylase, and angiogenin. Vitamin D also exerts its effects on cancer through nongenomic factors, e.g., bacillus Calmette-Guerin vaccination, interleukin-10, Wntß-catenin signaling pathways, mitogen-activated protein kinase pathways, and the reduced form of the nicotinamide adenine dinucleotide phosphate. In conclusion, vitamin D might have a beneficial role in PD. Calcitriol is best used for PD because it is the active form of the vitamin D(3) metabolite and modulates inflammatory cytokine expression. Further investigation with calcitriol in PD is needed.