Metformin activates AMPK and mTOR to Inhibit RANKL-stimulated osteoclast formation.

OBJECTIVE: Metformin is a medication used to treat type 2 diabetes by inhibiting hepatic glucose production through adenosine monophosphate-activated protein kinase (AMPK) activation. Autophagy is closely related to the homeostasis and stress mechanisms of the body. In recent years, much research has arisen on therapeutic methods utilizing autophagy mechanisms to treat diagnoses such as metabolic diseases, tumors, and Alzheimer's disease. This study thus aimed to investigate the effects of metformin treatment on the differentiation of osteoclasts and changes in AMPK mechanisms, which play an important role in regulating energy homeostasis, and mTOR, a highly conserved kinase that regulates autophagy. MATERIALS AND METHODS: Experimentation, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, tartrate-resistant acid phosphate (TRAP) staining, pit formation assay, immunofluorescence, western blotting, and real-time polymerase chain reaction (PCR) was performed to investigate the effects of metformin on osteoclast differentiation. Additionally, to investigate its association with AMPK and pathways, the AMPK inhibitor compound C and mammalian targets of rapamycin (mTOR) activator leucine were used to examine the expression of osteoclast- or autophagy-related proteins, genes, and TRAP-positive cells. RESULTS: Metformin showed no cytotoxic effects on mouse osteoblastic cell lines (MC3T3-E1) and murine macrophage cell lines (RAW264.7) but did inhibit osteoclast differentiation. Furthermore, metformin was found to inhibit osteoclast differentiation through AMPK activation and mTOR inhibition. In turn, AMPK inhibition using compound C promoted osteoclast differentiation, and mTOR activation using leucine inhibited autophagy and osteoclast differentiation. CONCLUSIONS: Metformin activates the AMPK pathway while functioning as an activator of mTOR, thereby leading to the inhibition of autophagy and osteoclast differentiation.

METTL3-mediated downregulation of splicing factor SRSF11 is associated with carcinogenesis and poor survival of cancer patients.

OBJECTIVE: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications in eukaryotic RNA. As m6A modifications play an important role in RNA processing, abnormal m6A regulation caused by aberrant expression of m6A regulators is closely related to carcinogenesis. In this study, we aimed to determine the role of METTL3 expression in carcinogenesis, regulation of splicing factor expression by METTL3, and their effects in survival period and cancer-related metabolisms. MATERIALS AND METHODS: We investigated the correlation between each splicing factor and METTL3 in breast invasive ductal carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD) and gastric adenocarcinoma (STAD). Survival analysis was performed based on the expression of each splicing factor. To determine the molecular mechanism of SRSF11 in carcinogenesis, gene set enrichment analysis using RNA sequencing data was performed according to SRSF11 expression. RESULTS: Among the 64 splicing factors used for correlation analysis, 13 splicing factors showed a positive correlation with METTL3 in all four cancer types. We found that when METTL3 expression was decreased, the expression of SRSF11 was also decreased in all four types of cancer tissue when compared to that in normal tissue. Decreased SRSF11 expression was associated with poor survival in patients with BRCA, COAD, LUAD, and STAD. Gene set enrichment analysis according to SRSF11 expression showed that the p53/apoptosis, inflammation/immune response, and ultraviolet/reactive oxygen species stimulus-response pathways were enriched in cancers with decreased SRSF11 expression. CONCLUSIONS: These results suggest that METTL3 regulates SRSF11 expression, which could influence mRNA splicing in m6A modified cancer cells. METTL3-mediated downregulation of SRSF11 expression in cancer patients correlates with poor prognosis.

Automated Detection of TMJ Osteoarthritis Based on Artificial Intelligence.

The purpose of this study was to develop a diagnostic tool to automatically detect temporomandibular joint osteoarthritis (TMJOA) from cone beam computed tomography (CBCT) images with artificial intelligence. CBCT images of patients diagnosed with temporomandibular disorder were included for image preparation. Single-shot detection, an object detection model, was trained with 3,514 sagittal CBCT images of the temporomandibular joint that showed signs of osseous changes in the mandibular condyle. The region of interest (condylar head) was defined and classified into 2 categories-indeterminate for TMJOA and TMJOA-according to image analysis criteria for the diagnosis of temporomandibular disorder. The model was tested with 2 sets of 300 images in total. The average accuracy, precision, recall, and F1 score over the 2 test sets were 0.86, 0.85, 0.84, and 0.84, respectively. Automated detection of TMJOA from sagittal CBCT images is possible by using a deep neural networks model. It may be used to support clinicians with diagnosis and decision making for treatments of TMJOA.

Development and clinical application of an evidence-based pharmaceutical care service algorithm in acute coronary syndrome.

WHAT IS KNOWN AND OBJECTIVE: Drug therapies are critical for preventing secondary complications in acute coronary syndrome (ACS). The purpose of this study was to develop and apply a pharmaceutical care service (PCS) algorithm for ACS and confirm that it is applicable through a prospective clinical trial. METHODS: The ACS-PCS algorithm was developed according to extant evidence-based treatment and pharmaceutical care guidelines. Quality assurance was conducted through two methods: literature comparison and expert panel evaluation. The literature comparison was used to compare the content of the algorithm with the referenced guidelines. Expert evaluations were conducted by nine experts for 75 questionnaire items. A trial was conducted to confirm its effectiveness. Seventy-nine patients were assigned to either the pharmacist-included multidisciplinary team care (MTC) group or the usual care (UC) group. The endpoints of the trial were the prescription rate of two important drugs, readmission, emergency room (ER) visit and mortality. RESULTS AND DISCUSSION: The main frame of the algorithm was structured with three tasks: medication reconciliation, medication optimization and transition of care. The contents and context of the algorithm were compliant with class I recommendations and the main service items from the evidence-based guidelines. Opinions from the expert panel were mostly positive. There were significant differences in beta-blocker prescription rates in the overall period (P = .013) and ER visits (four cases, 9.76%, P = .016) in the MTC group compared to the UC group, respectively. WHAT IS NEW AND CONCLUSION: We developed a PCS algorithm for ACS based on the contents of evidence-based drug therapy and the core concept of pharmacist services.

Dietary total, animal, vegetable calcium and type 2 diabetes incidence among Korean adults: The Korean Multi-Rural Communities Cohort (MRCohort).

BACKGROUND AND AIMS: Although a possible mechanism for developing type 2 diabetes in relation to calcium intake has been suggested, there is currently little epidemiological evidence on the association between dietary calcium and type 2 diabetes (T2D). This study aimed to evaluate the prospective association between dietary calcium and T2D incidence among adults 40 years of age or over, from the Multi-rural Communities Cohort (MRCohort), South Korea. METHODS AND RESULTS: In total, 8313 participants (3033 men and 5280 women) who did not have diabetes at baseline were recruited between 2005 and 2013. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator. During follow-up (31,570 person-years), 322 T2D cases were newly diagnosed. Dietary calcium (total and vegetable calcium) were inversely associated with the risk of T2D incidence among women (IRR = 0.61, 95% CI = 0.43-0.86, P for trend = 0.007 in third tertile of baseline total calcium intake comparing to the first tertile; IRR = 0.57, 95% CI = 0.39-0.84, P for trend = 0.006 for baseline vegetable calcium intake), not for men. The tendency of those inverse associations remained in both the normal fasting blood glucose group and the impaired fasting blood glucose group and were independent of obesity, smoking, and magnesium intake. CONCLUSIONS: Total and vegetable calcium may be inversely associated with T2D incidence among women, regardless of impaired fasting blood glucose group or normal group. The associations may be potentially dose-responsive. Moderate dietary calcium may be related to lower risk of T2D incidence comparing to low intake group among women.

Ion size effects on the osmotic pressure and electrocapillarity in a nanoslit: Symmetric and asymmetric ion sizes.

We analyze the effect of asymmetric finite ion size in nanoconfinement in the view of osmotic pressure and electrocapillarity. When the confinement width becomes comparable with the Debye length, the overlapped electric double layer is significantly deformed by the steric effects. We derive the osmotic pressure from the modified Poisson-Boltzmann equation in a nanoslit to examine the deviation from the ideal osmotic pressure and the repulsive force on the wall considering the asymmetry of ion sizes. Then the electrocapillarity due to the steric effect is investigated under constant potential condition with the flat interface assumption. Later, the deformation by the electrocapillarity is also considered in the first order approximation.

Pharmacist-involved care for patients with heart failure and acute coronary syndrome: a systematic review with qualitative and quantitative meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Many trials have indicated that interventions by pharmacists resulted in beneficial outcomes with positive effects on cardiovascular diseases. The interventions through pharmacist-involved pharmaceutical care in patients with heart failure (HF) and acute coronary syndrome (ACS) were reviewed systemically and examined. METHODS: A systematic literature search was conducted to identify relevant articles describing pharmacist interventions in HF and ACS. Most studies were evaluated qualitatively, and the strength of evidence was graded according to the Agency for Healthcare Research and Quality (AHRQ) guidelines. Some of the studies were also assessed by a meta-analysis. RESULTS: A total of 26 studies containing data on 9415 patients were identified. For all studies, the strength of the body of evidence was reviewed and graded, and 14 studies among them were meta-analysed. The evidence was not strong enough to determine the effects of pharmaceutical care on major and patient-centred outcomes, except the prescription rates of angiotensin-converting-enzyme inhibitors (ACEI) with a high strength of evidence. In the meta-analysis, all-cause hospitalization [odds ratio (OR), 0·74; 95% confidence interval (CI), 0·58-0·94] was reduced and the prescription rates of angiotensin-converting-enzyme inhibitors (ACEI; OR 1·43; 95% CI, 1·07-1·91) and beta-blockers (OR 1·92; 95% CI, 1·24-2·96) were significantly higher in the pharmaceutical care group compared with the usual care group. WHAT IS NEW AND CONCLUSIONS: All-cause hospitalization showed improvement in the pharmaceutical care group. However, the strength of evidence for the majority of outcomes with pharmaceutical care, except direct performance measures such as prescription rates, was either insufficient or low. This could be explained by the presence of imprecision and inconsistency derived from the diversity of pharmaceutical care, the heterogeneity of patient populations or clinical settings. Moreover, it may indicate the necessity for homogeneous applicable criteria for assessment. A standardized consensus of the guidelines for pharmaceutical care service should be considered to improve homogeneity.

Pharmacogenomic information in FDA-approved drug labels: Application to pediatric patients.

Pharmacogenomic (PGx) information is increasingly being incorporated into US Food and Drug Administration-approved drug labels. We reviewed the data source (adults vs. pediatrics) of PGx information in approved drug labels and assessed the suitability of applying adult-derived PGx information and related prescribing recommendations to the care of pediatric patients. We identified 65 drugs with labels containing PGx information and that have also been evaluated in children and found that in the majority of cases (56/65, 86%), the PGx information described was derived from adult studies. The application of PGx information from adults to pediatrics was deemed suitable for 71.4% (n = 40) of the drugs and unclear for 28.6% (n = 16). An ontogeny effect, limited or conflicting data regarding ontogeny of the genetic biomarker, or a difference in the pathophysiology or progression of the adult vs. pediatric disease were the primary reasons for deeming direct application from adults to pediatrics unclear.

Emissions of amides (N,N-dimethylformamide and formamide) and other obnoxious volatile organic compounds from different mattress textile products.

The emission rates of N,N-dimethylformamide (DMF), formamide (FAd), and certain hazardous volatile organic compounds (VOCs) were measured from seventeen mattress textile samples with four different raw material types: polyurethane (PU: n=3), polyester/polyethylene (PE: n=7), ethylene vinyl acetate (EV: n=3), and polyvinyl chloride (PC: n=4). To simulate the emissions in a heated room during winter season, measurements were made under temperature-controlled conditions, i.e., 50°C by using a mini-chamber system made of a midget impinger. Comparison of the data indicates that the patterns were greatly distinguished between DMF and FAd. PU products yielded the highest mean emission rates of DMF (2940 µg m(-2)h(-1): n=3) followed by PE (325 µg m(-2)h(-1): n=7), although its emission was not seen from other materials (EV and PC). In contrast, the pattern of FAd emission was moderately reversed from that of DMF: EV>PC>PE>PU. The results of our analysis confirm that most materials used for mattress production have the strong potential to emit either DMF or FAd in relatively large quantities while in use in children׳s care facilities, especially in winter months. Moreover, it was also observed that an increase in temperature (25°C to 50°C) had a significant impact on the emission rate of FAd and other hazardous VOCs. In addition to the aforementioned amides, the study revealed significant emissions of a number of hazardous VOCs, such as aromatic and carbonyl compounds.

Different role of spinal 5-HT(hydroxytryptamine)7 receptors and descending serotonergic modulation in inflammatory pain induced in formalin and carrageenan rat models.

BACKGROUND: Spinal serotonin (5-HT) receptors 3 (5-HT3R) and 7 (5-HT7R) are differentially involved in facilitatory or inhibitory descending modulation, respectively. Electrophysiological studies of the spinal cord have demonstrated that 5-HT3R is involved in nociception induced by intraplantar injection of formalin, but not carrageenan. In addition, depletion of spinal serotonin has been shown to attenuate pain behaviour in the formalin test, but there have been no such reports regarding the carrageenan model. This study compared the role of 5-HT7R and the influence of descending serotonergic modulation between formalin- and carrageenan-induced inflammatory pain. METHODS: Effects of intrathecal (i.t.) AS-19 (5-HT7R agonist) and SB-269970 (5-HT3R antagonist) on flinching response in the formalin test and mechanical allodynia in the carrageenan model were evaluated in male Sprague-Dawley rats. The effect of serotonin depletion by i.t. 5,7-dihydroxytryptamine was also examined in the two models. RESULTS: Intrathecal AS-19 significantly reduced the flinching responses in the formalin test (P<0.01), which was reversed by i.t. SB269970. However, neither AS-19 nor SB269970 produced a significant change in mechanical allodynia in the carrageenan model. Depletion of spinal serotonin attenuated the flinching response in phase 2 of the formalin test (P<0.01), but increased mechanical allodynia in the carrageenan model compared with controls (P<0.01). CONCLUSIONS: Spinal 5-HT7R plays a significant inhibitory role in descending serotonergic modulation in pain induced by formalin but not carrageenan. Descending serotonergic modulation is differentially involved in inflammatory pain induced by formalin and carrageenan, with facilitatory and inhibitory effects, respectively.

Some insights into the relationship between urban air pollution and noise levels.

The relationship between noise and air pollution was investigated in eight different districts across Seoul, Korea, between September and November 2010. The noise levels in each district were measured at both roadside and non-roadside locations. It was found that the maximum levels of noise were generally at frequencies of around 1000 Hz. The equivalent noise levels (L(eq)), over all districts, averaged 61.4 ± 7.36 dB which is slightly lower than the noise guidelines set by the World Health Organization (WHO) of 70 dB for industrial, commercial, traffic, and outdoor areas. Comparison of L(eq) levels in each district consistently indicates that noise levels are higher at roadside sites than non-roadside sites. In addition the relative dominance of noise during daytime as compared to nighttime was also apparent. Moreover, the results of an analysis relating sound levels with air pollutant levels indicate strongly that the correlation between these two parameters is the strongest at roadside sites (relative to non-roadside sites) and during nighttime (relative to daytime). The results of our data analysis point to a positive, but complex, correlation between noise levels and air pollution.

Optimal dose of vancomycin for treating methicillin-resistant Staphylococcus aureus pneumonia in critically ill patients.

A prospective cohort study was performed to determine the optimal dose of vancomycin to maintain a serum trough concentration of at least 15 to 20 mg/l and to assess the efficacy of this target vancomycin concentration in the treatment of methicillin-resistant Staphylococcus aureus pneumonia. Vancomycin pharmacokinetic parameters were estimated using a CAPSIL software program from serum concentrations of 141 patients with pneumonia treated with vancomycin, regardless of methicillin-resistant Staphylococcus aureus status, at a 28-bed medical intensive care unit. Vancomycin trough concentrations and other pharmacokinetic parameters were compared between five groups of patients differing in their renal function: (1) creatinine clearance > or =60 ml/minute, (2) creatinine clearance 30 to 60 ml/minute, (3) creatinine clearance <30 ml/minute, (4) on intermittent haemodialysis, and (5) on continuous renal replacement therapy. More than 70% of patients failed to reach the recommended therapeutic serum trough concentrations: a higher dose of vancomycin is necessary to maintain serum trough concentration at 15 to 20 mg/l, particularly in critically ill patients with creatinine clearance above 60 ml/minute and in those on intermittent haemodialysis. Among patients with methicillin-resistant Staphylococcus aureus pneumonia, no significant differences were observed in the treatment success rate, length of intensive care unit stay, and intensive care unit mortality rate between patients with vancomycin trough concentrations of >20 mg/l, 15 to 20 mg/l and <15 mg/l.

Electrowetting driven optical switch and tunable aperture.

We demonstrate an electrowetting based optical switch with tunable aperture. Under the influence of an electric field a non-transparent oil film can be replaced locally by a transparent water drop creating an aperture through which light can pass. Its diameter can be tuned between 0.2 and 1.2 mm by varying the driving voltage or frequency. The on and off response time of the switch is in the order of 2 and 120 ms respectively. Finally we demonstrate an array of switchable apertures that can be tuned independently or simultaneously.

Wetting of a drop on a sphere.

In this work, the equilibrium morphology of a drop on a sphere is analyzed as a function of the contact angle and drop volume experimentally and with analytical effective interfacial energy calculations. Experimentally, a drop on a sphere geometry is realized in an oil bath by placing a water drop on a sphere coated with a dielectric, of which the radii of curvature are comparable with that of the drop. Electrowetting (EW) is used to change the contact angle of the water drop on the sphere. To validate the applicability of EW and the Lippman-Young equation on nonflat surfaces, we systematically investigate the response of the contact angle to the applied voltage (EW response) for various drop volumes and compared the results with the case of a planar surface. The effective interfacial energy of two competing morphologies, namely, the spherically symmetric "completely engulfing" and "partially engulfing" morphologies are calculated analytically. The analytical calculations are then compared to the experimental results to confirm which morphology is energetically more favored for a given contact angle and drop volume. Our findings indicate that the "partially engulfing" morphology is always the energetically more favorable morphology.

Expression of human TIM-3 and its correlation with disease activity in rheumatoid arthritis.

OBJECTIVE: T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) is a novel transmembrane protein that is involved in the regulation of T-helper 1 (Th1)-cell-mediated immunity. This study was undertaken to investigate the expressions of TIM-3 and its ligand galectin 9 (Gal-9) with respect to disease activity in rheumatoid arthritis (RA). METHODS: Blood was collected from 39 RA patients and 31 healthy controls. Blood leucocyte TIM-3 and Gal-9 mRNA levels and RA disease activity were determined. Synovial tissue (ST) from five RA patients and five osteoarthritis (OA) patients were examined for TIM-3 mRNA expression and were also analysed for TIM-3 by immunohistology. RESULTS: TIM-3 mRNA expression was significantly higher in the ST of RA patients than in the ST of OA patients. TIM-3 was expressed in the synovial sublining area in ST of RA patients but not in OA ST. TIM-3 mRNA expression from peripheral blood mononuclear cells (PBMCs) of RA patients was negatively correlated with the 28-joint Disease Activity Score (DAS28). Gal-9 mRNA level in PBMCs of RA patients was higher than in healthy controls, and was significantly higher in patients with low disease activity compared to those with moderate to high disease activity. Gal-9 mRNA expression in PBMCs of RA patients was positively correlated with forkhead box P3 (FoxP3) mRNA expression. CONCLUSION: TIM-3 and its interaction with Gal-9 are closely associated with RA disease activity and may play an important role in the pathogenesis of RA. In addition to the negative regulatory effect of Gal-9 mediated through the TIM-3-Gal-9 pathway, Gal-9 may exert its suppressive effect on RA disease activity by modulation of regulatory T (Treg) cells.

Electrical switching of wetting states on superhydrophobic surfaces: a route towards reversible Cassie-to-Wenzel transitions.

We demonstrate that the equilibrium shape of the composite interface between superhydrophobic surfaces and drops in the superhydrophobic Cassie state under electrowetting is determined by the balance of the Maxwell stress and the Laplace pressure. Energy barriers due to pinning of contact lines at the edges of the hydrophobic pillars control the transition from the Cassie to the Wenzel state. Barriers due to the narrow gap between adjacent pillars control the lateral propagation of the Wenzel state. We demonstrate how reversible switching between the two wetting states can be achieved locally using suitable surface and electrode geometries.

Anisotropic and hindered diffusion of colloidal particles in a closed cylinder.

Video microscopy and particle tracking were used to measure the spatial dependence of the diffusion coefficient (D(α)) of colloidal particles in a closed cylindrical cavity. Both the height and radius of the cylinder were equal to 9.0 particle diameters. The number of trapped particles was varied between 1 and 16, which produced similar results. In the center of the cavity, D(α) turned out to be 0.75D(0) measured in bulk liquid. On approaching the cylindrical wall, a transition region of about 3 particle diameters wide was found in which the radial and azimuthal components of D(α) decrease to respective values of 0.1D(0) and 0.4D(0), indicating asymmetrical diffusion. Hydrodynamic simulations of local drag coefficients for hard spheres produced very good agreement with experimental results. These findings indicate that the hydrodynamic particle-wall interactions are dominant and that the complete 3D geometry of the confinement needs to be taken into account to predict the spatial dependence of diffusion accurately.

Polycyclic aromatic hydrocarbon concentration levels on the Korean peninsula between 2006 and 2008.

Concentrations of seven polycyclic aromatic hydrocarbon (PAH) compounds - benzo(a)anthracene (BaA), chrysene (CHRY), benzo(b)fluoranthene (BbF), benzo(k)fluoranthene (BkF), dibenz(a,h)anthracene (DahA), indeno(1,2,3-cd)pyrene (I123P), and benzo(a)pyrene (BaP) - in air were measured as the sum of gas and particle fractions at 32 monitoring stations dispersed across Korea during a 2-year period (February 2006 to January 2008). The data sets were collected at intervals of 1 day (24 h) per month from each monitoring station. According to our analysis, the spatial distribution of PAH is distinguished by manmade activities between different land use types. Evaluation of total PAH (T-PAH) concentration levels, which were derived by summing up all individual compounds, revealed that the T-PAH value varied on the order of commercial (4.85 + or - 4.40 ng m(-3)) rural (4.42 + or - 2.73 ng m(-3)), industrial (4.27 + or - 1.79 ng m(-3)), greenland (3.09 + or - 3.86 ng m(-3)), and background (2.60 + or - 2.54 ng m(-3)) areas. The PAH values, when compared across seasons, tend to peak consistently during the winter (or spring) due to the active consumption of fossil fuels. The overall results of this study confirm that the pollution status of PAH compounds are clearly discernible not only between areas with different levels of anthropogenic activities, but also between periods with changes in environmental conditions.

Strong tunable slow and fast lights using a gain-clamped semiconductor optical amplifier.

Previously demonstrated slow light is still far from applications, particularly due to the limited bandwidth and control speed. Although semiconductor-based slow light has the high bandwidth and sub-nanosecond control speed, slow light was observed only in the absorption regime with attenuation, while fast light observed in the gain regime with amplification. The large power difference in two regimes makes the use of the optical delay impractical. We report novel slow light in the gain regime, with a high power comparable to that of fast light, utilizing the anomalous gain characteristic in a gain-clamped semiconductor optical amplifier. The slow light is tunable to fast light with the current as the only variable. Additional high speed operation, fast delay control, and wide range of operation wavelength make the present approach practical.

Stability analysis of zinc oxide-nanoencapsulated conjugated linoleic acid and gamma-linolenic acid.

Conjugated linoleic acid (CLA) and gamma-linolenic acid (GLA) were encapsulated with hydrated zinc oxide nanoparticles in an effort to improve their time and thermal stability. Encapsulated and nonencapsulated CLA and GLA were stored at 20, 30, 40, and 50 degrees C for 49 d. At various time points, encapsulated CLA and GLA were extracted, methylated, and analyzed using GC-FID. Both encapsulated CLA and control CLA were stable when stored at 20, 30, and 40 degrees C for up to 49 d. However, control CLA was 100% degraded after 28 d at 50 degrees C, whereas encapsulated CLA was stable at 50 degrees C for 49 d. Similarly, both encapsulated GLA and control GLA were stable when stored at 20 degrees C for 49 d, but nonencapsulated GLA was 92% degraded after 49 d at 30 degrees C; encapsulated GLA was stable at 30 degrees C. Therefore, nanoencapsulation improves the time and temperature stability of CLA and GLA.