miR-277 targets the proapoptotic gene-hid to ameliorate Aß42-mediated neurodegeneration in Alzheimer's model.

Alzheimer's disease (AD), an age-related progressive neurodegenerative disorder, exhibits reduced cognitive function with no cure to date. One of the reasons for AD is the accumulation of Amyloid-beta 42 (Aß42) plaque(s) that trigger aberrant gene expression and signaling, which results in neuronal cell death by an unknown mechanism(s). Misexpression of human Aß42 in the developing retina of Drosophila exhibits AD-like neuropathology. Small non-coding RNAs, microRNAs (miRNAs), post-transcriptionally regulate the expression of their target genes and thereby regulate different signaling pathways. In a forward genetic screen, we identified miR-277 (human ortholog is hsa-miR-3660) as a genetic modifier of Aß42-mediated neurodegeneration. Loss-of-function of miR-277 enhances the Aß42-mediated neurodegeneration. Whereas gain-of-function of miR-277 in the GMR > Aß42 background downregulates cell death to maintain the number of neurons and thereby restores the retinal axonal targeting defects indicating the functional rescue. In addition, gain-of-function of miR-277 rescues the eclosion- and climbing assays defects observed in GMR > Aß42 background. Thus, gain-of-function of miR-277 rescues both structurally as well as functionally the Aß42-mediated neurodegeneration. Furthermore, we identified head involution defective (hid), an evolutionarily conserved proapoptotic gene, as one of the targets of miR-277 and validated these results using luciferase- and qPCR -assays. In the GMR > Aß42 background, the gain-of-function of miR-277 results in the reduction of hid transcript levels to one-third of its levels as compared to GMR > Aß42 background alone. Here, we provide a novel molecular mechanism where miR-277 targets and downregulates proapoptotic gene, hid, transcript levels to rescue Aß42-mediated neurodegeneration by blocking cell death. These studies shed light on molecular mechanism(s) that mediate cell death response following Aß42 accumulation seen in neurodegenerative disorders in humans and provide new therapeutic targets for neurodegeneration.

Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in Rats.

Sildenafil citrate, an oral drug used to treat erectile dysfunction, has low water solubility and oral bioavailability. The solubility is greatly influenced by the pH, changing from 37.25 mg/mL to 0.22 mg/mL with a change in pH from 1.2 to 8.0. This indicates that the absorption may decrease in patients who use drugs, such as proton pump inhibitors (PPIs), for gastroesophageal reflux disease. To improve the absorption of sildenafil citrate at various gastric pH levels, a sildenafil citrate orally disintegrating tablet (ODT), which has a rapid disintegration feature, was produced by a 3D printing technique. Our study investigated the pharmacokinetic parameters of the sildenafil citrate ODT in rats after oral administration and compared the absorption of the sildenafil citrate ODT and sildenafil citrate commercial tablet (RLD), with and without PPI treatment. The LC/MS/MS analysis of the plasma sildenafil concentration revealed that the area under curve from time 0 to infinity (AUC0-∞) of sildenafil in the sildenafil citrate ODT group was significantly higher than in the sildenafil citrate RLD group whether it was in combination with the PPI or not (274.8% and 144%, respectively; p < 0.05). The relative systemic bioavailability of sildenafil citrate RLD significantly decreased with the PPI, but that of sildenafil citrate ODT was not affected by the PPI. These results indicate that the relative systemic bioavailability of sildenafil citrate ODT was increased when it was prepared using the 3D printing technique and the absorption of this formulation was not affected by the PPI.

Simvastatin Attenuated Tumor Growth in Different Pancreatic Tumor Animal Models.

Newly diagnosed pancreatic cancer increases year by year, while the prognosis of pancreatic cancer has not been very good. Statin drugs were found to have protective effects against a variety of cancers, but their association with pancreatic cancer remains to be clarified. This study used different pancreatic cancer cell lines and in different animal models to confirm the relationship between simvastatin and pancreatic cancer. Flow cytometry and luciferase-based bioluminescent images were used to investigate the cell cycle and tumor growth changes under simvastatin treatment. Simvastatin decreased the MIA PaCa-2 cells, PANC-1 cells, and BxPC-3 cell viability significantly and may arrest the cell cycle in the G0 phase. During in vivo study, subcutaneously implanted simvastatin pre-treated pancreatic cancer cells and intraperitoneally treated simvastatin continuously demonstrated a slower tumor growth rate and decreased the tumor/body weight ratio significantly. In intravenous implant models, implanted simvastatin-pre-treated BxPC-3 cells and cells treated along with simvastatin significantly decreased the tumor growth curve. Implanting the simvastatin-pre-treated pancreatic cells in the subcutaneous model showed better growth inhibition than the intravenous model. These results suggest simvastatin treatment may relate to different signaling pathways in local growth and metastasis. Pancreatic cancer cells presented different growth patterns in different animal-induced models, which could be important for clinical reference when it comes to the relationship of long-term statin use and pancreatic cancer.

Topical Application of Antrodia cinnamomea Ointment in Diabetic Wound Healing.

The number of diagnosed diabetic patients is increasing worldwide. Many people with diabetes develop wounds that are slow to, or never, heal, which can lead to serious health issues. Diabetes causes long-term excessive blood glucose buildup in human body, which leads to an over-reactive inflammatory response and excessive oxidative stress. As a result, varied wound healing effects were observed according to different circumstances and stage of healing. We used two diabetic wound animal models to analyze the wound healing effect of Antrodia cinnamomea ointment in either topical application and/or oral administration, and explored its mechanism by Western blot analysis. The results showed that topical Antrodia cinnamomea treatment can significantly promote wound healing. The increased expressions of angiopoietin 1 and angiopoietin 2 protein and reduction of CD68 expression were found around wound area. Simultaneous treatment of oral and topical Antrodia cinnamomea ointment did not show an accelerated healing effect in our animal model. This study is the first report to demonstrate the effect of topical application of Antrodia cinnamomea ointment on diabetic wounds healing, and its relationship with angiogenesis. This may also open a new field for future development and application of Taiwan Antrodia cinnamomea.

Serotonin receptor subtype-2B signaling is associated with interleukin-18-induced cardiomyoblast hypertrophy in vitro.

Background: In patients with heart failure, interleukin-18 (IL-18) levels increase in the circulatory system and injured myocardial tissue. Serotonin (5-hydroxytryptamine) receptors subtype 2B (HTR2B) play an essential role in cardiac function and development, and their overexpression in rats leads to myocardial hypertrophy. Epigallocatechin gallate (EGCG) is cardioprotective in myocardial ischemia-reperfusion injury in rats and can prevent pressure overload-mediated cardiac hypertrophy in vivo. Mice deficient in peroxisome proliferator-activated receptor delta (PPARδ) can have cardiac dysfunction, myocardial hypertrophy, and heart failure. Matrix metalloproteinases (MMPs) are possibly involved in cardiac remodeling. However, the relationship between IL-18 signaling, cardiac hypertrophy, and the molecular mechanisms involved remain to be fully elucidated. Objectives: To elucidate the relationship between HTR2B and IL-18-induced myocardial hypertrophy and examine the antihypertrophic effects of EGCG and PPARδ. Methods: We induced H9c2 cardiomyoblast hypertrophy with IL-18 in vitro and investigated the downstream signaling by real-time polymerase chain reaction (PCR) and western blotting. Hypertrophy was assessed by flow cytometry. We determined the effects of EGCG and PPARδ on IL-18-induced hypertrophic signaling via HTR2B-dependent mechanisms. Results: IL-18-induced H9c2 hypertrophy upregulated brain natriuretic peptide (BNP) protein and mRNA expression by inducing the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the hypertrophy was attenuated by pretreatment with EGCG (20 µM) and L-165,041 (2 µM), a PPARδ agonist. IL-18 upregulated the expression of HTR2B, which was inhibited by pretreatment with EGCG and L-165,041. SB215505 (0.1 µM), a HTR2B antagonist and siRNA for HTR2B, attenuated H9c2 hypertrophy significantly. Inhibition of HTR2B also downregulated the expression of MMP-3 and MMP-9. Conclusions: IL-18 and HTR2B play critical roles in cardiomyoblast hypertrophy. EGCG and L-165,041 inhibit the expression of HTR2B and augment remodeling of H9c2 cardiomyoblasts, possibly mediated by MMP-3 and MMP-9.

The Cell Protective Effect of Adenine on Hypoxia-Reoxygenation Injury through PPAR Delta Activation.

Ischemia followed by blood supply reperfusion in cardiomyocytes leads to an overproduction of free radicals and a rapid decrease of adenosine triphosphate concentration. The cardioprotective effect of a potential drug, adenine, was evaluated using H9c2 rat cardiomyoblasts. After hypoxia-reoxygenation (HR) treatment consisting of hypoxia for 21 h followed by reoxygenation for 6 h, it was revealed that pretreatment with 200 µM adenine for 2 h effectively prevented HR-induced cell death. Adenine also significantly decreased the production of reactive oxygen species and reduced cell apoptosis after HR injury. The antioxidant effect of adenine was also revealed in this study. Adenine pretreatment significantly reduced the expression of activating transcription factor 4 (ATF4) and glucose-regulated protein 78 (GRP78) proteins, and protein disulfide isomerase induced a protective effect on mitochondria after HR stimulation. Intracellular adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor delta (PPARδ), and perilipin levels were increased by adenine after HR stimulation. Adenine had a protective effect in HR-damaged H9c2 cells. It may be used in multiple preventive medicines in the future.

Pancreatic Fibrosis (Early Chronic Pancreatitis) as Emerging Diagnosis in Structural Causes of Dyspepsia: Evidence from Endoscopic Ultrasonography and Shear Wave Elastography.

A new concept for the diagnosis and management of non-functional dyspepsia in guidelines was lacking in the past decade. Medical advancement has proven pancreatic fibrosis (essential image evidence of early chronic pancreatitis) to be a cause of dyspepsia and related to pancreatic exocrine dysfunction. This study aimed to analyze the clinical picture, biomarker, and percentage of pancreatic fibrosis in the dyspeptic population. A total of 141 consecutive patients were retrospectively enrolled. They were diagnosed with peptic ulcer disease, 9.2% (n = 13); pancreatic fibrosis, 17% (n = 24); pure Helicobacter pylori infection, 19.9% (n = 28); functional dyspepsia, 53.2% (n = 75); and chronic pancreatitis, 0.7% (n = 1). Among those with pancreatic fibrosis, (n = 24), 11 were diagnosed on the basis of a pancreatic acoustic radiation force impulse exceeding 1.4 m/s, and the remaining 13 were diagnosed with early chronic pancreatitis with at least three of the Japanese endoscopic ultrasonography criteria. The anatomic distribution of parenchymal criteria of early chronic pancreatitis was head, 53%; body, 38%; and tail, 9%. There were 17 cases (71%, 17/24) without Helicobacter pylori and whose dyspepsia improved after pancreatic enzyme replacement with a ratio of 82.3% (14/17). Of the 141 cases, 19 received gastric emptying scintigraphy and Western blot analysis of chromogranin-A in duodenal mucosa. Delayed gastric emptying was more common in functional dyspepsia and chromogranin-A was expressed more in pancreatic fibrosis. In conclusion, pancreatic fibrosis (including early chronic pancreatitis) outnumbered peptic ulcer disease in the dyspeptic population and pancreatic enzyme therapy was effective for 82% of cases. In early chronic pancreatitis, pancreatic fibrosis is dominant in the head location, and duodenum mucosa chromogranin-A is a potential biomarker with increased expression in an age-matched manner.

Household preparedness for emergency events: a cross-sectional survey on residents in four regions of China.

OBJECTIVE: This study aimed to assess household preparedness for emergency events and its determinants in China. DESIGN: A cross-sectional questionnaire survey was conducted on 3541 households in China in 2015. PARTICIPANTS: Households were selected using a stratified cluster sampling strategy, representing central, eastern, western and southern regions of China. The designed questionnaires were administered through face-to-face interviews. OUTCOME MEASURES: Household emergency preparedness was measured with 14 indicators, tapping into the supply of nine emergency necessities (food and water, extra batteries, battery-powered radio, battery-operated torch, first-aid kit, gas mask, fire extinguisher, escape ropes, whistle), coverage of accident insurance, knowledge of local emergency response systems (emergency numbers, exit routes and shelters) and availability of a household evacuation plan. If an individual acted on 9 of the 14 indicators, they were deemed well prepared. Logistic regression models were established to identify predictors of well preparedness based on 3541 returned questionnaires containing no missing values. RESULTS: Only 9.9% of households were well prepared for emergencies: 53.6% did not know what to do and 31.6% did not want to think about it. A higher level of preparedness was found in the respondents who have attained higher education (adjusted OR=0.826 compared with the higher level), participated in emergency training activities (adjusted OR=2.299), had better emergency knowledge (adjusted OR=2.043), reported less fate-submissiveness (adjusted OR=1.385) and more self-reliance (adjusted OR=1.349), prior exposure to emergency events (adjusted OR=1.280) and held more positive attitudes towards preparedness (adjusted OR=1.286). CONCLUSION: Household preparedness for emergency events is poor in China. Lack of motivation, negative attitude to preparedness and knowledge shortfall are major but remediable barriers for household preparedness.

Combination of inductive effect of lipopolysaccharide and in situ mechanical conditioning for forming an autologous vascular graft in vivo.

Autologous vascular grafts have the advantages of better biocompatibility and prognosis. However, previous studies that implanted bare polymer tubes in animals to grow autologous tubular tissues were limited by their poor yield rates and stability. To enhance the yield rate of the tubular tissue, we employed a design with the addition of overlaid autologous whole blood scaffold containing lipopolysaccharides (LPS). Furthermore, we applied in vivo dynamic mechanical stimuli through cyclically inflatable silicone tube to improve the mechanical properties of the harvested tissues. The effectiveness of the modification was examined by implanting the tubes in the peritoneal cavity of rats. A group without mechanical stimuli served as the controls. After 24 days of culture including 16 days of cyclic mechanical stimuli, we harvested the tubular tissue forming on the silicone tube for analysis or further autologous interposition vascular grafting. In comparison with those without cyclic dynamic stimuli, tubular tissues with this treatment during in vivo culture had stronger mechanical properties, better smooth muscle differentiation, and more collagen and elastin expression by the end of incubation period in the peritoneal cavity. The grafts remained patent after 4 months of implantation and showed the presence of endothelial and smooth muscle cells. This model shows a new prospect for vascular tissue engineering.

Adenine accelerated the diabetic wound healing by PPAR delta and angiogenic regulation.

Wound healing is one of the major complications of diabetes, and problems with wound healing in diabetics often lead to amputation and even death. AMP-activated protein kinase (AMPK) is a protein involved in intracellular metabolism. Activated AMPK can reduce visceral fat and cholesterol synthesis and even inhibit hepatic gluconeogenesis. Activation of AMPK has been widely used in the treatment of type II diabetes. We applied an AMPK activator (Adenine) to human fibroblasts and to the wounds of streptozotocin-induced diabetic mice. We applied Adenine ointment to the wounds on 7 consecutive days and observed the healing status as well as activation of AMPK and angiogenic factors. Based on the appearance of the wounds, the results showed that after 7 days of treatment the wound area was smaller in the Adenine-treated group relative to the control group. The results for tissue protein expression showed that, compared to the control group, angiogenic related protein, PPARδ were increased and receptor for advanced glycation endproducts (RAGE) was decreased in the Adenine-treated group. Our studies indicate that Adenine has the potential to become a useful drug in the treatment of diabetic wound healing.

Glucagon-like peptide receptor agonists attenuate advanced glycation end products-induced inflammation in rat mesangial cells.

BACKGROUND: Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production play major roles in progression of diabetic nephropathy. Anti-RAGE effect of peroxisome proliferator-activated receptor-delta (PPARδ) agonists was shown in previous studies. PPARδ agonists also stimulate glucagon-like peptide-1 (GLP-1) secretion from human intestinal cells. METHODS: In this study, the individual and synergic anti-inflammatory effects of GLP-1 receptor (exendin-4) and PPARδ (L-165,041) agonists in AGE-treated rat mesangial cells (RMC) were investigated. RESULTS: The results showed both exendin-4 and L-165,041 significantly attenuated AGE-induced IL-6 and TNF-α production, RAGE expression, and cell death in RMC. Similar anti-inflammatory potency was seen between 0.3 nM exendin-4 and 1 µM L-165,041. Synergic effect of exendin-4 and L-165,041 was shown in inhibiting cytokines production, but not in inhibiting RAGE expression or cell death. CONCLUSIONS: These results suggest that both GLP-1 receptor and PPARδ agonists have anti-inflammatory effect on AGE-treated rat mesangial cells.

Clinical Effects of Laser Acupuncture plus Chinese Cupping on the Pain and Plasma Cortisol Levels in Patients with Chronic Nonspecific Lower Back Pain: A Randomized Controlled Trial.

OBJECTIVES: Chronic nonspecific lower back pain (LBP) is a common disease. Insufficient data is currently available to conclusively confirm the analgesic effects of laser acupuncture on LBP. This study evaluated the effectiveness of laser acupuncture plus Chinese cupping in LBP treatment. METHODS: Patients with chronic nonspecific LBP were enrolled for a randomized controlled trial and assigned to the laser acupuncture group (laser acupuncture plus Chinese cupping) and control group (sham laser plus Chinese cupping). Laser acupuncture (808 nm; 40 mW; 20 Hz; 15 J/cm2) and Chinese cupping were applied on the Weizhong (BL40) and Ashi acupoints for 5 consecutive days. Plasma cortisol levels were assessed before and after the 5-day treatment session. The visual analog scale (VAS) scores were recorded at baseline and throughout the 5-day treatment session. RESULTS: After the treatment session, the plasma cortisol levels and VAS scores decreased significantly in both groups. In the laser acupuncture group, the VAS scores decreased significantly on days 4 and 5, and an enhanced reduction in VAS scores was observed. CONCLUSION: Laser acupuncture plus Chinese cupping at the Weizhong (BL40) and Ashi acupoints effectively reduced pain and inflammation in chronic nonspecific LBP. This therapy could be a suitable option for LBP treatment in clinical settings.

Per-O-acetylation of cellulose in dimethyl sulfoxide with catalyzed transesterification.

Cellulose acetylation was investigated in dimethyl sulfoxide (DMSO) with isopropenyl acetate (IPA) as acetylating reagent and 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) as catalyst at 70-130 °C for 3-12 h. The degree of substitution (DS) of acetylated cellulose was comparatively determined by titration and ¹H NMR and confirmed by FT-IR analysis. The results indicated that per-O-acetylation was achieved at >90 °C for a relatively long duration. The three well-resolved peaks of carbonyl carbons in ¹³C NMR spectra also provided evidence of per-O-acetylation. The solubility of cellulose acetates in common organic solvents was examined, and the result showed that chloroform can be an alternative choice as a solvent for fully acetylated cellulose formed in this study besides DMSO. The intrinsic viscosity of acetylated cellulose solution implied almost no degradation of cellulose during acetylation in DMSO except at higher temperature (130 °C) for a long time.

L-165,041, troglitazone and their combination treatment to attenuate high glucose-induced receptor for advanced glycation end products (RAGE) expression.

Diabetic nephropathy is the leading cause of end-stage renal disease in the most developed countries of the world. Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production, pro-inflammatory cytokine secretion, and oxidative stress activation play major roles in kidney cell injury and apoptosis. Peroxisome proliferator-activated receptor-gamma (PPARγ) agonists are used clinically as insulin sensitizers. This study evaluated the renoprotective effect of PPARγ (troglitazone) and PPARδ (L-165,041) agonists on human embryonic kidney 293 (HEK) and mesangial cells. Troglitazone (10 µM) and L-165,041 (1 µM) significantly inhibited high glucose (25mM)-induced interleukin-6 and TNF-α production, RAGE expression and NF-κB translocation in HEK cells. Furthermore, Troglitazone (10 µM) and L-165,041(1 µM) significantly increased SOD expression and attenuated apoptosis in HEK and mesangial cells. The inhibitory effect between 1 µM L-165,041 and 10 µM troglitazone showed no difference. Furthermore L-165,041 and troglitazone together did not increase the effects. These results provide important information for future application of PPAR agonists in diabetic nephropathy treatment.

The effectiveness of an exercise programme for elders with dementia in a Taiwanese day-care centre.

The purpose was to examine the effectiveness of an exercise programme for elders with dementia in Taiwan aimed to maintain their activities of daily living such as feeding, dressing, grooming, washing and toileting. This was a single study group, repeated measure research design. Twenty-six dementia elders were recruited from a day-care centre located in southern Taiwan. Caregivers of the day-care centre provided all subjects an exercise programme. The exercise programme consisted of stretching and walking five times per week, and leg-weight bearing at least three times per week for 20-30 min each. The data were obtained three times (baseline, 2 months post intervention and 4 months post intervention). Results showed slight changes in the scores of one-leg-standing, 30 s chair rise, functional reach and get up and go test but were not statistically significant. Results also indicated that scores in the performance of activities of daily living were significantly higher than at baseline and at 4 months post intervention. In conclusion, this study provides information for dementia day-care centres in Taiwan about how elders with dementia can maintain physical fitness and perform activities of daily living.

Peroxisome proliferator-activated receptor delta agonists attenuated the C-reactive protein-induced pro-inflammation in cardiomyocytes and H9c2 cardiomyoblasts.

C-reactive protein (CRP) has emerged as a new marker for cardiovascular diseases. Activation of peroxisome proliferator-activated receptor delta (PPARdelta) plays beneficial roles in cardiac disorders. However, the relationship between CRP and PPARdelta in cardiac cells remains unclear. This study focused on the underlying molecular mechanisms of CRP and PPARdeltaagonists. Cardiomyocytes and cardiomyoblast cell line (H9c2) were used in different groups: Untreated; 15 microg/ml CRP with or without 1 microM PPARdelta agonists (L-165041). CRP increased PPARdelta and interleukin-6 expression in cardiomyocytes and H9c2 cardiomyoblasts. NF-kappaB inducing kinase (NIK) and NF-kappaB pathway also activated by CRP stimulation. These changes could be inhibited by L-165041 through p38MAPK and c-JNK pathways. However, transfection with siRNA of CD32 CRP receptor did not decrease CRP signaling or reverse the effects of L-165041 in CRP-treated cardiomyocytes and H9c2. Pretreatment with L-165041 attenuated apoptosis induced by hypoxia with or without CRP in H9c2 cardiomyoblasts. CRP up-regulated PPARdelta expression in cardiomyocytes and H9c2. L-165041 attenuated CRP-induced pro-inflammatory signaling through p38MAPK and c-JNK in H9c2 cardiomyoblasts. However, PPARdelta activation attenuated CRP-induced NF-kappaB pathway may be independent of CD32. These results may provide new evidence of PPARdelta beneficial effects for inflammatory cardiomyopathy.

Comparison of PPARδ and PPARγ in inhibiting the pro-inflammatory effects of C-reactive protein in endothelial cells.

BACKGROUND: Inflammation associated with endothelial cell dysfunction is a key step of atherogenesis. C-reactive protein (CRP), used to serve as a nonspecific clinical inflammation marker, has now emerged as a new marker for cardiovascular diseases. Recently, PPARδ has revealed benefits for dealing with inflammation. The relationship between CRP-induced inflammation and PPARδ agonist remains unclear. METHODS: Human umbilical vein endothelial cells (HUVECs) were separated into the following groups: 25 µg CRP alone for 15 hours; CRP-treated with 1 µM PPARδ(L-165041) or 10 µM PPARγ(troglitazone) agonists, and untreated HUVECs. This research focused on the CRP underlying signaling pathways and the effects of PPAR agonists on monocyte attachment to endothelial cells. RESULTS: Levels of interleukin-6 (IL-6) and IL-8 increased by CRP were both significantly attenuated by pretreatment with PPARδ or PPARγ agonists, but the needed dose of PPARδ to reach the same effect was less than PPARγ agonist. After incubation with CRP, immunoblotting showed a significant increase in NF-κB activation and CD32 receptor. These changes were associated with a significant increase of MCP-1 and VCAM-1 expression. PPARδ treatment not only decreased these pro-inflammatory effects in HUVECs but also significantly attenuated monocyte adhesion to endothelial cells in less dosage than PPARγ. CONCLUSIONS: The results suggest that PPARδ attenuated CRP-induced pro-inflammatory effects may through CD32 and NF-κB pathway. PPARδ may serve as a more potent therapeutic target than PPARγ in atherosclerosis or inflammatory therapy.