Why do pre-clinical medical students learn ultrasound? Exploring learning motivation through ERG theory.

BACKGROUND: In recent years, point-of-care ultrasound (POCUS) has become an essential field of medical education. Bedside ultrasound has become a necessary skill for clinical physicians. Previous studies have already discussed the importance of advancements in ultrasound education. However, learning motivations for ultrasound education have seldom been analyzed in the literature. For medical students, learning ultrasound could have a relevance for their future career. The Existence, Relatedness and Growth (ERG) theory extended Maslow's hierarchy of needs through these three concepts. This theory has been widely used in the workplace to analyze employee job performance but has not yet been applied in medical education. In this study ERG theory was applied to analyze pre-clinical medical students' learning motivation toward ultrasound education. METHOD: This mixed method study used online questionnaires consisting of open-ended questions as a data collection tool, and based on these results, both qualitative and quantitative analysis were conducted. Participants answered a series of neutral and open-ended questions regarding their motivations to learn ultrasonography. After data collection, a three-step analysis was conducted based on the grounded theory approach. Finally, the results of the thematic coding were used to complete additional quantitative analysis. RESULTS: The study involved 140 pre-clinical medical students, and their responses fell into 13 specific categories. The analysis demonstrated that students' motivations toward ultrasound education were unbalanced across the three ERG domains (F = 41.257, p < .001). Pairwise comparisons showed that students mentioned existence motivation (MD = 39.3%; p < .001) and growth motivation (MD = 40.7%; p < .001) more frequently than relatedness motivation. However, there was no significant difference between existence motivation and growth motivation (MD = - 1.4%; p = .830). CONCLUSION: The results revealed that students placed a high value on existence and growth needs rather than relatedness based on the survey. In addition, the findings suggest that ERG theory can be a useful tool to conduct medical education motivation analysis.

Ruthenium derivatives attenuate LPS-induced inflammatory responses and liver injury via suppressing NF-κB signaling and free radical production.

Ruthenium metal complex has been shown to exert several chemical and biological activities. A series of three novel ruthenium derivatives (TQ 1, 2 and 4) were synthesized to evaluate the anti-inflammatory and hepatoprotective activities in lipopolysaccharide (LPS)-stimulated macrophages and mice liver injury. The hydroxyl radical (OH°) scavenging activity of these derivatives has also been evaluated. The results revealed that among the tested compounds, TQ-4 effectively attenuated LPS-induced abnormal alteration in liver histoarchistructure via reducing alanine transaminase (ALT) and aspartate transaminase (AST). This compound exhibited significant inhibition of inflammatory cytokines (TNF-α and IL-1ß), inflammatory enzyme (iNOS), the component of NF-κB signaling pathway (p65) and JNK phosphorylation in LPS-induced mice liver tissues. In vitro results showed that TQ-4 had the best inhibition of NO production and iNOS expression in LPS-induced RAW 264.7 cells. Mechanistic approach indicated that TQ-4 inhibited the LPS-induced JNK phosphorylation, IκBα degradation, NF-κB p65 phosphorylation and its nuclear translocation, and hydroxyl radical (OH°) productions in RAW 264.7 cells. However, the compounds TQ-1 and 2 had no effects in this study. TQ-4 also inhibited LPS-induced OH° production. This study reveals the protective effect of TQ-4 against LPS-induced acute liver injury, inflammation, and oxidative reaction by destructing JNK/NF-κB signaling pathways. The result of this study may infer that TQ-4 might be a promising ruthenium metal derivative and/or therapeutic agent for treating liver injury.

Gender differences in the acquisition of suturing skills with the da Vinci surgical system.

BACKGROUND: The percentage of female medical students has been significant elevating worldwide. The demographic shift is expected to influence the proportion of male versus female surgeons soon. The objective of this study was to evaluate the gender differences in the acquisition of robotic suturing skills. METHODS: We compared the robotic suturing performance between 39 male and 19 female medical students. We separated the training into two parts: phase I, involving virtual reality (VR) robotic simulation, and phase II, involving robotic dry-laboratory simulation training. Participants first conducted step-by-step exercises on the VR robotic simulator and then the robotic skin-suturing pad using the da Vinci robot. RESULTS: The metric analysis of the VR task "suture sponge" showed that female students required less time (difference: -170.7 seconds, 95% CI: -247.4 to -94.0) and had fewer errors (error difference: -50, 95% CI: -74.2 to -25.8) to complete the suture sponge exercise compared to male students. Moreover, female students completed more stitches than male students (differences in mean stitch achieved: .35; 95% CI: .06 to .65). However, there was no difference in the quality scores of stitches by gender (p = 0.85). CONCLUSION: Female medical students performed better in the VR task of suture spongy and achieved more stitches than male students with the da Vinci system despite no difference in robotic suture quality by gender. Because this is the first study comparing gender performance on a robotic platform, further studies are required to investigate if different training approaches will affect the performance by gender.

A dipeptidyl peptidase-4 inhibitor promotes wound healing in normoglycemic mice by modulating keratinocyte activity.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a well-known and novel class of oral antihyperglycaemic drugs. DPP-4 inhibition facilitates ulcer healing in patients with diabetes. However, the actual mechanisms, which are independent of lower blood glucose levels, are still unknown. Therefore, the aim of this study was to analyse the effect of the DPP-4 inhibitor sitagliptin on wound healing through a glucose-independent pathway. In this study, DPP-4 inhibitors facilitate keratinocyte differentiation and the proliferation, increase blood flow in the cutaneous of wounds in healthy C57BL/6 mice. Additionally, the administration of the DPP-4 inhibitor ameliorates wound healing and enhances adiponectin expression in healthy C57BL/6 mice. Taken together, our results reveal a protective role for the DPP-4 inhibitor sitagliptin in wound healing by regulating adiponectin and phospho-eNOS levels in keratinocytes. Based on these results, the DPP-4 inhibitor may have therapeutic potential for healing wounds through a diabetes-independent mechanism.

Embryonic exposure to 4-methylimidazole leads to zebrafish myofibril misalignment.

4-methylimidazole (4-MI) is an imidazole-derived organic chemical compound that can be used as a raw material in the manufacture of diverse chemicals and has been identified as an ingredient of caramel color in soybean sauce, beers, and other soft drinks. The aim of the present study was to investigate the teratogenic effects of 4-MI during zebrafish embryogenesis. Zebrafish embryos were treated with different dosages of 4-MI (0-120 mM) for different exposure durations (12-60 hours). The percentages of embryos with malformed phenotypes increased as the exposure dosages and duration time of 4-MI increased. We also used immunofluorescence and transmission microscopy to evaluate the subtle changes in the myofibril alignment and ultrastructure of muscle organization. Our data showed that 4-MI treatment disturbs muscle fiber alignment. Electron microscopy data indicated that Z-lines were undetectable in the 4-MI-treated embryos. Although the thick and thin filaments were visible, they were all disorganized. In addition, zebrafish embryos treated by 4-MI exhibited aberrant expression of 2 muscle-specific genes, myod and myogenin. Taken together, we concluded that early exposure to 4-MI affects zebrafish myogenesis, especially in myofibril alignment.

Low Second-To-Fourth Digit Ratio Has High Explosive Power? A Prepubertal Study.

Hsu, CC, Fong, TH, Chang, HM, Su, B, Chi, CP, Kan, NW, and Hsu, MC. Low second-to-fourth digit ratio has high explosive power? A prepubertal study. J Strength Cond Res 32(7): 2091-2095, 2018-A recent study reported that lower limb explosive power had no correlation with the index finger: ring finger (2D:4D) ratio. However, many studies hypothesized that a lower 2D:4D ratio (reflecting a relative higher testosterone exposure) predicts higher physical fitness. The aim of this study was to replicate the study of explosive power and the 2D:4D ratio in a sample of Taiwanese children. A total of 541 Taiwanese prepubertal children (257 girls and 284 boys aged 9-10 years) participated in this study. This study analyzed the relationship between the 2D:4D ratio and explosive power. Explosive power of the lower limbs was assessed using the standing long jump (SLJ) test. The lengths of the second and fourth fingers of the right hand were measured to calculate the 2D:4D ratio. The SLJ length was correlated with the 2D:4D ratios (r = -0.144, p = 0.015) in boys. After controlling for age and the body mass index, this correlation remained significant (r = -0.134, p = 0.024). For girls, 2D:4D ratios were not significantly correlated with SLJ scores. These results indicate that the SLJ distance was negatively correlated with the 2D:4D ratio in boys, but not in girls. These findings might suggest that prenatal testosterone exposure is negatively correlated with the explosive power in men, but not in women.

YC-1 induces lipid droplet formation in RAW 264.7 macrophages.

BACKGROUND: 3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) is a potential anticancer drug that may activate soluble guanylyl cyclase (sGC) and increase the level of cyclic guanosine monophosphate (cGMP). The aim of this study was to explore the effects of YC-1 on lipid droplet accumulation and foam cell formation in macrophages. RESULTS: Human-oxidized low density lipoprotein (ox-LDL) was used to induce accumulation of lipid droplets in a murine macrophage cell line, RAW 264.7. Oil red O staining showed that treatment with 20 µM YC-1 for 24 h increased the area of intracellular lipid droplets in macrophages. The results of high content screening (HCS) with the AdipoRed™ assay further revealed that YC-1 enhanced ox-LDL-induced foam cell formation. This was evidenced by an increase in the total area of lipid droplets and the mean fluorescence intensity per cell. Inhibition of cGMP-dependent protein kinase (PKG) using KT5823 significantly reduced YC-1-enhanced lipid droplet formation in ox-LDL-induced macrophage foam cells. CONCLUSION: YC-1 induces lipid droplet formation in macrophages, possibly through the sGC/cGMP/PKG signaling pathway. This chemical should be tested with caution in future clinical trials.

Comparative decline of the protein profiles of nebulin in response to denervation in skeletal muscle.

The sliding filament model of the sarcomere was developed more than half a century ago. This model, consisting only of thin and thick filaments, has been efficacious in elucidating many, but not all, features of skeletal muscle. Work during the 1980s revealed the existence of two additional filaments: the giant filamentous proteins titin and nebulin. Nebulin, a giant myofibrillar protein, acts as a protein ruler to maintain the lattice arrays of thin filaments and plays a role in signal transduction and contractile regulation. However, the change of nebulin and its effect on thin filaments in denervation-induced atrophic muscle remains unclear. The purpose of this study is to examine the content and pattern of nebulin, myosin heavy chain (MHC), actin, and titin in innervated and denervated tibialis anterior (TA) muscles of rats using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), densitometry and electron microscopic (EM) analyses. The results revealed that denervation induced muscle atrophy is accompanied by decreased nebulin content in a time-dependent manner. For instant, the levels of nebulin in denervated muscles were markedly (P < 0.05) decreased, about 24.6% and 40.2% in comparison with innervated muscle after denervation of 28 and 56 days, respectively. The nebulin/MHC, nebulin/actin, and nebulin/titin ratios were decreased, suggesting a concomitant reduction of nebulin in denervated muscle. Moreover, a western blotting assay proved that nebulin declined faster than titin on 28 and 56 days of denervated muscle. In addition, EM study revealed that the disturbed arrangements of myofilaments and a disorganized contractile apparatus were also observed in denervated muscle. Overall, the present study provides evidence that nebulin is more sensitive to the effect of denervation than MHC, actin, and titin. Nebulin decline indeed resulted in disintegrate of thin filaments and shortening of sarcomeres.

Perturbation of cytosolic calcium by 2-aminoethoxydiphenyl borate and caffeine affects zebrafish myofibril alignment.

The objective of the current study was to investigate the effects of Ca(2+) levels on myofibril alignment during zebrafish embryogenesis. To investigate how altered cytoplasmic Ca(2+) levels affect myofibril alignment, we exposed zebrafish embryos to 2-aminothoxyldiphenyl borate (2-APB; an inositol 1,4,5-trisphosphate receptor inhibitor that reduces cytosolic Ca(2+) levels) and caffeine (a ryanodine receptor activator that enhances cytosolic Ca(2+) levels). The results demonstrated that the most evident changes in zebrafish embryos treated with 2-APB were shorter body length, curved trunk and malformed somite boundary. In contrast, such malformed phenotypes were evident neither in untreated controls nor in caffeine-treated embryos. Subtle morphological changes, including changes in muscle fibers, F-actin and ultrastructures were easily observed by staining with specific monoclonal antibodies (F59 and α-laminin), fluorescent probes (phalloidin) and by transmission electron microscopy. Our data suggested that: (1) the exposure to 2-APB and/or caffeine led to myofibril misalignment; (2) 2-APB-treated embryos displayed split and short myofibril phenotypes, whereas muscle fibers from caffeine-treated embryos were twisted and wavy; and (3) zebrafish embryos co-exposed to 2-APB and caffeine resulted in normal myofibril alignment. In conclusion, we proposed that cytosolic Ca(2+) is important for myogenesis, particularly for myofibril alignment.

Elite collegiate tennis athletes have lower 2D: 4D ratios than those of nonathlete controls.

The ratio of the length of the second finger (index finger) to the fourth finger (ring finger) (2D:4D ratio) is a putative marker for prenatal hormones. Physiological research has suggested a low 2D:4D ratio correlates with high athletic ability. Athletes of specific sports (e.g., American football) have lower 2D:4D ratios than those of nonathletes, whereas athletes of some sports (e.g., rowing, gymnastics, and soccer) do not. This study investigated the 2D:4D ratios among collegiate tennis athletes, elite collegiate tennis athletes, and nonelite collegiate tennis athletes and compared them with nonathletes of both sexes. The participants included 43 elite collegiate tennis athletes (Level I intercollegiate athletes in Taiwan; 27 males and 16 females), 107 nonelite collegiate tennis athletes (Level II athletes; 55 males and 52 females), and 166 nonathlete college students (80 males and 86 females). The principle findings suggest that (a) regardless of sex, collegiate tennis athletes have lower 2D:4D values than those of nonathletes; (b) elite collegiate tennis athletes have lower 2D:4D values than those of nonathletes; (c) among females but not males, athletes and nonelite athletes have lower 2D:4D values than those of nonathletes; and (d) males have lower 2D:4D values than those of females.

Hinokitiol Exerts Anticancer Activity through Downregulation of MMPs 9/2 and Enhancement of Catalase and SOD Enzymes: In Vivo Augmentation of Lung Histoarchitecture.

Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP)-2 and -9. Evidence has shown that natural dietary antioxidants are capable of inhibiting cancer cell growth. Our recent studies showed that hinokitiol, a natural bioactive compound, inhibited vascular smooth muscle cell proliferation and platelets aggregation. The present study is to investigate the anticancer efficacy of hinokitiol against B16-F10 melanoma cells via modulating tumor invasion factors MMPs, antioxidant enzymes in vitro. An in vivo mice model of histological investigation was performed to study the patterns of elastic and collagen fibers. Hinokitiol inhibited the expression and activity of MMPs-2 and -9 in B16-F10 melanoma cells, as measured by western blotting and gelatin zymography, respectively. An observed increase in protein expression of MMPs 2/9 in melanoma cells was significantly inhibited by hinokitiol. Notably, hinokitiol (1-5 µM) increased the activities of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) from the reduction in melanoma cells. Also, hinokitiol (2-10 µM) concentration dependently reduced in vitro Fenton reaction induced hydroxyl radical (OH·) formation. An in vivo study showed that hinokitiol treatment increased elastic fibers (EF), collagens dispersion, and improved alveolar alterations in the lungs of B16/F10 injected mice. Overall, our findings propose that hinokitiol may be a potent anticancer candidate through down regulation of MMPs 9/2, reduction of OH· production and enhancement of antioxidant enzymes SOD and CAT.

Toxicity assessments of chalcone and some synthetic chalcone analogues in a zebrafish model.

The aim of this study was to investigate the in vivo toxicities of some novel synthetic chalcones. Chalcone and four chalcone analogues 1a-d were evaluated using zebrafish embryos following antibody staining to visualize their morphological changes and muscle fiber alignment. Results showed that embryos treated with 3'-hydroxychalcone (compound 1b) displayed a high percentage of muscle defects (96.6%), especially myofibril misalignment. Ultrastructural analysis revealed that compound 1b-treated embryos displayed many muscle defect phenotypes, including breakage and collapse of myofibrils, reduced cell numbers, and disorganized thick (myosin) and thin (actin) filaments. Taken together, our results provide in vivo evidence of the myotoxic effects of the synthesized chalcone analogues on developing zebrafish embryos.

Damage from periorbital ageing to the multilayered structures and resilience of the skin in Chinese population.

Ageing dynamically disrupts the multilayered supporting components of the skin that are held together by cell adhesion molecules (CAMs). Skin specimens from 33 female Chinese patients undergoing lower blepharoplasty were divided into three age groups and examined by haematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) and Elastica-van Gieson (EVG) stains, western blotting, surface electron microscopy (SEM) and biomechanical tension analysis. The SEM density (skin surface topology) showed a negative linear relationship with age. The triangular pattern of the skin surface in the younger group gradually broke down into quadrangular and irregular patterns in the older group. Collagens and elastic fibres in the dermis showed anisotropy and decreased density in the older groups compared with the younger group, especially in the papillary dermis. Anisotropy means that physical properties differ according to the direction of measurement. E-cadherin and integrin αv (whose functions are to bind epidermal and dermal elements respectively) increased and decreased, respectively, in the oldest group. Skin resilience decreased significantly in this group under repetitive stress. In conclusion, a loss of skin surface textures, integrin αv expressions, epidermal-dermal connections and dermal compactness led to the multilayered structure of the skin becoming separated. This in turn decreased resilience during ageing. These findings may therefore explain why aged skins cannot tolerate repetitive facial expressions, and why this action produces further dynamic wrinkles.

The effect of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) on cell viability under hypoxia.

PURPOSE: The synthetic compound 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) reduces the protein stability of hypoxia-inducible factor (HIF)-1α and can serve as a potential anticancer agent. Our previous study elucidated that YC-1 decreased the protein level of HIF-1α and inhibited cell proliferation under normoxic conditions. In the present study, we explored the inhibitory effect of YC-1 on the regulation of HIF-1α and cell survival under hypoxia. METHODS: Chemical and physical hypoxia using cobalt chloride and an anaerobic incubator, respectively, was induced in the photoreceptor cell line 661W. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and morphological observation were used to analyze cell survival. Flow cytometry with a LIVE/DEAD cell viability assay and annexin V was used to determine the number of live and dead cells or cell apoptosis, respectively. Cell proliferation was analyzed with high-content screening of MKI67 (K(i)-67) immunofluorescent staining. Immunoblotting and a quantitative reverse-transcription PCR were used to assess the protein and mRNA levels, respectively. RESULTS: Our results showed that 661W cells exposed to YC-1 decreased cell survival through the induction of cell apoptosis and cell-cycle arrest under hypoxia. We also found that YC-1 reduced the HIF-1α protein level after 2 h of hypoxia, but the mRNA level of HIF-1α was not affected. In addition, YC-1 significantly increased levels of p53, the proapoptotic gene BCL2-associated X protein (Bax), and cell proliferation-related gene, cyclin-dependent kinase inhibitor 1A (p21) mRNAs under hypoxia. CONCLUSIONS: Unlike normoxia, YC-1 not only inhibited cell proliferation but also induced cell death under hypoxia. We also found that YC-1 inhibited hypoxia-induced HIF-1α and partially affected hypoxia-regulated gene expression.

Multifaceted effects of rapamycin on functional recovery after spinal cord injury in rats through autophagy promotion, anti-inflammation, and neuroprotection.

BACKGROUND: Spinal cord injuries (SCIs) are serious and debilitating health problems that lead to severe and permanent neurological deficits resulting from the primary mechanical impact followed by secondary tissue injury. During the acute stage after an SCI, the expression of autophagy and inflammatory responses contribute to the development of secondary injury. In the present study, we examined the multifaceted effects of rapamycin on outcomes of rats after an SCI. MATERIALS AND METHODS: We used 72 female Sprague-Dawley rats for this study. In the SCI group, we performed a laminectomy at T10, followed by impact-contusion of the spinal cord. In the control group, we performed only a laminectomy without contusion. We evaluated the effects of rapamycin using the Basso, Beattie, and Bresnahan scale for functional outcomes, Western blot analyses for analyzing LC3-II, tumor necrosis factor expression, and p70S6K phosphorylation, and an immunostaining technique for localization and enumeration of microglial and neuronal cells. RESULTS: Basso, Beattie, and Bresnahan scores after injury significantly improved in the rapamycin-treated group compared with the vehicle group (on Day 28 after the SCI; P < .05). The Western blot analysis demonstrated that rapamycin enhanced LC3-II expression and decreased p70S6K phosphorylation compared with the vehicle (P < .01), which implies promotion of autophagy through mammalian target of rapamycin inhibition. Furthermore, rapamycin treatment significantly attenuated tumor necrosis factor production and microglial expression (P < .05). Immunohistochemistry of NeuN (antibodies specific to neurons) showed remarkable neuronal cell preservation in the rapamycin-treated group compared with the vehicle-treated group (P < .05), which suggests a neuroprotective effect of rapamycin. CONCLUSIONS: Rapamycin is a novel neuroprotectant with multifaceted effects on the rat spinal cord after injury. Use of such a clinically established drug could facilitate early clinical trials in selected cases of human SCIs.

Dynamic analysis of modified transcutaneous lower blepharoplasty based on biochemical and biophysical principles.

In this study, we analyzed the key parameters of modified transcutaneous lower blepharoplasty based on multidisciplinary principles (biochemical findings and biophysical wrinkling theory). A total of 408 female patients received our subciliary lower blepharoplasty between March 2002 and January 2010. The severity of the eyebags (dynamic wrinkle numbers and prolapse) was evaluated through preoperative and postoperative photography, whereas the excised lower eyelid skin specimens from 56 patients were investigated with hematoxylin and eosin staining. The modified techniques produced significant improvements in the severity of eyebags in all age groups (P < 0.001). Poor surgical outcome was found to correlate significantly with preoperative dynamic wrinkle numbers (P < 0.001). Age, dynamic wrinkle numbers, and prolapse correlated significantly with dermal fiber density (P = 0.004, 0.000, and 0.000, respectively) but not epidermal, rete ridge, and dermal thickness or the number of rete ridges. In conclusion, modified transcutaneous lower blepharoplasty provides significant improvement to dynamic wrinkles and prolapse in the eyebags. Periorbital aging progressively disturbs the dermal compactness (fiber density) until the structure can no longer hold its integrity at the critical age (around the age of 40).

Effects of dietary adjustment of n-3:n-6 fatty-acid ratio to 1:2 on anti-inflammatory and insulin-signaling pathways in ovariectomized mice with high fat diet-induced obesity.

Estrogen deficiency increases the secretion of inflammatory mediators and can lead to obesity. Consequently, estrogen deficiency can cause metabolic syndrome, particularly insulin resistance during menopause. Both fish oil and perilla oil contain n-3 fatty acids, which may regulate several inflammatory cytokines. Additionally, adjusting the dietary n-3:n-6 fatty-acid ratio to 1:2 may help treat or prevent chronic diseases. Therefore, we investigated the effect of anti-inflammatory and insulin-signaling pathways, not solely in relation to the (n-3:n-6 fatty-acid ratio at 1:2), but also considering the origin of n-3 fatty acids found in fish oil and perilla oil, in a mouse model of estrogen deficiency induced by ovariectomy and obesity induced by a high-fat diet (HFD). Female C57BL/6J mice were divided into five groups: sham mice on a normal diet; ovariectomized (OVX) mice on a normal diet (OC); OVX mice on a HFD plus lard oil (OL), fish oil (OF), or perilla oil (OP). The dietary n-3:n-6 ratio in the OF and OP groups was adjusted to 1:2. The results showed OF group exhibited significantly lower abdominal adipose tissue weight, fewer liver lipid droplets, and smaller uterine adipocytes, compared with the OL group. Compared with the OL group, the OF and OP groups exhibited higher oral glucose tolerance and lower serum alanine aminotransferase activity, triacylglycerol levels, and total cholesterol levels. Hepatic JAK2, STAT3, and SOCS3 mRNA expression and p-NF-κB p65 and IL-6 levels were significantly lower in the OF and OP groups than in the OL group. Only the OF group exhibited an increase in PI3K and Akt mRNA expression, decrease in GLUT2 mRNA expression, and considerable elevation of p-Akt. Both fish and perilla oil reduced inflammatory signaling markers. However, only fish oil improved insulin signaling (PI3K, Akt, and GLUT2). Our data suggest that fish oil can alleviate insulin signaling through activating the PI3K-Akt-GLUT2 cascade signaling pathway.

YC-1 targeting of hypoxia-inducible factor-1α reduces RGC-5 cell viability and inhibits cell proliferation.

PURPOSE: The survival of retinal ganglion cells (RGCs) is a hallmark of many optic neurodegenerative diseases such as glaucoma. YC-1, a potential anticancer drug, is known to be able to decrease the stability and protein expression of hypoxia-inducible factor (HIF)-1α that is triggered by hypoxia and related to RGC survival. We hypothesized that YC-1 may alter RGC cell viability through the down-regulation of HIF-1α. METHODS: Cell viability of the RGC-5 cell line was measured with a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometry, a LIVE/DEAD viability assay, and high-content screening (HCS) with MKI67 (K(i)-67) monoclonal antibodies were used to detect cell death and cellular proliferation. RESULTS: We found that cells treated with 20 µM YC-1 for 24 h decreased the HIF-1α level in an RGC-5 cell line using immunoblotting and reduced the live cell number in an MTT assay. Results of flow cytometry and HCS demonstrated that reducing the cell proliferation of RGC-5 cells, not cell death, led to the decreased level in the MTT assay. CONCLUSIONS: Our findings demonstrate that YC-1-induced down-regulation of HIF-1α might reduce RGC cell proliferation and viability under normoxia, which implies a role of YC-1 in the neuroprotective effect for further clinical applications.

Caffeic Acid Phenethyl Ester Inhibits Basal Lipolysis by Activating PPAR-Gamma and Increasing Lipid Droplet-Associated Perilipin in Mature Rat Adipocytes.

Abnormal lipolysis is correlated with metabolic syndrome. Caffeic acid phenethyl ester (CAPE), a natural product from honeybee hives, has been reported to improve metabolic syndrome. However, the effects of CAPE on lipolysis and perilipin-1 (the major lipid droplet-associated protein) in mature adipocytes were not clarified. In this study, mature adipocytes were isolated from the epididymal fat pads of male rats and incubated with CAPE to estimate lipolysis by measuring glycerol release. It was found that the basal lipolysis was inhibited by CAPE in a dose- and time-dependent manner. The lipid droplet-associated perilipin-1 and phosphorylated peroxisome proliferator-activated receptor (PPAR) gamma levels increased following CAPE treatment by Western blot analysis. Moreover, a specific PPAR-gamma inhibitor (T0070907) could partly reverse the effect of CAPE on basal lipolysis. Furthermore, treatment of adipocytes with dibutyryl-cAMP (db-cAMP) or isoproterenol (ISO) increased lipolysis, but the drug-induced lipolysis was abrogated by combination treatment with CAPE. The lipid droplet-associated perilipin-1 level was also decreased in the drug-induced groups but increased when combined treatment with CAPE. In conclusion, our results revealed that a decrease in basal lipolysis and an increase in lipid droplet-associated perilipin-1 levels induced by CAPE may be involved in the regulation of lipid metabolism through activation of PPAR-gamma in mature adipocytes.

Cobalt Chloride Induces Macrophage Foam Cell Formation: A Chemical Hypoxia Model for Anti-Atherosclerotic Drug Screening.

Macrophages would engulf circulating oxidized (ox)- low-density lipoprotein and form lipid droplet-laden foam cells. Macrophage foam cells are considered an important therapeutic target of atherosclerosis. The aim of the study was to investigate a hypoxic foam cell model for anti-atherosclerotic drug screening using the chemical hypoxia-mimicking agent cobalt chloride (CoCl2). The oil red O stating results showed that treatment with CoCl2 could induce lipid accumulation and lead to cell transformation to spindle-shaped and lipid-rich foam cells in RAW 264.7 macrophages. Incubation with 150 µM CoCl2 for 24 h significantly increased the area of intracellular lipid droplets in macrophages, compared with the control group. Our findings indicate that CoCl2-triggered macrophage foam cells should be a potential in vitro hypoxia model for atherosclerosis drug discovery.