Robot-assisted laparoscopic adenomyomectomy of adenomyotic nodule implanted in the uterine endometrium manifesting as endometrial cancer: a case report and literature review.

Thickened uterine endometrium with abnormal uterine bleeding highly suggests endometrial hyperplasia or endometrial carcinoma. A case of 35-year-old nulliparous woman came to our department with endometrial mass manifesting as endometrial cancer. Transrectal ultrasonography and magnetic resonance imaging (MRI) showed an 8x6 cm multicystic, ill-defined mass compacted at the uterine endometrium, the anterior wall of the uterus, and 3x3 cm heterogenous mass at the left adnexa. The edometrial mass showed multiple septations with enhancement and low-signal intensity on T2-weighted images. After endometrial biopsy was done and simple hyperplasia without atypia was observed at the histopathologic finding, the patient underwent robot-assisted laparoscopy and diagnosed as adenomyoma at the frozen pathology. After adenomyomectomy, permanent pathologic analysis revealed the same result and she recovered without any complications and responded well to gonadotropin-releasing hormone (GnRH) agonist therapy.

Robotic-assisted single incision myomectomy in large myoma cases.

INTRODUCTION: Laparo-endoscopic single-incision surgery (LESS) has been developed and gradually adopted for both benign and malignant gynecological procedures. However, LESS has been hindered for use in procedures like myomectomy by limitations in natural architecture and instrumentation, especially in suturing. The da Vinci system features a single-site platform and wristed needle driver, which may help overcome conventional LESS limitations. This case report study describes the feasibility of this robotic single-site (RSS) platform in large myoma cases and offers suggestions. RESULTS: Two cases of myomectomy with large myomas (with maximum diameters of 160 and 120 mm) with different locations, were addressed by RSS. Operative time was 180 and 240 minutes. Estimated blood loss was 200 and 150 ml. Pathologic analysis revealed uterine leiomyomas of 910 and 870 grams. No serious peri- or post-operative complications occurred. DISCUSSION: Myomectomy with large myoma has presented a surgical challenge. RSS myomectomy appears to be a safe and feasible technique for it regardless of its localization. Advantages include less postoperative pain, fast recovery, less impact on quality of life, and improved cosmesis. LESS surgery has been challenging concerning suturing and multi-laparoscopic or multi-port robotic myomectomy can be difficult to extract myoma, especially with morcellation. RSS could be a solution that enables ease of manipflation and extraction.

Early intracellular signaling events induced by in vitro metreleptin administration in cardiac myocytes and uterine smooth muscle cells.

Intracellular signaling pathways regulated by leptin have largely been studied in metabolically important organs such as adipose tissue and peripheral blood mononuclear cells, suggesting that leptin plays a key role in pathophysiology of insulin resistance. However, whether synthetic analog of leptin, metreleptin, has similar effects on cardiac myocytes (CM) and uterine smooth muscle cells (USMC) has not yet been studied. Hence, in order to address these questions, we extended previous observations and investigated in vitro signaling study whether metreleptin may activate key signaling pathways. We observed that metreleptin activates Jak2 and STAT3 signaling pathways in dose- and time-dependent manner in CM and USMC. Also, we found that metreleptin increases ERK1/2, JNK and/or p38 phosphorylation in CM. In vitro metreleptin administration also increased ERK1/2 and/or p38 phosphorylation in USMC. By contrast, JNK was not regulated by in vitro metreleptin administration in USMC. Moreover, metreleptin-activated all signaling pathways were blocked by pre-treatment of PD98095 (ERK inhibitor), SB203580 (p38 inhibitor) and/or SP600125 (JNK inhibitor), respectively. Finally, metreleptin increased cell size (hypertrophy) in both CM and USMC. Our data provide novel insights into the role of Jak2, STAT3, ERK1/2, JNK and/or p38 as probable mediators of the action of leptin in regulating hypertrophy in CM and USMC.

Effects of alendronate on the peri-implant bone in rats.

OBJECTIVES: The purpose of this study was to determine the effects of alendronate on the peri-implant bone in rat maxillae with the aid of micro-computed tomographic, histologic, and biochemical analyses. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley rats were used. After extraction of the maxillary first molars, each rat was given periodic subcutaneous injections of either alendronate (alendronate group) or saline (control group). Customized implants were placed bilaterally 4 weeks after these injections. The rats were sacrificed at either 4, 8, or 12 weeks after implantation (4-, 8-, and 12-week groups, respectively; n = 6 rats per group). Microcomputed tomographic and histologic analyses were conducted for all rats. Biochemical analyses were performed at four time points for the 12-week groups. RESULTS: There were no significant differences between the groups on microcomputed tomographic and histologic analyses. All of the measured biochemical parameters tended to decrease over time, with significant differences among some time points within each group. The serum osteocalcin level was significantly lower in the 12-week alendronate group than in the control group (P < 0.05). CONCLUSIONS: Three approaches were utilized in evaluating the effects of alendronate. It appears serum osteocalcin levels may serve as an adjuvant marker for this purpose, although further studies are required to confirm this.

Higher C-peptide levels are associated with regional cortical thinning in 1093 cognitively normal subjects.

BACKGROUND AND PURPOSE: Recent studies have demonstrated an association between increased insulin secretion and cognitive impairment. However, there is no previous study that directly evaluates the association between increased insulin secretion and cortical thickness to our knowledge. Therefore, our aim was to evaluate the effect of hyperinsulinemia, as measured by C-peptide level, on cortical thickness in a large sample of cognitively normal individuals. METHODS: Cortical thickness was measured in 1093 patients who visited the Samsung Medical Health Promotion Center and underwent brain magnetic resonance imaging (MRI) and a blood test to measure C-peptide concentration. Automated surface-based analyses of the MRI data were used to measure cortical thickness. C-peptide levels were divided into quartiles for comparison. Patients in the first to third quartiles were used as the reference category. RESULTS: Patients in the highest quartile group (Q4) of C-peptide levels showed cortical thinning, predominantly in both medial temporal lobes, the right inferior temporal gyrus, both medial prefrontal lobes and the right superior parietal lobule, compared with the lower quartile groups (Q1-Q3) after controlling for age, gender, body mass index, history of hypertension, hyperlipidemia, previous stroke, cardiovascular disease and fasting glucose level. CONCLUSIONS: A higher C-peptide level is associated with regional cortical thinning, even in cognitively normal individuals.

The effects of ErhBMP-2-/EGCG-coated BCP bone substitute on dehiscence around dental implants in dogs.

OBJECTIVES: The purpose was to evaluate the effect of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2)-/epigallocatechin-3-gallate (EGCG)-coated biphasic calcium phosphate (BCP) and titanium barrier membrane on dehiscence defects in dogs. MATERIALS AND METHODS: In five mongrel dogs, the dehiscence bony defects around dental implants were surgically created and in total three implants were placed at edentulous ridge of which teeth had been extracted 12 weeks before. For the control group, BCP was applied to the dehiscence defect. For experimental groups, ErhBMP-2-coated BCP and ErhBMP-2-/EGCG-coated BCP were applied. The newly designed titanium barrier membrane was used to apply all the defects. The defects were evaluated histologically and histometrically after 12 weeks. The comparative statistics of the groups were obtained through Kruskal-Wallis test. RESULTS: In bone-to-implant contact (BIC), bone density (BD), bone regeneration height (BRH), and bone mineralization apposition rate (BMAR), differences among groups were not found. ErhBMP-2/EGCG group appeared to have higher value. In fluorescence analysis, bone remodeling around graft material was more active in the ErhBMP-2/EGCG group. CONCLUSION: Within the limit of this study, it is reasonable to assume that BMP-2-/EGCG-coated biphasic BCP and the newly designed titanium membrane were more beneficial in dehiscence defect healing with increased bone remodeling.

Comparison of alfuzosin 10 mg with or without propiverine 10 mg, 20 mg in men with lower urinary tract symptom and an overactive bladder: randomised, single-blind, prospective study.

PURPOSE: The efficacy and safety of treatment with alfuzosin 10 mg plus propiverine 10 or 20 mg in men with lower urinary tract symptoms (LUTS) and an overactive bladder were investigated. MATERIALS AND METHODS: In this parallel-arm, prospective, multicentre, single-blind study, men who were ≥ 40 years old, had an International Prostate Symptom Score (IPSS) of ≥ 8, an Overactive Bladder Symptom Score (OABSS) of ≥ 3 and an OABSS urgency item score of ≥ 2 were randomised in a 1 : 1 :1 ratio to receive alfuzosin 10 mg alone (Group A) or with propiverine 10 mg (Group B) or 20 mg (Group C) for 8 weeks. Four and 8 weeks after commencing treatment, OABSS was measured along with IPSS, maximal urinary flow rate (Qmax ) and postvoid residual volume (PVR). Adverse events were recorded. RESULTS: A total of 135 men, including 43 in Group A, 48 in Group B and 44 in Group C, completed the study. Relative to baseline, all groups demonstrated significant reductions in OABSS and the IPSS after eight treatment weeks (p < 0.005). The improvement of OABSS in Group C was significantly greater than Group A and B (Group A: 0.70 ± 1.94; Group B: 2.50 ± 2.98; Group C: 4.30 ± 3.40; p < 0.005). An observed improvement of Qmax and PVR in the three groups did not achieve statistical significance. Overall adverse event rates were higher in Group C but not significant compared with others. CONCLUSION: In patients with LUTS and overactive bladder, combined therapy with alfuzosin 10 mg plus propiverine 20 mg was significantly more effective than alfuzosin monotherapy and propiverine 10 mg combined therapy in terms of improving OABSS while not significantly affecting Qmax or PVR.

Amylin-induced downregulation of hippocampal neurogenesis is attenuated by leptin in a STAT3/AMPK/ERK-dependent manner in mice.

AIMS/HYPOTHESIS: Both leptin and insulin sensitivity have been linked with pathophysiological processes involving the central nervous system in general, and the hippocampus in particular, but the role of leptin in hippocampal neurogenesis has not yet been elucidated. Also, no previous studies have evaluated whether amylin or the endogenous insulin sensitiser adiponectin interact with leptin to alter hippocampal neurogenesis in mouse hippocampal neuronal (HN) cells or investigated the role of leptin, amylin or adiponectin signalling in mouse HN cells. METHODS: Hippocampal neurogenesis and leptin, amylin and adiponectin signalling were studied in vitro using mouse H19-7 HN cell lines. RESULTS: Amylin decreased cell proliferation in a dose-dependent manner. This effect was diminished by leptin administration and was dependent on signal transducer and activator of transcription 3 (STAT3)/AMP-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK). Adiponectin effects were null. We also observed, using immunocytochemical analysis, that amylin decreased activation of microtubule-associated protein 2, a specific neurite outgrowth marker, and synapsin, a specific synaptogenesis marker. By contrast, both effects were attenuated by co-administration of leptin. Finally, we observed that these effects were blocked by pre-treatment with AG490, a STAT3 inhibitor, and STAT3 small interfering RNA administration. CONCLUSIONS/INTERPRETATION: Our data suggest that amylin in pharmacological concentrations may have a neurotoxic effect whereas leptin in physiological and pharmacological concentrations has a protective effect counteracting amylin-decreased hippocampal neurogenesis via STAT3/AMPK/ERK signalling in mouse H19-7 HN cell lines. Overall, our data support a novel role for leptin and amylin in the processes of mouse hippocampal neurogenesis and provide new insights into the mechanisms of neurogenic regulation.

Amylin and leptin activate overlapping signalling pathways in an additive manner in mouse GT1-7 hypothalamic, C2C12 muscle and AML12 liver cell lines.

AIMS/HYPOTHESIS: It has been suggested that amylin amplifies leptin's effects and affects energy homeostasis synergistically with leptin in animals and humans. However, no previous study has reported on amylin and leptin signalling in hypothalamic, muscle and liver cells. METHODS: Leptin and amylin signalling studies were performed in vitro in mouse GT1-7 hypothalamic, C2C12 muscle and AML12 liver cell lines. RESULTS: Treatment of mouse GT1-7 and C2C12 cells with leptin or amylin increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in a dose- and time-dependent manner. In mouse AML12 cells, leptin and amylin produced a biphasic response of STAT3 activity. Importantly, all leptin and amylin signalling pathways were saturable at leptin and amylin concentrations of ∼100 and ∼50 to 100 ng/ml, respectively. Leptin and amylin in combination activated STAT3, AMP-activated protein kinase (AMPK), extracellular signal-regulated kinase (ERK) 1/2 and Akt signalling pathways in an additive manner, effects that were abolished under endoplasmic reticulum (ER) stress. Leptin, but not amylin, increased IRS-1 phosphorylation in GT1-7 hypothalamic, but not in C2C12 muscle and AML12 liver cell lines. CONCLUSIONS/INTERPRETATION: Our data suggest that leptin and amylin have overlapping and additive, but not synergistic, effects in the activation of intracellular signalling pathways. ER stress may induce leptin and amylin resistance in hypothalamic, muscle and liver cell lines. These novel insights into the mode of action of leptin and amylin suggest that these hormones may play an additive role in regulating energy homeostasis in humans.

Structure-activity relationships of piscidin 4, a piscine antimicrobial peptide.

Piscidin 4, an antimicrobial peptide recently isolated from mast cells of hybrid striped bass (Morone chrysops female × Morone saxatilis male), is unusual in that it is twice as long (44 amino acids) as the typical members of the piscidin family. We previously showed that native piscidin 4 had a modified amino acid at position 20, but synthetic piscidin 4 (having an unmodified Trp at position 20) had similar potent activity against a number of both human and fish bacterial pathogens. In this study, the structure and membrane topology of synthetic piscidin 4 were examined using liposomes as model bilayers. Circular dichroism analyses revealed that it had a disordered structure in aqueous solution and folded to form a relatively weak α-helical structure in both membrane-mimetic trifluoroethanol solutions and liposome suspensions. Fluorescence data (piscidin 4 embedded in liposomes) and leakage experiments indicated that piscidin 4 interacted strongly with the hydrophobic part of the liposome. Binding of piscidin 4 to liposomes induced significant blue shifts of the emission spectra of the single Trp residue (Trp20). Quenching of Trp20 by water-soluble quencher (either acrylamide or I-) indicated that the fluorescence of Trp20 decreased more in the presence of liposomes than in buffer solution, thus revealing that Trp20 is less accessible to the quenchers in the presence of liposomes. The relative leakage abilities of piscidin 4 (1 µM) with liposomes were in the following order: DPPC (100%)≥EYPC (94%)>DPPC/DPPG (65%)>EYPC/EYPG (0%). This high activity against DPPC and EYPC liposomes was contrary to our data suggesting that piscidin 4 has a much weaker tendency to form an α-helix than other piscidins, such as piscidin 1. However, the structural similarity of protozoan membranes to EYPC liposomes might explain our discovery of the potent activity of piscidin 4 against the important skin/gill parasite ich (Ichthyophthirius multifiliis), but its negligible hemolytic activity against vertebrate membranes (hybrid striped bass or human erythrocytes). It also suggests that other conformation(s) in addition to the α-helix of this peptide may be responsible for its selective activity. This differential toxicity also suggests that piscidin 4 plays a significant role in the innate defense system of hybrid striped bass and may be capable of functioning extracellularly.

Effect of alendronate on healing of extraction sockets and healing around implants.

OBJECTIVES: The purpose of this study was to evaluate the effect of alendronates on healing of extraction sockets and healing around implants in the maxilla of rats. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were used. The rats in bisphosphonate group were subcutaneously injected with alendronate (5.0 mg kg(--1)) three times a week for 4 weeks. Both sides of the maxillary first molars were extracted, and customized titanium implants (Ø1.5 × 2.0 mm) were placed immediately into one side. Rats were killed at 3, 7, 14, or 28 days following surgery. RESULTS: New bone formation in extraction sockets, bone area around the implant site, and bone-implant contact were not delayed in the bisphosphonate group. The tartrate-resistant acid phosphatase positive cell count did not differ between bisphosphonate and control groups; however, empty lacunae were observed significantly more in bisphosphonate group. The differences in empty lacunae were shown at different time points between the implant sites and extraction sites: at 7 days after extraction, and at 14 and 28 days after implantation. CONCLUSIONS: Alendronates seemed to decrease bone resorption but not to decrease bone formation. Empty lacunae were observed significantly more at later time points in implant sites compared to extraction sockets.

Peripherally acting CB1-receptor antagonist: the relative importance of central and peripheral CB1 receptors in adiposity control.

OBJECTIVE: To investigate whether drugs targeting peripheral cannabinoid-1 (CB1) receptor ameliorate adiposity comparable to central CB1-receptor antagonist or not. MEASUREMENTS: Receptor binding assay and functional assay in vitro. Pharmacokinetic parameters in mice, brain uptake clearance of compounds in rats and antagonism on the CB1-agonist-induced hypothermia in mice. Diet consumption, body weight changes, hepatic gene expression of sterol-regulatory element-binding protein-1 (SREBP-1) and plasma/tissue concentrations of compounds in HF diet-induced obese (HF-DIO) mice after acute and chronic treatment. RESULTS: Compound-1, an SR141716A derivative, is a peripheral CB1-receptor-selective antagonist that is 10 times less potent than SR141716A in in vitro evaluations. Although the plasma concentrations of Compound-1 are five times higher than those of SR141716A, its potency is still 10 times lower than that of SR141716A in reducing the consumption of normal or HF diet by mice. Through evaluations of brain uptake and the effect on CB1-agonist-induced hypothermia, it was verified that the blood-brain barrier (BBB) penetration of Compound-1 is much lower than that of SR141716A. In HF-DIO mice, chronic treatment by Compound-1 showed dose-dependent antiobesity activities, while its brain distribution was very low as compared with that of SR141716A. Compound-1's effective doses for antiobesity activity were just over 30 mg kg(-1). However, Compound-1 completely suppressed the elevated hepatic SREBP-1 expression even at 10 mg kg(-1). CONCLUSION: These results suggest that (1) central CB1 receptors mediate anorectic response of CB1-receptor antagonists and (2) peripheral modulations, including SREBP-1 expression, are not major mechanisms in the antiobesity effects of CB1-receptor antagonists.

Proceedings from the OMS Resurgence Conference for resuming clinical practice after COVID-19 in the USA.

The COVID-19 pandemic has altered and reshaped the delivery of oral and maxillofacial surgery (OMS) over the past few months. As the USA gradually lifts restrictions and re-opens, surgeons must adjust accordingly. Therefore, the OMS Resurgence Conference: Safely Resuming Practice with a New Normal was organized for 11 May 2020 to gather and disseminate expert opinions and recommendations for OMSs to thoughtfully resume work with efficiency and safety. This manuscript offers a summary of the highlights from the conference discussion.

Multidrug-resistant tuberculosis in South Korea: a retrospective analysis of national registry data in 2011-2015.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) poses a threat to public health as a result of high treatment costs and unsatisfactory outcomes.OBJECTIVE: To elucidate trend, demographic and clinical characteristics and treatment outcomes of patients with MDR-TB between 2011 and 2015 in South Korea.METHOD: Data of patients with MDR-TB diagnosed between 1 January 2011 and 31 December 2015 were retrieved from the nationwide Internet-based TB notification system and analysed retrospectively.RESULTS: During the study period, 5192 MDR-TB patients were notified. We identified an increasing number of MDR-TB patients among foreign populations (from 1.3% to 7.7%), decreasing resistance rates to other anti-TB drugs (e.g., resistance to pyrazinamide, from 40.9% to 28.2%), a decreasing interval from treatment initiation to negative conversion of sputum culture (from 165.7 to 103.7 days) and shortening of treatment duration (719.7 to 613.2 days). However, treatment success rates did not change, and had an average of 65.7%.CONCLUSION: Despite decreasing resistance rates to other drugs and faster treatment responses, treatment outcomes did not improve during the study period. Strict management of MDR-TB patients on treatment should be adopted to improve treatment outcomes.

Effect of fudosteine on mucin production.

Fudosteine is a novel mucoactive agent, although little is known about how fudosteine decreases mucin production. The present study examined the effects of fudosteine on MUC5AC mucin synthesis and cellular signalling. An animal model of lipopolysaccharide (LPS)-induced inflammation and a bronchial epithelial cell line model of tumour necrosis factor (TNF)-alpha-induced inflammation were used. Fudosteine was administered before stimulation with LPS or TNF-alpha. The MUC5AC mucin levels were assayed and the expression of the MUC5AC gene was measured. Western blotting was carried out for the detection of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and phosphorylated extracellular signal-related kinase (p-ERK). MUC5AC mucin synthesis and the expression of the MUC5AC gene were increased by LPS in rats or TNF-alpha in NCI-H292 cells; these effects were inhibited by fudosteine treatment. After stimulation with LPS or TNF-alpha, the expression of p-EGFR, p-p38 MAPK and p-ERK were detected. Fudosteine treatment reduced the expression levels of p-p38 MAPK and p-ERK in vivo and of p-ERK in vitro. The present results suggest fudosteine inhibits MUC5AC mucin hypersecretion by reducing MUC5AC gene expression and the effects of fudosteine are associated with the inhibition of extracellular signal-related kinase and p38 mitogen-activated protein kinase in vivo and extracellular signal-related kinase in vitro.

Comparison of the pathogenicity in three different Korean canine parvovirus 2 (CPV-2) isolates.

Canine parvovirus type 2 (CPV-2) is a major pathogen inducing acute hemorrhagic gastroenteritis in dogs. Despite the identification of numerous CPV-2 variants (from CPV-2a to CPV-2c), the pathogenic differences among the CPV-2 variants in dogs have not been evaluated. The aim of this study was to compare the pathogenicity of CPV-2 variants (CPV-2a-I, CPV-2a-V and CPV-2b) isolated mainly from Korea. We evaluated the pathogenicity of three different CPV-2 variants, by performing clinical, hematological, serological and histopathological examinations after experimentally inoculating three types of CPV-2 variants into young puppies. We found that the overall pathogenicity of the CPV-2a variants (CPV-2a-I and 2a-V) was severer compared to the CPV-2b variant. In addition, there was no significant difference in pathogenicity between the two CPV-2a variants. Our findings indicate that there are differences in the pathogenicity of CPV-2 variants in dogs, which may be useful to understand the different pathobiology of the CPV-2 variants.

The cardiac sodium-calcium exchanger gene (NCX-1) is a potential canine cardiac biomarker of chronic mitral valvular insufficiency.

BACKGROUND: The cardiac sodium-calcium exchanger gene (NCX-1) is upregulated in humans and mice with congestive heart failure (CHF). HYPOTHESIS: NCX-1 expression is upregulated in dogs with heart failure from chronic mitral valvular insufficiency (CMVI). ANIMALS: Client-owned 14 healthy control dogs and 30 dogs with CMVI. METHODS: Prospective, controlled, observational study. We investigated the levels of NCX-1 expression in dogs at different stages of CMVI with real-time reverse transcription polymerase chain reaction. RESULTS: The mRNA expression levels of NCX-1 were determined in peripheral blood samples obtained from the animals used in this study. Dogs were graded by the severity of disease. The fold differences in the levels of mRNA expression compared with controls were 1.39 +/- 0.88 (group I), 1.32 +/- 0.65 (group II), 4.86 +/- 1.25 (group III), and 5.96 +/- 1.69 (group IV). NCX-1 expression was significantly higher in groups III and IV (P < .05) compared with the healthy controls, whereas groups I and II were not. CONCLUSIONS AND CLINICAL IMPORTANCE: The level of NCX-1 expression was significantly higher in groups of dogs with moderate to severe CMVI (groups III and IV) compared with the controls. Our findings indicate that NCX-1 can be a biomarker for chronic valvular disease in dogs and is a potential biomarker for severity of heart disease.

Coherent multi-frequency optical source generation using a femto-second laser and its application for coherent population trapping.

We present a coherent multi-frequency source generated from a mode-locked femto-second laser. The key concept for the coherent multi-frequency source generation is using the mode-locked femto-second laser as many continuous wave (CW) optical sources. We simultaneously selected and amplified the desired modes of the optical frequency comb using femto-second laser injection-locking (FSLIL). Using two coherent sources generated by the mode-locked femto-second laser, we have demonstrated a coherent spectroscopy in a Lambda-type system of the Cs D2 line. The proposed coherent multi-frequency source generation technique will be a useful technique for optical frequency standards based on multi-photon schemes.

Regulation of adipocyte differentiation by PEGylated all-trans retinoic acid: reduced cytotoxicity and attenuated lipid accumulation.

Obesity is major risk factor for many disorders, including diabetes, hypertension and heart disease. Unfortunately, there is a dearth of therapeutic agents available to clinicians for the treatment of obesity. The principal aim of this study was to investigate whether PEGylated all-trans retinoic acid (PRA) can have favorable stability and biological activity in 3T3-L1 preadipocytes as an antiobesity drug. Here, we found that PRA inhibits the process of adipogenesis, including survival of adipocytes and differentiation to mature adipocytes. The results showed that RA nanoparticles (NPs) were prepared by PEGylation; below 200 nm, PRA-NPs were obtained. Moreover, PRA decreased glycerol-3-phosphate dehydrogenase activity in 3T3-L1 preadipocytes by acting with major adipocyte marker proteins such as PPARgamma2, C/EBPalpha and aP2 modulators. Apoptosis, in addition, increased as the level of RA increased from 10 to 20 microM, whereas PRA reduced apoptosis with increasing concentrations. Our data suggest that PRA-NP has potential as an antiobesity drug carrier due to its small particle size and PEGylated core-shell structure. In addition, our results suggest that PRA inhibits the process of adipogenesis and may be developed to treat obesity. Based on these results, PRA is suitable for adipocyte studies, and an enhanced effect of PRA with adipocyte differentiation offers a challenging approach for pharmaceutical applications.