Morphology of the aortic arch branching pattern in raccoon dogs (Nyctereutes procyonoides, Gray, 1834).

BACKGROUND: Aortic arch (AA) branching patterns vary among different mammalian species. Most previous studies have focused on dogs, whereas those on raccoon dogs remain unexplored. OBJECTIVES: The objective of this study was to describe the AA branching pattern in raccoon dogs and compare their morphological features with those of other carnivores. METHODS: We prepared silicone cast specimens from a total of 36 raccoon dog carcasses via retrograde injection through the abdominal aorta. The brachiocephalic trunk (BCT) branching patterns were classified based on the relationship between the left and right common carotid arteries. The subclavian artery (SB) branching pattern was examined based on the order of the four major branches: the vertebral artery (VT), costocervical trunk (CCT), superficial cervical artery (SC), and internal thoracic artery (IT). RESULTS: In most cases (88.6%), the BCT branched off from the left common carotid artery and terminated in the right common carotid and right subclavian arteries. In the remaining cases (11.4%), the BCT formed a bicarotid trunk. The SB exhibited various branching patterns, with 26 observed types. Based on the branching order of the four major branches, we identified the main branching pattern, in which the VT branched first (98.6%), the CCT branched second (81.9%), the SC branched third (62.5%), and the IT branched fourth (52.8%). CONCLUSIONS: The AA branching pattern in raccoon dogs exhibited various branching patterns with both similarities and differences compared to other carnivores.

A nationwide study of regional preference and graft survival of kidney transplantation in South Korea: patterns of centralization in the capital area.

Purpose: This study aims to investigate regional patterns and graft survival rates in kidney transplantation (KT) within South Korea using the National Health Insurance Service database. Methods: By analyzing KT data from 2002 to 2017, including patient residency, KT location, and post-KT dialysis information, graft survival was assessed through post-KT dialysis and validated against Ulsan University Hospital and the Korean Organ Transplantation Registry's 2017 report. Results: Among the 20,978 KTs, 60.5% occurred in the Korean capital, Seoul, whereas 39.5% occurred outside. The overall graft survival rate was 81.5% with a median survival duration of 57 months. Patient survival was 83.8%, with a median survival duration of 61 months. For KTs from 2002 to 2007, the 10-year graft and patient survival rates were 89.1% and 90.3%, respectively. The KT recipients living outside Seoul who underwent the KT within their residential regions had a graft survival rate of 88.3%, and those receiving KTs outside their original region had a graft survival rate of 88.0%. Among Seoul residents who underwent KTs in the city, the graft survival rate was 90.5%. Importantly, hospital location did not significantly affect graft survival rates (P = 0.136). Conclusion: This study revealed a regional preference for KT in South Korea, particularly in the capital city, likely because of nonresidents. Nevertheless, the graft and patient survival rates showed no significant regional disparities. These findings emphasize the necessity for equitable KT service access across regions in order to optimize patient outcomes.

Whole-exome sequencing analysis of patent ductus arteriosus in a Japanese macaque (Macaca fuscata).

We performed whole-exome sequencing using a human exome capture kit to analyze the potential genetic factors related to patent ductus arteriosus in Japanese macaques. Compared with the reference sequences of other primates, we identified potential missense variants in five genes: ADAM15, AZGP1, CSPG4, TNFRSF13B, and EPOR.

Morphological and morphometric study of the scapulae of Korean wild deer.

Korean water deer (Hydropotes inermis argyropus; Heude, 1884) and Siberian roe deer (Capreolus pygargus; Pallas, 1771) are Korean wild deer classified in the tribe Capreolini. C. pygargus in Korea were previously considered a single species; however, it was recently suggested that roe deer living on Jeju Island (Jeju roe deer; Capreolus pygargus jejuensis) is a distinct subspecies from roe deer living on the Korean peninsula (mainland roe deer; Capreolus pygargus tianschanicus) based on several studies demonstrating genetic and morphological features. In this study, we suggests that the scapular morphology and osteometric data can be used for interspecies discrmination between Korean wild deer. To compare the morphological characteristics of scapula among the three groups of deer, we analyzed the features and nine osteomorphological measurements of 31 H. i. argyropus (14 males and 17 females), 18 C. p. jejuensis (4 males and 14 females), and 23 C. p. tianschanicus (16 females and 7 males). The estimated ages of the deer were over 32-35 months. Data were analyzed by one-way repeated measures analysis of variance with post hoc Duncan test and discriminant functional analysis (DFA). H. i. argyropus and C. p. tianschanicus had the smallest and largest scapulae, respectively. The scapulae of the three Korean wild deer had a similar triangular shape, which was obscured by the tuber of the scapular spine, pointed acromion, broad infraspinous fossa, narrow supraspinous fossa, and partial ossification of scapular cartilage in older deer. H. i. argyropus had certain distinctive features, including a caudally pointed acromion, a notch between the supraglenoid tubercle and glenoid cavity (NBSG), a glenoid notch, and no sexual dimorphism, except for the longest dorsal length (Ld) and the scapular index (SI). C. p. jejuensis had a larger scapular index (SI) (61.74 ± 0.74%), compared with the SIs of H. i. argyropus and C. p. tianschanicus. The unique features of the scapula in C. p. jejuensis include its S-shaped cranial border. The C. p. jejuensis had a cranially pointed acromion, less frequent presence of glenoid notch and NBSG, short length of supraglenoid tubercle, and no sexual dimorphism. The C. p. tianschanicus had elevated cranial margin of the glenoid cavity, and frequent presence of glenoid notch and NBSG, similar to the H. i. argyropus. Similar to C. p. jejuensis, C. p. tianschanicus had a cranially pointed acromion. However, sexual dimorphism was observed in C. p. tianschanicus. DFA using osteometric data showed 97.22% of specimens were classified correctly into their species, meaning the osteometric parameters can be used for interspecies discrimination of Korean wild deer. Our findings indicate that the scapular morphologies of the three Korean wild deer have certain similarities and differences, suggesting that C. p. jejuensis are distinct from C. p. tianschanicus.

Morphology of aortic arch branching patterns in the Eurasian Otter (Lutra lutra, Linnaeus, 1758).

In this study, we investigated the aortic arch (AA) branching pattern in the Eurasian otter (Lutra lutra). We performed arterial silicone casting of the AA of 18 Eurasian otters (8 males and 10 females). We analyzed the AA branching pattern at three levels: the AA, brachiocephalic trunk (BCT), and subclavian artery (SB), using different classification methods at each level. We introduced new criteria for classifying the SB branching pattern applicable for Eurasian otter and other carnivores based on the sequence of the four main branches: vertebral artery (VT), internal thoracic artery (IT), costocervical artery (CCT), and superficial cervical artery (SC). In all Eurasian otters, two major branches emerged directly from the AA, i.e., the BCT and left SB. The BCT branched off the left common carotid artery and terminated in the right common carotid artery and right SB in 17 of 18 Eurasian otters; the BCT formed a bicarotid artery in the remaining case. The SBs showed various branching patterns, with the main branching pattern involving branching to the VT and IT at the same position, followed by the CCT and SC. The SB branching pattern in the Eurasian otter differed from that in dogs in that the two first branching arteries were VT and IT, rather than VT and CCT. Here, we present the anatomical characteristics of the AA branching patterns in the Eurasian otter and new analysis methods applicable for comparative studies of other carnivores.

Effectiveness of Clonidine in Child and Adolescent Sleep Disorders.

OBJECTIVE: We aimed to investigate the improvement in sleep quantity and quality when clonidine was used in children and adolescents with insomnia. We also examined how sociodemographic characteristics such as age, sex, underlying psychological problems, and levels of depression and anxiety affected the effect of clonidine. METHODS: We retrospectively reviewed outpatients aged 6 to 24 who took clonidine due to insomnia from September 2019 to September 2021 at the Department of Psychiatry at Eunpyeong St. Mary's Hospital of Catholic University. We used the Pittsburgh Sleep Quality Index (PSQI), Children's Depression Inventory (CDI), and State-Trait Anxiety Inventory (STAI) for our study. RESULTS: A total of 62 participants were included in our study (34 females, mean age 13.94±4.94 years). After using clonidine, there was a significant decrease in PSQI components 1, 2, and 5, especially PSQI component 2. There was a greater decrease in sleep latency when clonidine was used in females, those aged between 13 and 24, those with mood/anxiety disorder or attention-deficit/hyperactivity disorder, those whose sleep latency exceeded 60 minutes at baseline, and those who used clonidine for more than 14 days. Those with higher STAI-Trait scores and CDI scores at baseline showed less improvement in total PSQI scores. CONCLUSION: Considering that there are currently no Food and Drug Administration-approved sleep drugs for children and adolescents and no apparent difference in efficacy and safety among sleep drugs, we demonstrated that treatment with clonidine might be a good approach to improve sleep quality and quantity for children and adolescents.

Olanzapine Ameliorates Ischemic Stroke-like Pathology in Gerbils and H2O2-Induced Neurotoxicity in SH-SY5Y Cells via Inhibiting the MAPK Signaling Pathway.

Olanzapine (OLNZ) is used to treat psychotic disorders. To look into the neurological basis of this phenomenon, we investigated the neuroprotective effects of OLNZ in gerbils and SH-SY5Y cells. Gerbils were subjected to transient global cerebral ischemia (TGCI) by blocking both common carotid arteries, and OLNZ (10 mg/kg) was injected intraperitoneally. Hydrogen peroxide (H2O2) was used to induce oxidative-stress-mediated damage in the SH-SY5Y cells. The results indicated that OLNZ administration markedly reduced neuron damage and glial cell triggering within CA1 zone of the hippocampus. We used RNA sequencing to assess the numbers of up-and downregulated genes involved in TGCI. We found that OLNZ treatment downregulated the expression of complement-component-related genes and the expression of mitogen-activated protein kinases (MAPKs) in the hippocampus. In cells, OLNZ co-treatment significantly improved cell viability and reduced lactate dehydrogenase (LDH), and reactive oxygen species (ROS) generation. Expression of antioxidant superoxide dismutase-1,2 enzymes (SOD-1, SOD-2) was also intensely upregulated by OLNZ, while the expression of MAPKs and NF-κB were reduced. Co-incubation with OLNZ also regulated apoptosis-related proteins Bax/Bcl-2 expression. Finally, the results demonstrated that treatment with OLNZ showed neuroprotective effects and that the MAPK pathway could involve in the protective effects.

Fermented Mentha arvensis administration provides neuroprotection against transient global cerebral ischemia in gerbils and SH-SY5Y cells via downregulation of the MAPK signaling pathway.

BACKGROUND: Globally, ischemic stroke is a major health threat to humans that causes lifelong disability and death. Mentha arvensis (MA) has been used in traditional medicine to alleviate oxidative stress and inflammation-related disorders. In the present study, the neuroprotective properties of fermented MA (FMA) extract were investigated in the gerbil and SH-SY5Y cells. model of transient global cerebral ischemia. METHODS: Bilateral common carotid artery occlusion-induced transient global cerebral ischemia in gerbil and hydrogen peroxide (H2O2)-mediated neurotoxic effects in human neuroblastoma cells (SH-SY5Y) were investigated. FMA (400 mg/kg) was orally administered for 7 days before induction of ischemic stroke. To evaluate the neuroprotective activity of FMA, we implemented various assays such as cell viability assay (MTT), lactate dehydrogenase (LDH) assay, histopathology, immunohistochemistry (IHC), histofluorescence, and western blot. RESULTS: FMA pretreatment effectively decreased transient ischemia (TI) induced neuronal cell death as well as activation of microglia and astrocytes in the hippocampal region. The protective effects of FMA extract against H2O2-induced cytotoxicity of SH-SY5Y cells were observed by MTT and LDH assay. However, FMA pretreatment significantly increased the expression of the antioxidant marker proteins such as superoxide dismutase-1 (SOD-1) and superoxide dismutase-2 (SOD-2) in the hippocampus and SH-SY5Y cells. Furthermore, the activation of mitogen-activated protein kinase (MAPK) further activated a cascade of outcomes such as neuroinflammation and apoptosis. FMA pretreatment notably decreased TI and H2O2 induced activation of MAPK (c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38) proteins in hippocampus and SH-SY5Y cells respectively. Besides, pretreatment with FMA markedly reduced H2O2 mediated Bax/Bcl2 expression in SH-SY5Y cells. CONCLUSION: Thus, these results demonstrated that neuroprotective activities of FMA might contribute to regulating the MAPK signaling pathway.

Analysis of trauma scoring system for patients with abdominal trauma.

BACKGROUND: This study investigated the correlations between several trauma scoring systems, including the injury severity score (ISS), clinical abdominal scoring system (CASS), new injury severity score (NISS), and clinical outcomes, including laparotomy, in-hospital mortality (IHM), and long hospital stay (LS) in patients with abdominal trauma. METHODS: Data of 749 patients with abdominal trauma between January 2009 and December 2019 were reviewed retrospectively. Data from medical records included age, sex, initial vital signs, type and mechanism of trauma, hospital stay, laparotomy, and IHM. Injured organs and grades were collected using computed tomography. Correlations between the scoring system and clinical outcomes were analyzed using the area under Curves (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: The mean age of the patients was 40.14±19.47 years. Blunt trauma was the most common type of trauma in 704 patients (94.0%), and traffic accident was the most common mechanism in 475 (63.4%). Injured organs included liver (45.1%) and spleen (25.1%). A total of 179 patients (23.9%) underwent laparotomy and IHM was reported in 35 (4.6%). The AUC of ROC for ISS, NISS, and CASS was significantly associated with laparotomy (0.682; p=0.001, 0.713; p=0.001; 0.845; p=0.001). The AUCs showed significant for IHM (0.606; p=0.034, 0.626; p=0.012, 0.701; p=0.001). The AUCs for LS were 0.554 (p=0.041), 0.549 (p=0.062), and 0.581 (p=0.002). CONCLUSION: The CASS is excellent for predicting laparotomy, IHM, and LS in patients with abdominal trauma. The NISS is more appropriate than the ISS for predicting laparotomy and IHM.

Determining the etiology of small bowel obstruction in patients without intraabdominal operative history: a retrospective study.

PURPOSE: Most of the causes of small bowel obstruction (SBO) in patients without a history of abdominal surgery are unclear at initial assessment. This study was conducted to identify the etiology and clinical characteristics of SBO in virgin abdomens and discuss the proper management. METHODS: A retrospective review involving operative cases of SBO from a single institute, which had no history of abdominal surgery, was conducted between January 2010 and December 2020. Clinical information, including radiological, operative, and pathologic findings, was investigated to determine the etiology of SBO. RESULTS: A total of 55 patients were included in this study, with a median age of 57 years and male sex (63.6%) constituting the majority. The most frequently reported symptoms were abdominal pain and nausea or vomiting. Neoplasm as an underlying cause accounted for 34.5% of the cases, of which 25.5% were malignant cases. In patients aged ≥60 years (n=23), small bowel neoplasms were the underlying cause in 12 (52.2%), of whom 9 (39.1%) were malignant cases. Adhesions and Crohn disease were more frequent in patients aged <60 years. Coherence between preoperative computed tomography scans and intraoperative findings was found in 63.6% of the cases. CONCLUSION: There were various causes of surgical cases of SBO in virgin abdomens. In older patients, hidden malignancy should be considered as a possible cause of SBO in a virgin abdomen. Patients with symptoms of recurrent bowel obstruction who have no history of prior abdominal surgery require thorough medical history and close follow-up.

Chemical Composition, Antioxidant, and Anti-Inflammatory Activity of Essential Oil from Omija (Schisandra chinensis (Turcz.) Baill.) Produced by Supercritical Fluid Extraction Using CO2.

Schisandra chinensis (Turcz.) Baill., which is known as omija in South Korea, is mainly cultivated in East Asia. The present study aimed to investigate the chemical composition of essential oil from the omija (OMEO) fruit obtained by supercritical fluid extraction using CO2 and to confirm the antioxidant and anti-inflammatory activity of OMEO using HaCaT human keratinocyte and RAW 264.7 murine macrophages. As a result of the chemical composition analysis of OMEO using gas chromatography-mass spectrometry, a total of 41 compounds were identified. The detailed analysis results are sesquiterpenoids (16), monoterpenoids (14), ketones (4), alcohols (3), aldehydes (2), acids (1), and aromatic hydrocarbons (1). OMEO significantly reduced the increased ROS levels in HaCaT keratinocytes induced by UV-B irradiation (p < 0.05). It was confirmed that 5 compounds (α-pinene, camphene, ß-myrcene, 2-nonanone, and nerolidol) present in OMEO exhibited inhibitory activity on ROS production. Furthermore, OMEO showed excellent anti-inflammatory activity in RAW 264.7 macrophages induced by lipopolysaccharide. OMEO effectively inhibited NO production (p < 0.05) by suppressing the expression of the iNOS protein. Finally, OMEO was investigated for exhibition of anti-inflammatory activity by inhibiting the activation of NF-κB pathway. Taken together, OMEO could be used as a functional food ingredient with excellent antioxidant and anti-inflammatory activity.

Effect of Korean Red Ginseng through comparative analysis of cardiac gene expression in db/db mice.

Korean Red Ginseng (KRG) is an herbal oriental medicine known to alleviate cardiovascular dysfunction. To analysis the expression of diabetic cardiac complication-associated genes in db/db mice, we studied the cardiac gene expression following KRG treatment. In result, a total of 585 genes were found to be changed in db/db mice. Among the changed expression, 245 genes were found to 2-fold upregulated, and 340 genes were 2-fold downregulated. In addition, the changed gene expressions were ameliorated by KRG. In conclusion, KRG may be possible to normalize cardiac gene expressions in db/db mice.

MiR-141-3p promotes mitochondrial dysfunction in ovariectomy-induced sarcopenia via targeting Fkbp5 and Fibin.

Post-menopausal conditions exacerbate the biological aging process and this is often accompanied by visceral adiposity with sarcopenia. Mitochondrial impairment is a hallmark of frailty and sarcopenia in the elderly. However, the exact mechanism underlying the development of obesogenic sarcopenia and the involvement of mitochondria remains unclear. This study confirmed that there is a decline in muscle mass and function as well as mitochondrial dysfunction in the quadriceps of ovariectomized (OVX) mice. To investigate the role of microRNA (miRNA) in this process, we performed miRNA and mRNA arrays and found that miR-141-3p directly targets and downregulates FK506 binding protein 5 (Fkbp5) and Fibin. Overexpression of miR-141-3p decreased mitochondrial function and inhibited myogenic differentiation in C2C12 cells. These effects were mediated by Fkbp5 and Fibin inhibition. Conversely, knockdown of miR-141-3p increased mitochondrial respiration and enhanced myogenesis. Treatment with ß-estradiol effectively reversed the palmitic acid-induced upregulation of miR-141-3p and subsequent downregulation of Fkbp5 and Fibin. In conclusion, miR-141-3p is upregulated in OVX mice, and this is associated with mitochondrial dysfunction through inhibition of Fkbp5 and Fibin. These findings suggest that inhibiting miR-141-3p could be a therapeutic target for alleviating obesogenic sarcopenia.

Syk/NF-κB-targeted anti-inflammatory activity of Melicope accedens (Blume) T.G. Hartley methanol extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Melicope accedens (Blume) Thomas G. Hartley is a plant included in the family Rutaceae and genus Melicope. It is a native plant from Vietnam that has been used for ethnopharmacology. In Indonesia and Malaysia, the leaves of M. accedens are applied externally to decrease fever. AIM OF THE STUDY: The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages. MATERIALS AND METHODS: We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE2). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS. RESULTS: Ma-ME suppressed the production of NO and PGE2 and the mRNA expression of proinflammatory genes (iNOS, IL-1ß, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-κB activation by suppressing signaling molecules such as IκBα, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-κB signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1ß and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin. CONCLUSIONS: Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-κB signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.

Withaferin A exerts an anti-obesity effect by increasing energy expenditure through thermogenic gene expression in high-fat diet-fed obese mice.

BACKGROUND: The enhancement of energy expenditure has attracted attention as a therapeutic target for the management of body weight. Withaferin A (WFA), a major constituent of Withania somnifera extract, has been reported to possess anti-obesity properties, however the underlying mechanism remains unknown. PURPOSE: To investigate whether WFA exerts anti-obesity effects via increased energy expenditure, and if so, to characterize the underlying pathway. METHODS: C57BL/6 J mice were fed a high-fat diet (HFD) for 10 weeks, and WFA was orally administered for 7 days. The oxygen consumption rate of mice was measured at 9 weeks using an OxyletPro™ system. Hematoxylin and eosin (H&E), immunohistochemistry, immunoblotting, and real-time PCR methods were used. RESULTS: Treatment with WFA ameliorated HFD-induced obesity by increasing energy expenditure by improving of mitochondrial activity in brown adipose tissue (BAT) and promotion of subcutaneous white adipose tissue (scWAT) browning via increasing uncoupling protein 1 levels. WFA administration also significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the BAT of obese mice. Additionally, WFA activated mitogen-activated protein kinase (MAPK) signaling, including p38/extracellular signal-regulated kinase MAPK, in both BAT and scWAT. CONCLUSION: WFA enhances energy expenditure and ameliorates obesity via the induction of AMPK and activating p38/extracellular signal-regulated kinase MAPK, which triggers mitochondrial biogenesis and browning-related gene expression.

The antioxidant activities of Korean Red Ginseng (Panax ginseng) and ginsenosides: A systemic review through in vivo and clinical trials.

A wide range of studies have steadily pointed out the relation of oxidative stress to the primary and secondary causes of human disease and aging. As such, there have been multiple misconceptions about oxidative stress. Most of reactive oxygen species (ROS) generated from chronic diseases cause oxidative damage to cell membrane lipids and proteins. ROS production is increased by abnormal stimulation inside and outside in the body, and even though ROS are generated in cells in response to abnormal metabolic processes such as disease, it does not mean that they directly contribute to the pathogenesis of a disease. Therefore, the focus of treatment should not be on ROS production itself but on the prevention and treatment of diseases linked to ROS production, including types 1 and 2 diabetes, cancer, heart disease, schizophrenia, Parkinson's disease, and Alzheimer's disease. In this regard, Korean Red Ginseng (KRG) has been traditionally utilized to help prevent and treat diseases such as diabetes, cancer, inflammation, nervous system diseases, cardiovascular disease, and hyperlipidemia. Therefore, this review was intended to summarize in vivo animal and human clinical studies on the antioxidant activities of KRG and its components, ginsenosides.

Mir214-3p and Hnf4a/Hnf4α reciprocally regulate Ulk1 expression and autophagy in nonalcoholic hepatic steatosis.

Macroautophagy/autophagy, a self-degradative process, regulates metabolic homeostasis in response to various stress conditions and is a therapeutic target for nonalcoholic fatty liver disease. We found that autophagic activity was inhibited as a result of a significant reduction in the expression of autophagy-related genes such as Ulk1 in a mouse model and patients with fatty liver. This downregulation was caused by increased Mir214-3p levels and decreased Hnf4a/Hnf4α mRNA levels in hepatocytes. Mir214-3p suppressed Ulk1 expression through direct binding at a 3' untranslated region sequence. Hnf4a directly activated transcription of Ulk1. We investigated lipid accumulation and the expression of autophagy-related genes in the livers of mice treated with anti-Mir214-3p. Hepatic steatosis was alleviated, and Ulk1 mRNA levels were significantly increased by locked nucleic acid-mediated Mir214-3p silencing. Additionally, autophagosome formation and MAP1LC3/LC3-II protein levels were increased, indicating an increase in autophagic activity. Interestingly, suppression of Mir214-3p did not ameliorate fatty liver under Ulk1 suppression, suggesting that reduced Mir214-3p levels mitigate hepatic steatosis through upregulation of Ulk1. These results demonstrate that inhibition of Mir214-3p expression ameliorated fatty liver disease through increased autophagic activity by increasing the expression of Ulk1. Thus, Mir214-3p is a potential therapeutic target for nonalcoholic fatty disease.Abbreviations: AMPK: adenosine monophosphate-activated protein kinase; ATG: autophagy-related; ChIP: chromatin immunoprecipitation; CTSB: cathepsin B; CTSL: cathepsin L; CQ: chloroquine; HFD: high-fat diet; HNF4A: hepatocyte nuclear factor 4, alpha; IF: immunofluorescence; IHC: immunohistochemistry; LDs: lipid droplets; Leup: leupeptin; LFD: low-fat diet; LNA: locked nucleic acid; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; miRNA: microRNA; MTOR: mechanistic target of rapamycin kinase; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PCR: polymerase chain reaction; TEM: transmission electron microscopy; TF: transcription factor; TLDA: TaqMan low-density array; ULK1: unc-51 like kinase 1; UTR: untranslated region.

Tunisian Olea europaea L. leaf extract suppresses Freund's complete adjuvant-induced rheumatoid arthritis and lipopolysaccharide-induced inflammatory responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Olea europaea L. (olive) is traditionally used as a folk remedy and functional food in Europe and Mediterranean countries to treat inflammatory diseases. O. europaea contains phenolic compounds and have been reported to prevent cartilage degradation. However, the function and mechanism of O. europaea in rheumatoid arthritis are not known. AIM OF THE STUDY: In this study, we aimed to examine anti-inflammatory and anti-arthritic effects of Tunisian O. europaea L. leaf ethanol extract (Oe-EE). MATERIALS AND METHODS: To do this, we employed an in vitro macrophage-like cell line and an in vivo Freund's complete adjuvant (AIA)-induced arthritis model. Levels of inflammatory genes and mediators were determined from in vivo samples. RESULTS: The Oe-EE clearly reduced the production of the lipopolysaccharide-mediated inflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2), in RAW264.7 cells. The results of HPLC showed that Oe-EE contained many active compounds such as oleuropein and flavonoids. In AIA-treated rats, swelling of paws, pain, and cartilage degeneration were alleviated by oral Oe-EE administration. Correlating with in vitro data, PGE2 production was significantly reduced in paw samples. Furthermore, the molecular mechanism of Oe-EE was dissected, and Oe-EE regulated the gene expression of interleukin (IL)-6, inducible NO synthase (iNOS), and MMPs and inflammatory signaling activation. CONCLUSION: Consequently, Oe-EE possesses anti-inflammatory and anti-rheumatic effects and is a potential effective treatment for rheumatoid arthritis.

The Anti-Cancer Effect of Linusorb B3 from Flaxseed Oil through the Promotion of Apoptosis, Inhibition of Actin Polymerization, and Suppression of Src Activity in Glioblastoma Cells.

Linusorbs (LOs) are natural peptides found in flaxseed oil that exert various biological activities. Of LOs, LOB3 ([1-9-NαC]-linusorb B3) was reported to have antioxidative and anti-inflammatory activities; however, its anti-cancer activity has been poorly understood. Therefore, this study investigated the anti-cancer effect of LOB3 and its underlying mechanism in glioblastoma cells. LOB3 induced apoptosis and suppressed the proliferation of C6 cells by inhibiting the expression of anti-apoptotic genes, B cell lymphoma 2 (Bcl-2) and p53, as well as promoting the activation of pro-apoptotic caspases, caspase-3 and -9. LOB3 also retarded the migration of C6 cells, which was achieved by suppressing the formation of the actin cytoskeleton critical for the progression, invasion, and metastasis of cancer. Moreover, LOB3 inhibited the activation of the proto-oncogene, Src, and the downstream effector, signal transducer and activator of transcription 3 (STAT3), in C6 cells. Taken together, these results suggest that LOB3 plays an anti-cancer role by inducing apoptosis and inhibiting the migration of C6 cells through the regulation of apoptosis-related molecules, actin polymerization, and proto-oncogenes.

3-Deazaadenosine, an S-adenosylhomocysteine hydrolase inhibitor, attenuates lipopolysaccharide-induced inflammatory responses via inhibition of AP-1 and NF-κB signaling.

3-Deazadenosine (3-DA) is a general methylation inhibitor that depletes S-adenosylmethionine, a methyl donor, by blocking S-adenosylhomocysteine hydrolase (SAHH). In this study, we investigated the inhibitory activity and molecular mechanisms of 3-DA in inflammatory responses. 3-DA suppressed the secretion of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide-treated RAW264.7 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated U937 cells. It also reduced mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin-1ß (IL-1 ß), and IL-6, indicating that 3-DA has anti-inflammatory properties in murine and human macrophages. Moreover, 3-DA strongly blocked AP-1 and NF-κB luciferase activity under PMA-, MyD88-, and TRIF-stimulated conditions and decreased the translocation of c-Jun, c-Fos, p65, and p50 into the nucleus. In addition, the p-ERK level in AP-1 signaling and the p-IκBα level in NF-kB signaling were diminished by 3-DA treatment. Interestingly, 3-DA did not alter the phosphorylation of MEK1/2, an ERK modulator, or IKKα/ß, an IκBα regulator. Instead, 3-DA prevented MEK1/2 and IKKα/ß from combining with ERK and IκBα, respectively, and directly suppressed MEK1/2 and IKKα/ß kinase activity. These results indicate that MEK1/2 and IKKα/ß are direct targets of 3-DA. In addition, suppression of SAHH by siRNA or treatment with adenosine dialdehyde, another SAHH inhibitor, showed inhibitory patterns against p-ERK and IκBα similar to those of 3-DA. Taken together, this study demonstrates that 3-DA inhibits AP-1 and NF-κB signaling by directly blocking MEK1/2 and IKKα/ß or indirectly mediating SAHH, resulting in anti-inflammatory activity.