The application of flipped learning to a gross anatomy dissection course.

We implemented flipped learning for a gross anatomy dissection course and compared its effects on students' motivation and academic achievement with those of traditional dissection methods. We invited 142 first-year medical students at Chonnam National University Medical School to participate in this study. All participants engaged in traditional dissection methods in the first part of the study and flipped learning in the latter part. Medical students' motivation to learn anatomy by cadaveric dissection was measured using the ARCS (Attention, Relevance, Confidence, and Satisfaction) model. Thereafter, all students completed a written examination consisting of 96 multiple-choice questions. The students' mean motivational score regarding attention was significantly higher in association with flipped learning than with traditional learning. However, the students' mean motivational scores regarding relevance, confidence, and satisfaction were not significantly different between the methods. Additionally, the mean anatomy practice test score was significantly higher in association with flipped learning than with traditional learning. The students' motivational scores and anatomy practice test scores associated with flipped learning positively correlated with the extent of learning material completion. The students' responses indicated that flipped learning helped enhance the learning process, improve time management, reduce confusion during practice, and promote independent practice. The application of flipped learning to a cadaveric dissection course increased individual learning motivation, which improved learning activities both in and out of class, as well as academic achievement.

Distribution of the tensor of the vastus intermedius.

The tensor of the vastus intermedius (TVI) was first described by Grob et al. in 2016. It originates from the anteroinferior greater trochanter and inserts into the upper patella and receives blood and nerves independently of other muscles. It has been overlooked, but since micro-surgery and detailed rehabilitation treatments are being developed, more research on it is warranted. Here we report on the TVI in a Korean cadaveric study. A total of 58 cadavers (41 males and 17 females) were included. Thighs were examined using a standardized dissection protocol. The quadriceps femoris muscle was identified and its components were defined by blunt dissection. A total of 116 lower limbs were dissected. In 40 of them, there was a separately innervated TVI muscle belly between the fasciae of the vastus lateralis (VL) and the vastus intermedius (VI) muscles. TVIs were classed as independent (ID), VI, and VL types according to the relative relationship between the TVI, VL, and VI, and subdivided into two parts: Part 1 was the proximal muscular portion of the TVI attached to the VL or VI, and part 2 was the distal aponeurotic area. TVIs were analyzed in detail via 58 Korean cadavers. We subdivided them on the basis of their location and association with related muscles. A larger study is needed to clarify the function and prevalence of the TVI.

Anatomical Characteristics of the Anterior Jugular Vein and Its Clinical Relevance.

INTRODUCTION: The anterior jugular vein (AJV) is part of the superficial venous drainage system of the head and neck. Recently, interest in AJV is increasing as various surgical procedures have been developed. The authors conducted a cadaveric study to determine characteristics of AJV in Koreans. METHODS: A total of 44 cadavers were dissected. Anatomical characteristics were analyzed for 34 cadavers in which AJV was well observed. RESULTS: In this study, 21 were males and 13 were females. There were 8 cadavers with only 1 AJV from both sides. There was no significant difference in anatomical characteristics according to gender or AJV variation except for a difference in the length of the neck according to gender. However, it was possible to find a safety zone at the main landmark of the neck that could avoid AJV damage. CONCLUSIONS: By using this safety zone, it is possible to prevent damage to the AJV and reduce complications during various surgical procedures on the head and neck.

A heptamethine cyanine dye serves as a potential marker for myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with inhibitory effects on T cell-mediated immune response. MDSCs accumulate under many pathological conditions, including cancers, to avoid anticancer immunity. Unlike mouse MDSCs, common specific surface markers for human MDSCs are not clearly defined, mainly due to the complexity of MDSC subsets. In this study, we investigate specific responses of the infrared dye MHI-148 to MDSCs. Mice bearing 4T1 breast cancer cells were established, and splenocytes were isolated. Flow cytometric analyses demonstrated that MHI-148 was reactive to over 80% of MDSC-specific cells manifesting CD11b+/Gr-1+ acquired from both tumor-bearing mice and naive mice. Cells sorted positive for either CD11b/Gr-1 or MHI-148 were also identical to their counterparts (99.7% and 97.7%, respectively). MHI-148, however, was not reactive to lymphocyte or monocyte populations. To determine whether MHI-148-reactive cells exert inhibitory effects on T cell proliferation, an EdU-based T cell assay was performed. MHI-148 reactive cells significantly reduced T cell proliferation with increased arginase activity and nitrite production. In an attempt to test MHI-148 as a marker for human MDSCs, MHI-148 was specifically reactive to CD11b+/CD33+/CD14- granulocytic MDSCs acquired from selected cancer patients. This study demonstrates that the near-infrared dye MHI-148 specifically reacts to mouse splenocytes with known MDSC-specific markers that have T cell suppressive functions. The dye also selectively binds to a subpopulation of immature myeloid cells acquired from cancer patients. While it is not clear how MHI-148 specifically stains MDSCs, this dye can be a novel tool to detect MDSCs and to predict the prognosis of human cancer patients.

Elevated procalcitonin levels in patients with acetaminophen intoxication: two case reports: A CARE-compliant article.

RATIONALE: Procalcitonin (PCT) is used as a biomarker for identifying the occurrence of sepsis. Previous studies have reported high levels of PCT with acetaminophen intoxication without evidence of infection. Here, we report two patients with acetaminophen intoxication with high levels of PCT without showing any symptoms of bacterial infection. PATIENT CONCERNS: This case study examined two unrelated patients with acetaminophen intoxication admitted to emergency at different times. The first patient was admitted to the emergency department after ingesting approximately 8000 mg (153.8 mg/kg) of acetaminophen. On admission, C-reactive protein (CRP), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were normal. PCT and acetaminophen levels were 31.89 ng/mL and below 0.5 µg/mL, respectively. The second patient was admitted to the emergency department 8 h after ingesting ∼23,600 mg (280.6 mg/kg) of acetaminophen. By the second day of admission, GOT and GPT increased to 2508 and 1473 IU/L, respectively. PCT was 45.66 ng/mL with acetaminophen level at 116.9 µg/mL. Both patients were clear of symptoms associated with bacterial infection. DIAGNOSIS: Acetaminophen intoxication. INTERVENTIONS: N-acetylcysteine was given intravenously to both patients for 20 h per protocol. OUTCOMES: Both patients were discharged without complications. LESSONS: Observations suggests that elevated levels of PCT in patients intoxicated with acetaminophen may be associated with involvement of other organs impacted by cytokine stimuli from sterile inflammation resulting from hepatic damage rather than PCT secretion directly caused by hepatic cell damage.

[Effects of a video education program for patients with benign uterine tumors receiving high-intensity focused ultrasound treatment]. / ê³ ê°•ë„ 집속 초음파 치료를 받는 ìžê¶ì–‘ì„±ì¢ ì–‘ 환자의 동영상 교육프로그램 효과.

Purpose: The purpose of this study was to examine the effects of a video education program in women receiving high-intensity focused ultrasound (HIFU) treatment. Methods: This was a quasi-experimental study with a nonequivalent control group non-synchronized design. The participants were 54 patients who had benign uterine tumors and adenomyosis. The data were collected from June to August 2018. A 10-minute video education program on HIFU and post-procedural care was developed based on the literature. The experimental group was provided the video education program with a question-and-answer session for 10 minutes after viewing the video. The control group received usual care (i.e., verbal instructions on post-procedural self-care). The questionnaire survey was conducted twice: before the educational program and before being discharged from the hospital. Differences in uncertainty, emotions, and self-efficacy among patients were analyzed. Data were analyzed using the chi-square test, Shapiro-Wilk test, paired t-test, and t-test with SPSS version 23.0. Results: The participants in the experimental group showed a decrease in uncertainty(t=4.33, p<.001), improvements in anxiety(t=-4.07, p<.001) and depression (t=-3.55,p<.001), and an enhancement ofself-efficacy (t=-4.39,p<.001) compared to the control group. Conclusion: This nursing intervention was effective at reducing uncertainty, improving emotions, and enhancing self-efficacy. This intervention is feasible for use in nursing practice as an aid for patients when considering treatment methods.

Zinc Inhibits Expression of Androgen Receptor to Suppress Growth of Prostate Cancer Cells.

The prostate gland contains a high level of intracellular zinc, which is dramatically diminished during prostate cancer (PCa) development. Owing to the unclear role of zinc in this process, therapeutic applications using zinc are limited. This study aimed to clarify the role of zinc and its underlying mechanism in the growth of PCa. ZnCl2 suppressed the proliferation of androgen receptor (AR)-retaining PCa cells, whereas it did not affect AR-deficient PCa cells. In LNCaP and TRAMP-C2 cells, zinc downregulated the expression of AR in a dose- and time-dependent fashion. Zinc-mediated AR suppression accordingly inhibited the androgen-mediated transactivation and expression of the androgen target, prostate specific antigen (PSA). This phenomenon resulted from facilitated protein degradation, not transcriptional control. In studies using mice bearing TRAMP-C2 subcutaneous tumors, the intraperitoneal injection of zinc significantly reduced tumor size. Analyses of both xenograft tumors and normal prostates showed reduced expression of AR and increased cell death. Considering the significant loss of intracellular zinc and the dominant growth-modulating role of AR during PCa development, loss of zinc may be a critical step in the transformation of normal cells to cancer cells. This study provides the underlying mechanism by which zinc functions as a PCa suppressor, and forms the foundation for developing zinc-mediated therapeutics for PCa.

Targeting CD46 Enhances Anti-Tumoral Activity of Adenovirus Type 5 for Bladder Cancer.

CD46 is generally overexpressed in many human cancers, representing a prime target for CD46-binding adenoviruses (Ads). This could help to overcome low anti-tumoral activity by coxsackie-adenoviral receptor (CAR)-targeting cancer gene therapy viruses. However, because of scarce side-by-side information about CAR and CD46 expression levels in cancer cells, mixed observations of cancer therapeutic efficacy have been observed. This study evaluated Ad-mediated therapeutic efficacy using either CAR-targeting Ad5 or CD46-targeting Ad5/35 fiber chimera in bladder cancer cell lines. Compared with normal urothelia, bladder cancer tissue generally overexpressed both CAR and CD46. While CAR expression was not correlated with disease progression, CD46 expression was inversely correlated with tumor grade, stage, and risk grade. In bladder cancer cell lines, expression levels of CD46 and CAR were highly correlated with Ad5/35- and Ad5-mediated gene transduction and cytotoxicity, respectively. In a human EJ bladder cancer xenograft mouse model, with either overexpressed or suppressed CD46 expression levels, Ad5/35-tk followed by ganciclovir (GCV) treatment significantly affected tumor growth, whereas Ad5-tk/GCV had only minimal effects. Overall, our findings suggest that bladder cancer cells overexpress both CAR and CD46, and that adenoviral cancer gene therapy targeting CD46 represents a more suitable therapy option than a CAR-targeting therapy, especially in patients with low risk bladder cancers.

The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis.

Irisin, a recently identified hormone secreted by skeletal muscle in response to exercise, exhibits anabolic effects on the skeleton primarily through the stimulation of bone formation. However, the mechanism underlying the irisin-stimulated anabolic response remains largely unknown. To uncover the underlying mechanism, we biosynthesized recombinant irisin (r-irisin) using an Escherichia coli expression system and used it to treat several osteoblast cell types. Our synthesized r-irisin could promote proliferation and differentiation of osteoblasts as evidenced by enhanced expression of osteoblast-specific transcriptional factors, including Runt-related transcription factor-2 (Runx2), Oster (Osx), as well as early osteoblastic differentiation markers such as alkaline phosphatase (Alp) and collagen type I alpha 1 (Col1a1). Furthermore, we showed that the promotion of r-irisin on the proliferation and differentiation of osteoblast lineage cells are preferentially through aerobic glycolysis, as indicated by the enhanced abundance of representative enzymes such as lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase kinase 1 (PDK1), together with increased lactate levels. Suppression of r-irisin-mediated aerobic glycolysis with Dichloroacetate blunted its anabolic effects. The favorite of the aerobic glycolysis after r-irisin treatment was then confirmed in primary calvarial cells by metabolic analysis using gas chromatography-mass spectrometry. Thus, our results suggest that the anabolic actions of r-irisin on the regulation of osteoblast lineage cells are preferentially through aerobic glycolysis, which may help to develop new irisin-based bone anabolic agents.

Assessment of Plasma Neutrophil Gelatinase-Associated Lipocalin for Early Detection of Acute Kidney Injury and Prediction of Mortality in Severely Burned Patients.

The purpose of this study was to assess the plasma neutrophil gelatinase-associated lipocalin (NGAL) for early detection of acute kidney injury (AKI) and prediction of mortality in severely burned patients. From January 2014 to September 2015, 76 consecutive patients with more than 20% of TBSA burned were enrolled. Blood samples for plasma NGAL were collected at 0, 7, 14, 21, and 28 days after admission and analyzed with injury severity, clinical outcome, and AKI development. Plasma NGAL was significantly affected by the TBSA burned, AKI, and mortality, and it was significantly increased after operation and septic shock. Plasma NGAL was significantly increased within 7 days before AKI development in total patients (P < .001) and septic shock patients (P < .001) but not significantly increased in patients without septic shock (P = .167). Though, in a receiver operating characteristic curve analysis for predicting AKI, continuous renal replacement therapy application, and mortality, plasma NGAL was statistically significant; plasma NGAL was not independently associated with mortality in a multivariate logistic regression analysis. Plasma NGAL should be interpreted carefully in the major burn patients because it can reflect both inflammatory condition and AKI.

Delta neutrophil index: A reliable marker to differentiate perforated appendicitis from non-perforated appendicitis in the elderly.

BACKGROUND: Delta neutrophil index (DNI) is a new inflammatory marker and the present study aimed to evaluate the predictive value of the DNI for the presence of a perforation in elderly with acute appendicitis. METHODS: This retrospective observational study was conducted on 108 consecutive elderly patients (≥65 years old) with acute appendicitis treated over a 24-month period. RESULTS: Sixty-nine of the 108 patients (median, IQR: 72, 67-77 years) were allocated to the perforated appendicitis group (63.9%) and 39 to the non-perforated appendicitis group (36.1%). WBC, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and DNI were significantly higher in the perforated group. In multiple logistic regression analyses, initial DNI was the only independent marker that can significantly predict the presence of perforation in multiple regression [odds ratio 9.38, 95% confidence interval (2.51-35.00), P=.001]. Receiver operator characteristic curve analysis showed that DNI is a good predictor for the presence of appendiceal perforation at an optimal cut-off for DNI being 1.4% (sensitivity 67.7%, specificity 90.0%, AUC 0.807). CONCLUSION: Clinicians can reliably differentiate acute perforated appendicitis from non-perforated appendicitis by DNI level of 1.4 or more in elderly patients.

Delta neutrophil index as an early predictor of acute appendicitis and acute complicated appendicitis in adults.

BACKGROUND: This retrospective study aimed to evaluate the ability of the delta neutrophil index (DNI) to predict histologically normal appendicitis preoperatively and to differentiate between simple and complicated appendicitis. METHODS: The data from 650 patients were divided into positive and negative appendectomy groups (histologically normal appendicitis). The patients in the acute appendicitis group were further sub-divided into simple and complicated appendicitis groups. RESULTS: The DNI was significantly higher in the positive group than in the negative appendectomy group (0.4 vs. -0.4, p < 0.001) as well as in the complicated group compared with that in the simple appendicitis group (1.2 vs. 0.3, p < 0.001). The DNI independently predicted a positive appendectomy and an acute complicated appendicitis in multivariate logistic regression analysis [odds ratio (OR) 2.62, 95% confidence interval (CI) (1.11~6.16), p = 0.028 and odds ratio (OR) 4.10, 95% confidence interval (CI) (2.94~5.80), p < 0.001]. The optimum cut-off for a positive appendectomy and acute complicated appendicitis were 0.2 [area under curve (AUC) 0.709] and 0.6 (AUC 0.727). CONCLUSIONS: We suggest that obtaining a preoperative DNI is a useful parameter to aid in the diagnosis of histologically normal appendicitis and to differentiate between simple and complicated appendicitis.

Long-Term Prognostic Value of Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With and Without Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting.

The value of late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) for the prediction of functional recovery after surgical revascularization has been previously established. However, the impact of LGE-MRI on the long-term prognosis after coronary artery bypass grafting (CABG) remains incompletely understood. Therefore, we aimed to evaluate the long-term prognostic value of LGE-MRI, based on the presence or absence of left ventricular (LV) dysfunction, in patients with coronary artery disease undergoing CABG. One hundred forty-six consecutive patients underwent cine- and LGE-MRI before CABG. Adverse cardiac events included cardiac death, nonfatal myocardial infarction, heart failure, and unstable angina. A 3-year landmark analysis of the primary end point was also performed for patients surviving beyond 3 years after CABG. During a median follow-up of 9.4 years, 44 patients (30%) experienced adverse cardiac events. Although a LV ejection fraction <50% was associated only with adverse cardiac events at 3 years after CABG, LGE was associated with a worse outcome both at and beyond 3 years after CABG. In the overall study population, LGE presence (adjusted hazard ratio [HR] 2.58; p = 0.027), score (adjusted HR 1.06; p <0.001), and extent (adjusted HR 1.08; p <0.001) were independent predictors of adverse cardiac events. Moreover, in both the LV ejection fraction <50% and ≥50% groups, the LGE extent was an independent predictor of adverse cardiac events. In conclusion, our qualitative and quantitative analyses of LGE-MRI provide long-term prognostic information after surgical revascularization. The LGE extent was a strong predictor of adverse cardiac events, independent of the LV function.

Efficacy of CD46-targeting chimeric Ad5/35 adenoviral gene therapy for colorectal cancers.

CD46 is a complement inhibitor membrane cofactor which also acts as a receptor for various microbes, including species B adenoviruses (Ads). While most Ad gene therapy vectors are derived from species C and infect cells through coxsackie-adenovirus receptor (CAR), CAR expression is downregulated in many cancer cells, resulting inefficient Ad-based therapeutics. Despite a limited knowledge on the expression status of many cancer cells, an increasing number of cancer gene therapy studies include fiber-modified Ad vectors redirected to the more ubiquitously expressed CD46. Since our finding from tumor microarray indicate that CD46 was overexpressed in cancers of the prostate and colon, fiber chimeric Ad5/35 vectors that have infection tropism for CD46 were employed to demonstrate its efficacy in colorectal cancers (CRC). CD46-overexpressed cells showed a significantly higher response to Ad5/35-GFP and to Ad5/35-tk/GCV. While CRC cells express variable levels of CD46, CD46 expression was positively correlated with Ad5/35-mediated GFP fluorescence and accordingly its cell killing. Injection of Ad5/35-tk/GCV caused much greater tumor-suppression in mice bearing CD46-overexpressed cancer xenograft compared to mock group. Analysis of CRC samples revealed that patients with positive CD46 expression had a higher survival rate (p=0.031), carried tumors that were well-differentiated, but less invasive and metastatic, and with a low T stage (all p<0.05). Taken together, our study demonstrated that species B-based adenoviral gene therapy is a suitable approach for generally CD46-overexpressed CRC but would require careful consideration preceding CD46 analysis and categorizing CRC patients.

Modified carotid sinus massage using an ultrasonography for maximizing vagal tone: a crossover simulation study.

INTRODUCTION: The aim of this study was to ascertain if a modified carotid sinus massage (CSM) using ultrasonography is superior to the conventional CSM for vagal tone generation. METHODS: This was a prospective, crossover, clinical trial including 30 subjects with sinus rhythm. Participants were paired, and they performed 2 types of CSM to each other. To perform the conventional technique, pressure was exerted at the point where the maximal impulse of the carotid pulse was palpated. In the modified technique, participants localized the point of maximal diameter just above the bifurcation of the common carotid artery using ultrasonography and applied pressure to that point. Mean differences between premaneuver and postmaneuver R-R intervals and heart rates were compared. The distance from the midline of the neck (x distance) to the angle of the mandible (y distance) was measured, and the mean distance between the 2 techniques was compared. RESULTS: The baseline mean premaneuver R-R interval and heart rate did not differ significantly between the 2 techniques. The postmaneuver R-R interval and heart rate as well as the mean R-R interval and heart rate differences were significantly greater in the modified CSM. The mean location determined using the modified CSM was located 0.8 cm lateral and 0.8 cm superior to the mean location of the conventional CSM. CONCLUSION: The modified CSM using ultrasonography might be more useful than the conventional CSM in reverting episodes of paroxysmal supraventricular tachycardia and may be a suitable alternative for treating the same in the emergency department.

Study design of the influence of SErotonin inhibition on patients with RENAl impairment or diabetes undergoing drug-eluting stent implantation (SERENADE) study: A multicenter, open-label, prospective, randomized study.

BACKGROUND: The rates of stent failure after percutaneous coronary intervention have decreased since the introduction of the drug-eluting stent (DES). However, chronic kidney disease (CKD) and diabetes mellitus (DM) remain strong clinical predictors of poor prognosis despite DES implantation. Sarpogrelate, a selective serotonin (5-hydroxytryptamine (HT)2a [5-HT2A]) receptor antagonist, has antiproliferative effects, reducing neointimal hyperplasia and smooth muscle cell proliferation, as well as potent antiplatelet action, inhibiting 5-HT-induced platelet aggregation. However, efficacy and safety data for sarpogrelate in patients with CKD or DM are limited. We aim to determine whether sarpogrelate has beneficial effects in patients with CDK or DM treated with DES implantation. METHODS/DESIGN: The SERENADE trial is a multicenter, open-label, prospective, randomized study that will test the superiority of triple anti-platelet therapy (TAT; aspirin, clopidogrel, and sarpogrelate) to conventional dual antiplatelet therapy (DAT; aspirin and clopidogrel) in preventing late lumen loss 9 months after the index procedure in patients with CKD or DM. A total of 220 patients diagnosed with coronary artery disease with DM or CKD will be randomized to the TAT or DAT groups (1:1 ratio) after DES implantation. The primary endpoint is late lumen loss at 9 months assessed by quantitative coronary angiography. Secondary efficacy endpoints are composites of major adverse cardiovascular events including cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Secondary safety endpoints are major bleeding events and hepatic or renal impairment. DISCUSSION: The SERENADE trial will provide insight on the efficacy of adjunctive therapy with sarpogrelate after DES implantation for patients with high-risk profiles such as CKD or DM. TRIAL REGISTRATION: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov NCT02294643).

Endotracheal tube-assisted orogastric tube insertion in intubated patients in an ED.

BACKGROUND AND AIMS: Inserting a nasogastric tube (NGT) in intubated patients may be difficult because they cannot follow swallowing instructions, resulting in a high rate of first-attempt failure. We introduce a simple technique for inserting an orogastric tube in an emergency department (ED). METHODS: Fifty-six patients in the ED, who were intubated and required NGT insertion, were randomly allocated to 2 groups. We inserted the NGT using a conventional technique from the nostril (control group) and an endotracheal tube (ET)-assisted technique from the mouth (ET group). The procedures' success rate, insertion duration, and complications were compared between the groups. RESULTS: There was a significantly higher overall success rate in the ET group than the control group (100% vs 64%, P<.001). Endotracheal tube group showed 100% first-attempt success rate, but 50% of the control group failed at first attempt. Mean duration of the first trial was not significantly different between the ET and control groups (58.0±16.9 vs 57.3±29.5 seconds, P=.903), but total time for successful insertion was longer in the control group than the ET group (58.0±16.9 vs 111.7±74.5 seconds, P<.001). There was less NGT kinking and more mucosal bleeding in the ET group than in the control group (0% vs 16%, P=.019; 16% vs 7%, P=.225, respectively). CONCLUSION: Endotracheal tube-assisted orogastric tube insertion technique showed a higher rate of successful insertion and shorter total duration. With this result, ET-assisted orogastric tube insertion would be useful in ED.

Ginsenoside Rg3 inhibits lipopolysaccharide-induced adhesion molecule expression in human umbilical vein endothelial cell and C57BL/6 mice.

Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), P- and E-selectin play a key role for initiation of vascular inflammation. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for health promotion in Korea. In this study, we investigated the mechanism by which ginsenoside Rg3 may inhibit ICAM-1 and VCAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC) and C57BL/6 mice. LPS increased ICAM-1 and VCAM-1 expression. Ginsenoside Rg3 prevented LPS-mediated increase of ICAM-1 and VCAM-1 expression. LPS induced IkappaBα (IκBα) degradation within 1 hr. Ginsenoside Rg3 prevented the IκBα degradation stimulated with LPS. Moreover, ginsenoside Rg3 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, which was prevented by ginsenoside Rg3. These data provide a novel mechanism where the ginsenoside Rg3 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing prevention against vascular inflammatory disease.

VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy.

The features and regulation of uterine angiogenesis and vascular remodelling during pregnancy are poorly defined. Here we show that dynamic and variable decidual angiogenesis (sprouting, intussusception and networking), and active vigorous vascular remodelling such as enlargement and elongation of 'vascular sinus folding' (VSF) and mural cell drop-out occur distinctly in a spatiotemporal manner in the rapidly growing mouse uterus during early pregnancy - just after implantation but before placentation. Decidual angiogenesis is mainly regulated through VEGF-A secreted from the progesterone receptor (PR)-expressing decidual stromal cells which are largely distributed in the anti-mesometrial region (AMR). In comparison, P4 -PR-regulated VEGF-A-VEGFR2 signalling, ligand-independent VEGFR3 signalling and uterine natural killer (uNK) cells positively and coordinately regulate enlargement and elongation of VSF. During the postpartum period, Tie2 signalling could be involved in vascular maturation at the endometrium in a ligand-independent manner, with marked reduction of VEGF-A, VEGFR2 and PR expressions. Overall, we show that two key vascular growth factor receptors - VEGFR2 and Tie2 - strikingly but differentially regulate decidual angiogenesis and vascular remodelling in rapidly growing and regressing uteri in an organotypic manner.