Abstract: It has been determined that there is extensive communication between the immune system and the central nervous system (CNS). Proinflammatory cytokines play a key role in this communication. There is an emerging realization that glia and microglia, in particular, (which are the brain’s resident macrophages), are an important source of inflammatory mediators and may have fundamental roles in CNS disorders. Microglia respond also to proinflammatory signals released from other non-neuronal cells, principally those of immune origin, such as mast cells. Mast cells reside in the CNS and are capable of migrating across the blood-brain barrier (BBB) in situations where the barrier is compromised as a result of CNS pathology. Mast cells are both sensors and effectors in communication among nervous, vascular, and immune systems. In the brain, they reside on the brain side of the BBB, and interact with astrocytes, microglia, and blood vessels via their neuroactive stored and newly synthesized chemicals. They are first responders, acting as catalysts and recruiters to initiate, amplify, and prolong other immune and nervous responses upon activation. Mast cells both promote deleterious outcomes in brain function and contribute to normative behavioral functioning, particularly cognition and emotion. Mast cells may play a key role in treating systemic inflammation or blockade of signaling pathways from the periphery to the brain.

Abstract: BACKGROUND Resveratrol exhibits beneficial effects against numerous degenerative diseases at different stages of pathogenesis. This study investigated potential mechanisms and resveratrol effects on high glucose (HG)-induced oxidative stress (30 mM D-glucose, 30 min) and cell proliferation (30 mM D-glucose, 24 h) in vascular smooth muscle cells (VSMCs). MATERIAL/METHODS Intracellular reactive oxygen species (ROS) generation was detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA). Total antioxidant capacity (TAC), malonyldialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were measured to evaluate oxidative stress. VSMC proliferation was measured by CCK-8 assays and through propidium iodide-based cell cycle analysis. Expression of NAD(P)H oxidase, proliferation proteins, and cell signalling were assessed by immunoblot analysis. RESULTS Co-treatment of primary cultures of VSMCs with 1-100 μM resveratrol decreased HG-induced ROS overproduction (P<0.05). Resveratrol also abolished HG-induced phosphorylation of oxidase subunit p47 phox and reduced HG-induced cyclin D1, cyclin E, and PCNA expression in a concentration-dependent manner. Furthermore, resveratrol (10 μM) attenuated HG-induced phosphorylation of Akt, p38 mitogen-activated protein kinase (MAPK), ERK 1/2, and JNK1/2 without affecting total levels. HG stimulation enhanced downstream IκB-α phosphorylation and NF-κB activity, and resveratrol repressed these effects. CONCLUSIONS Resveratrol inhibits HG-induced oxidative stress and VSMC proliferation by suppressing ROS generation, NADPH oxidase, Akt phosphorylation, p38 MAPK/JNK/ERK phosphorylation, and IκB-α and NF-κB activities.

Abstract: Background Previous research has shown a reduction in blood pressure (BP) immediately after the practice of alternate nostril yoga breathing (ANYB) in normal healthy male volunteers and in hypertensive patients of both sexes. The BP during ANYB has not been recorded. Material/methods Participants were 26 male volunteers (group mean age ±SD, 23.8±3.5 years). We assessed (1) heart rate variability, (2) non-invasive arterial BP, and (3) respiration rate, during (a) ANYB and (b) breath awareness (BAW) sessions. Each session was 25 minutes. We performed assessments at 3 time points: Pre (5 minutes), during (15 minutes; for ANYB or BAW) and Post (5 minutes). A naive-to-yoga control group (n=15 males, mean age ±SD 26.1±4.0 years) were assessed while seated quietly for 25 minutes. Results During ANYB there was a significant decrease (repeated measures ANOVA) in systolic BP and respiration rate; while RMSSD (the square root of the mean of the sum of squares of differences between adjacent NN intervals) and NN50 (the number of interval differences of successive normal to normal intervals greater than 50 ms) significantly increased. During BAW respiration rate decreased. In contrast, respiration rate increased during the control state. ANYB and BAW were significantly different (2-factor ANOVA) in RMSSD and respiration rate. BAW and control were different with respect to respiration rate. Conclusions The results suggest that vagal activity increased during and after ANYB, which could have contributed to the decrease in BP and changes in the HRV.

Abstract: The endothelium performs a crucial role in maintaining vascular integrity leading to whole organ metabolic homeostasis. Endothelial dysfunction represents a key etiological factor leading to moderate to severe vasculopathies observed in both Type 2 diabetic and Alzheimer's Disease (AD) patients. Accordingly, evidence-based epidemiological factors support a compelling hypothesis stating that metabolic rundown encountered in Type 2 diabetes engenders severe cerebral vascular insufficiencies that are causally linked to long term neural degenerative processes in AD. Of mechanistic importance, Type 2 diabetes engenders an immunologically mediated chronic pro-inflammatory state involving interactive deleterious effects of leukocyte-derived cytokines and endothelial-derived chemotactic agents leading to vascular and whole organ dysfunction. The long term negative consequences of vascular pro-inflammatory processes on the integrity of CNS basal forebrain neuronal populations mediating complex cognitive functions establish a striking temporal comorbidity of AD with Type 2 diabetes. Extensive biomedical evidence supports the pivotal multi-functional role of constitutive nitric oxide (NO) production and release as a critical vasodilatory, anti-inflammatory, and anti-oxidant, mechanism within the vascular endothelium. Within this context, we currently review the functional contributions of dysregulated endothelial NO expression to the etiology and persistence of Type 2 diabetes-related and co morbid AD-related vasculopathies. Additionally, we provide up-to-date perspectives on critical areas of AD research with special reference to common NO-related etiological factors linking Type 2 diabetes to the pathogenesis of AD.

Abstract: Background This experiment was performed to compare the effects of Phenytoin (PHT) and Hypericin (HP) cream on healing of burn wounds in rats. Material and methods Twenty rats were divided into 3 groups and second-degree burn wounds were created. The burn wounds in the first, second, and third groups were covered twice daily with PHT cream, HP cream, and saline (control), respectively. At the end of days 3, 7, 14, and 21, full-thickness skin biopsies were done for histopathologic and immunohistochemical analyses. Results Histopathologic evaluations at the 14th day showed that re-epithelialization scores were greater in the HP group than the PHT group, but on day 21, re-epithelialization scores were higher in the PHT group than the HP group. Collagen content on days 3 and 14 in the PHT group was found to be higher than in the HP group. Well-vascularized granulation tissue on day 7 in the PHT group was higher than in other groups. HP and PHT groups had a significant increase in VEGF and TGF-b expression in burn wound healing area compared to the control group on all days. Conclusions Topical application of HP can promote re-epithelialization in burn wounds to shorten the wound healing time for superficial burns. Phenytoin, on the other hand, contributes to healing by increasing vascularized granulation tissue and collagen synthesis through re-epithelialization. The increased VEGF and TGF-b expression following PHT and HP treatment strongly indicate that PHT and HP treatment promotes VEGF and TGF-b production and action in the burn wound area.

Abstract: Tissue engineering was introduced by Vacanti and Langer in the 80’s, exploring the potential of this new technology starting with the well-known “human ear on the mouse back”. The goal is to create a substitute which supplies an individual therapy for patients with regeneration, remodeling and growth potential. The growth potential of these subjects is of special interest in congenital cardiac surgery, avoiding repeated interventions and surgery. Initial applications of tissue engineered created substitutes were relatively simple cardiovascular grafts seeded initially by end-differentiated autologous endothelial cells. Important data were collected from these initial clinical autologous endothelial cell seeded grafts in peripheral and coronary vessel disease. After these initial successfully implantation bone marrow cell were used to seed patches and pulmonary conduits were implanted in patients. Driven by the positive results of tissue engineered material implanted under low pressure circumstances, first tissue engineered patches were implanted in the systemic circulation followed by the implantation of tissue engineered aortic heart valves. Tissue engineering is an extreme dynamic technology with continuously modifications and improvements to optimize clinical products. New technologies are unified and so this has also be done with tissue engineering and new application features, so called transcatheter valve intervention. First studies are initiated to apply tissue engineered heart valves with this new transcatheter delivery system less invasive. Simultaneously studies have been started on tissue engineering of so-called whole organs since organ transplantation is restricted due to donor shortage and tissue engineering could overcome this problem. Initial studies of whole heart engineering in the rat model are promising and larger size models are initiated.

Abstract: is a significant reduction in the “time spent in the escape platform’s quadrant” in 24-month-old rats compared to 4-month-old rats in the probe trial of the MWM test. YC-1 treatment reversed the reduction of the “time spent in the escape platform’s quadrant” of 24-month-old rats. In the PA test, there was no significant differ ence in the 1 st -day latency of rats in all groups. On the 2nd day, retention latency significantly decreased in the 24-month-old rats compared to 4-month-olds. YC-1 reversed the diminished retention latency in 24-monthold rats. YC-1 treatment and aging did not affect results of the locomotor activity test or the foot-shock sensi tivity test, suggesting our results were not due to a change in motor activity or disability of the animals. Conclusions: Our findings suggest that activation of the NO-sGC-cGMP pathway plays an important role in spatial and emo tional learning and memory functions in aged rats.

Abstract: Background In the past, successful use of decellularized xenogenic tissue was shown in the pulmonary circulation. This study, however, evaluates a newly developed decellularized equine pericardial patch under high pressure circumstances. Material and methods Seven decellularized equine pericardial scaffolds were implanted into the descending aorta of the juvenile sheep. The implanted patches were oversized to evaluate the durability of the decellularized tissue under high surface tension (Law of Laplace). After 4 months of implantation, all decellularized patches were inspected by gross examination, light microscopy (H&E, Serius red, Gomori, Weigert, and von Kossa straining), and immunohistochemical staining. Results The juvenile sheep showed fast recovery after surgery. There was no mortality during follow-up. At explantation, only limited adhesion was seen at the surgical site. Gross examination showed a smooth and pliable surface without degeneration, as well as absence of aneurysmatic dilatation. Light microscopy showed a well preserved extracellular scaffold with a monolayer of endothelial cells covering the luminal side of the patch. On the outside part of the patch, a well developed neo-vascularization was seen. Host fibroblasts were seen in all layers of the scaffolds. There was no evidence for structural deterioration or calcification of the decellularized equine pericardial scaffolds. Conclusions In the juvenile sheep, decellularized equine tissue showed no structural deterioration, but regeneration and remodeling processes at systemic circulation.

Abstract: Background Effects of acupuncture stimulation on blood glucose concentration and body weight were investigated in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model for type-2 diabetes. Material and methods Three groups of rats were used: OLETF, acupuncture-treated OLETF (AcOLETF), and Long-Evans Tokushima Otsuka (LETO) rats (as control for the OLETF rats). In AcOLETF rats, acupuncture stimulation was applied twice a week to 6 points (zhongwan, tianshu, qihai, ganshu, pishu, shenshu) and changes in blood glucose concentration and body weight were measured. Results Initially, at 6 weeks old, there was no significant difference in blood glucose levels between groups. Blood glucose levels increased with age in each group, reaching a maximum of about 430 mg/dl at 37 weeks in OLETF rats. In AcOLETF rats, blood glucose levels increased at a slower rate than in OLETF rats, reaching a maximum concentration of about 280 mg/dl at 37 weeks of age, significantly lower than that in OLETF rats. The concentration of blood glucose in LETO rats had stabilized at a maximum value of 120~140 mg/dl by 16 weeks, remaining at this level for up to 39 weeks. In each group, body weight increased with age and was not affected by acupuncture treatment. Conclusions In OLETF rats, acupuncture treatment significantly reduced blood glucose levels, but not their body weight, suggesting that acupuncture therapy was effective in preventing the development of type-2 diabetes mellitus.

Abstract: BACKGROUND The aim of this study was to investigate the sensitivity to rapamycin of endometrial cancer cells with different phosphatase and tensin homologue (PTEN) expression to understand the mechanism of resistance to mammalian target of rapamycin (mTOR) inhibitors in the treatment of endometrial cancer MATERIAL AND METHODS Twenty specific pathogen-free female BALB/c mice received transplants of either HEC-1A (PTEN-positive) or Ishikawa (PTEN-negative) cells Mice in the treatment group were injected intraperitoneally once a week for 4 consecutive weeks The control group was injected weekly with phosphate buffer saline (PBS) for 4 consecutive weeks Tumor volume, tumor mass, growth curves, and inhibition rate were measured, after which the mice were killed RESULTS Both tumor growth rate and size were slower in the treatment group than in the control group for all mice that received transplants of either HEC-1A or Ishikawa cells The tumor inhibition rates in the treatment group were 481% and 671% in mice transplanted with HEC-1A and Ishikawa cells, respectively CONCLUSIONS The inhibitory effects of rapamycin were enhanced in PTEN-negative Ishikawa tumor cells compared with PTEN-positive HEC-1A cells, which could explain the reduced effect of rapalogues in some endometrial cancer patients and help to understand the mechanism of resistance to this drug

Abstract: BACKGROUND It has been demonstrated that atrial electrical remodeling contributes toward atrial fibrillation (AF) maintenance, and that angiotensin II (AngII) is involved in the pathogenesis of atrial electrical remodeling. Peroxisome proliferator activated receptor-γ (PPAR-γ) agonists have been shown to inhibit atrial electrical remodeling, but the underlying mechanisms are poorly understood. In the present study we investigated the regulating effects of PPAR-g agonist on AngII-induced potassium channel remodeling in atrial myocytes. MATERIAL/METHODS Whole-cell patch-clamp technique was used to record transient outward potassium current (Ito), ultra-rapid delayed rectifier potassium (Ikur), and inward rectifier potassium current (Ik1). Real-time PCR was used to assess potassium channel subunit mRNA expression. RESULTS Compared with the control group, AngII reduced Ito and Ikur current density as well as amplified Ik1 current density, which were partially prevented by pioglitazone. Furthermore, pioglitazone alleviated the downregulation of Ito subunit (Kv 4.2) and Ikur subunit (Kv 1.5), as well as the upregulation of Ik1 subunit (Kir 2.1 and Kir 2.2) mRNA expression stimulated by AngII. CONCLUSIONS These results suggest that pioglitazone exhibits a beneficial effect on AngII-induced potassium channel remodeling. PPAR-γ agonists may be potentially effective up-stream therapies for AF.

Abstract: Background 4-Nonylphenol is a ubiquitous environmental toxin that is formed as a byproduct in the manufacturing and/or sewage treatment of regular household items Previous work in our lab has implicated 4-NP in the progression of autoimmune diseases such as inflammatory bowel disease in which macrophages mistakenly attack the intestinal linings, causing chronic inflammation Several key pro-and anti-inflammatory molecules have been shown to be involved in the manifestation of this disease, including IL-23A, COX-2, IL-8, TLR-4, and IL-10

Abstract: Background Phosphodiesterase (PDE) inhibitors in the central nervous system have been shown to stimulate neuronal functions and increase neurogenesis in Alzheimer disease (AD) patients.

Abstract: BACKGROUND Tissue engineering (TE) is a promising approach to overcome problems associated with biological heart valve prosthesis. Currently several animal models are used to advance this method. The rat subdermal model is uncomplicated and widely used, but its suitability for TE has not yet been shown. MATERIAL AND METHODS Using the rat subdermal model we implanted two decellularized porcine aortic wall specimens (of which one was endothelialized) and one native porcine aortic wall specimen in 30 Lewis rats, respectively. Endothelial cells (EC) were harvested from the rat jugular veins. After explantation Hematoxylin/Eosin-staining, CD-68-positive cell staining, fibroblast-staining and Von-Willebrand factor staining were performed. RESULTS All animals survived without complications. Endothelialization was confirmed to be effective by Giemsa staining. Histological evaluation of specimens in Hematoxylin/Eosin staining showed significant decrease (p<0.05) of inflammatory reaction (confirmed by CD-68-positive cell staining) after decellularization. All specimens showed strongest inflammatory reactions at areas of destroyed extracellular matrix. Fibroblasts could be detected in all specimens, with strongest infiltration in decellularized specimens (p<0.05). Surrounding endothelialized specimens had no monolayer of endothelial cells, but a higher density of blood vessels occurred (p<0.05). CONCLUSIONS The subdermal model provides excellent contact of host tissue with implanted specimens leading to rapid cellular infiltration; therefore, we could ascertain reduced inflammatory response to decellularized tissue. Due to the subdermal position, an absence of blood stream and mechanical stress occurs, which influences cellular repopulation; therefore, endothelialization did not lead to an EC monolayer, but rather to increased vascularization. Thus, the model appears ideal for investigating basic biological compatibility, but further questions must be researched using other models.

Abstract: BACKGROUND: Social defect and chronic pain are 2 major health problems and recent data has demonstrated that they generally exist concurrently. However, a powerful evaluation model on the behavioral change is lacking. This study was designed to evaluate the behavioral curves using a statistically modeled trajectory analysis in neuropathic animals with or without social defect exposure. MATERIAL/METHODS: After approval by the institutional animal care committee, Sprague-Dawley rats were randomized into different interventional groups with 15 animals each. Sprague-Dawley rats underwent spared nerve injury (SNI) to establish the neuropathic pain model, of which the mechanical withdrawal threshold was measured using von Frey filaments for a period of 105 days. Otherwise, a modified version of the resident (Long-Evans rats)-intruder paradigm was applied to produce a social defect animal model through the elevated plus maze (EPM). After raw data collection, we modeled them into a powerful statistical effects analysis to build up the behavioral change tendency in single SNI or in combined SNI and social defect animals. RESULTS: The random and fixed effects analyses of the pain behavior after SNI were successfully modeled and demonstrated a gradient recovery tendency during the 15-week post-injury observational period. Correspondingly, SNI rats exhibited increased social defected symptoms, as indicated by the increased anxiety-like behavior in the EPM test. In addition, continuous social defect stress for 5 days or 10 days, respectively, partially attenuated and exacerbated SNI-induced allodynia in both random and fixed effects models. Five days but not 10 days social defect ameliorated SNI-associated anxiety-like behavior. CONCLUSIONS: These data suggest that statistically powerful analysis of nerve injury-induced neuropathic pain is a highly sensitive model to determine the behavioral change tendency and distinguish them among behavior curves with or without social defect, and the combination of SNI with resident-intruder paradigm may be a suitable model for behavior evaluation of neuropathic pain with social defect.

Abstract: Background: Sildenafil is a selective PDE5 inhibitor that increases cGMP levels in the target tissues and is an effective treat ment agent for erectile dysfunction. The nitric oxide-cGMP pathway might be implicated in regulation of certain CNS functions, including locomotor activity and anxiety. Material/Methods: The aim of the current study was to investigate effects of sildenafil (3 and 10 mg/kg) on anxiety and locomo tor activity in open field and elevated plus maze (EPM) tests in young and aged mice. Results: Sildenafil (3 and 10 mg/kg) significantly decreased the percent of time spent in the open arms compared to the control group in young animals in the EPM test, but only the 10 mg/kg dose significantly decreased the per centage of total number of entries to the open arms in young animals. Sildenafil (3 and 10 mg/kg) significant ly decreased the percentage of total number of entries to the open arms in aged animals in the EPM test, but it significantly increased total distance moved and speed of the animals in the locomotor activity test in young animals. The total distance moved and the speed of the animals significantly decreased in aged animals com pared to the young control group, although sildenafil (3 and 10 mg/kg) did not alter these parameters in aged mice. Conclusions: Our results show that sildenafil had anxiogenic effects in young as well as aged mice, but it enhanced locomo tor activity only in the young mice in the EPM test. Thus, sildenafil seems to exert different effects on anxiety and locomotion in young and aged animals.

Abstract: Background: Eprosartan is an angiotensin II receptor antagonist used as an antihypertensive. We sought to evaluate the regional effect of Eprosartan on postinfarct ventricular remodeling and myocardial function in an isolated swine working heart model of ischemia-reperfusion injury. Material/Methods: 22 swine hearts were perfused with the Langendorff perfusion apparatus under standard experimental con ditions. Myocardial ischemia was induced by a 10-min left anterior descending artery ligation. Hearts were reperfused with either saline (control group, n=11), or Eprosartan (treatment group, n=11). Left ventricular pressure (LVP) and regional heart parameters such as intramyocardial pressure (IMP), wall thickening rate (WTh), and pressure-length-loops (PLL) were measured at baseline and after 30 min of reperfusion. Results: Measured parameters were statistically similar between the 2 groups at baseline. The administration of Eprosartan led to a significantly better recovery of IMP and WTh: 44.4±2.5 mmHg vs. 51.2±3.3 mmHg, p<0.001 and 3.8±0.4 µm vs. 4.4±0.3 µm, p=0.001, respectively. PLL were also significantly higher in the treatment group following reperfusion (21694±3259 units vs. 31267±3429 units, p<0.01). There was no difference in the LVP re sponse to Eprosartan versus controls (63.6±3.0 mmHg vs. 62.5±3.1 mmHg, p=0.400). Conclusions: Pre-treatment with Eprosartan is associated with a significant improvement in regional cardiac function under ischemic conditions. Pharmacological treatment with eprosartan may exert a direct cardioprotective effect on ischemic myocardium.

Abstract: Background The increase in the amount of extended spectrum beta-lactamases (ESBL)-producing gram-negative bacteria is seriously threatening human health in recent years. Therefore, it is necessary to develop a rapid and reliable method for identification of ESBLs. The purpose of this study was to establish a novel method to discriminate between ESBL-producing and non- ESBL-producing bacteria by using the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) technique. Material/methods We detected hydrolyzed production of cefotaxime after incubation with 69 gram-negative bacteria by using MALDI-TOF-MS. Then we established genetic algorithm (GA), supervised neural networks (SNN), and quick classifier (QC) models using several peaks to identify ESBL-producing strains. To confirm the clinical applicability of the models established, a blinded validation test was performed in 34 clinical isolated strains. Results Using ClinPro Tools software, we identified 4 peaks (456 Da, 396 Da, 370 Da, and 371 Da) in mass spectra of cefotaxime solution that have high enough specificity to discriminate ESBL-producing from non- ESBL-producing strains. Recognition capability of models established were 97.5% (GA), 92.5% (SNN), and 92.5% (QC), and cross validation rates were 90.15% (GA), 97.62 (SNN), and 97.62% (QC). The accuracy rates of the blinded validation test were 82.4% (GA), 88.2% (SNN), and 82.4% (QC). Conclusions Our results demonstrate that identification of ESBLs strains by MALDI-TOF-MS has potential clinical value and could be widely used in the future as a routine test in clinical microbiology laboratories.

Abstract: BACKGROUND The aim of this study was to evaluate the feasibility of treating vertebral compression fractures using an autonomously developed nitinol memory alloy vertebral stent. MATERIAL AND METHODS Thoracolumbar vertebral specimens from adult human cadavers were made into models of compression fractures. The models were divided into group A, which received percutaneous kyphoplasty (PKP), balloon dilation, and nitinol memory alloy vertebral stent implantation (PKP + nitinol stent group); group B, which received percutaneous vertebroplasty (PVP) and direct implantation of a nitinol memory alloy vertebral stent (PVP + nitinol stent group); and group C, which received PKP, balloon dilation, and bone cement vertebroplasty (PKP + polymethylmethacrylate (PMMA) group). Vertebral heights were measured before and after the surgery and the water bath incubation to compare the impact of the 3 different surgical approaches on reducing vertebral compression. RESULTS The 3 surgical groups could all significantly restore the heights of compressed vertebral bodies. The vertebral heights of the PKP + nitinol stent group, PVP + nitinol stent group, and PKP + PMMA group were changed from the preoperative levels of (1.59±0.08) cm, (1.68±0.08) cm, and (1.66±0.11) cm to the postoperative levels of (2.00±0.09) cm, (1.87±0.04) cm, and (1.99±0.09) cm, respectively. After the water bath, the vertebral heights of each group were changed to (2.10±0.07) cm, (1.98±0.09) cm, and (2.00±0.10) cm, respectively. Pairwise comparison of the differences between the preoperative and postoperative vertebral heights showed that group A and group B differed significantly (P=0.000); group B and group C differed significantly (P=0.003); and group A and group C had no significant difference (P=0.172). Pairwise comparison of the differences in the vertebral heights before and after the water bath showed that group A and group C differed significantly (P=0.000); group B and group C differed significantly (P=0.000); and group A and group B had no significant difference (P=0.157). CONCLUSIONS The nitinol memory alloy stents can effectively support and reduce the compression of vertebral endplates and can be used to treat vertebral compression fractures without neurological symptoms.

Abstract: End-stage heart failure is a major health problem, but implementation of guidelines and optimizing medical therapy for this devastating disease should decrease mortality. If optimal conservative therapy is no longer sufficient, a mechanical support system may be required as final destination therapy or as bridge-to-transplant. Since the first heart transplantation in 1967, this therapy has become the criterion standard for end-stage heart failure, but is limited due to organ shortage. Tissue engineering could help overcome this limitation and provide regeneration, remodeling, and growth potential. This so-called bio-artificial heart would be available, created by a decellularized extracellular matrix and seeded with in vitro proliferated autologous cardiovascular cells. Results of the first experimental studies have been promising, but numerous challenges must be met before this procedure will be available.

Abstract: BACKGROUND Roots and leaves of the Cermela Hutan (Phyllanthus gomphocarpus Hook F) plant were studied to determine antioxidant activity, phytochemical compounds, proportion of carbohydrate, crude protein, moisture, ash, fat, total phenolic content (TPC), and total flavonoid content (TFC) MATERIAL/METHODS Ten percent (10%) aqueous extract from both Phyllanthus gomphocarpus roots (PGR) and leaves (PGL) were used in this study Antioxidant activity characterization by TPC, TFC, Ferric Reducing Antioxidant Power (FRAP), 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, and phytochemical screening, as well as proximate analysis from both extracts were analyzed in this study RESULTS Phyllanthus gomphocarpus roots (PGR) and leaves (PGL) tested positive for flavonoid, saponin, tannins, and terpenoids, but PGR showed negative result for anthraquinones In average weight of 1000 g dry sample, the carbohydrates, protein, moisture, ash, fat, and energy content in PGR and PGL were 809%, 55%, 78%, 34%, 24%, and 367 Kcal/100g, and 665%, 148%, 107%, 65%, 15%, and 399 Kcal/100 g, respectively Antioxidant assessments using FRAP and DPPH assay showed that PGL extracts possessed higher antioxidant capacity by reducing the ferric ion-TPTZ complex by 014 mg/ml ±00018 and higher scavenging activity, 8383% ±054 as compared to PGR, 007 mg/ml ±00035 for FRAP and 6287% ±133 for DPPH, respectively The total phenolics content was significantly higher in PGL (20877 mg GAE/g ±379) as compared to PGR (2753 mg GAE/g ±042) However, there was no significant different in the total flavonoid contents for PGR (348 mg QE/g ±312) and PGL (3243 mg QE/g ±392) CONCLUSIONS Further investigations are suggested to isolate and characterize the other active constituents from this plant in combatting diseases

Abstract: BACKGROUND Age-associated immune senescence is a catch-all phrase that has been used to describe a plethora of changes to the immune system across the lifespan. Aging is associated with a decline in immune function. Our aim in this study was to investigate how lymphocyte subgroups in peripheral blood are affected by aging among males and females. MATERIAL/METHODS Study participants were 70 healthy individuals from 3 different age groups, observed from January 2010 to January 2012. The average levels of CD3+, CD4+, CD8+, CD19+, CD16+/CD56+, CD3+/CD69+, and CD19+/CD69+ were determined for each group and compared in terms of age and sex. RESULTS We found significant reduction in the level of CD3+T cells related with age, but no significant changes in CD19+ B cell levels (p<0.005). Aging significantly reduces activated B cell (CD19+/CD69+) levels in males (p<0.005). CONCLUSIONS Our results show that there may be differences between males and females in terms of immune senescence.

Abstract: Background: Nitric oxide (NO) is an intercellular messenger that plays a critical role in learning and memory processes Effects of nitric oxide synthase (NOS) inhibitors and guanylate cyclase (GC) inhibitors on cognitive function re main controversial Material/Methods: The aim of this study was to investigate effects of an NOS inhibitor, 7-nitroindazole (7-NI), and a GC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on different aspects of memory in passive avoidance (PA), novel object recognition (NOR), and social transmission of food preference (STFP) tests Male Balb-c mice were treated intraperitoneally with 7-NI (15 mg/kg), ODQ (3,10 mg/kg), L-arginine (100 mg/kg) + 7-NI (15 mg/kg), or physiological saline Results: ODQ (10 mg/kg) and 7-NI (15 mg/kg) significantly decreased second-day latency in PA test 7-NI (15 mg/kg) and ODQ (10 mg/kg) significantly decreased the ratio index in the NOR test 7-NI and ODQ (10 mg/kg) decreased cued/non-cued food eaten in STFP test Amount of time spent in center zone significantly increased in ODQ (10 mg/kg) and 7-NI (15 mg/kg) groups in open field test, but there was no effect on total distance moved and speed of animals ODQ (10 mg/kg) significantly increased number of entries into new compartments in ex ploratory activity apparatus, while 7-NI had no effect Administration of L-arginine (100 mg/kg) before 7-NI re versed 7-NI-induced effects, supporting the role of NO in cognition Conclusions: Our results confirm that inhibition of NO/cGMP/GS pathway might disturb emotional, visual, and olfactory memory in mice Also, 7-NI and ODQ had anxiolytic effects in open field test, and ODQ also enhanced explor atory activity

Abstract: Background Parkinson's disease (PD) continues to be an important neurological disorder. It is caused by the loss of dopaminergic neurons in the substantia nigra. Dopamine, the neurotransmitter produced from dopaminergic neurons, is a major precursor of endogenous morphine. There are approximately 18 genes associated with PD; their roles have not yet been completely established. PARK2 is a gene that encodes for the protein parkin, and PINK1 is a gene that encodes for PTEN-induced putative kinase 1. Material and methods Our objective was to determine if morphine treatment of HTB-11 cells affects the expression of PINK1 and PARK2. HTB-11 cells were treated with 10-7 M morphine for 2 h and a microarray analysis was conducted. To verify the microarray analysis, 3 Q-PCR trials were run using 10-6 M naloxone, morphine (10-7 M), or a naloxone/morphine mix. Results In both the microarray analysis and the Q-PCR analysis, PARK2 was up-regulated and PINK1 was down-regulated. Conclusions Morphine can affect the expression of PD-associated genes.

Abstract: Background Acinetobacter baumannii is a significant hospital pathogen, possessing a considerable degree of antimicrobial resistance. A. baumannii resistance to carbapenems and aminoglycosides is mostly conferred by class D OXA carbapenemases and aminoglycoside-modifying enzymes, respectively. The aim of this study was to determine the prevalence of selected genes encoding OXA carbapenemases and aminoglycoside-modifying enzymes in multidrug-resistant strains of A. baumannii.

Abstract: Background Cytotoxicity of root canal irrigants is important due to their close contact with host tissues. The aim of this study was to assess the cytotoxic effect of NaOCl 3%, Chx 2%, and MTAD on rat periodontal ligament fibroblasts, at 0.1 and 100 µl/mL, using WST-1 colorimetric method. Material and methods Rat ligamental fibroblasts were exposed to the irrigants and their viability was assessed after 1, 24, 48, and 72 h. The measurements were determined using WST-1 assay, using a micro ELISA reader. Results At 100 ml/L all 3 irrigants were strongly cytotoxic, although CHX was less so than NaOCl and MTAD. At the 0.1 ml/L concentration, NaOCl and MTAD were only moderately cytotoxic, whereas Chx was highly deleterious to cell viability at all time points. There was a significant influence of the dilution rate of the substance, because the odds ratio for cell viability being over 50% was increased 51 times between the 100 ml/L and 0.1 ml/L dilutions. Conclusions It seems that irrigating solutions should be used at lower concentrations to enhance cell viability.

Abstract: BACKGROUND Sirtuin 1 (SIRT1) is a class III histone deacetylase that may play a critical role in several biological functions, including lifespan, stress, and inflammation. Our main objective was to evaluate SIRT1 activity in peripheral blood mononuclear cells (PBMCs) in patients with osteoporosis and to analyze the relationship between the SIRT 1 activity and markers of inflammation and bone remodelling. MATERIAL AND METHODS We performed a prospective monocentric study of patients with osteoporosis and measured the nuclear and cytoplasmic activities of SIRT1 in PBMCs. Levels of proinflammatory cytokines were assessed in culture supernatants of PBMCs isolated from the osteoporosis patients. The level of serum C-terminal cross-linking telopeptide of type I collagen (CTX), a marker of bone resorption, was measured in the serum of osteoporosis patients. RESULTS Sixteen women with osteoporosis were included. A statistically significant correlation between the cytoplasmic and nuclear SIRT 1 activities was found in PBMCs of patients with osteoporosis. Although non-significant, we observed a negative trend between nuclear SIRT 1 activity and the rate of serum CTX and a positive trend between IL-6 and CTX levels in patients with osteoporosis. CONCLUSIONS This study shows that the cytoplasmic and nuclear SIRT 1 activities are measurable in circulating PBMCs of patients with osteoporosis and that these 2 activities are correlated. The potential role of inflammation in bone resorption in patients with osteoporosis was also studied.

Abstract: Background Comorbid neurobehavioral disturbances and type-2 diabetes mellitus (T2DM) warrant immediate research attention. Exenatide, which is a potent and selective agonist for the glucagon-like peptide-1 (GLP-1), is used in the treatment of T2DM. Exenatide displays a multitude of effects in the central nervous system. The aim of this study was to investigate the anxiolytic- and antidepressant-like effects and analgesic effects of exenatide in a type-2 diabetic mouse model.

Abstract: Background This study aimed to investigate the expression and significance of 5 types of miRNAs in breast cancer to provide a theoretical and practical foundation for using these miRNAs in the diagnosis and treatment of breast cancer, thereby improving medical services.