Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis C virus infection: Molecular pathways to metabolic syndrome

Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype‐dependent fashion, thus contributing to steatosis, progression of fibrosis and resistance to interferon therapy. The molecular mechanisms in genotype 1 patients that lead to metabolic syndrome are still ambiguous. Based on our current understanding, HCV proteins associate with mitochondria and endoplasmic reticulum and promote oxidative stress. The latter mediates signals involving the p38 mitogen‐activated protein kinase and activates nuclear factor kappa B. This transcription factor plays a key role in the expression of cytokines, tumor necrosis factor alpha (TNF‐α), interleukin 6, interleukin 8, tumor growth factor beta, and Fas ligand. TNF‐α inhibits the function of insulin receptor substrates and decreases the expression of the glucose transporter and lipoprotein lipase in peripheral tissues, which is responsible for the promotion of insulin resistance. Furthermore, reduced adiponectin levels, loss of adiponectin receptors, and decreased anti‐inflammatory peroxisome proliferator‐activated receptor alpha in the liver of HCV patients may contribute to reduced fatty acid oxidation, inflammation, and eventually lipotoxicity. This chain of events may be initiated by HCV‐associated IR and provides a direction for future research in the areas of therapeutic intervention. (HEPATOLOGY 2008.)
The Role of Tyrosine Phosphorylation of Cortactin in the Locomotion of Endothelial Cells*

Cortactin, a filamentous actin cross-linking protein and a substrate of Src protein tyrosine kinase, is phosphorylated at tyrosine residues upon stimulation by extracellular signals. We have previously demonstrated that the filamentous actin cross-linking activity of cortactin is attenuated by Src (Huang, C., Ni, Y., Gao, Y., Haudenschild, C. C., and Zhan, X. (1997) J. Biol. Chem. 272, 13911–13915). In vitro, tyrosine phosphorylation of cortactin occurs specifically within the region between the proline-rich sequence and the Src homology 3 domain. Among the nine tyrosine residues in this region, mutations at Tyr421, Tyr466, and Tyr482significantly reduced Src-meditated tyrosine phosphorylation bothin vitro and in vivo. Ectopic expression of wild-type cortactin in ECV304, a spontaneously transformed human umbilical endothelial cell line, resulted in an enhanced cell migration. In contrast, overexpression of a cortactin mutant deficient in tyrosine phosphorylation impaired the migration of endothelial cells. These findings reveal an intracellular signaling mechanism whereby the motility of endothelial cells is regulated by a Src-mediated tyrosine phosphorylation of cortactin.
Biological active compounds from Georgian Galanthus shaoricus.

Amaryllidaceae alkaloids exhibit antitumour, antiviral and anticholinergic activities. Some of them have been used in the treatment of myasthenia gravis, myopathy and diseases of the nervous system. In this study, the characterization of these compounds from Amaryllidaceae plants along with some biological activities and some regulations to conserve the native flora will be reviewed. Plants materials: Galanthus shaoricus Kem. -Nath. , were collected in 2007-2008 during the flowering period in Georgia. The preparation of extracts and fractions were obtained using methanolic maceration. Crude alkaloidal extracts were typically puriﬁed by liquid-liquid partitioning of their basic forms in chloroform. Lycorine, galantamine and tazettine has been found as one of the major alkaloid from Amaryllidaceae plants. Galanthus shaoricus have shown good antimalarial and cytotoxic activity in a dose-dependent manner. Methanolic extracts from bulbs demonstrated significant growth inhibition on human Hela and HCT-116 cells lines with IC50 (μg/mL) 16.3±1.8; 22.1±2.9 (aerial parts) and 12.8±1.7; 16.5±1.9 (Bulbs), respectively. Concerning the Amaryllidaceae alkaloids, lycorine with IC50 (μM) 0.8±0.5 and 2.6±0.2, haemantaimene (IC50=1.1±0.7 and 2.7±0.8 μM), hamaine (IC50=3.4±1.0 and 6.2 ±1.4 μM), homolycorine (IC50=1.4±0.9 and 3.3±1.0 μM), hipeastrine (IC50=2.8±1.0 and 7.5±1.8 μM) were found to be responsible for the cytotoxic activity on HCT-116 and Hela cell lines, respectively.
Coordinated Hybrid Beamforming for Millimeter Wave Multi-User Massive MIMO Systems

Massive Millimeter Wave (mmWave) Multiple Input Multiple Output (MIMO) systems utilize hybrid beamforming techniques to alleviate the implementation complexity of combining a large number of antennas. To solve the optimization problem in the hybrid design supporting multiple users and multiple data streams per user, we first propose a coordinated Radio Frequency (RF) beamforming technique based on the Generalized Low Rank Approximation of Matrices (GLRAM) approach and then develop an efficient Modified GLRAM (MGLRAM) algorithm. The proposed scheme only requires the information of the composite channel, instead of the complete physical channel matrix which is assumed to be known in the existing literature. It takes advantage of the coordination between the base station and users to achieve a maximal array gain and has no dimensionality constraint. The multiplexing gain is then exploited by applying the Block Diagonalization (BD) technique. It is shown that our proposed scheme is a practical and competing solution, which can be easily applied to both the Time Division Duplex (TDD) and Frequency Division Duplex (FDD) systems.
The efficacy of steroids for edema and ecchymosis after Rhinoplasty: A meta‐analysis

Postoperative periorbital edema and ecchymosis following rhinoplasty can result in dissatisfaction for both the surgeon and the patient. The goal of this study was to perform a systematic review of the literature on the efficacy of steroids on edema and ecchymosis during rhinoplasty.
Pathogenesis and Management of Macular Hole: Review of Current Advances

Macular hole has been believed to be a disorder of vitreomacular interface, which forms as a result of abnormal vitreous traction from incomplete vitreous detachment. However, our recent studies demonstrated that dynamic forces, caused by mobile posterior cortical vitreous with fluid currents, exist already at early stages of macular hole development. Therefore, in eyes with flexible vitreous, the contributions of tractional forces due to vitreous shrinkage are unlikely. These facts indicate that in the development of idiopathic macular holes, there is a greater contribution of dynamic forces than has been previously reported. This review also evaluates the recent findings in the assessment of the idiopathic macular holes and the recent therapeutic strategies for optimal management. Inner limiting membrane is considered to improve anatomical closure rate; however, it is still questionable if peeling is necessary in holes less than 250 µm. There are plenty of publications indicating that in the management of small and medium size hole (less than 400 µm), use of long-lasting gas and face-down position is not always required; however, it may be necessary for the treatment of large holes. Ocriplasmin and expansile gas had been reported to be successful for management of small- and medium-sized holes and vitreomacular attachment.
Smart Wireless Impulse Radio Sensor Networks

This paper introduces the work performed towards an impulse radio wireless sensor network system. An overview of the fundamentals of the system is reported, from concept sections including applications and requirements, to the design and development of the hardware platform, networking protocols or routing algorithms. The low power, size and cost are key requirements influencing the whole system definition. An initial complete prototype has been designed, implemented and tested with Zigbee PHY. This has set the bases for the current Impulse Radio Sensor Network under development, for which the PHY has been designed and developed.
Processing heterogeneous biomass: Overcoming the hurdles in model building

Plants have been developed as an alternative platform for the production of biopharmaceutical proteins, culminating recently with the FDA approval of the first plant-derived recombinant pharmaceutical enzyme for human use (ELELYSOÔ by Protalix Biotherapeutics). Among the many different plant-based technologies that have been proposed, transient expression mediated by Agrobacterium tumefaciens has proven to be particularly suitable for the rapid production of vaccines in response to emerging pandemics. However, one potential drawback of transient expression in whole plants is the large variation in recombinant protein expression levels among different leaves, which introduces a level of uncertainty in process design that can increase the regulatory burden and production costs. Transient expression is also used to test expression constructs prior to the longer and more expensive process of generating transgenic plants, and here the variation can produce misleading results leading to erroneous conclusions about the relative activity of different promoters and other regulatory elements. Such variation can be caused by loosely controlled environmental and process factors such incubation temperature, plant characteristics and the method and timing of harvesting. Here we discuss differences between transgenic plants and transient expression in intact plants, and their specific pitfalls for model building. We also highlight which aspects researchers should consider when using a DoE approach to investigate protein expression in plants, both for fundamental research and process development.
Ginsenoside Rg1 inhibits inflammatory responses via modulation of the nuclear factor-κB pathway and inhibition of inflammasome activation in alcoholic hepatitis

Ginsenoside Rg1 (G-Rg1) is an active ingredient of Panax ginseng, which has previously been reported to attenuate alcohol-induced hepatic damage; however, the underlying mechanisms remain largely unknown. The present study aimed to investigate the protective effects of G-Rg1 on alcohol-induced cell injury in vitro and on a rat model of alcoholic hepatitis in vivo. For the in vitro model, L-O2 cells were incubated with ethanol in the presence or absence of G-Rg1. For the in vivo model, rats were administered ethanol by intragastric injection and were treated with G-Rg1, or dexamethasone as a control. The results indicated that serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase and total bilirubin, as well as the expression of nuclear factor (NF)-κB pathway-associated inflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α and IL-1β, were elevated in response to alcohol; however, they were significantly decreased by G-Rg1 treatment. Furthermore, NF-κB pathway activation was reduced by treatment with G-Rg1. G-Rg1 also decreased oxidative stress by inhibiting cytochrome P450 2E1 expression and reactive oxygen species production, and promoting glutathione peroxidase expression. Furthermore, G-Rg1 inhibited the expression levels of caspase-3 and -8, which may be associated with decreased hepatocyte apoptosis. These data suggested that G-Rg1 may protect hepatocytes against alcohol-induced injury, through preventing excessive inflammation and hepatocellular apoptosis.
Studies on the closure of the ductus arteriosus. IX. Transitory effect of phenoxybenzamine on ductal closure in the guinea-pig.

The effect of phenoxybenzamine on the closure of the ductus arteriosus in the guinea-pig was studied by means of the whole-body freezing technique. Foetuses were injected intraperitoneally with 1 mg phenoxybenzamine 10 minutes before surgical delivery and sacrified 10 or 30 minutes later. A delay in ductal closure was observed 10 minutes but not 30 minutes after delivery. The observation suggests that ductal closure in the guinea-pig is not solely mediated through the α-adrenergic, cholinergic or histamine receptors.
Benefit of nanocarrier of magnetic magnesium in rat malathion-induced toxicity and cardiac failure using non-invasive monitoring of electrocardiogram and blood pressure

Medical management in acute organophosphate (OP) poisoning is not always successful because of tissue hypoxia which results in a reduction of heart contractility and cell damage. This study reports improvement of malathion (MAL)-induced cardiac failure by a nanocarrier of magnetic isotope of Mg (PMC16). A rat model of acute MAL poisoning was set up. PMC16 nanoparticle at doses of 0.05, 0.1, 0.2 LD50 = 896 mg/kg) were administered intravenously (iv) 30 minutes after a single intraperitoneal (ip) injection of MAL (0.25 LD50= 207 mg/kg). Atropine (AT; 40 mg/kg, ip) plus pralidoxime (PAM; 40 mg/kg, ip) and magnesium sulfate (MgSO 4; 600 mg/kg, iv) were used as standard therapy or controls. Anesthetized animals were monitored for heart rate, electrocardiogram, blood pressure, and blood oxidative stress biomarkers like cellular lipid peroxidation, total thiol molecules, antioxidant power, gamma glutamil transpeptidase, and acetylcholinesterase (AChE) as a marker of OP toxicity. Results indicated that after MAL administration, heart rate and BP decreased and R-R duration increased. PMC16 markedly restored BP at all doses as compared with MgSO4. PMC16 at the dose of 0.05 LD50 significantly increased BP in comparison to AT + PAM. PMC16 restored heart rate at dose of 0.2 LD50 and reduced lipid peroxidation at dose of 0.05 LD50 as compared to MgSO4. PMC16 also improved total antioxidant power at all doses when compared to AT + PAM and reduced GGT activity at dose of 0.2 LD50 but did not affect total thiol molecules. MgSO4 could improve MAL-induced reduction of total antioxidant power. After 24 h, PMC16 significantly improved MAL-suppressed AChE activity at doses of 0.05 and 0.1 LD50. PMC16 at all doses significantly recovered MAL-induced arrhythmia when compared to standard therapies. It is concluded that PMC16 is able to control OP-induced cardiac failure and toxicity.
Anthrax Lethal Toxin Inhibits Growth of and Vascular Endothelial Growth Factor Release from Endothelial Cells Expressing the Human Herpes Virus 8 Viral G Protein–Coupled Receptor

Purpose: In this study, we tested the hypothesis that inhibition of mitogen-activated protein kinase kinases (MKK) inhibits tumor growth by acting on angiogenic signaling and by extension may form the basis of an effective strategy for treatment of Kaposi's sarcoma. Experimental Design: Murine endothelial cells expressing the human herpes virus 8 G protein–coupled receptor (vGPCR-SVEC) were treated with anthrax lethal toxin (LeTx). LeTx is a binary toxin ordinarily secreted by Bacillus anthracis and is composed of two proteins: protective antigen (the binding moiety) and lethal factor (the active moiety). Lethal factor is a protease that cleaves and inactivates MKKs. Results:In vitro, treatment of vGPCR-SVEC with LeTx inhibited MKK signaling, moderately inhibited cell proliferation, and blocked the ability of these cells to form colonies in soft agar. Treatment with LeTx also blocked the ability of these cells to release several angioproliferative cytokines, notably vascular endothelial growth factor (VEGF). In contrast, inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 with U0126 caused a substantial inhibition of proliferation but only modestly inhibited VEGF release. In xenograft models, i.v. injection of LeTx caused reduced tumor growth characterized immunohistochemically by inhibition of MKK signaling, decreased rates of proliferation, and reduced levels of VEGF and VEGF receptor 2, with a corresponding decrease in vascular density. Conclusions: These data support a role for MKK signaling in tumor growth and vascularization and are consistent with the hypothesis that inhibition of MKK signaling by LeTx or a similar agent may be an effective strategy for the treatment of Kaposi's sarcoma as well as other vascular tumors.
Prevalence and Correlates of HIV Testing Among Sexually Active African American Adolescents in 4 US Cities

Background: Routine HIV testing is recommended for all adolescents ages 13 years and older. This study aims to report the prevalence of HIV testing among black adolescents, describe characteristics of adolescents who have been tested, and identify potentially modifiable factors associated with greater likelihood of testing across gender. Methods: Black adolescents ages 13 to 18 were recruited from community-based outreach in 4 US cities. Present analyses include sexually active participants (N = 990; 52.3% female). Results: Twenty-nine percent of adolescents had ever been tested for HIV. In a multivariate logistic regression adjusted for significant demographics, the strongest predictor of HIV testing among girls was prior STI testing (OR = 88.39) followed by pregnancy (OR = 2.75), risk reduction self-efficacy (OR = 2.28), and STI knowledge (OR = 2.25). Among boys, having had an STI test (OR = 38.09), having talked about testing with partners (OR = 3.49), and less religiosity (OR = 2.07) were associated with HIV testing. Conclusions: Blacks adolescents are disproportionately at risk for HIV/AIDS, yet less than one-third of participants reported being tested. Those receiving sexual or reproductive healthcare services were most likely to be tested, but many teens at risk for HIV do not seek available services and others may face barriers to accessing healthcare. Findings provide support for increasing school-based educational programs due to the low rates of STI/HIV knowledge among teens. Additionally, culturally-sensitive programs promoting HIV testing among teens should foster skill-building for preventive behaviors and increase partner communication about testing.
Overexpression of apolipoprotein B attenuates pathologic cardiac remodeling and hypertrophy in response to catecholamines and after myocardial infarction in mice

Introduction. The heart produces apolipoprotein (apo) B-containing lipoproteins which enables cardiac export of potentially cardiotoxic lipids. We hypothesized that overexpression of apoB attenuates the pathologic cardiac remodeling and hypertrophic response following pathological stimuli such as chronic adrenergic overstimulation and myocardial infarction (MI). Methods. Cardiac hypertrophy was induced by a chronic infusion of isoproterenol (ISO) 15 mg/kg/day for 3 weeks in human apoB transgenic mice (n = 9) and in non-transgenic wild-type mice (n = 10). As controls, apoB transgenic (n = 10) and wild-type mice (n = 10) saline infusions were used. Transthoracic echocardiography was performed at baseline and after 3 weeks of treatment to evaluate left ventricular (LV) function and morphology. To investigate the effects of expression on postinfarct hypertrophic response we induced MI in apoB transgenic mice (n = 8) and in wild-type controls (n = 11). The hearts were explanted and weighed 6 weeks post MI. Results. At baseline, WT mice had higher BW and LV mass (LVM) compared to the apoB mice. The increase in LV mass and dimensions after 3 weeks of treatment with ISO was significantly lower while systolic function was significantly better in the apoB group. Six weeks post MI the apoB mice had significantly lower heart weight and heart weight to body weight ratio. The infarct size was similar in both groups. Conclusion. Overexpression of apoB attenuates the pathologic remodeling and hypertrophic response to chronic adrenergic stimulation and MI. Our results indicate that cardiac expression of apoB-containing lipoproteins might be an important regulator of myocardial structure and function.
Neuroprotective effect of recombinant human erythropoietin in experimental subarachnoid hemorrhage.

BACKGROUND Acute cerebral vasoconstriction and subsequent brain ischemia, often occurring in the early phase of subarachnoid hemorrhage (SAH), are critical problems in the management of patients affected by ruptured intracranial aneurysms. It is known that nitric oxide (NO) decreases during SAH with impairment of cerebrovascular relaxation, and glutamate is mainly involved in the consequent brain ischemic damage. Recently, erythropoietin (EPO) has shown to exert a neuroprotective effect during cerebral ischemia by enhancing the NO system activity. In the present study the effect of systemic administration of recombinant human erythropoietin (rHuEPO) has been investigated in a rabbit model of SAH. METHODS Thirty-two rabbits were assigned to four groups: 1) Control; 2) SAH; 3) SAH plus placebo; 4) SAH plus rHuEPO. Experimental SAH was induced by injecting autologous blood into the cisterna magna. rHuEPO, at a dose of 1000 IU/kg, and placebo were given 5 minutes after SAH. Administration was repeated three times during 24 hours. The animals were killed 24 hours after SAH by a perfusion-fixation method. Luminal cross-sections of the basilar artery were measured by computer-assisted morphometric analysis. Ischemic injury was histologically evaluated by analysis of the frequency of ischemia-induced damaged cortical neurons. RESULTS Administration of rHuEPO significantly reversed the vasoconstriction of the basilar artery in Group 4 compared with the other groups (p<0.05). Histological examination showed a significant reduction in total damaged neurons count in Group 4 compared with the other groups (p<0.01). CONCLUSIONS These results suggest that rHuEPO is effective in attenuating acute cerebral vasoconstriction and ischemic brain injury following experimental SAH.
Health Care Market Reform in Congress: The Uncertain Path from Proposal to Policy

In 1980 Ronald Reagan swept into the presidency on a wave of antigovernment sentiment after promising deregulation, decentralization, and restoration of individual responsibility and opportunity. This pro-competitive, antiregulatory temperament was captured in legislative proposals to stimulate competition in the financing and delivery of health services.1 In the 96th and 97th Congresses from 1979 to 1983, several bills were introduced to create financial incentives to expand consumer choice in purchasing health services, induce greater price competition among health care professionals and institutions, improve efficiency in the organization and delivery of services, and ultimately lower the costs of health care. The moment appeared ripe for an earnest attempt at structural reform of the health care system: national health care expenditures continued to increase at a pace well above the costs of other consumer goods and services, with ho-spital expenditures leading the way. The highly regulatory hospital cost containment program offered by President Jimmy Carter had gone down to defeat in 1979.
Which of the direct acting anti-viral agents is the better drug in terms of efficacy, cost and safety, Boceprevir or Telaprevir?

Objective: Hepatitis C virus can cause chronic hepatitis with 20-30% of those infected are developing liver cirrhosis and some developing hepatocellular carcinoma. It is a global health problem with 130-170 million people infected worldwide. The current treatment uses pegylated interferon and Ribavirin. As of 2011, two new drugs have been approved in the U.S.A and Europe, the protease inhibitors Boceprevir and Telaprevir. The aim of this structured review is to investigate which of these two new drugs is better in terms of efficacy, safety and cost. A literature search was conducted using various primary and secondary sources. A database search was conducted to find three journals for critical review. Conclusion: The articles showed that the two drugs are equally effective and more effective than standard therapy. Boceprevir is potentially significantly cheaper. Boceprevir may also have a slightly better adverse effects profile. However, it is evident that direct clinical trials comparing the two drugs are required.