- Role of AMPK in the expression of tight junction proteins in heat-treated porcine Sertoli cells. [Journal Article]
- TTheriogenology 2018 Aug 11; 121:42-52
- Hyperthermia can cause dysfunction of the tight junctions (TJs) in testes. Adenosine 5'-monophosphate-activated protein kinase (AMPK) participates in the regulation of TJs in testis. However, whether...
Hyperthermia can cause dysfunction of the tight junctions (TJs) in testes. Adenosine 5'-monophosphate-activated protein kinase (AMPK) participates in the regulation of TJs in testis. However, whether AMPK regulates the expression of TJ proteins in the response of Sertoli cells to heat treatment remains unknown. We subjected Sertoli cells from 3-week-old piglets to heat treatment (43 °C, 30 min), which decreased cell viability, and increased the early apoptosis rate. These effects were reversible and the cells gradually recovered to normal viability at 48 h post-heat treatment. Expression of TJ proteins (claudin 11, JAMA, occludin, and ZO1) was detected in immature porcine Sertoli cells. The mRNA and protein levels of TJ proteins significantly decreased at 1 h after heat exposure, but recovered with increasing recovery time. Additionally, the expression of claudin 11 in the cytoplasm was also markedly decreased by heat treatment. AMPK phosphorylation, the cellular ATP level, and Ca2+/calmodulin-dependent protein kinase kinase B (CaMKKB) level, but not the liver kinase B1 (LKB1) level, were downregulated by heat treatment. More importantly, activation or overexpression of AMPK, which is a regulator of the assembly of TJs, partially rescued the heat treatment-induced downregulation of TJ proteins. By contrast, AMPK knockdown using small interfering RNA (siRNA) further decreased the expression levels of TJ proteins. In addition, claudin 11 was almost undetectable post heat treatment. Collectively, this study demonstrated that heat treatment could reversibly perturb the expression of TJ proteins in immature porcine Sertoli cells by inhibiting the AMPK signaling pathway.
- Involvement of serotonergic and relaxin-3 neuropeptide systems in the expression of anxiety-like behavior. [Journal Article]
- NNeuroscience 2018 Aug 17
- Anxiety-related defensive behavior is controlled by a distributed network of brain regions and interconnected neural circuits. The dorsal raphe nucleus (DR), which contains the majority of forebrain-...
Anxiety-related defensive behavior is controlled by a distributed network of brain regions and interconnected neural circuits. The dorsal raphe nucleus (DR), which contains the majority of forebrain-projecting serotonergic neurons, is a key brain region involved in fear states and anxiety-related behavior via modulation of this broad neural network. Evidence suggests that relaxin-3 neurons in the nucleus incertus (NI) may also interact with this network, however, the potential role of the NI in the control of anxiety-related defensive behavior requires further investigation. In this study, we examined the response of an anxiety-related neuronal network, including serotonergic neurons in the DR and relaxin-3-containing neurons in the NI, to administration of an anxiogenic drug and exposure to an aversive environment. We administered an anxiogenic dose of the adenosine receptor antagonist, caffeine (50 mg/kg, i.p.), or vehicle, to adult male Wistar rats and 30 min later exposed them to either an elevated plus-maze (EPM) or a home-cage environment. Administration of caffeine and exposure to the EPM activated a broad network of brain regions involved in control of anxiety-like behaviors, including serotonergic neurons in the DR, as measured using c-Fos immunohistochemistry. However, only exposure to the EPM activated relaxin-3-containing neurons in the NI, and activation of these neurons was not correlated with changes in anxiety-like behavior. These data suggest activation of the NI relaxin-3 system is associated with expression of behavior in tests of anxiety, but may not be directly involved in the approach-avoidance conflict inherent in anxiety-related defensive behavior in rodents.
- Simethicone is retained in endoscopes despite reprocessing: impact of its use on working channel fluid retention and adenosine triphosphate bioluminescence values (with video). [Journal Article]
- GEGastrointest Endosc 2018 Aug 17
- CONCLUSIONS: Use of medium/high concentration simethicone is associated with retention of increased fluid droplets and higher ATP bioluminescence values in endoscope working channels, compared with endoscopes in which water or low concentration simethicone was used. However, simethicone is detectable in endoscopes despite reprocessing, even when used in low concentration. Our data suggest that when simethicone is used, it should be used in the lowest concentration possible. Facilities may consider 2 AER cycles for reprocessing of endoscopes when simethicone has been used.
- Pre-clinical pharmacodynamic study of a novel oral factor Xa inhibitor zifaxaban. [Journal Article]
- EJEur J Pharmacol 2018 Aug 17
- Zifaxaban is an orally active, direct Factor Xa (FXa) inhibitor that is in development for the prevention and treatment of arterial and venous thrombosis. This study was conducted to investigate the ...
Zifaxaban is an orally active, direct Factor Xa (FXa) inhibitor that is in development for the prevention and treatment of arterial and venous thrombosis. This study was conducted to investigate the biochemical and pharmacological activity of zifaxaban. In vitro activity was evaluated by enzyme, platelet aggregation, and clotting assays. In vivo effects were examined in venous thrombosis, arteriovenous-shunt thrombosis, carotid thrombosis, and bleeding models in rats. Zifaxaban competitively inhibits human FXa (IC50 = 11.1 nM) with > 10,000-fold greater selectivity than other serine proteases. It did not impair platelet aggregation induced by collagen, adenosine diphosphate (ADP) or arachidonic acid. It significantly prolonged clotting time, prothrombin time (PT), and activated partial thromboplastin time (APTT) in the plasma of humans, rabbits, and rats, with a relatively weak effect on thrombin time (TT). In venous thrombosis models in rats, zifaxaban strongly suppressed thrombus formation with ED50 values of 3.09 mg/kg, and its best efficacy time occurred at 2 h after administration. In arteriovenous-shunt thrombosis and carotid thrombosis models in rats, it inhibited thrombus formation in a dose-dependent manner. And in the rat tail bleeding assay, it showed a trend of less bleeding than rivaroxaban at doses that achieved the same antithrombotic effect. In conclusion, zifaxaban is a selective and direct FXa inhibitor and a promising oral anticoagulant for the prophylaxis and treatment of thromboembolic diseases.
- Intravenous Regadenoson with Aminophylline Reversal is Safe and Equivalent to Intravenous Adenosine Infusion for Fractional Flow Reserve Measurements. [Journal Article]
- CCClin Cardiol 2018 Aug 19
- CONCLUSIONS: For FFR measurement, regadenoson and adenosine are equivalent hyperemic agents. Regadenoson with aminophylline reversal may be considered as an alternative to adenosine for FFR measurements. This article is protected by copyright. All rights reserved.
- "On-off-on" Photoelectrochemical/Visual Lab-on-Paper Sensing via Signal Amplification of CdS Quantum Dots@Leaf-Shape ZnO and Quenching of Au Modified Prism-Anchored Octahedral CeO2 Nanoparticles. [Journal Article]
- ACAnal Chem 2018 Aug 20
- An effective "on-off-on" photoelectrochemical (PEC)/visual sensing system based on cleaning-switchable lab-on-paper device was designed to achieve ultrasensitive detection of analytes. The first ampl...
An effective "on-off-on" photoelectrochemical (PEC)/visual sensing system based on cleaning-switchable lab-on-paper device was designed to achieve ultrasensitive detection of analytes. The first amplified ''signal on'' PEC state was gained by CdS quantum dots sensitized leaf-shape ZnO (CdS QDs/leaf-shape ZnO) structure, which was assembled on reduced graphene oxide (rGO) modified paper electrode. Then Au modified prism-anchored octahedral CeO2 nanoparticles (Au@PO-CeO2 NPs), as an efficient signal quencher, were immobilized on the CdS QDs/leaf-shape ZnO with the assistance of DNA hybridization, resulting in a noticeably photocurrent response decrement with the ''signal off'' PEC state. With the addition of analytes, the quencher Au@PO-CeO2 NPs were immediately released from the sensing surface and robust PEC response was recovered to the "signal on" state again. Meanwhile, the disengaged quencher in electrolyte solution flowed to the colorimetric detection area of lab-on-paper device and catalyzed oxidation of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine in the presence of H2O2 to form the colored product, making the analytes detection more convincing with the visual discrimination. Under optimal conditions, the proposed PEC/visual lab-on-paper device possessed the detection limits toward adenosine and potassium ion as low as 0.15 nM and 0.06 nM respectively. With ingenious design of actuating conversion process between hydrophilicity and hydrophobicity by slipping paper tab to solve cleaning issue in the assay procedures, the cleaning-switchable lab-on-paper device was constructed for high-performance biosensing applications. It provides an unambiguous simplicity and portable operation for exploring high reliability and sensitivity of novel point-of-care diagnostic tool with dual-signal readout.
- Mechanisms Underlying the Clinical Effects of Apremilast for Psoriasis. [Journal Article]
- JDJ Drugs Dermatol 2018 Aug 01; 17(8):835-840
- Psoriasis is a chronic, systemic, inflammatory disease with manifestations resulting from a dysregulated immune response. In psoriatic skin, expression of all phosphodiesterase 4 (PDE4) isoforms (A-D...
Psoriasis is a chronic, systemic, inflammatory disease with manifestations resulting from a dysregulated immune response. In psoriatic skin, expression of all phosphodiesterase 4 (PDE4) isoforms (A-D), part of a family of enzymes known to regulate cyclic adenosine monophosphate levels and immune homeostasis, is elevated compared with healthy controls. Agents that inhibit the enzymatic activity of PDE4, the predominant PDE in most immune cells, exert well-recognized anti-inflammatory effects. Apremilast is a selective PDE4 inhibitor approved for the treatment of adults with moderate to severe plaque psoriasis and/or psoriatic arthritis. In vitro and in vivo investigations have demonstrated the beneficial impact of apremilast treatment on PDE4 activity, inflammatory signal expression, and dermal psoriasiform signs. In patients with moderate to severe psoriasis, treatment with apremilast is associated with significant reductions in plasma levels of interleukin (IL)-17F, IL-17A, IL-22, and tumor necrosis factor-α compared with placebo as early as week 4; decreases in cytokine levels were sustained with continued treatment. Multivariate analyses demonstrated that while changes in IL-17F are the most important predictor of improvement in Psoriasis Area and Severity Index scores, apremilast exerts synergistic attenuating effects among a key group of cytokines involved in the pathology of psoriasis, and these effects correlate with improved skin symptoms. These in vitro and clinical data demonstrate that the beneficial effects of apremilast on known inflammatory mediators are associated with its clinical efficacy. J Drugs Dermatol. 2018;17(8):835-840. <p>THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.</p>.
- Goal Directed Platelet Transfusions Correct Platelet Dysfunction and May Improve Survival in Patients with Severe Traumatic Brain Injury. [Journal Article]
- JTJ Trauma Acute Care Surg 2018 Aug 17
- Platelet dysfunction, defined as adenosine diphosphate (ADP) inhibition greater than 60% on thromboelastogram (TEG), is an independent predictor of increased mortality in patients with severe traumat...
Platelet dysfunction, defined as adenosine diphosphate (ADP) inhibition greater than 60% on thromboelastogram (TEG), is an independent predictor of increased mortality in patients with severe traumatic brain injury (TBI). We changed our practice to transfuse platelets for all patients with severe TBI and platelet dysfunction. We hypothesized that platelet transfusions would correct platelet dysfunction and improve mortality in patients with severe TBI.
- Emerging and alternative therapies for Parkinson disease: an updated review. [Journal Article]
- CPCurr Pharm Des 2018 Aug 20
- Parkinson's disease (PD) is one of the most common neurodegenerative disorder with intricate progressive pathology. Currently, available conventional options for PD have certain limitations of their ...
Parkinson's disease (PD) is one of the most common neurodegenerative disorder with intricate progressive pathology. Currently, available conventional options for PD have certain limitations of their own, and as a result, patient compliance and satisfaction are low. Current contemporary treatment options provide only symptomatic relief with limited control to prevent disease progression, resulting in poor patient compliance and satisfaction. Several emerging pharmacotherapies for PD are in different stages of clinical development. These therapies include adenosine A2A receptor antagonists, glutamate receptor antagonists, monoamine oxidase inhibitors, anti-apoptotic agents, and antioxidants such as coenzyme Q10, N-acetyl cysteine, and edaravone. Other emerging nonpharmacotherapies include viral vector gene therapy, microRNAs, transglutaminases, RTP801, stem cells and glial-derived neurotrophic factor (GDNF). In addition, surgical procedures including deep brain stimulation, pallidotomy, thalamotomy and gamma knife surgery have emerged as alternative interventions for advanced PD patients who have completely utilized standard treatments and still suffer from persistent motor fluctuations. Complementary and Alternative medicine (CAM) modalities such as Yoga, acupuncture, Tai Chi, music therapies etc. are highly practiced in several countries, offer some of the safer and effective treatment modalities for PD. While several of these therapies hold much promise in delaying the onset of the disease and slowing its progression, more pharmacotherapies and surgical interventions need to be investigated in different stages of PD. It is hoped that these emerging therapies and surgical procedures will strengthen our clinical armamentarium for improved treatment of PD.
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- Cordycepin modulates body weight by reducing prolactin via an adenosine A1 receptor. [Journal Article]
- CPCurr Pharm Des 2018 Aug 20
- Cordycepin is an extract from the insect fungus Cordyceps. militaris with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the me...
Cordycepin is an extract from the insect fungus Cordyceps. militaris with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the mechanism is unclear. Evidences also showed that prolactin played an important role in body weight regulation, hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin. In vivo, obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupled with serum prolactin were reduced by treatment of cordycepin (P＜0.01) , the results suggested that cordycepin is a potential drug for lowering blood and liver lipids and reducing body weight which related with prolactin. Cordycepin also protects adipocytes from enlargement and hepatocytes from lipotoxicity caused inflammation. In vitro, cordycepin could inhibit prolactin secretion in GH3 cells via upregulating the expression of adenosine A1 receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, which demonstrated that cordycepin may work as an adenosine agonist. In addition, cordycepin could inhibit ERK/AKT/PI3K pathway in GH3 cells. Meanwhile, cordycepin could block prolactin induced the upregulation of lipogenesis genes PRLR, and phosphorylation of JAK2 in 3T3-L1 cells. In vivo study, cordycepin would down-regulate the expression of prolactin receptor (PRLR) but not phosphorylation of JAK2. Thus, we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine A1 receptor.