Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.     

D-limonene Inhibits Pentylenetetrazole-Induced Seizure via Adenosine A2A Receptor Modulation on GABAergic Neuronal Activity

Background: Epilepsy is a chronic neurological disorder characterized by the recurrence of seizures. One-third of patients with epilepsy may not respond to antiseizure drugs. Purpose: We aimed to examine whether D-limonene, a cyclic monoterpene, exhibited any antiseizure activity in the pentylenetetrazole (PTZ)-induced kindling mouse model and in vitro. Methods: PTZ kindling mouse model was established by administering PTZ (30 mg/kg) intraperitoneally to mice once every 48 h. We performed immunoblot blots, immunohistochemistry (IHC), and high-performance liquid chromatography (HPLC) analysis after the behavioral study. Results: An acute injection of PTZ (60 mg/kg) induced seizure in mice, while pretreatment with D-limonene inhibited PTZ-induced seizure. Repeated administration of PTZ (30 mg/kg) increased the seizure score gradually in mice, which was reduced in D-limonene (10 mg/kg)-pretreated group. In addition, D-limonene treatment increased glutamate decarboxylase-67 (GAD-67) expression in the hippocampus. Axonal sprouting of hippocampal neurons after kindling was inhibited by D-limonene pretreatment. Moreover, D-limonene reduced the expression levels of Neuronal PAS Domain Protein 4 (Npas4)-induced by PTZ. Furthermore, the adenosine A2A antagonist {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261 and ZM241385 inhibited anticonvulsant activity and gamma-aminobutyric acid (GABA)ergic neurotransmission-induced by D-limonene. Conclusion: These results suggest that D-limonene exhibits anticonvulsant activity through modulation of adenosine A2A receptors on GABAergic neuronal function.     

偏振CARS研究核苷分子振动结构

用偏振灵敏ＣＡＮＳ光谱研究尿嘧啶、胸腺嘧啶、胞嘧啶和腺嘌呤四种核苷分子的振动结构。谱的非共振背景被有效地消除，核苷的双键振动模清晰可辨，对每种核苷分子的特征谱线进行了标识，作为在生物分子中识别它们的标志。     

Adsorption des acides humiques sur charbon active en poudre. Influence du triphosphate de sodiumAdsorption of humic acids onto powdered activated carbon. The influence of sodium triphosphate

The use of activated carbon beds for the removal of natural humic and fulvic substances found in water supplies, has recently received considerable attention in water treatment operation (Lee et al., 1980; Le Cloirec et al., 1983). Moreover, the use of carbon adsorption for the reduction of haloform precursors (Anderson et al., 1981) and trihalomethanes produced by chlorination process, has contributed to a comprehensive investigation of adsorption characteristics of natural organic compounds (McCreary and Snoeyink, 1981). Many recent works showed the influence of adsorption system characteristics, such as pH, salt type, salt concentration and ionic heterogeneity in multicomponent adsorption systems, on the removal efficiency of humic and fulvic substances by activated carbon (McCreary and Snoeyink, 1980; Randtke and Jepsen, 1982; Weber et al., 1983). The purpose of this study is to examine the effect of a main component of domestic detergents, sodium triphosphate (STP), on the adsorptive capacities of powdered activated carbon (PAC) for commercially supplied humic acids, at different pH values in distilled water. Also, the effect of STP concentration and pH on the adsorption affinity of the PAC for humic acids, is discussed in relation with electrokinetic properties of carbon particles (zeta potential measurements).A first batch equilibrium study (Figs 1 and 2), showed an effective enhancement of adsorption capacity for humic acids as a function of STP concentration, in a non buffered media (pH of distilled water, close to 5.0). For example, visible absorption analysis of humic acids indicates an increase of 93% (500 mg l^?1 PAC) and 133% (1000 mg l^?1 PAC) in the carbon adsorption efficiency for a STP concentration from 0.2 to 1.0mM. A second batch equilibrium study (Figs 3 and 4) led to adsorption isotherms for humic acids in distilled water, as a function of STP concentration and initial pH value of the non buffered multicomponent system. Freundlich isotherms showed an increase in the adsorption capacity of the PAC for humic acids, with a decrease in pH and an increase in STP concentration. However, the adsorption capacity for humic acids is quite reduced at high pH values in presence of STP, in comparison with results obtained with distilled water.Electrokinetic measurements on PAC suspensions (Fig. 5) indicates that both humic acids and STP induce a negative variation of the zeta potential of carbon particles. In such a binary system, the zeta potential is a linear function of the pH; the negative surface charge of the carbon increasing with an elevation of pH (Fig. 6). Therefore, it appears that some adsorption of triphosphate polyanion from solution could occur, contributing then to the apparent negative surface charge of PAC particles.It has been previously showed that the type of anion in sodium salts, had little effect on the enhancement of adsorptive capacities of activated carbon for humic substances (Lafrance and Mazet, 1985), due to Na⁺ ions. However, adsorption of TP anions on the carbon surface may produce a source of repulsive charges, unfavourable to the co-adsorption of humic acids as the pH of the binary system reach more basic conditions. The influence of possible electrostatic interactions between adsorbates at the carbon surface, on the adsorption efficiency for humic acids, could then be studied by zeta potential measurements of PAC particles during the adsorption process.     

Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?

The influence of hyperhomocysteinemia (HHCy) on cardiovascular disease (CVD) remains unclear. HHCy is associated with inflammation and atherosclerosis, and it is an independent risk factor for CVD, stroke and myocardial infarction. However, homocysteine (HCy)-lowering therapy does not affect the inflammatory state of CVD patients, and it has little influence on cardiovascular risk. The HCy degradation product hydrogen sulfide (H₂S) is a cardioprotector. Previous research proposed a positive role of H₂S in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of H₂S, which decreases the expression of adenosine A_2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively.     

Adenosine Receptor Agonist HE-NECA Enhances Antithrombotic Activities of Cangrelor and Prasugrel in vivo by Decreasing of Fibrinogen Density in Thrombus

Blood platelets’ adenosine receptors (AR) are considered to be a new target for the anti-platelet therapy. This idea is based on in vitro studies which show that signaling mediated by these receptors leads to a decreased platelet response to activating stimuli. In vivo evidence for the antithrombotic activity of AR agonists published to date were limited, however, to the usage of relatively high doses given in bolus. The present study was aimed at verifying if these substances used in lower doses in combination with inhibitors of P2Y₁₂ could serve as components of dual anti-platelet therapy. We have found that a selective A_2A agonist 2-hexynyl-5’-N-ethylcarboxamidoadenosine (HE-NECA) improved the anti-thrombotic properties of either cangrelor or prasugrel in the model of ferric chloride-induced experimental thrombosis in mice. Importantly, HE-NECA was effective not only when applied in bolus as other AR agonists in the up-to-date published studies, but also when given chronically. In vitro thrombus formation under flow conditions revealed that HE-NECA enhanced the ability of P2Y₁₂ inhibitors to decrease fibrinogen content in thrombi, possibly resulting in their lower stability. Adenosine receptor agonists possess a certain hypotensive effect and an ability to increase the blood–brain barrier permeability. Therefore, the effects of anti-thrombotic doses of HE-NECA on blood pressure and the blood–brain barrier permeability in mice were tested. HE-NECA applied in bolus caused a significant hypotension in mice, but the effect was much lower when the substance was given in doses corresponding to that obtained by chronic administration. At the same time, no significant effect of HE-NECA was observed on the blood–brain barrier. We conclude that chronic administration of the A_2A agonist can be considered a potential component of a dual antithrombotic therapy. However, due to the hypotensive effect of the substances, dosage and administration must be elaborated to minimize the side-effects. The total number of animals used in the experiments was 146.     

Adenosine Signaling in Mast Cells and Allergic Diseases

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.     

Analysis of pentasodium triphosphate hydration kinetics

The present work analyzes the effect of various factors on the hydration of pentasodium triphosphate. The experimental method is based on application of the hydration test. Technical-quality products with different proportions of phase I and phase II have been used. The variables studied are phase I/phase II ratio, initial temperature, particle size, stirring rate and composition of the slurry (presence of hexahydrate crystals and water hardness). The results have been discussed according to a kinetics model that includes a series of stages of a physical nature (dissolution of anhydrous salt and the crystallization of the hexahydrate), as well as of a chemical nature (solvation of the ions in solution). Crystallization of the hexahydrate may be the controlling stage in the process.     

ATP的分析方法综述

本文综述了当前的ATP分析方法，比较了各方法的分析原理，优缺点及使用范围。     

毛细管气相色谱法同时测定三磷酸胞苷二钠中5种有机溶剂残留量

研究建立了同时测定三磷酸胞苷二钠中乙醇、丙酮、氯甲醚、甲苯、苯乙烯5种有机溶剂残留量的毛细管气相色谱法。样品以乙腈为溶剂,经DB-FFAP(30 m×0.32 mm×0.25μm)毛细管柱分离,氢火焰离子化检测器检测,这5种有机溶剂呈良好的线性响应,平均回收率在98.3%~99.5%,精密度RSD在0.21%~1.92%,最低检出限可达5.0~7.5 mg/kg。本方法简单、灵敏、准确,完全能满足药品中所述有机溶剂残留量的测定要求。