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Introduction: The process of bar creation involves improving the texture of the product to increase its palatability, which can be further induced by various physical or chemical changes during storage, such as sugar crystallization and molecular migrations in which Maillard's reaction occurs, forming the N-epsilon- (carboxymethyl) lysine (CML) adduct. In this study, we aimed to assess (the CML) adduct used in commercial bars today as meal substitutes or for athletic or sports purposes. The adduct CML is an advanced glycation end-product (AGEs) found in the human body (serum) and foods. It is the significant ligand for the Receptor for Advanced Glycation End Products (RAGE), resulting in chronic inflammation upon CML activation. Additionally, it aimed to assess the amount of AGEs-CML in various energy bars available on the Italian market., Method: CML OxiSelect ™ ELISA was used to assess the quantity of CML bars. The amount of AGE-CML was assessed in commercially available energy bars., Results: According to the ELISA analysis, CML concentrations per g protein in all the tested energy bars varied from 138,42 to 1387,54 μg/gr per bar and from 461,41 to 3970,46 μg/gr per 100 gr of product, which depends on the quantity of protein., Conclusion: The amount per gram of protein is relatively uniform (with a variation of about 10%), and when compared to other foods, it is positioned in a medium-low range., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Plants possess an arsenal of different classes of small RNAs (sRNAs) of variable size, which play a regulatory role in a multitude of physiological and pathological processes via transcriptional or post-transcriptional gene silencing. The hard challenges that agriculture will face in the next few decades, such as an increasing demand for agrifood production related to the global increase in population, have stimulated the development of innovative biotechnological approaches in agriculture. In this regard, the use of artificial sRNAs has already been exploited successfully for many purposes, including control of severe plant diseases, improvement of genetic and agronomic traits of cultivated species, and increasing the nutritional value of plant foodstuffs. This strategy relies on the application of synthetic sRNA molecules to induce specific physiological responses by triggering appropriate RNA silencing pathways. This review contextualizes the use of artificial sRNAs in consideration of the huge diversity of RNA silencing mechanisms in plants. Additionally, the discussion also examines microRNAs from edible plants and exosome-like vesicles, also known as plant-derived edible nanoparticles (ENPs), which themselves can act as micronutrients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

It is now well established that lifestyle, particularly eating habits, modulates the synthesis and action of microRNAs (miRNAs). In particular, several nutritional schemes have proven effective in improving body composition, but molecular mechanisms still need to be fully understood. Within the complex physiological network of food intake regulation, it is essential to understand the changes in endocrine activity after the reduction of adipose tissue during a weight loss program. This could be the key to identifying the optimal endocrine profile in high responders, the assessment of musculoskeletal status, and long-term management. In this review, we summarize the state of the art regarding miRNAs as a function of weight loss and as a mechanistic regulator of the effectiveness of the nutritional program., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 20 to 25 nucleotides, present in all body fluids; they can be used as biomarkers, but much more than this as a therapy to replace missing protein or to downregulate excess or aberrant synthesis; here we report possible insight to future studies, needed in this exciting field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

There is a huge need for pharmaceutical agents for the treatment of chronic Neuropathic Pain (NP), a complex condition where patients can suffer from either hyperalgesia or allodynia originating from central or peripheral nerve injuries. To date, the therapeutic guidelines include the use of tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors and anticonvulsants, beside the use of natural compounds and non-pharmacological options. Unfortunately, these drugs suffer from limited efficacy and serious dose-dependent adverse effects. In the last decades, the heptapeptide SP1-7, the major bioactive metabolite produced by Substance P (SP) cleavage, has been extensively investigated as a potential target for the development of novel peptidomimetic molecules to treat NP. Although the physiological effects of this SP fragment have been studied in detail, the mechanism behind its action is not fully clarified and the target for SP1-7 has not been identified yet. Nevertheless, specific binding sites for the heptapeptide have been found in brain and spinal cord of both mouse and rats. Several Structure-Affinity Relationship (SAR) studies on SP1-7 and some of its synthetic analogues have been carried out aiming to developing more metabolically stable and effective small molecule SP1-7-related amides that could be used as research tools for a better understanding of the SP1-7 system and, in a longer perspective, as potential therapeutic agents for future treatment of NP., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The Ketogenic Diet (KD) promotes metabolic changes and optimizes energy metabolism. It is unknown if microRNAs (miRs) are influenced by KD in obese subjects. The screening of circulating miRs was performed with the FDA approved platform n-counter flex and blood biochemical parameters were dosed by ADVIA 1800., Objectives: The aim of this study was to evaluate mir profile under 6 weeks of biphasic KD in obese subjects. We enrolled 36 obese subjects (18 females and 18 males) in stage 1 of Edmonton Obesity Staging System (EOSS) parameter., Result: Any correlation was found between biochemical parameter and three miRs, hsa-let-7b-5p, hsa-miR-143-3p and hsa-miR-504-5p influenced in an equal manner in both sexes. The KD resulted safe and ameliorate both biochemical and anthropometric factors in obese subjects re-collocating them into stage 0 of EOSS parameters., Conclusion: The miRs herein identified under KD might be a useful tool to monitor low carbohydrate nutritional regimens which reflect indirectly the regulatory biochemical mechanisms and cell signaling that orchestrate metabolic and signaling pathways., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Human Milk (HM) is a biological fluid representing the first nutrient for newborns. It directly impacts the development of the infant's immune system. In this concern, specific microRNAs (miRNAs) such as hsa-miR-21, hsa-miR-181a, hsa-miR-150 and hsa-miR-223 are known to be involved in the innate and acquired immune response., Objective: Herein, these miRNAs were evaluated in frozen and pasteurized samples of human colostrum and HM in order to elucidate the distribution and the expression profile of these biological mediators in both biological fluids., Methods: Using quantitative approach qRT-PCR, we analyzed immune-related microRNAs in both, colostrum and HM., Results: Our study provided evidence of a comparable profile of immune specific miRNAs in colostrum and HM. Although we detected all the four miRNAs tested, we point out the prevalence of hsamiR- 181a and hsa-miR-223 indicative to act on T and granulocytes cell populations as selective targets. Therefore, these biomolecules could affect newborn's immune homeostasis at early stages of life. While, variation in immune-related miRNAs was found in HM amongst lactating women, it was not evidenced in colostrum. Of interest, pasteurization procedure did not alter the distribution or the expression profile of the miRNAs tested in both colostrum and HM. Herein, we also proposed a simple method to determine the quantity of these biomolecules in biological fluids., Conclusion: Considering, this evidence the variation in immune-related miRNAs should be take into account and could be relevant for preterm and hospitalized infants who usually received pasteurized HM from donors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Migraine is a prevalent neurovascular disorders with a complex pathophysiology and therapeutic options characterized by important side effects or problems related to drug abuse. No specific biomarkers are recognized to be univocal for this subclinical condition, yet. In this concern microRNAs (miRNAs) have been suggested as potentially useful screening/diagnostic tool, and research is underway to recognize the most effective candidate(s). In this concern in the present review we Herein we highlighted miRs involvement in pain and migraine, as well as drug response and efficacy focusing also on miRs panel results from mice model with multiple induced pain conditions, and human patients with migraine in order to understand if there are similar miRs expression pattern may useful into human translational studies., Results: During human migraine attack specific miRs were found dysregulated, as well as in mouse models with different pain conditions. Amongst all the miRs screened in mice/human suffering of pain the miR-590-5p was found alterated. This latter miR, in mice is modulated by celecoxib, while in human is dysregulated in the complex regional pain syndrome, condition where migraine assume a risk factor for its development. Recently has been reported that pharmacological treatments, indirectly can pertubate miRNA expression results. Therefore, miR-590-5p could assume an interesting double meaning for a clinical point of view. It can be considered biomarker of general pain, including migraine and also biomarker to evaluate the efficacy of the drug treatment. This could be of great importance in infant-juvenile segment, where the diagnosis of migraine is very challenging. In this view, since therapy is often started with NSAIDs herein we discuss also how the discovery of the new role of miRNAs in determining drug efficacy open a new scenario in the pain-migraine tailored therapy and pharmacogenomics concept., Conclusion: miRNAs could have a pleiotropic meaning in the clinical management of migraine and could represent biomarkers of pathology, of drug efficacy as well as drug adherence to the treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Drug-Drug Interactions (DDIs) represent a common problem in clinical practice during drug treatments. DDIs can both induce the development of adverse drug reactions or reduce the clinical efficacy of each drug., Objectives: The main objective of this review was to analyze the pharmacokinetic and pharmacodynamic DDIs in cocaine consumers, focusing the interest on their clinical implications., Methods: The PubMed, Embase and Cochrane library databases were searched for articles published until January 10, 2017. Secondary search included articles cited in reference lists identified by the primary search. Papers were deemed eligible if they included any form of words: "adverse drug reaction", "drug interactions", "poly-therapy", "cocaine", "systemic diseases"., Results: In this review, the nodal points treated concern: i) cocaine biochemical metabolism described for both, inactive benzoylecgonine and ecgonine methyl esters and norcocaine active metabolites. We provided evidences of concepts deriving from rat/mice experimental studies speculating a translation approach to human in order to treat cocaine overdose. ii) Drug-drug interactions, which come out from clinical evidences as the case of CYP450 family enzyme inhibitors or inductors modulating cocaine toxicity. Particularly, we highlighted the lack of knowledge concerning cocaine and CYP3A4 inhibitors (such as ketoconazole, nefazodone, erythromycin, and clarithromycin). We recorded the worst association of cocaine and beta-blockers by direct and indirect action, particularly at postsynaptic levels on dopamine and norepinephrine reuptake, sympathetic activation and increase of heart rate, blood pressure and cardiovascular toxicity. Cocaine also induces increase in serotonin synaptic activity leading to the development of a serotoninergic syndrome when used with drugs that affect serotonin pathway. Genetic (i.e. glutathione peroxidase-1 deficiency) and epigenetic factors (i.e. microRNAs) may be involved in drug-drug interactions in cocaine-users are also being introduced., Conclusion: DDIs represent an important potential complication in cocaine users in clinical setting. The knowledge of DDIs can also be used to select treatments for patients, thus optimizing clinical response and minimizing toxicity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Among the clinical spectrum of neurological diseases, migraine is often associated with cerebro-vasculopathy. Impairment of neuroimmune mediators in the central nervous system has been recognized in the pathophysiology of migraine-related stroke. Although genetic correlation was found in patients with migraine-related stroke, the epidemiology of this disease indicates a need in biomarker searching discovery and validation. In this view, small molecule, called microRNAs (miRNAs), able to regulate immune and neuronal processes has been reported in patients with migraine and ischemic stroke and unambiguous miRNAs related to these diseases could be established as new molecular indicator of precocity for clinical and/or pharmacological intervention. Therefore, further exploration of this area is necessary, as greater understanding of these biomarkers could reveal the common mechanisms involved in the pathophysiology of migraine in patients with cerebral infarct., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Obesity, insulin resistance, metabolic syndrome and type 2 diabetes have reached epidemic proportions, from the term: diabesity. Vitamin A is delivered by a specific binding protein called retinol-binding protein 4 (RBP4) a soluble protein, emerging to have a role in insulin resistance, the major cause of diabetes is highly associated with adipose tissue inflammation and obesity with action. RBP4, interacts with two receptors, the Toll-like receptor 4 (TLR4) and the plasma membrane protein are stimulated by retinoic acid 6 (STRA6), leading to the activation of c-Jun N-terminal protein kinase (JNK) pathways and JAK2/STAT5 cascade, respectively. Both mechanisms sustain insulin resistance. Therefore, ablation of STRA6 protects mice from RBP4-induced suppression of insulin signaling. In addition, mice harboring deletion of a specific chaperon for retinol, show infiltration of α-cells in the core of pancreatic islets, where usually only β-cells reside, showing a pre-diabetic like phenotype. Not only proteins in vitamin A shuttle and signaling are emerging in diabesity, recently, the discovery of 9cis retinoic acid (9cRA) with effects on controlling glucose levels have opened a new scenario. So far, only pancreas β-cells have been shown to synthesize it, and high levels of 9cRA correlate with obesity mice models. In this article, we summarize the recent literature present on this topic raising the hypothesis.

The 9-(bromoalkyl)-1,4-dimethyl-9H-carbazole (2a-d) derivatives, characterized by the presence of five or seven methylenic spacer groups bonded to the carbazole nitrogen, have been synthesized from the corresponding 1,4- dimethyl-9H-carbazole and appropriate dibromoalkane following a general synthetic method. All the prepared species have been fully characterized by means of IR, and (1)H and (13)C NMR spectroscopy, GC-MS and Elemental analysis. Good crystals of the 2c have been obtained and the crystal structure has been solved by means of X-ray diffractometry. In order to study the cytotoxic effect of 2a, 2b, 2c, 2d carbazole derivatives on A2780 ovarian cancer cells, we performed MTT assay after exposure of this cell population to those compounds in a concentration range from 1 to 10μM. Finally, we want to verify whether the cytotoxic effect of the 2c carbazole is mediated by apoptotic mechanisms, by performing chromatin condensation assay on the A2780 cell cultures upon the carbazole treatment at concentration of 10 μM for 72h. All together our data demonstrate that carbazole derivatives exert inhibitory effects on ovarian cancer cell growth, highlighting a stronger and a dose-dependent anti proliferative activity displayed by 2c carbazole, designating this compound, as a better candidate in the treatment of human ovarian cancer.