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Topic Review
α-Synuclein Phosphorylation and Its Kinases
α-Synuclein is a protein with a molecular weight of 14.5 kDa and consists of 140 amino acids encoded by the SNCA gene. Missense mutations and gene duplications in the SNCA gene cause hereditary Parkinson’s disease. Highly phosphorylated and abnormally aggregated α-synuclein is a major component of Lewy bodies found in neuronal cells of patients with sporadic Parkinson’s disease, dementia with Lewy bodies, and glial cytoplasmic inclusion bodies in oligodendrocytes with multiple system atrophy. Aggregated α-synuclein is cytotoxic and plays a central role in the pathogenesis of the above-mentioned synucleinopathies. In a healthy brain, most α-synuclein is unphosphorylated; however, more than 90% of abnormally aggregated α-synuclein in Lewy bodies of patients with Parkinson’s disease is phosphorylated at Ser129, which is presumed to be of pathological significance. Several kinases catalyze Ser129 phosphorylation, but the role of phosphorylation enzymes in disease pathogenesis and their relationship to cellular toxicity from phosphorylation are not fully understood in α-synucleinopathy. G-protein-coupled receptor kinases, casein kinase II, and polo-like kinase possess the ability to phosphorylate α-synuclein protein. On this point, inhibition of these kinases is able to prevent α-synuclein phosphorylation, which indicates the potential therapeutic targets and availability of drug development for α-synucleinopathies. α-Synuclein phosphorylation can clinically be an accompanying event in the brains of patients with Parkinson’s disease rather than the critical factor for α-synuclein aggregation and toxicity. Nevertheless, increasing phosphorylated α-synuclein and the accumulation with disease progression is useful as a therapeutic target and biomarker.
  • 1.2K
  • 08 Jun 2022
Topic Review
Anticancer Potential of Piper nigrum
Current anticancer therapy suffers from several limitations, including lack of selectivity and multidrug resistance. Natural products represent an excellent opportunity for the identification of new therapeutic options due to their safety, low toxicity, and general availability. Piper nigrum is one of the most popular species in the world, with growing fame as a source of bioactive molecules with pharmacological properties. Undeniable anticancer properties are reportetd for different Piper nigrum constituents, such as its main alkaloid piperine.
  • 1.2K
  • 27 Feb 2021
Topic Review
Three-Dimensional Spheroids in Cancer Research
Three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models.
  • 1.2K
  • 09 Dec 2020
Topic Review
Memantine
Memantine is effective in blocking excessive activity of NMDA-type glutamate receptors and reduces the progression of dementia and may have benefits after TBI.
  • 1.2K
  • 07 Feb 2021
Topic Review
Novel Fucoidan Pharmaceutical Formulations and Their Potential Application
Fucoidan belongs to a family of sulfated, L-fucose-rich polysaccharides found in the cell wall matrix of various species of marine brown algae (Phaeophyta: Laminariaceae, Fucaceae, Chordariaceae and Alariaceae). Fucoidan can also be obtained from sea cucumbers (Holothuroidea: Stichopodidae, Holothuriidae), sea urchin eggs (Echinoidea: Strongylocentrotidae, Arbaciidae) and sea grasses (Cymodoceaceae).
  • 1.2K
  • 01 Aug 2023
Topic Review
Microfluidic for Cutaneous Wound Healing
Cutaneous wound healing is a complex, multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically, and biologically injured area, resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics are therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring, and eliminate chronic wounds. Following the global trend towards the automation, miniaturization, and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay and cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow for precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. 
  • 1.2K
  • 08 Jun 2021
Topic Review
Liposomal systems in Cancer immunotherapy
Cancer immunotherapy has shown remarkable progress in recent years. Nanocarriers, such as liposomes, have favorable advantages with the potential to further improve cancer immunotherapy and even stronger immune responses by improving cell type-specific delivery and enhancing drug efficacy. Liposomes can offer solutions to common problems faced by several cancer immunotherapies, including the following: (1) Vaccination: Liposomes can improve the delivery of antigens and other stimulatory molecules to antigen-presenting cells or T cells; (2) Tumor normalization: Liposomes can deliver drugs selectively to the tumor microenvironment to overcome the immune-suppressive state; (3) Rewiring of tumor signaling: Liposomes can be used for the delivery of specific drugs to specific cell types to correct or modulate pathways to facilitate better anti-tumor immune responses; (4) Combinational therapy: Liposomes are ideal vehicles for the simultaneous delivery of drugs to be combined with other therapies, including chemotherapy, radiotherapy, and phototherapy.
  • 1.2K
  • 24 Nov 2020
Topic Review
Anticancer Secondary Metabolites of Astragalus Species
Some of the most effective anticancer compounds are still derived from plants since the chemical synthesis of chiral molecules is not economically efficient. Rapid discovery of lead compounds with pronounced biological activity is essential for the successful development of novel drug candidates. The genus Astragalus L. is the largest in the family Fabaceae (syn. Leguminosae), with more than 3500 species. Astragalus, excluding Astracantha (formerly Astragalus subgenus Tragacantha), has a world total of ca. 2500 species, of which ca. 500 are in the Americas. Many of the species have conservation status “vulnerable” or “critically endangered”.
  • 1.2K
  • 09 Sep 2022
Topic Review
Approaches to Identify Functional SNPs in mRNA 3′UTRs
The complementary interaction of microRNAs (miRNAs) with their binding sites in the 3′untranslated regions (3′UTRs) of target gene mRNAs represses translation, playing a leading role in gene expression control. MiRNA recognition elements (MREs) in the 3′UTRs of genes often contain single nucleotide polymorphisms (SNPs), which can change the binding affinity for target miRNAs leading to dysregulated gene expression. Accumulated data suggest that these SNPs can be associated with various human pathologies (cancer, diabetes, neuropsychiatric disorders, and cardiovascular diseases) by disturbing the interaction of miRNAs with their MREs located in mRNA 3′UTRs. Numerous data show the role of SNPs in 3′UTR MREs in individual drug susceptibility and drug resistance mechanisms. This work brief the data on such SNPs focusing on the most rigorously proven cases. Some SNPs belong to conventional genes from the drug-metabolizing system (in particular, the genes coding for cytochromes P450 (CYP 450), phase II enzymes (SULT1A1 and UGT1A), and ABCB3 transporter and their expression regulators (PXR and GATA4)). Other examples of SNPs are related to the genes involved in DNA repair, RNA editing, and specific drug metabolisms. The gene-by-gene studies and genome-wide approaches utilized or potentially utilizable to detect the MRE SNPs associated with individual response to drugs discussed.
  • 1.2K
  • 24 Nov 2022
Topic Review
New Flavonoid & Myo-Inositol Supplement
Background and Aim. Cardiovascular risk is increased in women with menopause and metabolic syndrome. Aim of this study was to test the effect of a new supplement formula, combining cocoa polyphenols, myo-inositol, and soy isoflavones, on some biomarkers of cardiovascular risk in postmenopausal women with metabolic syndrome.Methods and Results. A total of 60 women were enrolled and randomly assigned (n=30per group) to receive the supplement (NRT: 30 mg of cocoa polyphenols, 80 mg of soy isoflavones, and 2 gr of myo-inositol), or placebo for 6 months. The study protocol included three visits (baseline, 6, and 12 months) for the evaluation of glucose, triglycerides, and HDL-cholesterol (HDL-C), adiponectin, visfatin, resistin, and bone-specific alkaline phosphatase (bone-ALP). At 6 months, a significant difference between NRT and placebo was found for glucose (96±7versus108±10 mg/dL), triglycerides (145±14versus165±18 mg/dL), visfatin (2.8±0.8versus3.7±1.1 ng/mL), resistin (27±7versus32±8 µg/L), and b-ALP (19±7versus15±5 µg/mL). No difference in HDL-C concentrations nor in adiponectin levels between groups was reported at 6 months.Conclusions.The supplement used in this study improves most of the biomarkers linked to metabolic syndrome. This Trial is registered withNCT01400724.
  • 1.2K
  • 01 Nov 2020
Topic Review
Heavy Metals Levels in Adolescents
In the Milazzo-Valle del Mela area, the presence of industrial plants and the oil refinery make local residents concerned for their health. For this reason, we evaluated the levels of heavy metals in 226 children aged 12–14 years, living in the 7 municipalities of the area. A control age-matched population (n = 29) living 45 km far from the industrial site was also enrolled. Arsenic, cadmium, chromium, mercury, nickel, and vanadium were analysed in 24 h urine samples, while lead concentration was evaluated in blood samples. A questionnaire regarding life style and risk perception was also administered. Adolescents from Milazzo-Valle del Mela had cadmium levels significantly higher compared to either controls (P < 0.0001) or the reference values of the European Germany Environmental Survey (GerES-IV) and the American National Health and Nutrition Examination Survey (NHANES). Furthermore, children had higher perception of living in a high-risk environment. The present data, for the first time, clearly indicate that adolescents living in Milazzo-Valle del Mela have increased body concentration of cadmium, which may be harmful to human health. These results deserve particular attention by the local and regional government to initiate prevention programmes in this susceptible population.
  • 1.2K
  • 01 Nov 2020
Topic Review
Therapeutic Applications of Solid Dispersions
Solid dispersions (SDs) are a technological strategy to improve the pharmacological potential of natural or synthetic bioactive molecules, due to the increase in its solubility and bioavailability, leading to a possible improvement of its biological activities. In this sense, the review sought to synthesize and critically examine the studies that address SDs with therapeutic applications, evaluated through in vitro and/or in vivo tests. This bibliographic survey shows the significant therapeutic potential of SDs in the context of the most diverse biological activities. Among these, including in vitro and/or in vivo antitumor, antiparasitic, antimicrobial, antioxidant, anti-inflammatory or cytoprotective activities, while additional activities, such as gastroprotective, hepatoprotective, antidiabetic or antinociceptive, were highlighted by in vivo studies. Although SDs have already been studied and cited in the literature, the number of studies published with a focus on in vitro and in vivo trials is still relatively small, considering the great potential of these formulations in pharmaceutical technology and with the most diverse applications. The results of biological activity studies showed that SDs, as a drug release tool, is not a limiting factor for the execution of in vitro and in vivo tests. Additionally, it stands out as a promising system in which the active principle and the carrier interact, allowing, in most cases, an increase in the pharmacological potential due to changes in the physicochemical properties of the constituents. Thus, SDs can represent a safe and effective alternative for the development and improvement of drugs directed to a wide range of pharmacological treatments.
  • 1.2K
  • 22 Oct 2020
Topic Review
Adverse Side Effects of Long-Term Lithium Therapy
Lithium remains the drug of first choice for prophylactic treatment of bipolar disorder, preventing the recurrences of manic and depressive episodes. The longitudinal experiences with lithium administration greatly exceed those with other mood stabilizers. Among the adverse side effects of lithium, renal, gastrointestinal, neurological, thyroid, metabolic, cognitive, dermatological, cardiologic, and sexual are listed. Probably, the most important negative effect of lithium, occurring mostly after 10–20 years of its administration, is interstitial nephropathy.
  • 1.2K
  • 06 Feb 2023
Topic Review
Lipid Nanoparticulate Drug Delivery Systems and Skin Disorders
Lipid nanoparticles (LN) are recognized as promising drug delivery systems (DDS) in treating skin disorders. Solid lipid nanoparticles (SLN) together with nanostructured lipid carriers (NLC) exhibit excellent tolerability as these are produced from physiological and biodegradable lipids. Moreover, LN applied to the skin can improve stability, drug targeting, occlusion, penetration enhancement, and increased skin hydration compared with other drug nanocarriers. Furthermore, the features of LN can be enhanced by inclusion in suitable bases such as creams, ointments, gels (i.e., hydrogel, emulgel, bigel), lotions, etc. 
  • 1.2K
  • 16 Nov 2021
Topic Review
The Anti-Neuroinflammatory Role of Anthocyanins
Anthocyanins are a large subclass of flavonoids, widely distributed in fruits and vegetables in the human diet. Among flavonoids, anthocyanins have gained prominence mainly due to their high intake in humans and their well-recognized antioxidant and anti-inflammatory activities [10,12], among others, making them promising agents for the prevention and treatment of distinct pathological conditions, such as cardiometabolic diseases, cancer, vision impairment, and neurological diseases [11,13,14,15,16,17].
  • 1.2K
  • 11 Jan 2021
Topic Review
Terpenoids in and beyond Cannabis Plant
Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself.
  • 1.2K
  • 16 Nov 2021
Topic Review
The Applications of Cyclodextrins in Food
Cyclodextrins (CDs) are a group of cyclic oligosaccharides produced from starch, consisting of a hydrophobic interior cavity and hydrophilic exterior. Cyclodextrins have gained significant and established attention as versatile carriers for the delivery of bioactive compounds derived from natural sources in various applications, including medicine, food and cosmetics. Their toroidal structure and hydrophobic cavity render them ideal candidates for encapsulating and solubilizing hydrophobic and poorly soluble compounds. Most medicinal, food and cosmetic ingredients share the challenges of hydrophobicity and degradation that can be effectively addressed by various cyclodextrin types.
  • 1.2K
  • 20 Sep 2023
Topic Review
Aqueous Prostaglandin Eye Drop Formulations
Glaucoma is one of the leading causes of irreversible blindness worldwide. It is characterized by progressive optic neuropathy in association with damage to the optic nerve head and, subsequently, visual loss if it is left untreated. Among the drug classes used for the long-term treatment of open-angle glaucoma, prostaglandin analogues (PGAs) are the first-line treatment and are available as marketed eye drop formulations for intraocular pressure (IOP) reduction by increasing the trabecular and uveoscleral outflow. PGAs have low aqueous solubility and are very unstable (i.e., hydrolysis) in aqueous solutions, which may hamper their ocular bioavailability and decrease their chemical stability. Additionally, treatment with PGA in conventional eye drops is associated with adverse effects, such as conjunctival hyperemia and trichiasis. It has been a very challenging for formulation scientists to develop stable aqueous eye drop formulations that increase the PGAs’ solubility and enhance their therapeutic efficacy while simultaneously lowering their ocular side effects.
  • 1.2K
  • 28 Oct 2022
Topic Review
Ascorbic Acid against Chronic Diseases
Ascorbic acid (ASC) is a key nutrient that serves as an antioxidant and a cofactor for numerous enzymatic reactions. However, humans, unlike most mammals, are unable to synthesize it. Consequently, ASC must be obtained through dietary sources, especially fresh fruit and vegetables. The value of administering exogenous micronutrients, to reestablish antioxidant concentrations in patients with severe disease, has been recognized for decades. Despite the suggestion that ASC supplementation may reduce oxidative stress and prevent several chronic conditions, few large, randomized clinical trials have tested it in patients with severe illness. This article reviews the recent literature on the pharmacological profile of ASC and the role of its supplementation in critically ill patients.
  • 1.2K
  • 11 Dec 2020
Topic Review
Fatty Acid Ethanolamides and Receptors
Oleoylethanolamide and palmitoylethanolamide are members of the fatty acid ethanolamide family, also known as acylethanolamides. Their physiological effects, including glucose homeostasis, anti-inflammation, anti-anaphylactic, analgesia, and hypophagia, have been reported. They have affinity for different receptor proteins, including nuclear receptors such as PPARα, channels such as TRPV1, and membrane receptors such as GPR119 and GPR55. In the present review, the pathophysiological functions of fatty acid ethanolamides have been discussed from the perspective of receptor pharmacology and drug discovery.
  • 1.2K
  • 30 Apr 2021
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