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Topic Review
Effects of Statins on Cancer via Autophagy
Cancer is one of the main causes of death globally. Most of the molecular mechanisms underlying cancer are marked by complex aberrations that activate the critical cell-signaling pathways that play a pivotal role in cell metabolism, tumor development, cytoskeletal reorganization, and metastasis. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway is one of the main signaling pathways involved in carcinogenesis and metastasis. Autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation, plays a dual role in cancer, as either a tumor promoter or a tumor suppressor, depending on the stage of the carcinogenesis. Statins are the group of drugs of choice to lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Experimental and clinical data suggest the potential of statins in the treatment of cancer. In vitro and in vivo studies have demonstrated the molecular mechanisms through which statins inhibit the proliferation and metastasis of cancer cells in different types of cancer. The anticancer properties of statins have been shown to result in the suppression of tumor growth, the induction of apoptosis, and autophagy.
  • 894
  • 09 Jun 2022
Topic Review
Sulforaphane
Sulforaphane (SFN) is a natural glucosinolate found in cruciferous vegetables that acts as a chemopreventive agent, but its mechanism of action is not clear. Due to antioxidative mechanisms being thought central in preventing cancer progression, SFN could play a role in oxidative processes. Since redox imbalance with increased levels of reactive oxygen species (ROS) is involved in the initiation and progression of bladder cancer, this mechanism might be involved when chemoresistance occurs.
  • 893
  • 02 Jul 2021
Topic Review
Beta-Blockers and Cancer
Cancer is one of the leading causes of death worldwide. After diagnosis, cancer treatment may involve radiotherapy, chemotherapy, and surgery. Several of the approaches used to treat cancer also attack normal cells and, thus, there is the need for more effective treatments that decrease the toxicity to normal cells and increase the success rates of treatment. The use of beta-blockers in cancer has been studied for their antagonist action on the adrenergic system through inhibition of beta-adrenergic receptors. Besides regulating processes such as blood pressure, heart rate, and airway strength or reactivity, beta-blockers block mechanisms that trigger tumorigenesis, angiogenesis, and tumor metastasis.
  • 892
  • 28 May 2021
Topic Review
NRF2-Activating Compounds Bearing α,β-Unsaturated Moiety
The surge of scientific interest in the discovery of Nuclear Factor Erythroid 2 (NFE2)-Related Factor 2 (NRF2)-activating molecules underscores the importance of NRF2 as a therapeutic target especially for oxidative stress. The chemical reactivity and biological activities of several bioactive compounds have been linked to the presence of α,β-unsaturated structural systems. The α,β-unsaturated carbonyl, sulfonyl and sulfinyl functional groups are reportedly the major α,β-unsaturated moieties involved in the activation of the NRF2 signaling pathway. The carbonyl, sulfonyl and sulfinyl groups are generally electron-withdrawing groups, and the presence of the α,β-unsaturated structure qualifies them as suitable electrophiles for Michael addition reaction with nucleophilic thiols of cysteine residues within the proximal negative regulator of NRF2, Kelch-like ECH-associated protein 1 (KEAP1). The physicochemical property such as good lipophilicity of these moieties is also an advantage because it ensures solubility and membrane permeability required for the activation of the cytosolic NRF2/KEAP1 system.
  • 889
  • 02 Sep 2022
Topic Review
Benign Prostatic Hyperplasia
The apoptosis machinery is a promising target against benign prostatic hyperplasia (BPH). Inhibitors of apoptosis proteins (IAPs) modulate apoptosis by direct inhibition of caspases. Serenoa Repens (SeR) may be combined with other natural compounds such as Lycopene (Ly) and Selenium (Se) to maximize its therapeutic activity in BPH. We investigated the effects of SeR, Se and Ly, alone or in association, on the expression of four IAPs, cIAP-1, cIAP-2, NAIP and survivin in rats with experimental testosterone-dependent BPH. Moreover, caspase-3, interleukin-6 (IL-6) and prostate specific membrane antigen (PSMA) have been evaluated. Rats were administered, daily, with testosterone propionate (3 mg/kg/sc) or its vehicle for 14 days. Testosterone injected animals (BPH) were randomized to receive vehicle, SeR (25 mg/kg/sc), Se (3 mg/kg/sc), Ly (1 mg/kg/sc) or the SeR-Se-Ly association for 14 days. Animals were sacrificed and prostate removed for analysis. BPH animals treated with vehicle showed unchanged expression of cIAP-1 and cIAP-2 and increased expression of NAIP, survivin, caspase-3, IL-6 and PSMA levels when compared with sham animals. Immunofluorescence studies confirmed the enhanced expression of NAIP and survivin with a characteristic pattern of cellular localization. SeR-Se-Ly association showed the highest efficacy in reawakening apoptosis; additionally, this therapeutic cocktail significantly reduced IL-6 and PSMA levels. The administration of SeR, Se and Ly significantly blunted prostate overweight and growth; moreover, the SeR-Se-Ly association was most effective in reducing prostate enlargement and growth by 43.3% in treated animals. The results indicate that IAPs may represent interesting targets for drug therapy of BPH.
  • 885
  • 01 Nov 2020
Topic Review
Phenothiazines Modified with Pyridine Ring
Azaphenothiazines are the largest and most perspective group of modified phenothiazines, and they exhibit variety of biological activities. The review sums up the current knowledge on the anticancer activity of isomeric pyridobenzothiazines and dipyridothiazines, which are modified azaphenothiazines with one and two pyridine rings, respectively, against 10 types of cancer cell lines. Some 10-substituted dipyridothiazines and even 10-unsubstituted parent compounds, such as 10H-1,9-diazaphenothiazine and 10H-3,6-diazaphenothiazine, exhibited very potent action with the IC50 values less than 1 µg/mL and 1 µM against selected cancer cell lines. The strength of the anticancer action depends both on the tricyclic ring scaffolds and the substituents at the thiazine nitrogen atom.
  • 885
  • 18 Mar 2021
Topic Review
Paroxetine Molecular Mechanisms of Action
In the 21st century and especially during a pandemic, the diagnosis and treatment of depression is an essential part of the daily practice of many family doctors. It mainly affects patients in the age category 15–44 years, regardless of gender. Anxiety disorders are often diagnosed in children and adolescents. Social phobias can account for up to 13% of these diagnoses. Social anxiety manifests itself in fear of negative social assessment and humiliation, which disrupts the quality of social functioning. Treatment of the above-mentioned disorders is based on psychotherapy and phar-macotherapy. Serious side effects or mortality from antidepressant drug overdose are currently rare. Recent studies indicate that paroxetine (ATC code: N06AB), belonging to the selective sero-tonin reuptake inhibitors, has promising therapeutic effects and is used off-label in children and adolescents.
  • 880
  • 26 Feb 2021
Topic Review
Cutaneous Reactions to Antidiabetic Agents
Diabetes is a common and complex disease affecting multiple organ systems throughout the body. With a consensus in care guidelines emphasizing the importance of glycemic control in determining the disease progression, people with diabetes worldwide have been placed on medication regimens targeting glucose stability from a variety of pathophysiologic pathways. Each of these medications also possesses its own potential for adverse events. 
  • 880
  • 04 Mar 2022
Topic Review
Oligodendroglial Cells
Oligodendrocytes (OLs) are ramified glial cells within the central nervous system (CNS) whose terminal processes generate myelin and enwrap neuronal axons. 
  • 879
  • 04 Aug 2021
Topic Review
Drug Carriers for Arthritis Therapy
Drug carriers are used to penetrate the biological barriers and deliver the requisite active pharmaceutical ingredients (API). This has greater significance for medication in arthritis therapies because the inflammatory progression of rheumatoid arthritis (RA) and osteoarthritis (OA) is complex, intertwined, and influenced by one another. For this purpose, the drug delivery systems (DDS) of this carrier are currently being investigated with exogenous triggers and endogenous stimuli. This flexible-release invention will solve the problems of multiple implantations and local toxic accumulation at the lesion sites.
  • 879
  • 10 Nov 2022
Topic Review
Mycotoxins
Mycotoxins are secondary metabolites produced by fungal species that commonly have a toxic effect on human and animal health. Different foodstuff can be contaminated and are considered the major source of human exposure to mycotoxins, but occupational and environmental exposure can also significantly contribute to this problem.
  • 877
  • 19 Feb 2021
Topic Review
Composition of Lipid–Polymer Hybrid Nanoparticles
Lipid nanoparticles (LNPs) are spherical vesicles composed of ionizable lipids that are neutral at physiological pH. Despite their benefits, unmodified LNP drug delivery systems have substantial drawbacks, including a lack of targeted selectivity, a short blood circulation period, and in vivo instability. lipid–polymer hybrid nanoparticles (LPHNPs) are the next generation of nanoparticles, having the combined benefits of polymeric nanoparticles and liposomes. LPHNPs are being prepared from both natural and synthetic polymers with various techniques, including one- or two-step methods, emulsification solvent evaporation (ESE) method, and the nanoprecipitation method. Varieties of LPHNPs, including monolithic hybrid nanoparticles, core–shell nanoparticles, hollow core–shell nanoparticles, biomimetic lipid–polymer hybrid nanoparticles, and polymer-caged liposomes, have been investigated for various drug delivery applications.
  • 877
  • 08 Sep 2023
Topic Review
Toxin Genes of Bacillus cereus
Bacillus cereus is a ubiquitous soil bacterium responsible for two types of food-associated gastrointestinal diseases. While the emetic syndrome is caused by the cyclic depsipeptide cereulide, proteinaceous enterotoxins provoke the diarrheal disease. Here, an overview on the distribution of the main toxin genes/operons ces (encoding cereulide), hbl (encoding the tripartite hemolysin BL), nhe (encoding the tripartite non-hemolytic enterotoxin), and cytK (encoding the single protein cytotoxin K) within the B. cereus group is given.
  • 872
  • 18 Feb 2021
Topic Review
Sphingosine Kinase/Sphingosine-1-Phosphate
Sphingolipid metabolites have emerged as critical players in the regulation of various physiological processes. Ceramide and sphingosine induce cell growth arrest and apoptosis, whereas sphingosine-1-phosphate (S1P) promotes cell proliferation and survival. 
  • 872
  • 28 Apr 2021
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.
  • 870
  • 22 Oct 2020
Topic Review
Ivermectin for the Treatment and/or Prophylaxis of COVID-19
The pathogenesis of Coronavirus Disease 2019 (COVID-19) is initiated by viral entry through the angiotensin-converting enzyme 2 (ACE-2) receptor in the host cell. After entry, RNA is translated into viral proteins upon its release in the cytoplasm. The resulting symptoms and clinical manifestations include fever, headache, myalgia, and respiratory symptoms. Several drugs have been and continue to be repurposed for the prophylaxis and treatment of COVID-19. Ivermectin (IVM) belongs to the naturally occurring family of avermectins produced by the bacterium Streptomyces avermitilis. Its broad antiparasitic spectrum is achieved through the hyperpolarization of the invertebrate’s cell membrane, with subsequent parasite paralysis. It was tested and confirmed for its in vitro antiviral activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Trials have put IVM to test for both the treatment and prophylaxis of COVID-19, as well as its potential role in combination therapy. Additionally, the targeted delivery of IVM was studied in animals and COVID-19 patients.
  • 869
  • 31 Oct 2022
Topic Review
Protamine-Based Strategies for RNA Transfection
Protamine is a natural cationic peptide mixture mostly known as a drug for the neutralization of heparin and as a compound in formulations of slow-release insulin. Protamine is also used for cellular delivery of nucleic acids due to opposite charge-driven coupling. This year marks 60 years since the first use of Protamine as a transfection enhancement agent. Since then, Protamine has been broadly used as a stabilization agent for RNA delivery. It has also been involved in several compositions for RNA-based vaccinations in clinical development. Protamine stabilization of RNA shows double functionality: it not only protects RNA from degradation within biological systems, but also enhances penetration into cells. A Protamine-based RNA delivery system is a flexible and versatile platform that can be adjusted according to therapeutic goals: fused with targeting antibodies for precise delivery, digested into a cell penetrating peptide for better transfection efficiency or not-covalently mixed with functional polymers.
  • 867
  • 07 Jul 2021
Topic Review
Zebrafish Motile Cilia
Zebrafish is a vertebrate teleost widely used in many areas of research. As embryos, they develop quickly and provide unique opportunities for research studies owing to their transparency for at least 48 h post fertilization. Zebrafish have many ciliated organs that include primary cilia as well as motile cilia. Using zebrafish as an animal model helps to better understand human diseases such as Primary Ciliary Dyskinesia (PCD), an autosomal recessive disorder that affects cilia motility, currently associated with more than 50 genes. 
  • 867
  • 22 Sep 2021
Topic Review
Current Insights on Antifungal Therapy
The high incidence of fungal infections has become a worrisome public health issue, having been aggravated by an increase in host predisposition factors. Despite all the drugs available on the market to treat these diseases, their efficiency is questionable, and their side effects cannot be neglected. Bearing that in mind, it is of upmost importance to synthetize new and innovative carriers for these medicines not only to fight emerging fungal infections but also to avert the increase in drug-resistant strains.
  • 864
  • 29 Sep 2020
Topic Review
Engineering Drug Delivery Systems
Engineering drug delivery systems (DDS) aim to release bioactive cargo to a specific site within the human body safely and efficiently. Hydrogels have been used as delivery matrices in different studies due to their biocompatibility, biodegradability, and versatility in biomedical purposes. Microparticles have also been used as drug delivery systems for similar reasons. The combination of microparticles and hydrogels in a composite system has been the topic of many research works. These composite systems can be injected in loco as DDS. The hydrogel will serve as a barrier to protect the particles and retard the release of any bioactive cargo within the particles. Additionally, these systems allow different release profiles, where different loads can be released sequentially, thus allowing a synergistic treatment. The reported advantages from several studies of these systems can be of great use in biomedicine for the development of more effective DDS.
  • 863
  • 04 Oct 2021
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