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Topic Review
Kainate Receptor Antagonists
Since the 1990s, ionotropic glutamate receptors have served as an outstanding target for drug discovery research aimed at the discovery of new neurotherapeutic agents. With the recent approval of perampanel, the first marketed non-competitive antagonist of AMPA receptors, particular interest has been directed toward ‘non-NMDA’ (AMPA and kainate) receptor inhibitors. Although the role of AMPA receptors in the development of neurological or psychiatric disorders has been well recognized and characterized, progress in understanding the function of kainate receptors (KARs) has been hampered, mainly due to the lack of specific and selective pharmacological tools. The findings in the biology of KA receptors indicate that they are involved in neurophysiological activity and play an important role in both health and disease, including conditions such as anxiety, schizophrenia, epilepsy, neuropathic pain, and migraine. 
  • 486
  • 31 Jan 2023
Topic Review
Bioactive Phytochemicals from Ruta angustifolia Pers.
The genus Ruta in the family Rutaceae includes about 40 species, such as the well-known plants R. graveolens L. (common rue) or R. chalepensis L. (fringed rue), but also much lesser-known species such as R. angustifolia Pers. (narrow-leaved fringed rue). This rue specie, originating from the Mediterranean region, is well-distributed in Southeast Asia, notably in the Indo-Chinese peninsula and other territories. In some countries, such as Malaysia, the plant is used to treat liver diseases and cancer. Extracts of R. angustifolia display antifungal, antiviral and antiparasitic effects. Diverse bioactive natural products have been isolated from the aerial parts of the plant, notably quinoline alkaloids and furocoumarins, which present noticeable anti-inflammatory, antioxidant and/or antiproliferative properties.
  • 486
  • 23 Feb 2023
Topic Review
Effects of Hydroxytyrosol in Endothelial Functioning
Pharmacologists have been emphasizing and applying plant and herbal-based treatments in vascular diseases. Olives, for example, are a traditional symbol of the Mediterranean diet. Hydroxytyrosol is an olive-derived compound known for its antioxidant and cardioprotective effects. Acknowledging the merit of antioxidants in maintaining endothelial function warrants the application of hydroxytyrosol in endothelial dysfunction salvage and recovery. Endothelial dysfunction (ED) is an impairment of endothelial cells that adversely affects vascular homeostasis. Disturbance in endothelial functioning is a known precursor for atherosclerosis and, subsequently, coronary and peripheral artery disease.
  • 486
  • 10 Mar 2023
Topic Review
TG2 in Inflammation and Sepsis
Transglutaminase 2 (TG2) is a crosslinking enzyme that forms a covalent bond between lysine and glutamine. TG2 plays important roles in diverse cellular processes, including extracellular matrix stabilization, cytoskeletal function, cell motility, adhesion, signal transduction, apoptosis, and cell survival.
  • 485
  • 10 Mar 2021
Topic Review
Gut Microbiota and Inflammatory Changes
Intestinal microbiota have a series of beneficial effects on the normal development of the human organism, but disturbing the homeostasis between the gut bacteria and the immune response can lead to inflammatory changes.
  • 485
  • 30 Jun 2021
Topic Review
Neuroendocrine–Immune Regulatory Network of Eucommia ulmoides Oliver
Eucommia ulmoides Oliver (E. ulmoides) is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine–immune (NEI) network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine.
  • 485
  • 22 Jun 2022
Topic Review
Mucosal DNA Vaccines Inoculated via the Airway
The highly vascularized URT is the primary route of ingress of inhaled pathogens. A dense network of mucosal-associated lymphoid tissues (MALTs) is in the mucosal tissues to help induce pathogen-specific immune responses, reducing occurrences of infections. 
  • 483
  • 29 Mar 2022
Topic Review
Anthracycline Dutomycin
Anthracycline dutomycin is a tetracyclic quinone glycoside produced by Streptomyces minoensis NRRL B-5482. SW91 is a C-12 demethylated dutomycin derivative. In vitro cytotoxicity and apoptosis assays of these two compounds were conducted to demonstrate their antiproliferation activities.
  • 483
  • 24 Jun 2022
Topic Review
Two Non-Tablet Oral Formulations of L-Thyroxine
Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T4) has improved individualization of dosing regimens. However, up to 40–45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to L-T4 replacement therapy includes all situations of unintended drug–drug and drug–food interactions as well as fasting conditions that are not necessarily respected by patients. The non-tablet L-T4 soft-gel capsules and solution have proven bioequivalence with the usual L-T4 tablet Princeps and generic formulations. Clinical studies have suggested higher performance of non-tablet formulations than tablet in those patients with suboptimal adherence. 
  • 483
  • 22 Jul 2022
Topic Review
Steroidal (Glyco)Alkaloids: Classification
Steroidal (glycol)alkaloids S(G)As are secondary metabolites made of a nitrogen-containing steroidal skeleton linked to a (poly)saccharide, naturally occurring in the members of the Solanaceae and Liliaceae plant families. The genus Solanum is familiar to all of us as a food source (tomato, potato, eggplant), but a few populations have also made it part of their ethnobotany for their medicinal properties. The recent development of the isolation, purification and analysis techniques have shed light on the structural diversity among the SGAs family, thus attracting scientists to investigate their various pharmacological properties. 
  • 483
  • 11 Jul 2023
Topic Review
Application of Probiotics for Acne Vulgaris Topical Therapies
The skin microbiome is an essential barrier for preventing the invasion of pathogens and regulating the immune responses. When this barrier is disrupted, several dermatoses, including acne vulgaris, may arise. Probiotics have proven to be an alternative to the use of antibiotics, often associated with undesirable effects, in the treatment and prevention of dermatological disorders such as acne. 
  • 480
  • 30 May 2023
Topic Review
Bimetallic Au–Ag Nanoparticles
Bimetallic nanoparticles (NPs) with two separate metals have been found to have stronger antibacterial potential than their monometallic versions. This enhanced antibacterial efficiency of bimetallic nanoparticles is due to the synergistic effect of their participating monometallic counterparts. To distinguish between bacteria and mammals, the existence of diverse metal transport systems and metalloproteins is necessary for the use of bimetallic Au–Ag NPs, just like any other metal NPs. Due to their very low toxicity toward human cells, these bimetallic NPs, particularly gold–silver NPs, might prove to be an effective weapon in the arsenal to beat emerging drug-resistant bacteria. The cellular mechanism of bimetallic nanoparticles for antibacterial activity consists of cell membrane degradation, disturbance in homeostasis, oxidative stress, and the production of reactive oxygen species. The synthesis of bimetallic nanoparticles can be performed by a bottom-up and top-down strategy. The bottom-up technique generally includes sol-gel, chemical vapor deposition, green synthesis, and co-precipitation methods, whereas the top-down technique includes the laser ablation method.
  • 480
  • 20 Jun 2023
Topic Review
Developments on 14-Oxygenated-N-methylmorphinan-6-ones
Adequate pain management, particularly chronic pain, remains a major challenge associated with modern-day medicine. Current pharmacotherapy offers unsatisfactory long-term solutions due to serious side effects related to the chronic administration of analgesic drugs. Morphine and structurally related derivatives (e.g., oxycodone, oxymorphone, buprenorphine) are highly effective opioid analgesics, mediating their effects via the activation of opioid receptors, with the mu-opioid receptor subtype as the primary molecular target. However, they also cause addiction and overdose deaths, which has led to a global opioid crisis in the last decades. Therefore, research efforts are needed to overcome the limitations of present pain therapies with the aim to improve treatment efficacy and to reduce complications.
  • 479
  • 30 Sep 2021
Topic Review
Methodologies for the physico-chemical characterization of biopharmaceuticals
Biopharmaceuticals are medicinal products obtained by biotechnological processes using molecular biology methods, which include proteins, sugars, nucleic acids, cells, tissues, used for therapeutic or diagnostic purposes in vivo. Genetically modified plants, animals, or microorganisms are also potentially used to produce biopharmaceuticals.
  • 479
  • 29 Mar 2022
Topic Review
Drug Delivery Hurdles in Skin Cancer Treatment
Chemotherapy of skin cancer can be either oral, parenteral, or topical. In the first case, only a limited amount of the drug reaches the target site, while the rest reaches other organs, tissues, and cells, and can cause harmful side effects. The case is quite similar in parenteral application together with its invasiveness. Therefore, the local application on different skin cancer forms can gain in therapeutic efficacy and safety. The various types of gel formulations applied topically in the treatment of skin cancer was discussed. The most common gelling agents, their concentration and mechanism of action is also provided. The possibility to combine nanotechnology for improvement of drug loading and delivery by incorporation of nanoparticles into hydrogels is also evaluated. The main methods for gel characterization in the light of topical delivery of chemotherapeutics were summarized.
  • 476
  • 05 May 2023
Topic Review
Peimine, an Anti-Inflammatory Compound from Chinese Herbal Extracts
Fritillaria bulbs are used in Traditional Chinese Medicine to treat several illnesses. Peimine (Pm), an anti-inflammatory compound from Fritillaria, is known to inhibit some voltage-dependent ion channels and muscarinic receptors, but its interaction with ligand-gated ion channels remains unexplored.
  • 474
  • 29 Mar 2022
Topic Review
Mechanistically Coupled PK (MCPK) Model of Dabrafenib Metabolism
Dabrafenib inhibits the cell proliferation of metastatic melanoma with the oncogenic BRAF(V600)-mutation. However, dabrafenib monotherapy is associated with pERK reactivation, drug resistance, and consequential relapse. A clinical drug-dose determination study shows increased pERK levels upon daily administration of more than 300 mg dabrafenib. To clarify whether such elevated drug concentrations could be reached by long-term drug accumulation, the pharmacokinetics (MCPK) of dabrafenib and its metabolites were mechanistically coupled. The MCPK model is qualitatively based on in vitro and quantitatively on clinical data to describe occupancy-dependent CYP3A4 enzyme induction, accumulation, and drug–drug interaction mechanisms. The prediction suggests an eight-fold increase in the steady-state concentration of potent desmethyl-dabrafenib and its inactive precursor carboxy-dabrafenib within four weeks upon 150 mg b.d. dabrafenib. While it is generally assumed that a higher dose is not critical, it was found experimentally that a high physiological dabrafenib concentration fails to induce cell death in embedded 451LU melanoma spheroids.
  • 474
  • 29 Jan 2022
Topic Review
Metformin in Diabetic and Non-Diabetic Bone Impairment
Metformin is a widely-used anti-diabetic drug in patients with type 2 diabetic mellitus (T2DM) due to its safety and efficacy in clinical. The classic effect of metformin on lowering blood glucose levels is to inhibit liver gluconeogenesis that reduces glucose production as well as increases peripheral glucose utilization. However, the factors such as hyperglycemia, insulin deficiency, reduced serum levels of insulin-like growth factor-1 (IGF-1) and osteocalcin, accumulation of advanced glycation end products (AGEs), especially in collagen, microangiopathy, and inflammation reduced bone quality in diabetic patients. However, hyperglycemia, insulin deficiency, reduced levels of insulin-like growth factor-1 (IGF-1) and osteocalcin in serum, accumulation of advanced glycation end products (AGEs) in collagen, microangiopathy, and inflammation, reduce bone quality in diabetic patients. Furthermore, the imbalance of AGE/RAGE results in bone fragility via attenuating osteogenesis. Thus, adequate glycemic control by medical intervention is necessary to prevent bone tissue alterations in diabetic patients. Metformin mainly activates adenosine 5′ -monophosphate-activated protein kinase (AMPK), and inhibits mitochondrial respiratory chain complex I in bone metabolism. In addition, metformin increases the expression of transcription factor runt-related transcription factor2 (RUNX2) and Sirtuin protein to regulate related gene expression in bone formation. Until now, there are a lot of preclinical or clinical findings on the application of metformin to promote bone repair. Taken together, metformin is considered as a potential medication for adjuvant therapy in bone metabolic disorders further to its antidiabetic effect. Taken together, as a conventional hypoglycemia drug with multifaceted effects, metformin has been considered a potential adjuvant drug for the treatment of bone metabolic disorders. 
  • 474
  • 01 Nov 2022
Topic Review
Treatment Advances in Sepsis and Septic Shock
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, and it affects over 25 million people every year. Even more severe, septic shock is a subset of sepsis defined by persistent hypotension, and hospital mortality rates are higher than 40%. As new pathophysiological mechanisms have been uncovered, immunostimulatory therapy has emerged as a promising path forward. Highly investigated treatment strategies include cytokines and growth factors, immune checkpoint inhibitors, and even cellular therapies.
  • 474
  • 04 May 2023
Topic Review
Docking Studies of Recently Synthesized MAO-B Inhibitors
With the significant growth of patients suffering from neurodegenerative diseases (NDs), novel classes of compounds targeting monoamine oxidase type B (MAO-B) are promptly emerging as distinguished structures for the treatment of the latter. As a promising function of computer-aided drug design (CADD), structure-based virtual screening (SBVS) is being heavily applied in processes of drug discovery and development. The utilization of molecular docking, as a helping tool for SBVS, is providing essential data about the poses and the occurring interactions between ligands and target molecules. 
  • 472
  • 13 Jul 2023
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