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Topic Review
Pharmacogenomics Variability of Lipid-Lowering Therapies
The exponential expansion of genomic data coupled with the lack of appropriate clinical categorization of the variants is posing a major challenge to conventional medications for many common and rare diseases. To narrow this gap and achieve the goals of personalized medicine, a collaborative effort should be made to characterize the genomic variants functionally and clinically with a massive global genomic sequencing of “healthy” subjects from several ethnicities. Familial-based clustered diseases with homogenous genetic backgrounds are amongst the most beneficial tools to help address this challenge
  • 752
  • 11 Oct 2021
Topic Review
Ligand-Free Signaling of G-Protein-Coupled Receptors
Numerous G-protein-coupled receptors (GPCRs) display ligand-free basal signaling with potential physiological functions, a target in drug development. As an example, the μ opioid receptor (MOR) signals in ligand-free form (MOR-μ*), influencing opioid responses. In addition, agonists bind to MOR but can dissociate upon MOR activation, with ligand-free MOR-μ* carrying out signaling. Opioid pain therapy is effective but incurs adverse effects (ADRs) and risk of opioid use disorder (OUD). Sustained opioid agonist exposure increases persistent basal MOR-μ* activity, which could be a driving force for OUD and ADRs. Antagonists competitively prevent resting MOR (MOR-μ) activation to MOR-μ*, while common antagonists, such as naloxone and naltrexone, also bind to and block ligand-free MOR-μ*, acting as potent inverse agonists. A neutral antagonist, 6β-naltrexol (6BN), binds to but does not block MOR-μ*, preventing MOR-μ activation only competitively with reduced potency. 
  • 752
  • 17 Oct 2022
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.
  • 750
  • 30 Jun 2021
Topic Review
Interventional Methods against Neuropathic Pain
Neuropathic pain affects more than one million people across the globe. The quality of life of people suffering from neuropathic pain has been considerably declining due to the unavailability of appropriate therapeutics. Available treatment options can only treat patients symptomatically, but they are associated with severe adverse side effects and the development of tolerance over prolonged use. Continuous efforts are evident, aiming to develop novel interventions with better efficacy instead of symptomatic treatment. Available pharmacotherapeutics are unable to manage pain on a long-term basis and patients are developing resistance and tolerance to pain management medications over time; therefore, it is necessary to investigate non-pharmacological or interventional approaches. Interventional treatments, including nerve blocks or surgeries for targeted drug delivery, or specific neural modulation, provide alternate strategies in refractory cases.
  • 749
  • 11 Aug 2022
Topic Review
Treating Epilepsy with Natural Products
Epilepsy is a neurological disease characterized by recurrent seizures that can lead to uncontrollable muscle twitching, changes in sensitivity to sensory perceptions, and disorders of consciousness. Although modern medicine has effective antiepileptic drugs, the need for accessible and cost-effective medication is urgent, and products derived from plants could offer a solution.
  • 749
  • 10 Aug 2023
Topic Review
Main Metabolic Pathways with Respect to Alzheimer’s Disease
Alzheimer’s disease (AD) is an aging-related neurodegenerative disease, leading to the progressive loss of memory and other cognitive functions. Metabolomics allows the study of biochemical alterations in pathological processes which may be involved in AD progression and to discover new therapeutic targets. Metabolites are substrates, intermediates, and products of metabolic body processes, which typically are small molecules with a molecular weight of less than ~1.5 kDa. Since low molecular weight metabolites are intermediates or end products of cellular metabolism, metabolomics, or the study of metabolism can be considered one of the core disciplines of systems biology. It can help in improving our understanding of changes in biochemical pathways, revealing crucial information that is closely related to human disease or therapeutic status.
  • 748
  • 21 Mar 2023
Topic Review
Therapeutic Potential of Serotonin Type 7 Receptor Modulation
Although a number of mood-stabilising atypical antipsychotics and antidepressants modulate serotonin type 7 receptor (5-HT7), the detailed contributions of 5-HT7 function to clinical efficacy and pathophysiology have not been fully understood. The mood-stabilising antipsychotic agent, lurasidone, and the serotonin partial agonist reuptake inhibitor, vortioxetine, exhibit higher binding affinity to 5-HT7 than other conventional antipsychotics and antidepressants. The initially expected rapid onset of antidepressant effects—in comparison with conventional antidepressants or mood-stabilising antipsychotics—due to 5-HT7 inhibition has not been observed with lurasidone and vortioxetine; however, several clinical studies suggest that 5-HT7 inhibition likely contributes to quality of life of patients with schizophrenia and mood disorders via the improvement of cognition. Furthermore, it reported that 5-HT7 inhibition might mitigate antipsychotic-induced weight gain and metabolic complication by blocking other monoamine receptors. Further preclinical studies for the development of 5-HT7 modulation against neurodevelopmental disorders and neurodegenerative diseases have been ongoing. Various findings from various preclinical studies indicate the possibility that 5-HT7 modifications can provide two independent strategies. The first is that 5-HT7 inhibition ameliorates the dysfunction of inter-neuronal transmission in mature networks. The other is that activation of 5-HT7 can improve transmission dysfunction due to microstructure abnormality in the neurotransmission network—which could be unaffected by conventional therapeutic agents—via modulating intracellular signalling during the neurodevelopmental stage or via loss of neural networks with aging.
  • 746
  • 24 Mar 2023
Topic Review
Physiological Cooperation between Aquaporin 5 and TRPV4
Aquaporins—among them, AQP5—are responsible for transporting water across biological membranes, which is an important process in all living organisms. The transient receptor potential channel 4 (TRPV4) is a cation channel that is mostly calcium-permeable and can also be activated by osmotic stimuli. It plays a role in a number of different functions in the body, e.g., the development of bones and cartilage, and it is involved in the body’s osmoregulation, the generation of certain types of sensation (pain), and apoptosis. Earlier studies on the uterus and the literature data aroused the interest in the physiological role of the cooperation of AQP5 and TRPV4. Understanding the cooperation between AQP5 and TRPV4 may contribute to the development of new drug candidates and the therapy of several disorders (e.g., preterm birth, cataract, ischemia/reperfusion-induced edema, exercise- or cold-induced asthma).
  • 744
  • 14 Oct 2022
Topic Review
3-Iodothyronamine and 3-Iodothyroacetic Acid
3-iodothyronamine (T1AM) and 3-iodothyroacetic acid (TA1) are thyroid-hormone-related compounds endowed with pharmacological activity through mechanisms that remain elusive. Some evidence suggests that they may have redox features.
  • 741
  • 21 Mar 2022
Topic Review
Dipeptidyl Peptidase 4 Inhibitors
Information on absorption, metabolism and excretion of drugs is necessary to support the studies on their pharmacokinetics and potential drug–drug interactions. Moreover, the knowledge on drug metabolism is one of the crucial factors used to assess their pharmacokinetic profile in patients with some dysfunctions. It is especially important in diabetic patients with higher incidence of chronic liver and kidney problems.
  • 741
  • 27 Jul 2023
Topic Review
Disrupting GPCR Complexes with Smart Drug-like Peptides
G protein-coupled receptors (GPCRs) are a superfamily of proteins classically described as monomeric transmembrane (TM) receptors. However, increasing evidence indicates that many GPCRs form higher-order assemblies made up of monomers pertaining to identical (homo) or to various (hetero) receptors. The formation and structure of these oligomers, their physiological role and possible therapeutic applications raise a variety of issues that are currently being actively explored. In this context, synthetic peptides derived from TM domains stand out as powerful tools that can be predictably targeted to disrupt GPCR oligomers, especially at the interface level, eventually impairing their action.
  • 740
  • 10 Feb 2022
Topic Review
Regulation of P-glycoprotein
P-glycoprotein (Pgp, ABCB1 protein, MDR1) is a transporter protein, the most studied representative of the ABC transporter superfamily. Pgp is an efflux protein: it ensures the outflow of molecules from cells into the extracellular space.
  • 738
  • 26 Feb 2024
Topic Review
Natural Molecules for Neurodegenerative Diseases
Natural molecules with favorable safety profile and broad pharmacological activities have shown great promise in the treatment of various neurodegenerative diseases (NDDs). Studies applying natural molecules against NDDs mainly focus on well-recognized conventional pathogenesis, such as toxic protein aggregation, oxidative stress, and neuroinflammation. However, accumulating evidence reveals that some underlying pathogenic mechanisms are involved earlier and more deeply in the occurrence and development of NDDs, such as ferroptosis, energy metabolism disorders, autophagy-lysosomal dysfunction, endoplasmic reticulum stress, and gut dysbiosis. Therefore, determining whether natural molecules can play therapeutic roles in these emerging pathogenic mechanisms will help clarify the actual targets of natural molecules and their future clinical translation.
  • 737
  • 14 Nov 2022
Topic Review
Cistus albidus L.
Cistus albidus is one of the approximately 20 species of the Cistus genus. The genus’ name is derived from the ancient Greek term kistos. It is supposed that the name alludes to the woody capsule fruits. Evergreen in its Mediterranean homeland and between 50 and 250 centimeters tall, this shrub is called albidus, not because of the colour of its flowers, but because its leaves are finely covered with white hair (trichomes).
  • 737
  • 23 May 2024
Topic Review
Autophagy in Uveal Melanoma
Autophagy is a form of programmed cell degradation that enables the maintenance of homeostasis in response to extracellular stress stimuli. Autophagy is primarily activated by starvation and mediates the degradation, removal, or recycling of cell cytoplasm, organelles, and intracellular components in eukaryotic cells. Autophagy is also involved in the pathogenesis of human diseases, including several cancers. Autophagy mechanisms and mediators have emerged as promising therapeutic targets that could be used to develop new treatment options for uveal melanoma (UM).
  • 735
  • 28 Feb 2024
Topic Review
BMVs for Drug Delivery Applications
Numerous factors need to be considered to develop a nanodrug delivery system that is biocompatible, non-toxic, easy to synthesize, cost-effective, and feasible for scale up over and above their therapeutic efficacy. With regards to this, worldwide, exosomes, which are nano-sized vesicles obtained from mammalian cells, are being explored as a biomimetic drug delivery system that has superior biocompatibility and high translational capability. However, the economics of undertaking large-scale mammalian culture to derive exosomal vesicles for translation seems to be challenging and unfeasible. Recently, Bacterial Membrane Vesicles (BMVs) derived from bacteria are being explored as a viable alternative as biomimetic drug delivery systems that can be manufactured relatively easily at much lower costs at a large scale. Until now, BMVs have been investigated extensively as successful immunomodulating agents, but their capability as drug delivery systems remains to be explored in detail. 
  • 734
  • 24 Sep 2021
Topic Review
Glucagon and Its Receptors in the Mammalian Heart
Glucagon exerts effects on the mammalian heart. These effects include alterations in the force of contraction, beating rate, and changes in the cardiac conduction system axis. The cardiac effects of glucagon vary according to species, region, age, and concomitant disease. Depending on the species and region studied, the contractile effects of glucagon can be robust, modest, or even absent. Glucagon is detected in the mammalian heart and might act with an autocrine or paracrine effect on the cardiac glucagon receptors. The glucagon levels in the blood and glucagon receptor levels in the heart can change with disease or simultaneous drug application. 
  • 733
  • 06 Sep 2023
Topic Review
Pyroptosis and Cancer
Pyroptosis is a programmed cell death characterized by the rupture of the plasma membranes and release of cellular content leading to inflammatory reaction. Four cellular mechanisms inducing pyroptosis have been reported, including the (i) caspase 1-mediated canonical, (ii) caspase 4/5/11-mediated non-canonical, (iii) caspase 3/8-mediated and (iv) caspase-independent pathways. Although discovered as a defense mechanism protecting cells from infections of intracellular pathogens, pyroptosis plays roles in tumor initiation, progression and metastasis of tumors, as well as in treatment response to antitumor drugs and, consequently, patient outcome. Pyroptosis induction following antitumor therapies has been reported in several tumor types, including lung, colorectal and gastric cancer, hepatocellular carcinoma and melanoma.
  • 731
  • 29 Jan 2023
Topic Review
HSP Injection Therapies in Stroke
Hemiplegic shoulder pain (HSP) is one of the most debilitating complications after stroke [1]. Hemiplegic shoulder pain (HSP) hampers post-stroke functional recovery and is not well managed with conservative treatments.
  • 730
  • 28 Sep 2021
Topic Review
Strategies for the Appropriateness of Medication Use
The evidence on the effectiveness of strategies and tools to promote and improve medication appropriateness and their sustainability largely derives from local and heterogeneous experiences with contrasting results. As a general framework, three main steps should be considered in implementing measures to improve the appropriateness of medications: prescription, acceptance by the patient, and continuous monitoring of adherence and the risk-benefit profile. Each step needs efforts from specific actors (physicians, patients, caregivers, healthcare professionals) and dedicated supporting tools. Moreover, how to support the appropriateness also strictly depends on the particular care setting (hospital, ambulatory or primary care, nursing home, long-term care) and available economic resources. 
  • 726
  • 23 Sep 2022
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