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Topic Review
Metabolism and Chemical Degradation of Glutides and Gliflozins
The drug metabolism and drug degradation pathways may overlap, resulting in the formation of similar constituents. Therefore, the metabolism data can be helpful for deriving safe levels of degradation impurities and improving the quality of respective pharmaceutical products. The entry contains considerations on possible links between metabolic and degradation pathways for new antidiabetic drugs such as glutides, gliflozins, and gliptins. Special attention was paid to their reported metabolites and identified degradation products. At the same time, many interesting analytical approaches to conducting metabolism as well as degradation experiments were mentioned, including chromatographic methods and radioactive labeling of the drugs. 
  • 275
  • 04 Aug 2023
Topic Review
Proteolytic Activation of the Epithelial Sodium Channel
Epithelial sodium channel (ENaC) are integral to maintaining salt and water homeostasis in various biological tissues, including the kidney, lung, and colon. They enable the selective reabsorption of sodium ions, which is a process critical for controlling blood pressure, electrolyte balance, and overall fluid volume. ENaC activity is finely controlled through proteolytic activation, a process wherein specific enzymes, or proteases, cleave ENaC subunits, resulting in channel activation and increased sodium reabsorption. This regulatory mechanism plays a pivotal role in adapting sodium transport to different physiological conditions.
  • 269
  • 29 Dec 2023
Topic Review
Natural Products as Novel Medications for Parkinson’s Disease
As the global population ages, the prevalence of Parkinson’s disease (PD) is steadily on the rise. PD demonstrates chronic and progressive characteristics, and many cases can transition into dementia. This increases societal and economic burdens, emphasizing the need to find effective treatments. Among the widely recognized causes of PD is the abnormal accumulation of proteins, and autophagy dysfunction accelerates this accumulation. The resultant Lewy bodies are also commonly found in Alzheimer’s disease patients, suggesting an increased potential for the onset of dementia. Additionally, the production of free radicals due to mitochondrial dysfunction contributes to neuronal damage and degeneration. The activation of astrocytes and the M1 phenotype of microglia promote damage to dopamine neurons. The drugs currently used for PD only delay the clinical progression and exacerbation of the disease without targeting its root cause, and come with various side effects. Thus, there is a demand for treatments with fewer side effects, with much potential offered by natural products. 
  • 266
  • 26 Jan 2024
Topic Review
Cyclodextrins and Their Derivatives as Drug Stability Modifiers
Cyclodextrins (CDs) are versatile excipients that are widely used in the pharmaceutical industry as receptor molecules to form complexes with drugs. CDs are cyclic oligosaccharides composed of α-1,4-linked D-glucopyranoside subunits obtained through enzymatic starch degradation.
  • 265
  • 09 Aug 2023
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.
  • 261
  • 26 Feb 2024
Topic Review
Drug–Drug Interactions Involving Dexamethasone in Clinical Practice
Concomitant administration of multiple drugs frequently causes severe pharmacokinetic or pharmacodynamic drug–drug interactions (DDIs) resulting in the possibility of enhanced toxicity and/or treatment failure. The activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), a drug efflux pump sharing localization and substrate affinities with CYP3A4, is a critical determinant of drug clearance, interindividual variability in drug disposition and clinical efficacy, and appears to be involved in the mechanism of numerous clinically relevant DDIs, including those involving dexamethasone. The recent increase in the use of high doses of dexamethasone during the COVID-19 pandemic have emphasized the need for better knowledge of the clinical significance of drug–drug interactions involving dexamethasone in the clinical setting. 
  • 258
  • 18 Dec 2023
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. 
  • 254
  • 06 Sep 2023
Topic Review
Pharmacological Properties of Steviol Glycosides
Stevia rebaudiana Bertoni (Asteraceae) is a small perennial herb endemic to South America. Dry stevia leaves have been used to sweeten traditional bitter drinks. Steviol glycosides exhibit a superior sweetener proficiency to that of sucrose and are noncaloric, noncariogenic, and nonfermentative. Scientific evidence encourages stevioside and rebaudioside A as sweetener alternatives to sucrose and supports their use based on their absences of harmful effects on human health. Moreover, these active compounds isolated from Stevia rebaudiana possess interesting medicinal activities, including antidiabetic, antihypertensive, anti-inflammatory, antioxidant, anticancer, and antidiarrheal activity. 
  • 251
  • 16 Aug 2023
Topic Review
RNA Combined with Nanoformulation to Advance Therapeutic Technologies
Nucleic acid-based therapies have the potential to address numerous diseases that pose significant challenges to more traditional methods. RNA-based therapies have emerged as a promising avenue, utilizing nanoformulation treatments to target a range of pathologies. Nanoformulation offers several advantages compared to other treatment modalities, including targeted delivery, low toxicity, and bioactivity suitable for drug loading. Various types of nanoformulations are available, such as liposomes, polymeric nanoparticles (NPs), magnetic NPs, nanoshells, and solid lipid nanoparticles (SLNs). RNA-based therapy utilizes intracellular gene nanoparticles with messenger RNA (mRNA) emerging prominently in cancer therapy and immunotechnology against infectious diseases. The approval of mRNA-based technology opens doors for future technological advancements, particularly self-amplifying replicon RNA (repRNA). RepRNA is a novel platform in gene therapy, comprising viral RNA with a unique molecular property that enables the amplification of all encoded genetic information countless times. As a result, repRNA-based therapies have achieved significant levels of gene expression.
  • 251
  • 19 Dec 2023
Topic Review
Anticancer Effects of α-Linolenic Acid
α-linolenic acid (ALA) belongs to the family of n-3 polyunsaturated fatty acids (n-3 PUFAs) and contains a carbon–carbon double bond on the third carbon atom at the methyl end of the carbon chain. This family of essential fatty acids also includes eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA has gradually attracted increased attention due to its nutritional and medicinal advantages. Studies have shown that ALA exerts beneficial effects on a variety of diseases, including cancer.
  • 248
  • 19 Mar 2024
Topic Review
Overexpression of Glutathione S-Transferases in Human Diseases
Glutathione S-transferases (GSTs) are a major class of phase II metabolic enzymes. Besides their essential role in detoxification, GSTs also exert diverse biological activities in the occurrence and development of various diseases. Much research interest has been paid to exploring the mechanisms of GST overexpression in tumor drug resistance. Correspondingly, many GST inhibitors have been developed and applied, solely or in combination with chemotherapeutic drugs, for the treatment of multi-drug resistant tumors. Moreover, novel roles of GSTs in other diseases, such as pulmonary fibrosis and neurodegenerative diseases, have been recognized, although the exact regulatory mechanisms remain to be elucidated.
  • 247
  • 27 Nov 2023
Topic Review
Impact of Solute Carrier Transporters in Glioma Pathology
Solute carriers (SLCs) are the largest family of transmembrane transporters (consisting of 439 proteins without the pseudogenes), which are divided into 65 subfamilies (60 of which have been identified in the brain). They play a crucial role in exchanging different substances such as nutrients, ions, metabolites, as well as drugs through biological membranes. Most SLCs share the same protein structure consisting of 12 presumed transmembrane segments with molecular mass ranging between 50 to 100 kDa.
  • 244
  • 06 Jun 2023
Topic Review
Non-Dopaminergic Antipsychotic Mechanisms of Neuroleptic Drugs
In 1957, Arvid Carlsson discovered that dopamine, at the time believed to be nothing more than a norepinephrine precursor, was a brain neurotransmitter in and of itself. By 1963, postsynaptic dopamine blockade had become the cornerstone of psychiatric treatment as it appeared to have deciphered the “chlorpromazine enigma”, a 1950s term, denoting the action mechanism of antipsychotic drugs.
  • 239
  • 23 Jan 2024
Topic Review
Impact of Pharmacogenomics in Clinical Practice
Polymorphisms of genes encoding drug metabolizing enzymes and transporters can significantly modify pharmacokinetics, and this can be associated with significant differences in drug efficacy, safety, and tolerability. Moreover, genetic variants of some components of the immune system can explain clinically relevant drug-related adverse events. Knowledge of how genetic variations can modify the effectiveness, safety, and tolerability of a drug can lead to the adjustment of usually recommended drug dosages, improve effectiveness, and reduce drug-related adverse events. 
  • 237
  • 19 Jan 2024
Topic Review
Cellular, Molecular, Pharmacological, and Nano-Formulation Aspects of Thymoquinone
The goal of an antiviral agent research is to find an antiviral drug that reduces viral growth without harming healthy cells. Transformations of the virus, new viral strain developments, the resistance of viral pathogens, and side effects are the current challenges in terms of discovering antiviral drugs. The time has come and it is now essential to discover a natural antiviral agent that has the potential to destroy viruses without causing resistance or other unintended side effects. The pharmacological potency of thymoquinone (TQ) against different communicable and non-communicable diseases has been proven by various studies, and TQ is considered to be a safe antiviral substitute. 
  • 232
  • 17 Oct 2023
Topic Review
Resveratrol and Gut Microbiota Synergy
Resveratrol (RSV) exerts beneficial properties in the modulation of cardiovascular, metabolic, and post-COVID-19-related disorders. In healthy individuals, it maintains an ergogenic capacity, prevents oxidative stress, and modulates the inflammatory response. Overall, it improves quality of life. The RSV–gut-microbiota interaction is beneficial in terms of maintaining human health. Along with physical activity, it is key for the prevention of chronic noncommunicable diseases.
  • 232
  • 22 Dec 2023
Topic Review
Health-Promoting Effect of Lycopene
Lycopene is a compound of colored origin that shows strong antioxidant activity. The positive effect of lycopene is the result of its pleiotropic effect. The ability to neutralize free radicals via lycopene is one of the foundations of its pro-health effect, including the ability to inhibit the development of many civilization diseases.
  • 226
  • 15 Sep 2023
Topic Review
Nano-Formulations for Pulmonary Delivery
With the development of nanotechnology and confronting the problems of traditional pharmaceutical formulations in treating lung diseases, inhalable nano-formulations have attracted interest. Inhalable nano-formulations for treating lung diseases allow for precise pulmonary drug delivery, overcoming physiological barriers, improving aerosol lung deposition rates, and increasing drug bioavailability. They are expected to solve the difficulties faced in treating lung diseases. 
  • 223
  • 07 Feb 2024
Topic Review
Opioid-Induced Constipation in Cancer Patients
Opioid-induced constipation (OIC) is a disabling symptom which 60–90 percent of cancer patients with chronic opioid use experience. Peripherally acting μ-opioid receptor antagonists (PAMORAs) are a class of medications aiming to reverse opioids’ adverse effects on the gut by interacting with opioid receptors in the gastrointestinal tract without significantly crossing the blood–brain barrier, and therefore they are not affecting the analgesic opioid effects in the central nervous system.
  • 223
  • 22 Mar 2024
Topic Review
Suicidality Risk of Chronic Pain Medications
Chronic pain is one of the main leading causes of disability in the world at present. A variety in the symptomatology, intensity and duration of this phenomenon has led to an ever-increasing demand of pharmacological treatment and relief. This demand for medication, ranging from well-known groups, such as antidepressants and benzodiazepines, to more novel drugs, was followed by a rise in safety concerns of such treatment options. 
  • 220
  • 30 Oct 2023
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