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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. 
  • 462
  • 17 Oct 2022
Topic Review
Pleiotropic Effects of Vitamin D in Inflammatory-Based Diseases
Numerous pleiotropic effects have been reported for vitamin D (vit D) since its discovery a century ago. Today it is well known that in addition to its pivotal role in calcium homeostasis and bone metabolism, vit D has antibacterial, anti-proliferative, immunomodulatory, and anti-inflammatory actions, among other beneficial properties. In the context of inflammatory-based diseases, vit D and its receptor VDR might fulfil their roles as gene regulators through direct gene regulation and epigenetic mechanisms.
  • 462
  • 10 Feb 2023
Topic Review
Agrimonolide from Agrimonia pilosa Ledeb.
Agrimonolide (AM), which is a derivative of isocoumarins, is found mainly in the herb Agrimonia pilosa Ledeb. This compound is highly lipophilic and readily crosses the blood–brain barrier. Interest has grown in the use of AM as a multitarget natural treatment for various diseases, such as cancer, inflammation, hepatic injury, myocardial damage, and diabetes mellitus. The potential mechanisms of these pharmacological effects have been clarified at cellular and molecular levels. AM shows no cytotoxicity over a range of concentrations in different types of cells, providing evidence for its good safety profile in vitro. These findings indicate that AM is a promising medicinal agent.
  • 462
  • 15 Feb 2023
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.
  • 460
  • 21 Mar 2022
Topic Review
Prunella vulgaris L.
Prunella vulgaris L. (PV) is a well-known renewable drug resource full of different groups of biologically active substances with a wide range of pharmacological actions and applications in medicine.
  • 460
  • 09 Aug 2023
Topic Review
Natural Polymer Nanofibrous Scaffold
Nanofibrous scaffolds mimicking artificial extracellular matrices provide a natural environment for tissue regeneration owing to their large surface area, high porosity, and appreciable drug loading capacity. Electrospun nanofibrous scaffolds have demonstrated promising potential in bone tissue regeneration using a variety of nanomaterials. Natural and synthetic polymeric nanofibrous scaffolds are extensively inspected to regenerate bone tissue. Bone tissue engineering (BTE) procedures make usage of various scaffolds (e.g., composite scaffolds, nanofibrous scaffolds, porous scaffolds, hydrogel scaffolds) in conjunction with biological materials.
  • 459
  • 17 Oct 2022
Topic Review
Therapeutic Potential of Myrtenal and Its Derivatives
Myrtenal is a perspective monoterpenoid with therapeutic potential in various fields of medicine. Its chemical modifications often lead to new or more pronounced biological effects. As an example, the conjugation of myrtenal with the established pharmacophore adamantane enables the augmentation of several of its pivotal properties. Myrtenal–adamantane derivatives exhibited a variety of beneficial characteristics, such as antimicrobial, antifungal, antiviral, anticancer, anxiolytic, and neuroprotective properties, which are worth examining in more detail and at length.
  • 457
  • 30 Oct 2023
Topic Review
Supramolecules in Traditional Chinese Medicine Decoction
The chemical components of traditional Chinese medicine have various sources and unique structures. During the high-temperature boiling process, various active components form supramolecules due to complex interactions. The supramolecular structure in a traditional Chinese medicine decoction can not only be used as a drug carrier to promote the absorption and distribution of medicinal components but may also have biological activities superior to those of single active ingredients or their physical mixtures. 
  • 456
  • 10 Jun 2022
Topic Review
Therapeutic Potential of Fungal Terpenes and Terpenoids
Terpenes and their derivatives comprise a diverse group of natural compounds with versatile medicinal properties. This article elucidates the general characteristics of fungal terpenes and terpenoids, encompassing their structure and biogenesis. The focal point of this work involves a comprehensive overview of these compounds, highlighting their therapeutic properties, mechanisms of action, and potential applications in treating specific skin conditions. Numerous isolated terpenes and terpenoids have demonstrated noteworthy anti-inflammatory and anti-microbial effects, rivalling or surpassing the efficacy of currently employed treatments for inflammation or skin infections. Due to their well-documented antioxidant and anti-cancer attributes, these compounds exhibit promise in both preventing and treating skin cancer. Terpenes and terpenoids sourced from fungi display the capability to inhibit tyrosinase, suggesting potential applications in addressing skin pigmentation disorders and cancers linked to melanogenesis dysfunctions.
  • 455
  • 15 Apr 2024
Topic Review
Xenobiotics Modulating Aryl Hydrocarbon Receptor in Energy Homeostasis
There are fundamental sex differences in the regulation of energy homeostasis. Better understanding of the underlying mechanisms of energy balance that account for this asymmetry will assist in developing sex-specific therapies for sexually dimorphic diseases such as obesity. Multiple organs, including the hypothalamus and adipose tissue, play vital roles in the regulation of energy homeostasis, which are regulated differently in males and females. Various neuronal populations, particularly within the hypothalamus, such as arcuate nucleus (ARC), can sense nutrient content of the body by the help of peripheral hormones such leptin, derived from adipocytes, to regulate energy homeostasis. Substances from diet and environmental contaminants can exert insidious effects on energy metabolism, acting peripherally through the aryl hydrocarbon receptor (AhR). Developmental AhR activation can impart permanent alterations of neuronal development that can manifest a number of sex-specific physiological changes, which sometimes become evident only in adulthood. AhR is being investigated as a potential target for treating obesity. The consensus is that impaired function of the receptor protects from obesity in mice. AhR also modulates sex steroid receptors.
  • 454
  • 01 Aug 2022
Topic Review
Kidney Tubular Damage Secondary to Deferasirox
Deferasirox is a first-line therapy for iron overload that can sometimes cause kidney damage. A proximal tubulopathy pattern may be observed on treatment with deferasirox. Since deferasirox-associated kidney damage is dose-dependent, physicians should prescribe the lowest efficacious dose. 
  • 451
  • 12 Jan 2022
Topic Review
Clinical Efficacy and Safety, Interchangeability of Biosimilars
Clinical safety and efficacy studies add substantial cost and time to the approval of biosimilars. However, this argument will have little weight if these studies were able to add additional value over and above the rest of the testing. Interchangeability is a legally defined path in the US biosimilar guidance.
  • 450
  • 27 Apr 2022
Topic Review
The Application of Smart Biomaterials in Diabetic Wounds
Diabetes mellitus is a complicated metabolic disease that has become one of the fastest-growing health crises in modern society. Diabetic patients may suffer from various complications, and diabetic foot is one of them. It can lead to increased rates of lower-extremity amputation and mortality, even seriously threatening the life and health of patients. Because its healing process is affected by various factors, its management and treatment are very challenging. To address these problems, smart biomaterials have been developed to expedite diabetic wound closure and improve treatment outcomes. 
  • 450
  • 09 Feb 2023
Topic Review
Nanoparticles in the Intestinal Epithelial Cell Membrane
Intestinal epithelial cells are the most abundant epithelial cells in the intestine, accounting for 90–95% of intestinal cells. They are columnar cells with hair-like projections called microvilli on the apical membrane, which greatly increase the surface area available for absorption. The transintestinal cell pathway refers to the process in which nanoparticles pass through apical and basolateral membranes via intercellular transport and then discharge from the basement membrane to the extracellular space. The entire process can be divided into three stages: the uptake of nanoparticles in the apical membrane of intestinal epithelial cells, the transport of endosomes in the cytoplasm and the exocytosis of nanoparticles in the basement membrane.
  • 450
  • 05 Jul 2023
Topic Review
Metabolic Approaches for Treatment of Dilated Cardiomyopathy
In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic inefficiency caused by an abnormal cardiac metabolism. Although underappreciated as a potential therapeutic target, the optimal metabolic milieu of a failing heart is still largely unknown and subject to debate. Because glucose naturally has a lower P/O ratio (the ATP yield per oxygen atom), the previous studies using this strategy to increase glucose oxidation have produced some intriguing findings. In reality, the vast majority of small-scale pilot trials using trimetazidine, ranolazine, perhexiline, and etomoxir have demonstrated enhanced left ventricular (LV) function and, in some circumstances, myocardial energetics in chronic ischemic and non-ischemic HF with a reduced ejection fraction (EF).
  • 449
  • 26 Jul 2023
Topic Review
Blood Biomarkers of Antipsychotic-Induced Metabolic Syndrome
A biomarker is a characteristic that is objectively measured and evaluated to detect disease in patients. Traditionally, laboratory diagnoses of Metabolic syndrome (MetS) and assessments of cardiovascular risk (CVR) include analyses of blood (serum or plasma) biomarkers, i.e., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), insulin and C-peptide.
  • 448
  • 18 Aug 2022
Topic Review
Complex Pharmacological Properties of Non-Selective Opioid Modulator Buprenorphine
Buprenorphine has high affinity for the mu-opioid receptor (MOR), delta (DOR), and kappa (KOR) and intermediate affinity for the nociceptin (NOR). Buprenorphine’s active metabolite, norbuprenorphine, crosses the blood–brain barrier, is a potent metabolite that attenuates the analgesic effects of buprenorphine due to binding to NOR, and is responsible for the respiratory depressant effects. The area under the concentration curves are very similar for buprenorphine and norbuprenorphine, which indicates that it is important to consider this metabolite. 
  • 447
  • 07 Nov 2023
Topic Review
Disparities in Prevalence and Barriers to Hypertension Control
Controlling hypertension (HTN) remains a challenge, as it is affected by various factors in different settings. The prevalence of hypertension control in the low and middle-income countries and high-income countries studies ranged from (3.8% to 50.4%) to (36.3% to 69.6%), respectively. Concerning barriers to hypertension control, patient-related barriers were the most frequently reported, followed by medication adherence barriers, lifestyle-related barriers, barriers related to the affordability and accessibility of care, awareness-related barriers, and, finally, barriers related to prescribed pharmacotherapy.
  • 446
  • 09 Dec 2022
Topic Review
Cancer Chemotherapy Resistance and Mechanism
Cancer is a global burden, and as per the latest GLOBOCAN 2020, over 19.3 and 10 million new cases and deaths occurred in 2020, respectively; female breast cancer has surpassed lung cancer and is now the most commonly diagnosed cancer (11.7%), followed by lung cancer (11.4%), colorectal cancer (10%), and prostate cancer (7.3%). Cancer chemoresistance is a growing concern in medical oncology.
  • 445
  • 18 Oct 2022
Topic Review
Endocannabinoid Signaling Pathways
Endocannabinoids play an important role as powerful regulators of synaptic function in the central nervous system where they regulate neural functions and behaviors. As fundamental modulators of synaptic function, endocannabinoids can regulate neural functions such as cognition, motor control, pain, and feeding behavior. The interaction between endogenous or exogenous ligands and endocannabinoid receptors initiates signaling pathways.
  • 445
  • 24 Apr 2023
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