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Topic Review
Natural Products in the Model Organism Caenorhabditis elegans
Natural products are small molecules naturally produced by multiple sources such as plants, animals, fungi, bacteria and archaea. They exert both beneficial and detrimental effects by modulating biological targets and pathways involved in oxidative stress and antioxidant response. Natural products’ oxidative or antioxidative properties are usually investigated in preclinical experimental models, including virtual computing simulations, cell and tissue cultures, rodent and nonhuman primate animal models, and human studies.
  • 784
  • 15 Apr 2022
Topic Review
Proadrenomedullin in Sepsis/Septic Shock
Sepsis and septic shock represent a leading cause of mortality in the Emergency Department (ED) and in the Intensive Care Unit (ICU). For these life-threating conditions, different diagnostic and prognostic biomarkers have been studied. Proadrenomedullin (MR-proADM) is a biomarker that can predict organ damage and the risk of imminent death in patients with septic shock.
  • 783
  • 08 Sep 2021
Topic Review
Battling Chemoresistance in Cancer
Chemoresistance remains a lethal challenge in the realm of cancer biology and clinics. Various determinants with their modes of action have been reported with clinical implications. However, many patients regrettably die due to chemoresistance-induced failure in treatment.
  • 782
  • 22 Sep 2021
Topic Review
Neuropeptides Inhibitors for Colorectal Cancer
Neuropeptides are mainly secreted from the human central and peripheral nervous systems. Neuropeptides bind to its cognate rhodopsin-like G-protein coupled receptor (GPCR) and perform various physiological functions. Conventional cancer treatments in clinical practice still present many drawbacks due to the lack of selectivity toward the target cell, drug-resistance, and side-effects, thus pushing for the development of new therapeutic agents and therapies. Recent research suggests that neuropeptides influence cancer cell proliferation, invasion, metastasis, and angiogenesis and, therefore, they could be exploited as a target for novel anticancer therapies. Very recently, targeted approaches that inhibit neuropeptides and their associated receptors are being developed in cancer treatment. 
  • 778
  • 29 Sep 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. 
  • 777
  • 01 Nov 2022
Topic Review
Renoprotective Mechanisms of Medicinal Plants
Diabetic nephropathy (DN), also recognized as diabetic kidney disease, is a kidney malfunction caused by diabetes mellitus. A possible contributing factor to the onset of DN is hyperglycemia. Poorly regulated hyperglycemia can damage blood vessel clusters in the kidneys, leading to kidney damage. Its treatment is difficult and expensive because its causes are extremely complex and poorly understood. Extracts from medicinal plants can be an alternative treatment for DN. The bioactive content in medicinal plants inhibits the progression of DN.
  • 777
  • 13 Mar 2023
Topic Review
Elevated Procalcitonin and COVID-19
PCT is a precursor of calcitonin, which is secreted by neuroendocrine cells such as C cells of the thyroid and pancreatic tissues.  PCT plays an important role in the diagnosis of systemic bacterial infection.  Elevated serum PCT levels have also been reported in patients with pulmonary infection. Additionally, the positive feedback between procalcitonin and proinflammatory cytokines subsequently culminates in a severe systemic inflammatory response.  
  • 776
  • 23 Jun 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.
  • 775
  • 29 Mar 2022
Topic Review
Diet-Induced Insulin Resistance
Insulin resistance (IR) is defined as the decreased ability of insulin to insert the glucose transporter (glut4) on the cell membrane facilitating glucose entry into body cells. IR in the hepatocytes is associated with increased de novo lipogenesis and gluconeogenesis, leading to hypertriglyceridemia and hyperglycemia.
  • 775
  • 06 Nov 2023
Topic Review
Use of Letermovir for Cytomegalovirus Prophylaxis
Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplant (allo-HSCT) is mainly due to an increase of latent viremia in previously exposed patients. Furthermore, CMV reactivation in this setting has a significant impact on patient survival. Traditional approach to CMV reactivation post allo-HSCT was a pre-emptive treatment with antivirals in the case of increased viremia. A new antiviral compound, letermovir, has been introduced in clinical practice and is deeply changing the common CMV approach. The toxicity profile of letermovir allowed its use in prophylaxes in patients at high risk of CMV reactivation.
  • 772
  • 09 May 2023
Topic Review
Gluten free diet
The aim of this entry was to assess the effects of a gluten free diet (GFD) in the management of epilepsy in people with coeliac disease (CD) or gluten sensitivity (GS). A systematic approach was used to undertake a literature review. Five electronic databases (PubMed; Scopus; Google Scholar; Cochrane Epilepsy Group specialised register; Cochrane Register of Controlled Trails (CENTRAL) via the Cochrane Register of Online Trials) were searched using predetermined relevant search terms. In total, 668 articles were identified. Duplicates were removed and predefined inclusion and exclusion criteria were applied, and a PRISMA flow chart was produced. Data was extracted using Covidence software. Twelve studies on Epilepsy and CD involving a total of 70 participants were selected for analysis; narrative synthesis was used owing to the small sample sizes in the selected studies. None of the 12 studies meeting inclusion criteria investigated gluten sensitivity and epilepsy. All the included studies support a link between epilepsy and CD. GFD was effective in 44 out of 70 participants across the studies in terms of a reduction of seizures, reduction of antiepileptic drugs (AEDs) or normalisation of EEG pattern. A total of 44 participants showed a reduction in seizures (across eight studies) and complete cessation of seizures was reported in 22 participants. In general, the earlier the GFD is implemented after the onset of seizures, the better the likelihood of the GFD being successful in supporting control of seizures. Mechanisms linking gluten with epilepsy are not fully understood; possible hypotheses include gluten mediated toxicity, immune-induced cortical damage and malabsorption. Evidence suggests the effectiveness of a GFD in supporting the management of epilepsy in patients with CD, although the quality of evidence is low. There appears to be a growing number of neurologists who are prepared to advocate the use of a GFD. A multidisciplinary approaches and further research are recommended. It could be argued that when balancing potential treatments such as AEDs or surgery, a GFD has a low likelihood of harm.
  • 771
  • 25 Sep 2020
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.
  • 771
  • 10 Feb 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.
  • 771
  • 10 Feb 2022
Topic Review
Pharmacists and Medication Regimen Complexity
Medication regimen complexity (MRC) may influence health outcomes, such as hospitalisation, hospital readmission and medication adherence. Pharmacists have been referred to as health professionals with the opportunity to act on MRC reduction.
  • 771
  • 31 Aug 2021
Topic Review
Single-Cell Analysis of Metallodrugs
Platinum compounds such as cisplatin (cisPt) embody the backbone of combination chemotherapy protocols against advanced lung cancer. However, their efficacy is primarily limited by inherent or acquired platinum resistance, the origin of which has not been fully elucidated yet, although of paramount interest.
  • 770
  • 09 Sep 2021
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. 
  • 769
  • 24 Sep 2021
Topic Review
Reporting Bias in COVID-19 mRNA Vaccine Clinical Trials
Relative risk reduction and absolute risk reduction measures in the evaluation of clinical trial data are poorly understood by health professionals and the public. The absence of reported absolute risk reduction in COVID-19 vaccine clinical trials can lead to outcome reporting bias that affects the interpretation of vaccine efficacy. 
  • 769
  • 14 Mar 2024
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. 
  • 766
  • 17 Oct 2022
Topic Review
Natural Products in Oncology
In recent decades, increasing interest in the use of natural products in anticancer therapy field has been observed, mainly due to unsolved drug-resistance problems. The antitumoral effect of natural compounds involving different signaling pathways and cellular mechanisms has been largely demonstrated in in vitro and in vivo studies. The encapsulation of natural products into different delivery systems may lead to a significant enhancement of their anticancer efficacy by increasing in vivo stability and bioavailability, reducing side adverse effects and improving target-specific activity. More and more studies in the nanomedicine field aim to design nanostructured systems containing natural compounds for new drug delivery tools in anticancer therapies.
  • 765
  • 22 Oct 2020
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
  • 765
  • 11 Oct 2021
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