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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. 
  • 749
  • 01 Nov 2022
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.
  • 748
  • 15 Apr 2022
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.
  • 746
  • 22 Sep 2021
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.
  • 742
  • 24 Mar 2023
Topic Review
Bisphenol A and Obesity
Lines of evidence have shown the embryogenic and transgenerational impact of bisphenol A (BPA), an endocrine-disrupting chemical, on immune-metabolic alterations, inflammation, and oxidative stress, while BPA toxic effects in adult obese mice are still overlooked. Here, we evaluate BPA’s worsening effect on several hepatic maladaptive processes associated to high-fat diet (HFD)-induced obesity in mice. After 12 weeks HFD feeding, C57Bl/6J male mice were exposed daily to BPA (50 μg/kg per os) along with HFD for 3 weeks. Glucose tolerance and lipid metabolism were examined in serum and/or liver. Hepatic oxidative damage (reactive oxygen species, malondialdehyde, antioxidant enzymes), and mitochondrial respiratory capacity were evaluated. Moreover, liver damage progression and inflammatory/immune response were determined by histological and molecular analysis. BPA amplified HFD-induced alteration of key factors involved in glucose and lipid metabolism, liver triglycerides accumulation, and worsened mitochondrial dysfunction by increasing oxidative stress and reducing antioxidant defense. The exacerbation by BPA of hepatic immune-metabolic dysfunction induced by HFD was shown by increased toll-like receptor-4 and its downstream pathways (i.e., NF-kB and NLRP3 inflammasome) amplifying inflammatory cytokine transcription and promoting fibrosis progression.
  • 741
  • 17 Dec 2020
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.
  • 741
  • 08 Sep 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.
  • 739
  • 09 Sep 2021
Topic Review
Neurodegenerative Disorders Characterized by Mitochondrial Involvement
Neurodegenerative diseases comprise a wide spectrum of pathologies characterized by progressive loss of neuronal functions and structures. Despite having different genetic backgrounds and etiology, many studies have highlighted a point of convergence in the mechanisms leading to neurodegeneration: mitochondrial dysfunction and oxidative stress have been observed in different pathologies, and their detrimental effects on neurons contribute to the exacerbation of the pathological phenotype at various degrees.
  • 739
  • 08 Mar 2023
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.
  • 738
  • 30 Jun 2021
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.
  • 735
  • 22 Oct 2020
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).
  • 735
  • 14 Oct 2022
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.
  • 734
  • 25 Sep 2020
Topic Review
Advice of Medicine Shortages in Europe
The following recommendations should be considered to handle the issue of drug shortages more effectively in Europe. Since drug shortages do not respect borders and cross-country collaboration would be beneficial for more effective shortage management, a unified European definition and reporting criteria of shortages would be necessary to assure internationally consistent monitoring, reporting, comparisons, responses, and solutions. National authorities across Europe should be aware of shortages through coordinated systems, increasing cross-country transparency, and facilitating solutions in every country. It was a significant step forward in the European Union that in July 2019, the EMA published the “Guidance on detection and notification of shortages of medicinal products for Marketing Authorisation Holders in the Union”. The document contains the effort to facilitate the more uniform reporting and communication of drug shortages and create a harmonization “drug shortage” definition. The document “Good practice guidance for communication to the public on medicines availability issues”contains communication guidelines for the national authorities and the EMA for patients and healthcare professionals.
  • 733
  • 06 Apr 2022
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.
  • 733
  • 14 Nov 2022
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. 
  • 732
  • 17 Oct 2022
Topic Review
SARS-CoV-2 Peptide Vaccines
Several times during the past two decades, epidemic viral diseases created global challenges. Although many solutions have been proposed to deal with this tight spot, it is still believed that public vaccination represents the most effective strategy to handle it. So far, various kinds of vaccines including protein subunits, virus-like particles, inactivated, live attenuated, viral vectors, RNA, and DNA vaccines have been used in the prevention of COVID-19. Among the various categories of vaccines, peptide vaccines have created a new hope for quick and trustworthy access due to the development of proteomics equipment.
  • 731
  • 14 Jul 2023
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.
  • 730
  • 06 Nov 2023
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.
  • 729
  • 10 Feb 2023
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).
  • 728
  • 23 May 2024
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.
  • 726
  • 09 May 2023
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