Safety of Inclisiran: A Disproportionality Analysis from the EudraVigilance Database.

The discovery of serine protease proprotein convertase subtilisin-kexin type 9 (PCSK9) has revolutionized pharmacological lipid-lowering treatments. The first PCSK9 antagonists (PCSK9-A), evolocumab and alirocumab, were approved in 2015. Targeting PCSK9 synthesis marked a major advancement in this field, leading to the development of inclisiran, a long-acting siRNA targeting PCSK9 mRNA.

Lycopene and Induce White-to-Brown Adipose Differentiation: An Innovative Strategy to Curb Obesity.

Obesity is considered one of the main risk factors for cardiovascular diseases. The browning process has been recently recognized as a promising anti-obesity therapy. Lycopene (LYC) and fruit extract (GE) might be important resources for anti-obesity drugs; therefore, the aim of this study was to investigate the anti-obesity effects of LYC and GE on 3T3-L1 adipocytes and Zucker rats.

Atrial fibrillation management in older hospitalized patients: Evidence of a poor oral anticoagulants prescriptive attitude from the Italian REPOSI registry.

Atrial fibrillation (AF) prevalence increases in older patients which also show a high thromboembolic risk. Oral anticoagulants (OACs) are recommended to prevent cardioembolic events and direct oral anticoagulants (DOACs) improved anti-thrombotic treatment. However, the benefits/risks of anticoagulant in older patients still need to be completely defined.

Melanoma and cannabinoids: A possible chance for cancer treatment.

The endocannabinoid system is composed by a complex and ubiquitous network of endogenous lipid ligands, enzymes for their synthesis and degradation, and receptors, which can also be stimulated by exogenous compounds, such as those derived from the Cannabis sativa. Cannabis and its bioactive compounds, including cannabinoids and non-cannabinoids, have been extensively studied in different conditions. Recent data have shown that the endocannabinoid system is responsible for maintaining the homeostasis of various skin functions such as proliferation, differentiation and release of inflammatory mediators.

Levosimendan and Dobutamin Attenuate LPS-Induced Inflammation in Microglia by Inhibiting the NF-κB Pathway and NLRP3 Inflammasome Activation via Nrf2/HO-1 Signalling.

Hypovolemic shock is a circulatory failure, due to a loss in the effective circulating blood volume, that causes tissue hypoperfusion and hypoxia. This condition stimulates reactive oxygen species (ROS) and pro-inflammatory cytokine production in different organs and also in the central nervous system (CNS). Levosimendan, a cardioprotective inodilator, and dobutamine, a β1-adrenergic agonist, are commonly used for the treatment of hypovolemic shock, thanks to their anti-inflammatory and antioxidant effects.

Tirbanibulin 1% Ointment for Actinic Keratosis: Results from a Real-Life Study.

: Tirbanibulin 1% ointment is a novel synthetic anti-proliferative agent that inhibits tubulin polymerization. It is approved for treating actinic keratosis (AK) on the face and scalp in adults. It has demonstrated good efficacy, an adequate safety profile and excellent patient adherence in the phase 3 clinical trials, however data about its real-life efficacy and safety are lacking.

Attention Deficit Hyperactivity Disorder (ADHD) and Polyphenols: A Systematic Review.

Polyphenols are natural compounds also contained in daily consumed foods that show their efficacy in different clinical fields. Both pre-clinical and clinical studies demonstrated that polyphenols may manage neuroinflammation and oxidative stress processes tightly connected to neurodegenerative diseases and mental disorders. Thus, a neuroinflammatory state may influence the neurotransmitters pathways, such as the noradrenergic, glutamatergic, serotoninergic, and, in particular, dopaminergic ones, whose impairment is strongly associated with attention deficit hyperactivity disorder (ADHD).

Stratification of COVID-19 Patients with Moderate-to-Severe Hypoxemic Respiratory Failure for Response to High-Flow Nasal Cannula: A Retrospective Observational Study.

In patients with COVID-19, high-flow nasal cannula (HFNC) and continuous positive airway pressure (CPAP) are widely applied as initial treatments for moderate-to-severe acute hypoxemic respiratory failure. The aim of the study was to assess which respiratory supports improve 28-day mortality and to identify a predictive index of treatment response. This is a single-center retrospective observational study including 159 consecutive adult patients with COVID-19 and moderate-to-severe hypoxemic acute respiratory failure.

Drug Safety and Relevant Issues in the Real-World.

The global impact of the COVID-19 pandemic has underscored the pivotal role of drug safety and effective communication within the realm of pharmacovigilance, particularly in times of unprecedented public health emergencies [...

Off-Target Effects of P2Y12 Receptor Inhibitors: Focus on Early Myocardial Fibrosis Modulation.

Several studies have demonstrated that, beyond their antithrombotic effects, P2Y12 receptor inhibitors may provide additional off-target effects through different mechanisms. These effects range from the preservation of endothelial barrier function to the modulation of inflammation or stabilization of atherosclerotic plaques, with an impact on different cell types, including endothelial and immune cells. Many P2Y12 inhibitors have been developed, from ticlopidine, the first thienopyridine, to the more potent non-thienopyridine derivatives such as ticagrelor which may promote cardioprotective effects following myocardial infarction (MI) by inhibiting adenosine reuptake through sodium-independent equilibrative nucleoside transporter 1 (ENT1).

Correction: Mannino et al. Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells. 2021, , 5741.

In the original publication [...

Insights into the antiosteoporotic mechanism of the soy-derived isoflavone genistein: Modulation of the Wnt/beta-catenin signaling.

Bone remodeling is a process that involves osteoblasts, osteoclasts, and osteocytes, and different intracellular signaling, such as the canonical Wnt/β-catenin pathway. Dysregulations of this pathway may also occur during secondary osteoporosis, as in the case of glucocorticoid-induced osteoporosis (GIO), which accelerates osteoblast and osteocyte apoptosis by reducing bone formation, osteoblast differentiation and function, accelerates in turn osteoblast, and osteocyte apoptosis. Genistein is a soy-derived nutrient belonging to the class of isoflavones that reduces bone loss in osteopenic menopausal women, inhibiting bone resorption; however, genistein may also favor bone formation.

Blunting Neuroinflammation by Targeting the Immunoproteasome with Novel Amide Derivatives.

Neuroinflammation is an inflammatory response of the nervous tissue mediated by the production of cytokines, chemokines, and reactive oxygen species. Recent studies have shown that an upregulation of immunoproteasome is highly associated with various diseases and its inhibition attenuates neuroinflammation. In this context, the development of non-covalent immunoproteasome-selective inhibitors could represent a promising strategy for treating inflammatory diseases.

Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment.

Oral cavity squamous cell carcinoma (OCSCC) represents a serious health and socio-economic problem in different geographical areas of the world. It is characterized by a high rate of mortality, recurrence and metastasis. Despite the therapeutic strategies implemented for its management and resolution, currently the survival estimate for locally advanced disease is about 50%.

Effects of genistein aglycone in glucocorticoid induced osteoporosis: A randomized clinical trial in comparison with alendronate.

Glucocorticoid-induced osteoporosis (GIO) complicates the clinical management of patients subjected to long-term glucocorticoid use. This study explored the effects of genistein on bone loss in a randomized double-blind alendronate-controlled trial in postmenopausal women with GIO. 200 postmenopausal women (taking at least 5 mg of prednisone equivalents) since 3 months, or more, and expected to continue for at least other 12 months, were randomized to receive genistein (54 mg/day daily) or alendronate (70 mg once a week) for 24 months.

Steady state plasma and tissue distribution of low molecular weight hyaluronic acid after oral administration in mice.

The oral administration is probably the most used and largely applicable method, even if absorption across the intestinal epithelium is a limiting factor that can invalidate the achievement of a therapy. The aim of this study was to assess the steady state bioavailability of very low molecular weight hyaluronic acid (vLMW-HA) and its distribution in different districts of mice. Adult female C57BL6/J mice ( = 26) were divided in three groups and orally treated for 7 days with: saline solution (SHAM-HA), high dose of vLMW-HA (5 kDa; 500 mg/kg/day; HD-vLMW-HA), and low dose of vLMW-HA (5 kDa; 100 mg/kg/day; LD-vLMW-HA).

Anti-oxidant and anti-inflammatory effects of ellagic and punicic acid in an in vitro model of cardiac fibrosis.

Cardiac fibrosis is a pathological process characterized by an excessive deposition of extracellular matrix (ECM) and an increased production of fibrillar collagen in the cardiac interstitium, mainly caused by the activation of cardiac fibroblasts and their transition into myofibroblasts. Oxidative stress is deeply implicated in the pathogenesis of cardiac fibrosis both directly and via its involvement in the tumor growth factor β1 (TGF-β1) signaling. Ellagic acid (EA) and punicic acid (PA) are the main components of the Punica granatum L (pomegranate) fruit and seed oil respectively, whose antioxidant, anti-inflammatory and anti-fibrotic effects have been previously described.