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Topic Review
Omega-3 PUFA in Pediatric Cancer
Epidemiological literature suggests a protective effect of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) against cancer. They are attributed to have significant anti-inflammatory properties, and are reported to directly inhibit carcinogenesis and tumor expansion, whilst also reducing the risk for secondary complications, thus representing a promising approach for adjunctive chemotherapy treatment. At the same time, the incidence of malnutrition amongst children with cancer is high and both under- and overnutrition are associated with detrimental consequences, including increased risks for morbidity and mortality, early relapse rates, and a higher prevalence of secondary complications during treatment. Taken together with the benefits of n-3 PUFA supplementation, an enhancement of the nutritional status is a potentially modifiable prognostic factor in pediatric oncology.
  • 1.1K
  • 08 Jun 2021
Topic Review
Impact of the Renin-Angiotensin System on Neurodegenerative Diseases
The renin-angiotensin-aldosterone system (RAS) is an endocrine axis which has important peripheral physiological functions (blood pressure and cardiovascular homeostasis, water and sodium balance, and systemic vascular resistance). In addition to the systemic action of RAS, recent research highlights its paracrine and autocrine actions in many tissues, including the central nervous system. The complex is located intracellularly and is involved in various intracellular processes.
  • 1.1K
  • 04 Nov 2022
Topic Review
MicroRNA Modulation
The prevalence of obesity has dramatically increased over the last decades. Weight loss obtained through diet and exercise leads to a  significant decrease in morbidity and mortality. Recently, there has been growing interest in the possible beneficial effects of dietary supplements (DSs), including polyphenols, fatty acids, and other plant-derived substances, as adjuvants in the management of obesity and metabolic diseases. Specifically, polyphenols, widely spread in vegetables and fruits, significantly modulate adipose tissue activities,  contrasting inflammation and improving insulin sensitivity in preclinical and clinical studies. Remarkably, polyphenols are involved in complex microRNA networks, which play crucial roles in metabolic processes. The administration of different polyphenols and other plant-derived compounds led to significant changes in the microRNA expression profile in peripheral tissues in a growing number of preclinical studies. In particular, these compounds were able to revert obesity-induced microRNA dysregulation, leading to the inhibition of adipogenesis and the induction of weight loss. Furthermore, through microRNA modulation, they attenuated key metabolic alterations, including insulin resistance and lipid anomalies, in animal models of obesity. Some of them were also able to reduce proinflammatory cytokines in adipose tissue. The aim of this review is to summarize current evidence about the effect of plant-derived DSs on microRNA expression in obesity.
  • 1.1K
  • 29 Jan 2021
Topic Review
Sphingolipids in Central Nervous System
Bioactive lipids are a newly defined class of lipids that are actively involved in the regulation of a variety of cellular events. As the name indicates, these molecular factors are subjected to action at the arrival of a specific stimulus and undergo subsequent transitions to cope up with the insult. Among these bioactive lipids, sphingolipids have emerged as distinctive mediators of various cellular processes, ranging from cell growth and proliferation to cellular apoptosis, executing immune responses to regulating inflammation. Recent studies have made it clear that sphingolipids, their metabolic intermediates (ceramide, sphingosine-1-phosphate, and N-acetyl sphingosine), and enzyme systems (cyclooxygenases, sphingosine kinases, and sphingomyelinase) harbor diverse yet interconnected signaling pathways in the central nervous system (CNS), orchestrate CNS physiological processes, and participate in a plethora of neuroinflammatory and neurodegenerative disorders.
  • 1.1K
  • 05 Aug 2021
Topic Review
Oxi-Inflamm-Aging Related Cardiorenal Syndrome
Kidney failure is also a major cause of cardiovascular morbidity and mortality. Indeed, epidemiological studies have demonstrated that chronic kidney disease (CKD) is a significant risk for cardiovascular events independently of classical risk. 
  • 1.1K
  • 06 Jan 2022
Topic Review
Trans-Synaptic Neurexin–Neuroligin Interaction
Synapses serve as the interface for the transmission of information between neurons in the central nervous system. The structural and functional characteristics of synapses are highly dynamic, exhibiting extensive plasticity that is shaped by neural activity and regulated primarily by trans-synaptic cell-adhesion molecules (CAMs). Prototypical trans-synaptic CAMs, such as neurexins (Nrxs) and neuroligins (Nlgs), directly regulate the assembly of presynaptic and postsynaptic molecules, including synaptic vesicles, active zone proteins, and receptors. Therefore, the trans-synaptic adhesion mechanisms mediated by Nrx–Nlg interaction can contribute to a range of synaptopathies in the context of pathological pain and other neurological disorders.
  • 1.1K
  • 01 Jul 2022
Topic Review
Remote Ischemic Preconditioning
Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in RIPC-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by 30 min transient blockade of the left coronary artery to simulate I/R injury. Hindlimb muscle and the heart were excised 24 h post reperfusion. RIPC prior to I/R upregulated autophagy in the rat heart at 24 h post reperfusion. In vitro, autophagy inhibition or stimulation prior to RIPC respectively, either ameliorated or stimulated the cardioprotective effect, measured as improved cell viability to mimic the preconditioning effect. Recombinant IL-6 treatment prior to I/R increased in vitro autophagy in a dose dependent manner activating the JAK-STAT pathway without affecting the other kinase pathways such as p38 MAPK, and GSK-3β pathways. Prior to I/R, in vitro inhibition of the JAK-STAT pathway reduced autophagy upregulation despite recombinant IL-6 pre-treatment. Autophagy is an essential component of RIPC-induced cardioprotection that may upregulate autophagy through an IL-6/JAK-STAT dependent mechanism, thus identifying a potentially new therapeutic option for the treatment of ischemic heart disease.
  • 1.1K
  • 29 Oct 2020
Topic Review
Endothelial Dysfunction
Any damage to the endothelial cells leads to the interruption of the barrier, an increased permeability, and an inflow of molecules that generate inflammatory response. Pulmonary endothelium is able to generate bioactive molecules and/or to use compounds present in the cell to reduce the effects of toxic stimuli and restore its conditions. If the damage is particularly extensive, the endothelium cannot tackle it and its permeability undergoes some alterations. The pulmonary endothelial barrier is completely destroyed in the case of chronic lung damages. A typical example of chronic inflammation of the alveolus-capillary unit is represented by virus infections.
  • 1.1K
  • 18 Jan 2022
Topic Review
Thirteen Potential TMPRSS2 Inhibitors
We identified a set of 13 approved or clinically investigational drugs with positively charged guanidinobenzoyl and/or aminidinobenzoyl groups, including the experimentally verified TMPRSS2 inhibitors Camostat and Nafamostat. Molecular docking suggested that the guanidinobenzoyl or aminidinobenzoyl group in all the drugs could form putative salt bridge interactions with the side-chain carboxyl group of Asp435 located in the S1 pocket of TMPRSS2. Molecular dynamics simulations further revealed the high stability of the putative salt bridge interactions over long-time simulations. These results suggest that the proposed compounds, in addition to Camostat and Nafamostat, could be effective TMPRSS2 inhibitors for COVID-19 treatment by occupying the S1 pocket with the hallmark positively charged groups.
  • 1.1K
  • 12 Jul 2021
Topic Review
Dendritic Cell-Based Approaches in Autoimmunity
Dendritic cells (DCs) dictate the outcomes of tissue-specific immune responses. DCs instruct T cells to respond to antigens (Ags), including self-Ags, leading to organ damage in the context of autoimmune diseases, or to becoming regulatory T cells (Tregs) promoting and perpetuating immune tolerance. DCs can acquire tolerogenic properties in vitro and in vivo in response to several stimuli, a feature that opens the possibility to generate or to target DCs to restore tolerance in autoimmune settings.
  • 1.1K
  • 09 Oct 2021
Topic Review
Gap-Juntions in the Oocyte
Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore they do play a fundamental role in the communication between the oocyte and accompanying cells.
  • 1.1K
  • 11 Jun 2021
Topic Review
Ischemic Stroke and Excitotoxicity
Stroke is a relevant cause of death, disability and dementia worldwide. In ischemic stroke, excitotoxicity is the main mechanism of neuronal death in the penumbra area, a potentially recoverable tissue surrounding the irreversibly damaged infarct core. In excitatory neurons, scaffold protein PSD-95 plays a central role in neuronal function but also survival/death choices. Thus, this protein is a promising target for development of neuroprotective strategies for stroke and other pathologies similarly associated to excitotoxicity.
  • 1.1K
  • 13 Dec 2021
Topic Review
Phytochemistry and Pharmacological Effect of Annona muricata
The Annonaceae family contains different types of bioactive chemical properties, such as alkaloids, acetogenins, flavonoids, terpenes, and essential oil, meaning the plants in this family are potential therapeutic agents. In vitro and in vivo studies have shown that A. muricata has the pharmacological effects of anti-cancer, anti-microbial, antioxidant, anti-ulcer, anti-diabetic, anti-hypertensive, and wound healing. 
  • 1.1K
  • 08 May 2023
Topic Review
Milk Exosomes as Drug Delivery Agents
Milk is a unique natural source of exosomes available in semi-preparative and preparative quantities. Milk exosomes are highly resistant to the harsh conditions of the gastrointestinal tract. In vitro studies have demonstrated that milk exosomes have an affinity to epithelial cells, are digested by cells by endocytosis mechanism, and can be used for oral delivery. With milk exosome membranes containing hydrophilic and hydrophobic components, exosomes can be loaded with hydrophilic and lipophilic drugs.
  • 1.1K
  • 21 Jun 2023
Topic Review
ORP5 and ORP8
Oxysterol binding related proteins 5 and 8 (ORP5 and ORP8) are two close homologs of the larger oxysterol binding protein (OSBP) family of sterol sensors and lipid transfer proteins (LTP). Early studies indicated these transmembrane proteins, anchored to the endoplasmic reticulum (ER), bound and sensed cholesterol and oxysterols. They were identified as important for diverse cellular functions including sterol homeostasis, vesicular trafficking, proliferation and migration. In addition, they were implicated in lipid-related diseases such as atherosclerosis and diabetes, but also cancer, although their mechanisms of action remained poorly understood. Then, alongside the increasing recognition that membrane contact sites (MCS) serve as hubs for non-vesicular lipid transfer, added to their structural similarity to other LTPs, came discoveries showing that ORP5 and 8 were in fact phospholipid transfer proteins that rather sense and exchange phosphatidylserine (PS) for phosphoinositides, including phosphatidylinositol-4-phosphate (PI(4)P) and potentially phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2). Evidence now points to their action at MCS between the ER and various organelles including the plasma membrane, lysosomes, mitochondria, and lipid droplets. Dissecting exactly how this unexpected phospholipid transfer function connects with sterol regulation in health or disease remains a challenge for future studies.
  • 1.1K
  • 15 Jul 2021
Topic Review
Natural Salicylates
Salicylic acid (SA) is a plant hormone which plays a crucial role in the plant defense against various pathogens and abiotic stresses.
  • 1.1K
  • 18 Mar 2021
Topic Review
The Fibroblast Growth Factor Receptors
Breast cancer (BC) is the most frequent form of malignancy and second only to lung cancer as cause of deaths in women. Notwithstanding many progresses made in the field, metastatic BC has a very poor prognosis. As therapies are becoming more personalized to meet the needs of patients, a better knowledge of the molecular biology leading to the disease unfolds the possibility to project more precise compounds or antibodies targeting definite alteration at the molecular level and functioning on such cancer-causing molecules expressed in cancer cells of patients, or present as antigens on the surface of cancer cell membranes. Fibroblast growth factor receptor (FGFR) is one of such druggable targets, activated by its own ligands -namely the Fibroblast Growth Factors (FGFs). This pathway provides a vast range of interesting molecular targets pursued at different levels of clinical investigation.
  • 1.1K
  • 01 Nov 2020
Topic Review
Oxidative Stress in Sepsis
Sepsis is the leading cause of acute kidney injury (AKI) and leads to increased morbidity and mortality in intensive care units. Current treatments for septic AKI are largely supportive and are not targeted towards its pathophysiology. Sepsis is commonly characterized by systemic inflammation and increased production of reactive oxygen species (ROS), particularly superoxide. Concomitantly released nitric oxide (NO) then reacts with superoxide, leading to the formation of reactive nitrogen species (RNS), predominantly peroxynitrite. Sepsis-induced ROS and RNS can reduce the bioavailability of NO, mediating renal microcirculatory abnormalities, localized tissue hypoxia and mitochondrial dysfunction, thereby initiating a propagating cycle of cellular injury culminating in AKI. 
  • 1.1K
  • 11 Oct 2021
Topic Review
Factors Influencing Gallstone Formation
Dysfunction of the gallbladder or other parts of the bile-secretion pathway can result in gallstone formation. Given that the bile-secretion pathway is a complex process, there are many reasons for the formation of gallstones. Evidence suggests that gallstones are related to age, gender, female physiological status, obesity, cardiovascular disease, microbiome, sugar metabolism, and various environmental exposures. Based on a large number of mouse and human studies, the interaction of five main factors were proposed. The pathogenesis of cholesterol gallstone disease is precipitated by: genetic factors; excessive cholesterol secretion by the liver (leading to supersaturation of cholesterol in gallbladder bile); rapid phase change by accelerating the growth of cholesterol crystals and solid cholesterol crystals; impairment of gallbladder motility; and intestinal factors. Intestinal factors can be further broken down into two categories: increased cholesterol absorption from the small intestine to the liver, eventually resulting in increased bile secretion, and microbiota that inhabit the intestinal tract. These factors will increase the production or growth of cholesterol crystals, eventually leading to the formation of stones.
  • 1.1K
  • 16 May 2022
Topic Review
NGF Peptides Bind Copper(II)
Nerve growth factor (NGF) is a protein essential to neurons survival, which interacts with its receptor as a non-covalent dimer. Copper affects biological activity of NGF and conversely NGF may regulates copper trafficking in synaptic cleft.
  • 1.1K
  • 10 Jun 2021
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