Oxidative Stress-Related Signaling Pathways Predict Oocytes' Fertilization In Vitro and Embryo Quality.

Oocyte development and fertilization are largely influenced by the microenvironment of the follicular fluid (FF), and the exploration of its molecular/metabolic composition may help in improving in vitro fertilization (IVF) outcomes. Here, the concentrations of molecules related to oxidative stress/inflammation were measured in FF from follicles at oocyte retrieval during IVF. Here, the FF antioxidant potential was correlated with the number of retrieved/mature oocytes and the number of fertilized ones.

The Role of Amyloid-β, Tau, and α-Synuclein Proteins as Putative Blood Biomarkers in Patients with Cerebral Amyloid Angiopathy.

Background: Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder characterized by the deposition of amyloid-β protein (Aβ) within brain blood vessels that develops in elderly people and Alzheimer's disease (AD) patients. Therefore, the investigation of biomarkers able to differentiate CAA patients from AD patients and healthy controls (HC) is of great interest, in particular in peripheral fluids.

Objective: The current study aimed to detect the neurodegenerative disease (ND)-related protein (i.

Discovery of MDM2-p53 and MDM4-p53 protein-protein interactions small molecule dual inhibitors.

MDM2 and MDM4 are key negative regulators of p53, an important protein involved in several cell processes (e.g. cell cycle and apoptosis).

α-Glyceryl-phosphoryl-ethanolamine protects human hippocampal neurons from ageing-induced cellular alterations.

Brain ageing has been related to a decrease in cellular metabolism, to an accumulation of misfolded proteins and to an alteration of the lipid membrane composition. These alterations act as contributive aspects of age-related memory decline by reducing membrane excitability and neurotransmitter release. In this sense, precursors of phospholipids (PLs) can restore the physiological composition of cellular membranes and ameliorate the cellular defects associated with brain ageing.

Endometrial Dysbiosis Is Related to Inflammatory Factors in Women with Repeated Implantation Failure: A Pilot Study.

An abnormal endometrial microbiota has been suggested to impair the process of embryo implantation, thus leading to repeated implantation failure (RIF) in women undergoing in vitro fertilization (IVF). However, the molecular mechanisms linking uterine microbiota and IVF out-comes are still an open question. The aim of this cohort study was to outline the relationship between endometrial microbiota, inflammation and IVF outcomes.

The Mediterranean Diet Positively Affects Resting Metabolic Rate and Salivary Microbiota in Human Subjects: A Comparison with the Vegan Regimen.

Salivary microbiota, comprising bacteria shed from oral surfaces, has been shown to be individualized, temporally stable, and influenced by macronutrient intake and lifestyle. Nevertheless, the effect of long-term dietary patterns on oral microbiota composition and the relationship between oral microbiota composition and metabolic rate remains to be examined. Herein, salivary microbiota composition and metabolic profile were analyzed in human subjects with vegan (VEG) or Mediterranean (MED) long-term dietary patterns.

Exploring Epithelial-Mesenchymal Transition Signals in Endometriosis Diagnosis and In Vitro Fertilization Outcomes.

Endometriosis (EMS) pathogenesis has been related to the release of inflammatory mediators in peritoneal fluid, creating an altered microenvironment that leads to low-grade oocyte/embryos and to the reduction of implantation rates. The Epithelial-Mesenchymal Transition (EMT), an inflammation-related process, can be a further contributing factor to EMS. This study aimed to investigate, among various cytokines and EMT markers (Cadherins, TGF-β, HIF-1α), diagnostic markers of EMS and prognostic factors of in vitro fertilization (IVF) outcomes.

Two mixed valence diruthenium(II,III) isomeric complexes show different anticancer properties.

In this paper it is demonstrated that the nature of the ligands of two Ru2(ii,iii) paddlewheel complexes dramatically affects the overall anticancer properties in cells. Herein, the complex [Ru2(EB776)4Cl] was found to be more active against a glioblastoma model with respect to its isomer [Ru2(EB106)4Cl]. These different effects depend on the steric hindrance, on the allowed conformations of the complexes and on the presence of hydrophilic regions in [Ru2(EB776)4Cl], which overall lead to a lower "steric protection".

Locking PDK1 in DFG-out conformation through 2-oxo-indole containing molecules: Another tools to fight glioblastoma.

The phosphoinositide-dependent kinase-1 (PDK1) is one of the main components of the PI3K/Akt pathway. Also named the "master kinase" of the AGC family, PDK1 plays a critical role in tumorigenesis, by enhancing cell proliferation and inhibiting apoptosis, as well as in cell invasion and metastasis formation. Although there have been done huge efforts in discovering specific compounds targeting PDK1, nowadays no PDK1 inhibitor has yet entered the clinic.

Long lasting MDM2/Translocator protein modulator: a new strategy for irreversible apoptosis of human glioblastoma cells.

The development of multi-target drugs and irreversible modulators of deregulated signalling proteins is the major challenge for improving glioblastoma multiforme (GBM) treatment. Reversible single-target drugs are not sufficient to sustain a therapeutic effect over time and may favour the activation of alternative signalling pathways and the onset of resistance phenomena. Thus, a multi-target compound that has a long-lasting mechanism of action might have a greater and longer life span of anti-proliferative activity.

Trazodone regulates neurotrophic/growth factors, mitogen-activated protein kinases and lactate release in human primary astrocytes.

Background: In the central nervous system, glial cells provide metabolic and trophic support to neurons and respond to protracted stress and insults by up-regulating inflammatory processes. Reactive astrocytes and microglia are associated with the pathophysiology of neuronal injury, neurodegenerative diseases and major depression, in both animal models and human brains. Several studies have reported clear anti-inflammatory effects of anti-depressant treatment on astrocytes, especially in models of neurological disorders.

Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death.

Therapies that target the signal transduction and metabolic pathways of cancer stem cells (CSCs) are innovative strategies to effectively reduce the recurrence and significantly improve the outcome of glioblastoma multiforme (GBM). CSCs exhibit an increased rate of glycolysis, thus rendering them intrinsically more sensitive to prospective therapeutic strategies based on the inhibition of the glycolytic pathway. The enzyme lactate dehydrogenase-A (LDH-A), which catalyses the interconversion of pyruvate and lactate, is up-regulated in human cancers, including GBM.

Trazodone treatment protects neuronal-like cells from inflammatory insult by inhibiting NF-κB, p38 and JNK.

Growing evidence suggests that alterations of the inflammatory/immune system contribute to the pathogenesis of major depression and that inflammatory processes may influence the antidepressant treatment response. Depressed patients exhibit increased levels of inflammatory markers in both the periphery and brain, and high co-morbidity exists between depression and diseases associated with inflammatory alterations. Trazodone (TDZ) is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors.

Combined inhibition of AKT/mTOR and MDM2 enhances Glioblastoma Multiforme cell apoptosis and differentiation of cancer stem cells.

The poor prognosis of Glioblastoma Multiforme (GBM) is due to a high resistance to conventional treatments and to the presence of a subpopulation of glioma stem cells (GSCs). Combination therapies targeting survival/self-renewal signals of GBM and GSCs are emerging as useful tools to improve GBM treatment. In this context, the hyperactivated AKT/mammalian target of the rapamycin (AKT/mTOR) and the inhibited wild-type p53 appear to be good candidates.

Oxysterols act as promiscuous ligands of class-A GPCRs: in silico molecular modeling and in vitro validation.

According to classical pharmacology, each neurotransmitter/hormonal receptor, including GPCRs, is exclusively activated by highly specific ligands. However, recent evidence challenges this dogma. Oxysterols are produced at inflammatory sites and can surprisingly potently activate the Epstein Barr virus induced gene receptor-2 (EBI2), a GPCR involved in adaptive immune responses.

A rapid and efficient immunoenzymatic assay to detect receptor protein interactions: G protein-coupled receptors.

G protein-coupled receptors (GPCRs) represent one of the largest families of cell surface receptors, and are the target of at least one-third of the current therapeutic drugs on the market. Along their life cycle, GPCRs are accompanied by a range of specialized GPCR-interacting proteins (GIPs), which take part in receptor proper folding, targeting to the appropriate subcellular compartments and in receptor signaling tasks, and also in receptor regulation processes, such as desensitization and internalization. The direction of protein-protein interactions and multi-protein complexes formation is crucial in understanding protein function and their implication in pathological events.