Increased Antioxidant Performance of Lignin by Biodegradation Obtained from an Extract of the Mushroom .

The aim of this study was to evaluate the antioxidant properties of the products derived from the biodegradation of lignin by the ligninolytic enzymes present in an aqueous extract of the mushroom . A mixture obtained after the incubation of lignin for 18 h with extract was tested in vitro for its total polyphenol content, reducing power, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl (OH) radical-scavenging activities. The results showed that the enzymatic treatment of lignin enhanced its antioxidant performance.

Use of a commercial feed supplement based on diatom earth and yeast products on oxidative status and in vitro immune response in buffaloes during peripartum.

The transition period is a critical metabolic phase for dairy ruminants, especially those with high production levels. In spite of this, little is still known about dairy water buffalo. The aim of this study was to evaluate the effect of a commercial feed additive based on diatomaceous earth and hydrolyzed yeasts on health status, milk quality, and immune response of buffalo cows during the transition period.

Resveratrol impinges on retrograde communication without inducing mitochondrial biogenesis in aged rat soleus muscle.

The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein.

Structure-based design of multitargeting ChEs-MAO B inhibitors based on phenyl ring bioisosteres: AChE/BChE selectivity switch and drug-like characterization.

A structure-based drug design approach was focused on incorporating phenyl ring heterocyclic bioisosteres into coumarin derivative 1, previously reported as potent dual AChE-MAO B inhibitor, with the aim of improving drug-like features. Structure-activity relationships highlighted that bioisosteric rings were tolerated by hMAO B enzymatic cleft more than hAChE. Interestingly, linker homologation at the basic nitrogen enabled selectivity to switch from hAChE to hBChE.

Inhibition of MMP-2 and MMP-9 by Dietary Antioxidants in THP-1 Macrophages and Sera from Patients with Breast Cancer.

Polyphenols, the main antioxidants of diet, have shown anti-inflammatory, antioxidant and anticarcinogenic activities. Here, we compared the effects of four polyphenolic compounds on ROS production and on the levels of matrix metalloproteinase (MMP)-2 and -9, which represent important pathogenetic factors of breast cancer. THP-1 differentiated macrophages were activated by LPS and simultaneously treated with different doses of a green tea extract (GTE), resveratrol (RSV), curcumin (CRC) and an olive fruit extract (oliplus).

Novel 6-hydroxybenzothiazol-2-carboxamides as potent and selective monoamine oxidase B inhibitors endowed with neuroprotective activity.

In neurodegenerative diseases, using a single molecule that can exert multiple effects to modify the disease may have superior activity over the classical "one molecule-one target" approach. Herein, we describe the discovery of 6-hydroxybenzothiazol-2-carboxamides as highly potent and selective MAO-B inhibitors. Variation of the amide substituent led to several potent compounds having diverse side chains with cyclohexylamide 40 displaying the highest potency towards MAO-B (IC = 11 nM).

Neuroprotective Effect of Resveratrol against Manganese-Induced Oxidative Stress and Matrix Metalloproteinase-9 in an "In Vivo" Model of Neurotoxicity.

Chronic exposure to manganese (Mn) leads to its accumulation in the central nervous system (CNS) and neurotoxicity with not well-known mechanisms. We investigated the involvement of matrix metalloproteinase (MMP)-2 and -9 in Mn neurotoxicity in an in vivo model of rats treated through an intraperitoneal injection, for 4 weeks, with 50 mg/kg of MnCl in the presence or in the absence of 30 mg/kg of resveratrol (RSV). A loss of weight was observed in Mn-treated rats compared with untreated and RSV-treated rats.

Biomarkers of Neurological Damage: From Acute Stage to Post-Acute Sequelae of COVID-19.

: Neurological symptoms (NS) in COVID-19 are related to both acute stage and long-COVID. We explored levels of brain injury biomarkers (NfL and GFAP) and myeloid activation marker (sCD163) and their implications on the CNS. In hospitalized COVID-19 patients plasma samples were collected at two time points: on hospital admission (baseline) and three months after hospital discharge (Tpost).

Tissue Inhibitor of Matrix Metalloproteinases-1 (TIMP-1) and Pulmonary Involvement in COVID-19 Pneumonia.

The aim of the study was to longitudinally evaluate the association between MMP-2, MMP-9, TIMP-1 and chest radiological findings in COVID-19 patients. COVID-19 patients were evaluated based on their hospital admission (baseline) and three months after hospital discharge (T post) and were stratified into ARDS and non-ARDS groups. As a control group, healthy donors (HD) were enrolled.

Bioisosteric replacement based on 1,2,4-oxadiazoles in the discovery of 1H-indazole-bearing neuroprotective MAO B inhibitors.

Following a hybridization strategy, a series of 5-substituted-1H-indazoles were designed and evaluated in vitro as inhibitors of human monoamine oxidase (hMAO) A and B. Among structural modifications, the bioisostere-based introduction of 1,2,4-oxadiazole ring returned the most potent and selective human MAO B inhibitor (compound 20, IC = 52 nM, SI > 192). The most promising inhibitors were studied in cell-based neuroprotection models of SH-SY5Y and astrocytes line against HO.

Antioxidant Compounds from Edible Mushrooms as Potential Candidates for Treating Age-Related Neurodegenerative Diseases.

The last century has seen an increase in our life expectancy. As a result, various age-related diseases, such as neurodegenerative diseases (NDs), have emerged, representing new challenges to society. Oxidative stress (OS), a condition of redox imbalance resulting from excessive production of reactive oxygen species, represents a common feature that characterizes the brains of elderly people, thus contributing to NDs.

Antioxidant Activity of Polysaccharides from the Edible Mushroom .

In this study the antioxidant and neuroprotective activity of an enriched polysaccharide fraction (EPF) obtained from the fruiting body of cultivated was evaluated. Proximate composition (moisture, proteins, fat, carbohydrates and ash) was determined using the AOAC procedures. The EPF was extracted by using, in sequence, hot water and alkaline extractions followed by deproteinization and precipitation with cold ethanol.

COVID-19 Affects Serum Brain-Derived Neurotrophic Factor and Neurofilament Light Chain in Aged Men: Implications for Morbidity and Mortality.

Background And Methods: Severe COVID-19 is known to induce neurological damage (NeuroCOVID), mostly in aged individuals, by affecting brain-derived neurotrophic factor (BDNF), matrix metalloproteinases (MMP) 2 and 9 and the neurofilament light chain (NFL) pathways. Thus, the aim of this pilot study was to investigate BDNF, MMP-2, MMP-9, and NFL in the serum of aged men affected by COVID-19 at the beginning of the hospitalization period and characterized by different outcomes, i.e.

Thioxanthenone-based derivatives as multitarget therapeutic leads for Alzheimer's disease.

A set of twenty-five thioxanthene-9-one and xanthene-9-one derivatives, that were previously shown to inhibit cholinesterases (ChEs) and amyloid β (Aβ) aggregation, were evaluated for the inhibition of tau protein aggregation. All compounds exhibited a good activity, and eight of them (5-8, 10, 14, 15 and 20) shared comparable low micromolar inhibitory potency versus Aβ aggregation and human acetylcholinesterase (AChE), while inhibiting human butyrylcholinesterase (BChE) even at submicromolar concentration. Compound 20 showed outstanding biological data, inhibiting tau protein and Aβ aggregation with IC = 1.

Edible Mushrooms as Source of Fibrin(ogen)olytic Enzymes: Comparison between Four Cultivated Species.

Cardiovascular diseases represent the main cause of death. A common feature of cardiovascular disease is thrombosis resulting from intravascular accumulation of fibrin. In the last years, several fibrinolytic enzymes have been discovered in many medicinal or edible mushrooms as potential new antithrombotic agents.

Retrograde response to mitochondrial dysfunctions associated to LOF variations in exon 2: unraveling the importance of RFVT2.

Flavin adenine dinucleotide (FAD) synthase (EC 2.7.7.

Longitudinal Assessment of Multiple Immunological and Inflammatory Parameters during Successful DAA Therapy in HCV Monoinfected and HIV/HCV Coinfected Subjects.

In the direct-acting antiviral (DAA) era, it is important to understand the immunological changes after HCV eradication in HCV monoinfected (mHCV) and in HIV/HCV coinfected (HIV/HCV) patients. In this study, we analyzed sub-populations of monocytes, dendritic cells (DCs), T-lymphocytes and inflammatory biomarkers following initiation of DAA in 15 mHCV and 16 HIV/HCV patients on effective antiretroviral therapy at baseline and after sustained virological response at 12 weeks (SVR12). Fifteen age- and sex-matched healthy donors (HD) were enrolled as a control group.

Neuro-Axonal Damage and Alteration of Blood-Brain Barrier Integrity in COVID-19 Patients.

Neurofilament light chain (NfL) is a specific biomarker of neuro-axonal damage. Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in blood-brain barrier (BBB) integrity. We explored neuro-axonal damage, alteration of BBB integrity and SARS-CoV-2 RNA presence in COVID-19 patients with severe neurological symptoms (neuro-COVID) as well as neuro-axonal damage in COVID-19 patients without severe neurological symptoms according to disease severity and after recovery, comparing the obtained findings with healthy donors (HD).

Lead exposure of rats during and after pregnancy induces anti-myelin proteolytic activity: a potential mechanism for lead-induced neurotoxicity.

Toxic effects of lead (Pb) are principally manifested in the central nervous system (CNS) and a mounting body of evidence indicates that excessive chronic exposure to Pb participates in the pathological processes of numerous neurodegenerative disorders in humans.In this study we evaluated whether the prolonged pre- and postnatal exposure of rat pups to lead, administrated through ingestion in drinking water, as a typical environmental exposure, can determine alterations of the protein pattern of CNS myelin and the induction of myelin-associated proteinases. Pregnant dams were given distilled water or 0.

Luminescent PLGA Nanoparticles for Delivery of Darunavir to the Brain and Inhibition of Matrix Metalloproteinase-9, a Relevant Therapeutic Target of HIV-Associated Neurological Disorders.

Human immunodeficiency virus (HIV) can independently replicate in the central nervous system (CNS) causing neurocognitive impairment even in subjects with suppressed plasma viral load. The antiretroviral drug darunavir (DRV) has been approved for therapy of HIV-infected patients, but its efficacy in the treatment of HIV-associated neurological disorders (HAND) is limited due to the low penetration through the blood-brain barrier (BBB). Therefore, innovations in DRV formulations, based on its encapsulation in optically traceable nanoparticles (NPs), may improve its transport through the BBB, providing, at the same time, optical monitoring of drug delivery within the CNS.

Neuroprotective potential of isothiocyanates in an in vitro model of neuroinflammation.

Isothiocyanates (ITCs), present as glucosinolate precursors in cruciferous vegetables, have shown anti-inflammatory, antioxidant and anticarcinogenic activities. Here, we compared the effects of three different ITCs on ROS production and on the expression of matrix metalloproteinase (MMP)-2 and -9, which represent important pathogenetic factors of various neurological diseases. Primary cultures of rat astrocytes were activated by LPS and simultaneously treated with different doses of Allyl isothiocyanate (AITC), 2-Phenethyl isothiocyanate (PEITC) and 2-Sulforaphane (SFN).

Dynamic changes of MMP-9 plasma levels correlate with JCV reactivation and immune activation in natalizumab-treated multiple sclerosis patients.

The aim of the study was to investigate the changes of matrix metalloproteinase (MMP)-2 and MMP-9 plasma levels during natalizumab treatment and their correlation with JC virus (JCV) reactivation and T-lymphocyte phenotypic modifications in peripheral blood samples from 34 relapsing-remitting multiple sclerosis (RRMS) patients. MMP-9 levels were assessed by zymography in plasma samples. JCV-DNA was detected through quantitative real time PCR in plasma samples.

In vitro effect of antiretroviral drugs on cultured primary astrocytes: analysis of neurotoxicity and matrix metalloproteinase inhibition.

There is little information available on the possible toxic effects that antiretroviral (ARV) drugs used for the treatment of human immunodeficiency virus (HIV)-infected subjects, may have on the central nervous system (CNS) resident cells. Moreover, it remains unclear whether the efficacy of the ARV drugs may also be due to their ability to exert extravirological effects on factors responsible for the development of HIV brain injury, e.g.

Marine pharmacology: therapeutic targeting of matrix metalloproteinases in neuroinflammation.

Alterations in matrix metalloproteinase (MMP) expression and activity are recognized as key pathogenetic events in several neurological disorders. This evidence makes MMPs possible therapeutic targets. The search for substances that can inhibit MMPs is moving progressively toward the screening of natural products.

Cytotoxicity Study on Luminescent Nanocrystals Containing Phospholipid Micelles in Primary Cultures of Rat Astrocytes.

Luminescent colloidal nanocrystals (NCs) are emerging as a new tool in neuroscience field, representing superior optical probes for cellular imaging and medical diagnosis of neurological disorders with respect to organic fluorophores. However, only a limited number of studies have, so far, explored NC applications in primary neurons, glia and related cells. Indeed astrocytes, as resident cells in the central nervous system (CNS), play an important pathogenic role in several neurodegenerative and neuroinflammatory diseases, therefore enhanced imaging tools for their thorough investigation are strongly amenable.