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The distribution of the T29C TGFβ1 gene polymorphism was analyzed in 198 hypertensives with left ventricular hypertrophy (LVH) and in 235 hypertensives without LVH. Circulating TGFβ1 levels, procollagen type III levels, microalbuminuria, and left ventricular geometry and function were evaluated in all the hypertensives with LVH subgrouped according to T29C TGFβ1 gene polymorphism. Circulating TGFβ1 was evaluated by ELISA technique, procollagen type III by a specific radioimmunoassay, microalbuminuria by radioimmunoassay, and left ventricular geometry and function by echocardiography. All groups were comparable for gender, age, and sex. Regarding T29C TGFβ1 gene polymorphism, prevalence of TC or CC genotypes was significantly (P < .05) higher in hypertensives with LVH than hypertensives without LVH TC and CC LVH hypertensives were characterized by a higher prevalence of subjects with microalbuminuria (P < .05 TC and CC versus TT), by increased levels of TGFβ1, procollagen type III, urinary albumin excretion, LVM, LVM/h2.7, and lower values of left ventricular ejection fraction (P < .05 TC and CC versus TT). Our data suggest that T29C TGFβ1 gene polymorphism was associated with clinical characteristics adequate to recognize a subset of LVH hypertensives with a higher severity of hypertension. [ABSTRACT FROM AUTHOR]

Simple Summary: Feed for laboratory mice is available in different physical forms. However, there is insufficient standardization in nutrient composition and physical forms. Results pertaining to energy and nutrient digestibility show that differentially processed feed (pelleted vs. extruded) and even batches from the same provider (pelleted vs. pelleted) differ in starch gelatinization. Here we show that feed processing impacts the mice's gastrointestinal microbiome. Reproducibility and comparability between experiments with differently processed feeds in laboratory mice should not be taken for granted. Therefore, details on dietary ingredients and feed processing should be specified in studies that include animal experiments. The composition of the microbiome is subject to the host's diet. In commercial laboratory mouse diets, different physical forms of the same diets are available, containing—according to their labels—identical ingredients and nutrient compositions. However, variations in nutrient composition and starch gelatinization due to production processes and their impact on digestibility have been described. In this study, a total of 48 C57BL/J6 mice were assigned to two equal groups and were fed diets (produced with different processes—extruded vs. pelleted) for eight weeks in two biological replicates. At the end of the experiment, samples were collected from five different gastrointestinal regions, including the stomach, small intestine, cecum, large intestine, and an extracorporeal region (feces), and the microbiome was analyzed with 16S rRNA gene amplicon sequencing. The replicates in both experiments differed significantly in their relative abundances of Muribaculaceae species. Furthermore, the gastrointestinal content of pellet-fed mice contained larger numbers of Lactobacillus species. These results indicate that starch gelatinization and ingredient composition significantly influence microbial makeup. In conclusion, different feed processing methods may affect fundamental digestive and metabolic processes, impacting animal experiments and biasing microbiome data. [ABSTRACT FROM AUTHOR]

Simple Summary: Obesity has become a global pandemic involving an increase in the amount and size of fat cells in the body. Obesity is highly associated with insulin resistance and type 2 diabetes. Several medicinal plants have been reported to be useful in the prevention of obesity. Forskolin, a bioactive compound of Coleus forskohlii, can promote lipolysis in mature adipocytes. However, the effect of forskolin on body weight, glucose metabolism and adipocyte size of diet-induced obesity is still rarely investigated. In this study, the effects of forskolin on the high-fat diet-induced obese model were evaluated. Results showed that forskolin administration improves glucose metabolism and reduces fat cell diameter in the high-fat diet-fed mice. Forskolin also suppresses adipocyte differentiation of murine mesenchymal stem cells. The purpose of this study was to investigate the effects of forskolin on body weight, glucose metabolism and fat cell diameter in high-fat diet-induced obese mice. Four-week-old male mice (C57BL/6) were randomly assigned to 1 of 3 treatment groups: a high-fat diet plus 5% dimethyl sulfoxide (vehicle), high-fat diet plus 2 mg/kg of forskolin (dissolved in 5% dimethyl sulfoxide) and high-fat diet plus 4 mg/kg of forskolin (dissolved in 5% dimethyl sulfoxide). Forskolin or dimethyl sulfoxide was administered intraperitoneally every two days. The results indicated that no significant difference was observed in the body weight, feed intake and serum lipid parameters among groups at 20 weeks of age. The blood glucose levels were significantly reduced in the groups treated with 2 mg/kg of forskolin before glucose tolerance test. Forskolin administration linearly decreased blood glucose levels of high-fat diet-fed mice at 90 min and total area under curve (AUC) after insulin tolerance test. The subcutaneous adipocyte diameter was significantly reduced in the groups treated with 2 mg/kg of forskolin. Forskolin administration linearly reduced the gonadal adipocyte diameter of high-fat diet-fed mice. Forskolin significantly reduced the differentiation of murine mesenchymal stem cells into adipocytes and this was accompanied by a decrease in intracellular triglyceride content and an increase in glycerol concentration in the culture medium. The subcutaneous adipocyte diameter, gonadal adipocyte diameter and total AUC of insulin tolerance test were moderately negatively correlated with the concentration of forskolin in the high-fat diet-induced obese model. These results demonstrate that forskolin can regulate glucose metabolism and reduce fat cell diameter of high-fat diet-fed mice and inhibit the adipocyte differentiation of murine mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Oxidative stress is considered one of the pathological mechanisms that cause Parkinson's disease (PD), which has led to the investigation of several antioxidants molecules as a potential therapeutic treatment against the disease. Although preclinical studies have demonstrated the efficacy of these compounds to maintain neuronal survival and activity in PD models, these results have not been reflected in clinical trials, antioxidants have not been able to act as disease modifiers in terms of clinical symptoms. Translational medicine currently faces the challenge of redesigning clinical trials to standardize criteria when testing molecules to reduce responses' variability. Herein, we discuss current challenges and opportunities regarding several non-enzymatic antioxidants' therapeutic molecules for PD patients' potential treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The processing of feed items has an impact on their nutritive properties, e.g., differences in the degree of starch gelatinization between pelleted and extruded diets are apparent. In many species, including humans, it is known that this influences the digestion process on enzymatic and microbial levels, and thus the animals´ ability to utilize the diet. Laboratory animal diets are often marketed as identical products, e.g., a standard maintenance diet, which can be purchased in pelleted or extruded form. The hypothesis that there are differences in energy and nutrient digestibility among such products, even though they are claimed to be the same diet, was investigated. The results of the digestibility trials confirm the hypothesis. Additionally, they show that even among batches of the same laboratory rodent diet in the same form, standardization is not always achieved. Starch gelatinization is a major determinant of carbohydrate digestibility and varies with diet processing. Laboratory rodent diets are often marketed as identical, but are sold in different forms, regardless of the markedly higher starch gelatinization in extruded than in pelleted diets. Our hypothesis was that this would impact energy and nutrient digestibility in mice fed pellets or extrudate, respectively. Trial 1 showed that feeding C57BL/6 mice a standard maintenance diet in extruded form results in a significantly higher digestibility of organic matter, energy, and carbohydrates than the identical diet in pelleted form. The replication of the experiment, however, revealed a variation between batches of the same pelleted diet regarding starch and total dietary fiber contents. Given the significant differences in diet digestibility and the potential impacts of digestibility on nutrient utilization, the intestinal microbiome, and intermediary metabolism, trials performed with differently processed diets are not comparable. This might partly explain failures to reproduce results, especially in gastrointestinal or microbiome research. Considering this impact on experimental animals, the degree of starch gelatinization should be declared in the diet information for laboratory animal diets. The differences between batches of laboratory animal diets as observed in the pellets are not acceptable. [ABSTRACT FROM AUTHOR]

Comminuted meat products are highly susceptible to safety and quality degradation partly because of their large interfacial area in the emulsion. The food industry extensively uses synthetic chemical preservatives to delay that degradation which is caused by microbial growth, enzyme activities and oxidation reactions. However, due to the potential health damage (e.g., cardiovascular diseases, neurodegenerative diseases, cancers among others) synthetic preservatives in meat may cause, consumers are becoming skeptical to buy meat products containing such additives. In the meat industry, the interest of finding natural food preservatives is intensifying. Polyphenolic-rich plants used as natural food preservatives offer the best alternative for a partial or a complete replacement of their synthetic counterparts. They can be extracted from natural sources such as olives, fruits, grapes, vegetables, spices, herbs, and algae, and among others. The common feature of these phenolic compounds is that they have one or more aromatic rings with one or more -OH group which are essential for their antimicrobial and antioxidant properties. This review article is intended to provide an overview of the plant-based phenolic molecules used as natural food preservative, their antimicrobial and antioxidant mechanism of action, and their potential application in comminuted meat. [ABSTRACT FROM AUTHOR]

An HS-SPME GC-MS analysis of the volatile compounds adsorbed at the outer surface of lemon and grapefruit pectins obtained via the hydrodynamic cavitation of industrial waste streams of lemon and grapefruit peels in water suggests important new findings en route to understanding the powerful and broad biological activity of these new pectic materials. In agreement with the ultralow degree of esterification of these pectins, the high amount of highly bioactive α-terpineol and terpinen-4-ol points to limonene (and linalool) decomposition catalyzed by residual citric acid in the citrus waste peel residue of the juice industrial production. [ABSTRACT FROM AUTHOR]

Background: Aphanizomenon flos-aquae (AFA) is a unicellular cyanobacterium considered to be a "superfood" for its complete nutritional profile and beneficial properties. We investigated possible beneficial effects of an AFA extract, commercialized as AphaMax®, containing concentrated amount of phycocyanins and phytochrome, in 2,4 dinitrobenzensulfonic acid(DNBS)-induced colitis in rats. Methods: Effects of preventive oral treatment of AphaMax® (20, 50 or 100 mg/kg/day) in colitic rats were assessed and then macroscopic and microscopic analyses were performed to evaluate the inflammation degree. Myeloperoxidase (MPO) activity and NF-κB, pro-inflammatory citockines, cycloxygenase-2 (COX-2), and inducible NOS (iNOS) levels of expression were determined, as Reactive Oxygen Species (ROS) and nitrite levels. Results: AphaMax® treatment attenuated the severity of colitis ameliorating clinical signs. AphaMax® reduced the histological colonic damage and decreased MPO activity, NF-κB activation, as well as iNOS and COX-2 expression. AphaMax® treatment improved the altered immune response associated with colonic inflammation reducing IL-1β, IL-6 expression. Lastly, AphaMax® reduced oxidative stress, decreasing ROS and nitrite levels. Conclusions: Preventive treatment with AphaMax® attenuates the severity of the inflammation in DNBS colitis rats involving decrease of the NF-kB activation, reduction of iNOS and COX-2 expression, and inhibition of oxidative stress. Due its anti-inflammatory and antioxidant proprieties AphaMax® could be a good candidate as a complementary drug in inflammatory bowel disease (IBD) treatment. [ABSTRACT FROM AUTHOR]

The present study evaluated the ability of KlamExtra®, an Aphanizomenon flos aquae (AFA) extract, to counteract metabolic dysfunctions due to a high fat diet (HFD) or to accelerate their reversion induced by switching an HFD to a normocaloric diet in mice with diet-induced obesity. A group of HFD mice was fed with an HFD supplemented with AFA (HFD-AFA) and another one was fed with regular chow (standard diet—STD) alone or supplemented with AFA (STD-AFA). AFA was able to significantly reduce body weight, hypertriglyceridemia, liver fat accumulation and adipocyte size in HFD mice. AFA also reduced hyperglycaemia, insulinaemia, HOMA-IR and ameliorated the glucose tolerance and the insulin response of obese mice. Furthermore, in obese mice AFA normalised the gene and the protein expression of factors involved in lipid metabolism (FAS, PPAR-γ, SREBP-1c and FAT-P mRNA), inflammation (TNF-α and IL-6 mRNA, NFkB and IL-10 proteins) and oxidative stress (ROS levels and SOD activity). Interestingly, AFA accelerated the STD-induced reversion of glucose dysmetabolism, hepatic and VAT inflammation and oxidative stress. In conclusion, AFA supplementation prevents HFD-induced dysmetabolism and accelerates the STD-dependent recovery of glucose dysmetabolism by positively modulating oxidative stress, inflammation and the expression of the genes linked to lipid metabolism. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 pandemic has caused a collapse of the world health systems. Now, vaccines and more effective therapies have reversed this crisis but the scenario is further aggravated by the appearance of a new pathology, occurring as SARS-CoV-2 infection consequence: the long-COVID-19. This term is commonly used to describe signs and symptoms that continue or develop after acute infection of COVID-19 up to several months. In this review, the consequences of the disease on mental health and the neurological implications due to the long-COVID are described. Furthermore, the appropriate nutritional approach and some recommendations to relieve the symptoms of the pathology are presented. Data collected indicated that in the next future the disease will affect an increasing number of individuals and that interdisciplinary action is needed to counteract it. [ABSTRACT FROM AUTHOR]

COronaVIrus Disease 2019 (COVID-19) is a newly emerging infectious disease that spread across the world, caused by the novel coronavirus Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Despite the advancements in science that led to the creation of the vaccine, there is still an urgent need for new antiviral drugs effective against SARS-CoV-2. This study aimed to investigate the antiviral effect of Paulownia tomentosa Steud extract against SARS-CoV-2 and to evaluate its antioxidant properties, including respiratory smooth muscle relaxant effects. Our results showed that P. tomentosa extract can inhibit viral replication by directly interacting with both the 3-chymotrypsin-like protease and spike protein. In addition, the phyto complex does not reduce lung epithelial cell viability and exerts a protective action in those cells damaged by tert-butyl hydroperoxide , a toxic agent able to alter cells' functions via increased oxidative stress. These data suggest the potential role of P. tomentosa extract in COVID-19 treatment, since this extract is able to act both as an antiviral and a cytoprotective agent in vitro. [Display omitted] • The study conducted on Paulownia tomentosa Steud (PTS) extract confirms its relevant properties. • PTS extract showed antiviral and virucidal activity against SARS-CoV-2 in vitro. • Antioxidant properties and respiratory smooth muscle relaxant effects of PTS extract were proved. • PTS extract is able to act both as an antiviral and a cytoprotective agent in in vitro models. • The data presented suggest the potential role of PTS in COVID-19 treatment. [ABSTRACT FROM AUTHOR]

The aim of the present work is the evaluation of biological effects of natural stilbenoids found in Vitis vinifera, with a focus on their activity as epigenetic modulators. In the present study, resveratrol, pterostilbene and for the first time their dimers (±)-trans-δ-viniferin, (±)-trans-pterostilbene dehydrodimer were evaluated in Caco-2 and HepG-2 cell lines as potential epigenetic modulators. Stilbenoids were added in a Caco-2 cell culture as a model of the intestinal epithelial barrier and in the HepG-2 as a model of hepatic environment, to verify their dose-dependent toxicity, ability to interact with DNA, and epigenomic action. Resveratrol, pterostilbene, and (±)-trans-pterostilbene dehydrodimer were found to have no toxic effects at tested concentration and were effective in reversing arsenic damage in Caco-2 cell lines. (±)-trans-δ-viniferin showed epigenomic activity, but further studies are needed to clarify its mode of action. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic, induced by the worldwide spreading of the SARS-CoV-2, is well known for its clinical picture consistent with respiratory symptoms. If pulmonary complications are the most common manifestation of the disease, neurological problems are also significantly present, with complications including acute cerebrovascular events, encephalitis, Guillain-Barré and Miller Fisher syndromes, acute necrotizing hemorrhagic encephalopathy and hemophagocytic lymphohistiocytosis. These medical signs can be considered direct effects of the virus on the nervous system, para-infectious or post-infectious immune-mediated diseases, and neurological complications of the systemic effects of the SARS-CoV-2. Case: In the present article, the encephalitis case in a 5-year-old girl positive for COVID-19 admitted to the emergency department complaining of fever and swelling in the neck is described. At this time, her neurological examination was unremarkable. Over the next few days, the fever went down and she experienced acute behavioral changes, mild confusion, and drowsiness. The brain MRI and electroencephalography (EEG) showed CNS involvement, suggestive of encephalitis. Conclusion: The dramatic improvement of the symptoms after immunotherapy with corticosteroids reinforced the hypothesis of an immune-related mechanism. [ABSTRACT FROM AUTHOR]

Schematic representation of the effect of altered insulin signaling on the different aspects of mitochondrial dysfunction and neurodegeneration, by using both in vitro and in vivo model systems. [Display omitted] • Altered insulin pathway induces mitochondrial dysfunction both in vivo and in vitro model systems. • Altered insulin pathway affects mitochondrial dynamics. • Insulin administration ameliorates mitochondrial dysfunction and apoptosis. • Effective mitophagy is an aging-dependent mechanism. Altered insulin signaling and insulin resistance are considered the link between Alzheimer's disease (AD) and metabolic syndrome. Here, by using an in vitro and an in vivo model, we investigated the relationship between these disorders focusing on neuronal mitochondrial dysfunction and mitophagy. In vitro Aβ insult induced the opening of mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (ΔΨm) loss, and apoptosis while insulin addition ameliorated these dysfunctions. The same alterations were detected in a 16 weeks of age mouse model of diet-induced obesity and insulin resistance. In addition, we detected an increase of fission related proteins and activation of mitophagy, proved by the rise of PINK1 and Parkin proteins. Nevertheless, in vitro, the increase of p62 and LC3 indicated an alteration in autophagy, while, in vivo decreased expression of p62 and increase of LC3 suggested removing of damaged mitochondria. Finally, in aged mice (28 and 48 weeks), the data indicated impairment of mitophagy and suggested the accumulation of damaged mitochondria. Taken together these outcomes indicate that alteration of the insulin pathway affects mitochondrial integrity, and effective mitophagy is age-dependent. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dysfunction is a critical factor in the onset and progression of neurodegenerative diseases. Recently, mitochondrial transplantation has been advised as an innovative and attractive strategy to transfer and replace damaged mitochondria. Here we propose, for the first time, to use rat brain extracted synaptosomes, a subcellular fraction of isolated synaptic terminal that contains mitochondria, as mitochondrial delivery systems. Results: Synaptosome preparation was validated by the presence of Synaptophysin and PSD95. Synaptosomes were characterized in terms of dimension, zeta potential, polydispersity index and number of particles/ml. Nile Red or CTX-FITCH labeled synaptosomes were internalized in LAN5 recipient cells by a mechanism involving specific protein–protein interaction, as demonstrated by loss of fusion ability after trypsin treatment and using different cell lines. The loading and release ability of the synaptosomes was proved by the presence of curcumin both into synaptosomes and LAN5 cells. The vitality of mitochondria transferred by Synaptosomes was demonstrated by the presence of Opa1, Fis1 and TOM40 mitochondrial proteins and JC-1 measurements. Further, synaptosomes deliver vital mitochondria into the cytoplasm of neuronal cells as demonstrated by microscopic images, increase of TOM 40, cytochrome c, Hexokinase II mitochondrial proteins, and presence of rat mitochondrial DNA. Finally, by using synaptosomes as a vehicle, healthy mitochondria restored mitochondrial function in cells containing rotenone or CCCp damaged mitochondria. Conclusions: Taken together these results suggest that synaptosomes can be a natural vehicle for the delivery of molecules and organelles to neuronal cells. Further, the replacement of affected mitochondria with healthy ones could be a potential therapy for treating neuronal mitochondrial dysfunction-related diseases. [ABSTRACT FROM AUTHOR]

Angiotensin II, the main effector of renin angiotensin system, plays an important role in the inflammatory process and most of its effects are mediated through the AT1 receptor activation. However, the knowledge about the AT2 receptor involvement in this process is still evolving. We previously found that in an experimental model of colitis, AT2 receptor activation can contribute to the impairment of the muscle contractility in vitro in the course of inflammation. Here, we investigated the potential alleviating effects of the in vivo treatment of PD123319 (1-[[4-(Dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate), AT2 receptor antagonist, in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced rat model of colitis. The effects of i.p PD123319 (0.3, 3 and 10 mg/kg) administration to rats subjected to intra-rectal DNBS instillation were investigated. The study revealed that the colon injury and the inflammatory signs were ameliorated by PD123319 when visualized by the histopathological examination. The colon shortening, myeloperoxidase activity, and colonic expression of IL-1β, IL-6 and iNOS were downregulated in a dose-dependent manner in DNBS-induced colitis rats treated with PD123319 and the anti-oxidant defense machinery was also improved. The mechanism of these beneficial effects was found in the ability of PD123319 to inhibit NF-κB activation induced by DNBS. The colonic contractility in inflamed tissues was also improved by PD123319 treatment. In conclusion, our data have demonstrated previously that undescribed proinflammatory effects for the AT2 receptors in DNBS-induced colitis in rats in which they are mediated likely by NF-κB activation and reactive oxygen species generation. Moreover, when the inflammatory process is mitigated by the AT2 receptor antagonist treatment, the smooth muscle is able to recover its functionality. [ABSTRACT FROM AUTHOR]

Natural products are a rich source of bioactive molecules that have potential pharmacotherapeutic applications. In this study, we focused on Artemisia annua (A. annua) and its enriched extracts which were biologically evaluated in vitro as virucidal, antiviral, and antioxidant agents, with a potential application against the COVID-19 infection. The crude extract showed virucidal, antiviral and antioxidant effects in concentrations that did not affect cell viability. Scopoletin, arteannuin B and artemisinic acid (single fractions isolated from A. annua) exerted a considerable virucidal and antiviral effect in vitro starting from a concentration of 50 µg/mL. Data from Surface Plasmon Resonance (SPR) showed that the inhibition of the viral infection was due to the interaction of these compounds with the 3CLpro and Spike proteins of SARS-CoV-2, suggesting that the main interaction of compounds may interfere with the viral pathways during the insertion and the replication process. The present study suggests that natural extract of A. annua and its components could have a key role as antioxidants and antiviral agents and support the fight against SARS-CoV-2 variants and other possible emerging Coronaviruses. [Display omitted] • A.annua extract play a significant role as antioxidant agent. • Scopoletin, arteannuin B and artemisinic acid inhibit SARS-CoV-2 viral replication. • Surface Plasmon Resonance confirms interaction of A. annua fraction with Spike and 3CLpro proteins of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat. Methods: Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed. Results: Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, guanosine in DNBS rats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite. Conclusions: In conclusion, guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling. [ABSTRACT FROM AUTHOR]