Nerve growth factor and striatal glutathione metabolism in a rat model of Huntington's disease

Purpose: To test the influence of nerve growth factor (NGF) on striatal glutathione (GSH) content and the activities of GSH-related enzymes from quinolinic acid-lesioned rats. Methods: Rats were intrastriatally injected with QA and NGF. Enzymatic and GSH assays were performed one week later. Results: NGF prevented the QA-induced decline in glutathione reductase activity and GSH content. Conclusions: NGF is able to prevent some of the disturbances induced by the excitotoxic insult in the striatal GSH metabolism.     

Halochromic Inks Applied on Cardboard for Food Spoilage Monitorization

Control of food spoilage is a critical concern in the current world scenario, not only to ensure the quality and safety of food but also to avoid the generation of food waste. This paper evaluates a dual-sensor strategy using six different pH indicators stamped on cardboard for the detection of spoilage in three different foods: beef, salmon, and strawberries. After function validation and formulation optimizations in the laboratory, the halochromic sensors methyl orange and bromocresol purple 2% (w/v) were stamped on cardboard and, in contact with the previously mentioned foods, were able to produce an easily perceptible signal for spoilage by changing color. Additionally, when it comes to mechanical characterization the inks showed high abrasion (>100 cycles) and adhesion resistance (>91%).     

Grapevine Plants Management Using Natural Extracts and Phytosynthesized Silver Nanoparticles

Starting from the well-known antimicrobial properties of silver nanoparticles, the goal of this study is to evaluate the influence of two “green” recipes, namely an alcoholic extract of Dryopteris filix-mas (L.) Schott and a dispersion of silver nanoparticles phytosynthesized using the extract on grapevine pathogens. The influence of some grapevine parameters (pith/wood rapport, soluble sugars, starch, total sugars, total water content, length of young shoots, number of grapes) in field experiments was also studied. The study was conducted on four clones (Feteasca alba 97 St., Feteasca neagra 6 St., Feteasca regala 72 St., and Cabernet Sauvignon 131 St.) located in vegetation pots inside a greenhouse. For the phytosynthesis of the silver nanoparticles (AgNPs) we used a scaled-up technology, allowing us to obtain large quantities of nanoparticles-containing solution. The AgNPs analysis by X-ray diffraction and transmission electron microscopy confirmed the synthesis of spherical and quasi-spherical nanoparticles of 17 nm average diameter and 6.72 nm crystallite size. The field experiments registered different responses of the four clones to the treatment, using both the natural extracts and phytosynthesized nanoparticles solution. Both recipes exhibited a protective effect against the Uncinula necator pathogen. For the treatment using phytosynthesized nanoparticles, significant increases in the pith/wood ratio for white wine clones (Feteasca alba 97 St. and Feteasca regala 72 St.) were observed. The biochemical analyses revealed other significant increases of soluble sugars (red wine clones—Feteasca neagra and Cabernet Sauvignon/second year), starch (Feteasca alba and Cabernet Sauvignon in 2021 for both clones), total sugars (Feteasca alba and Feteasca neagra in 2021 for both clones), and of total water content (Feteasca alba and Feteasca neagra in 2021 for both clones), respectively. The applied treatments also led to an increase of young shoots length and grape numbers for all clones as compared to the control (chemical pesticide), which would suggest a potential biostimulant effect of the recipes.     

Mucosal and systemic neutralizing antibodies to norovirus induced in infant mice orally inoculated with recombinant rotaviruses

Rotaviruses (RVs) preferentially replicate in the small intestine and frequently cause severe diarrheal disease, and the following enteric infection generally induces variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid only-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not yet been experimentally tested as potential vaccine vectors to immunize against other gastrointestinal pathogens in vivo. This is a newly available opportunity because several live-attenuated RV vaccines are already widely administered to infants and young children worldwide. To explore the feasibility of using RV as a dual vaccine vector, we rescued replication-competent recombinant RRVs harboring bicistronic gene segment 7 that encodes the native RV nonstructural protein 3 (NSP3) protein and a human norovirus (HuNoV) VP1 protein or P domain from the predominant genotype GII.4. The rescued viruses expressed HuNoV VP1 or P protein in infected cells in vitro and elicited systemic and local antibody responses to HuNoV and RRV following oral infection of suckling mice. Serum IgG and fecal IgA from infected suckling mice bound to and neutralized both RRV and HuNoV. These findings have encouraging practical implications for the design of RV-based next-generation multivalent enteric vaccines to target HuNoV and other human enteric pathogens.

Mucosal immunity plays a critical role in protecting against many pathogens in the respiratory and intestinal tracts. Live virus infections generally trigger more robust and effective mucosal immune response than oral administration of inactivated viruses or target protein antigens because they are self-amplifying and can more effectively elicit cellular as well as humoral immunity (1–4). Several studies have attempted to utilize recombinant viruses as vaccine vectors to induce an immune response against enteric pathogens (5–8); however, the most advanced of such enteric vaccine vectors are still in early stages of clinical development.Rotaviruses (RVs), the leading cause of acute gastroenteritis in infants, are a promising candidate for enteric vaccine vectors for several reasons. A) RV preferentially replicates in the small intestine, distinguishing it from several other enteric viruses that can also infect systemically or the colon. B) RV infection is acute, and the virus does not integrate into the host genome. C) RV is highly immunogenic and induces both systemic and mucosal immune responses in infected animals and humans (9, 10). D) Several live-attenuated human RV vaccines have been shown to be both safe and effective to use in very young children [e.g., RotaTeq (Merck) and Rotarix (GlaxoSmithKline)]. Other effective live-attenuated RV vaccines [Rotasiil, Rotavac, Lanzhou lamb rotavirus vaccine (LLR), and Rotavin-M1] are also licensed for use globally or primarily in their country of origin (11). E) Following substantial public health efforts, RV vaccines are now widely available in many low- and middle-income countries, as well as the more developed countries, and hence the administration of RV-based vaccines that included other heterologous antigens could potentially be piggybacked onto current RV immunization programs used globally. F) The RV double-stranded RNA (dsRNA) genome is segmented in nature, permitting easy genetic manipulation. G) With the insertion of heterologous antigens, RV replication can become attenuated in vitro (12, 13).Since a plasmid-based reverse genetics system was established in 2017, several studies have reported the generation of recombinant RVs that express fluorescent and bioluminescent reporter proteins (GFP, RFP, luciferase, etc.) and exogenous nucleotide sequences [e.g., endoribonuclease Csy4 target sequence and sequences encoding the receptor binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein] in vitro (12–22). To facilitate the assessment and development of RVs as potential enteric vaccine vectors, the capacity of recombinant RVs to induce an enteric immune response against other gastrointestinal (GI) pathogens needs to be evaluated in well-characterized preclinical small animal models. Rhesus rotavirus (RRV) is a prototype laboratory strain of simian RV that efficiently replicates in vitro (23, 24). Although RRV does not replicate well in a murine model (25–27), it does induce both systemic and mucosal immune responses in infected mice (28). In addition, RRV itself and RRV-based RV vaccine candidates have previously been shown to be a highly immunogenic and protective in several human vaccine trials and were, for a time, licensed for use in children in the United States (29, 30).Human norovirus (HuNoV) is a major cause of acute gastroenteritis in both young children and adults. Although B cells and human intestinal organoids support HuNoV replication (31, 32), there is not yet a widely available robust cell culture system for efficient HuNoV cultivation, which has impeded both the assessment of HuNoV immunity and vaccine development. The HuNoV virion consists of major capsid protein VP1 and minor capsid protein VP2 surrounding a positive-sense RNA genome (33–35). Exogenously expressed VP1 can form virus-like particles (VLPs) that are structurally and antigenically similar to HuNoV virions (36–38), and the parenteral administration of such VLPs provides some level of protective immunity to HuNoV in adults (39–41). Moreover, expression of the protruding or P domain of VP1 that bears the major antigenic sites of HuNoV can yield subunit “P particles” that can also induce immune responses (42, 43). Here, we demonstrate the induction of both systemic and mucosal antibody responses against HuNoV in suckling mice using recombinant RRVs expressing HuNoV VP1 or P domain. Our data suggest that recombinant RVs represent a potentially effective small-intestine–targeted vaccination platform to express exogenous genes in the human intestine and to protect people from other enteric pathogens such as HuNoV as well as RV.     

Clinical and Metabolomic Effects of Lactiplantibacillus plantarum and Pediococcus acidilactici in Fructose Intolerant Patients

Fructose intolerance (FI) is a widespread non-genetic condition in which the incomplete absorption of fructose leads to gastro-intestinal disorders. The crucial role of microbial dysbiosis on the onset of these intolerance symptoms together with their persistence under free fructose diets are driving the scientific community towards the use of probiotics as a novel therapeutic approach. In this study, we evaluated the prevalence of FI in a cohort composed of Romanian adults with Functional Grastrointestinal Disorders (FGIDs) and the effectiveness of treatment based on the probiotic formulation EQBIOTA^® (Lactiplantibacillus plantarum CECT 7484 and 7485 and Pediococcus acidilactici CECT 7483). We evaluated the impact of a 30-day treatment both on FI subjects and healthy volunteers. The gastrointestinal symptoms and fecal volatile metabolome were evaluated. A statistically significant improvement of symptoms (i.e., bloating, and abdominal pain) was reported in FI patient after treatment. On the other hand, at the baseline, the content of volatile metabolites was heterogeneously distributed between the two study arms, whereas the treatment led differences to decrease. From our analysis, how some metabolomics compounds were correlated with the improvement and worsening of clinical symptoms clearly emerged. Preliminary observations suggested how the improvement of gastrointestinal symptoms could be induced by the increase of anti-inflammatory and protective substrates. A deeper investigation in a larger patient cohort subjected to a prolonged treatment would allow a more comprehensive evaluation of the probiotic treatment effects.     

Prognostic impact of the preoperatory neutrophil/lymphocyte index on early surgical complications of patients with colorectal cancer

Colorectal cancer (CRC) is found among those with greatest frequency and exponential increase worldwide, with high mortality rates, which are observed as increasing due to the postsurgical complications that come to present. Systemic inflammation participates in the development and progression of cancer; therefore, inflammatory and/or immunological response markers such as the neutrophil/lymphocyte index (NLI) can aid us in predicting the poor results of our interventions. The purpose of our study was to determine the impact of an NLI of ≥2.6 as a predictor of early postsurgical complications. By means of a prospective cohort, we analyzed 158 patients with CRC who were submitted to elective surgery with a later 30-day follow-up. We found that the preoperatory NLI of ≥2.6 obtained an odds ratio (OR) = 2.24 (95% confidence interval [CI], 1.15-4.36) as a prognostic factor of early postsurgical complications according to the Clavien-Dindo classification scale, which represents a low prognostic impact due to its predictive yield with low accuracy, which is the opposite of what other reports have previously published. The use of chemotherapy before the surgical procedure was also determined to be a risk factor for post-surgical complications.     

Catabolic/Anabolic Imbalance Is Accompanied by Changes of Left Ventricular Steroid Nuclear Receptor Expression in Tachycardia-Induced Systolic Heart Failure in Male Pigs

BackgroundSteroid hormones play an important role in heart failure (HF) pathogenesis, and clinical data have revealed disordered steroidogenesis in male patients with HF. However, there is still a lack of studies on steroid hormones and their receptors during HF progression. Therefore, a porcine model of tachycardia-induced cardiomyopathy corresponding to HF was used to assess steroid hormone concentrations in serum and their nuclear receptor levels in heart tissue during the consecutive stages of HF.Methods and ResultsMale pigs underwent right ventricular pacing and developed a clinical picture of mild, moderate, or severe HF. Serum concentrations of dehydroepiandrosterone, testosterone, dihydrotestosterone, estradiol, aldosterone, and cortisol were assessed by enzyme-linked immunosorbent assay. Androgen receptor, estrogen receptor alpha, mineralocorticoid receptor, and glucocorticoid receptor messenger RNA levels in the left ventricle were determined by qPCR.The androgen level decreased in moderate and severe HF animals, while the corticosteroid level increased. The estradiol concentration remained stable. The quantitative real-time polymerase chain reaction revealed the downregulation of androgen receptor in consecutive stages of HF and increased expression of mineralocorticoid receptor messenger RNA under these conditions.ConclusionsIn the HF pig model, deteriorated catabolic/anabolic balance, manifested by upregulation of aldosterone and cortisol and downregulation of androgen signaling on the ligand level, was augmented by changes in steroid hormone receptor expression in the heart tissue.     

Liver disorders in COVID-19, nutritional approaches and the use of phytochemicals

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has affected millions of people globally. It was declared a pandemic by the World Health Organization in March 2020. The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a “cytokine storm” and the high oxidative stress responsible for the associated symptomatology. Not only respiratory symptoms are reported, but gastrointestinal symptoms (diarrhea, vomiting, and nausea) and liver abnormalities (high levels of aspartate aminotransferase, alanine aminotransferase transaminases, and bilirubin) are observed in at least 30% of patients. Reduced food intake and a delay in medical services may lead to malnutrition, which increases mortality and poor outcomes. This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury, taking energy and nutrient requirements and their impact on the immune response into account. The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.