Modification of pre-ictal cortico-hippocampal oscillations by medial ganglionic eminence precursor cells grafting in the pilocarpine model of epilepsy.

Cell replacement therapies using medial ganglionic eminence (MGE)-derived GABAergic precursors reduce seizures by restoring inhibition in animal models of epilepsy. However, how MGE-derived cells affect abnormal neuronal networks and consequently brain oscillations to reduce ictogenesis is still under investigation. We performed quantitative analysis of pre-ictal local field potentials (LFP) of cortical and hippocampal CA1 areas recorded in vivo in the pilocarpine rat model of epilepsy, with or without intrahippocampal MGE-precursor grafts (PILO and PILO+MGE groups, respectively). The PILO+MGE animals had a significant reduction in the number of seizures. The quantitative analysis of pre-ictal LFP showed decreased power of cortical and hippocampal delta, theta and beta oscillations from the 5 min. interictal baseline to the 20 s. pre-ictal period in both groups. However, PILO+MGE animals had higher power of slow and fast oscillations in the cortex and lower power of slow and fast oscillations in the hippocampus compared to the PILO group. Additionally, PILO+MGE animals exhibited decreased cortico-hippocampal synchrony for theta and gamma oscillations at seizure onset and lower hippocampal CA1 synchrony between delta and theta with slow gamma oscillations compared to PILO animals. These findings suggest that MGE-derived cell integration into the abnormally rewired network may help control ictogenesis.

Effects of Supplemental Calcium Propionate and Concentrate Level: Growth Performance, Body Fat Reserves, and Health of High-Risk Beef Calves.

The aim of this study was to examine the impact of daily calcium propionate (CaPr) supplementation (0 or 20 g/calf) on growth performance, dietary energetics, body fat reserves, serum metabolites, and hematological responses in high-risk beef calves fed diets with varying (50, 60, or 70%) concentrate (CON) levels. In addition, a cost/income analysis of CaPr supplementation was carried out. Forty-eight crossbred bull calves (152.8 ± 1.56 kg body weight and 5.5 months of age) were involved in a fully randomized experimental design employing a 2 × 3 factorial arrangement of treatments. Calves were allocated (n = 8 per treatment) to individual pens (3.14 × 5.25 m) and were subjected to one of the following treatments during 42 d: No CaPr supplementation in diets containing 50, 60, or 70% CON (NoCaPr + 50, NoCaPr + 60, NoCaPr + 70, respectively) or daily CaPr supplementation dosed at 20 g/calf in diets containing 50, 60, or 70% CON (20CaPr + 50, 20CaPr + 60, 20CaPr + 70, respectively). Non-supplemented calves exhibited decreased dry matter intake (DMI) with increasing CON levels in their diets, while CaPr-supplemented calves displayed the opposite effect (interaction, p = 0.04). In calves fed a lower-CON diet (50%), those supplemented with CaPr showed greater average daily gain (ADG, 20.2%, p = 0.05) and lower DMI (2.2%, p = 0.03), resulting in improved ADG/DMI ratio, dietary energy, and energy retention (24.6, 14.4, and 18%, p < 0.05). These effects diminished when calves received diets with 60 or 70% CON but led to a 14.2% increase in rump fat thickness (p = 0.04). Only in non-supplemented CaPr calves, increasing the level of CON from 50 to 70% in the diet increased ADG (21.2%), decreased DMI (2.2%), and improved the ADG/DMI ratio (22.7%), with no impact on dietary net energy utilization. Non-supplemented calves exhibited an increase in lymphocytes as CON levels rose in their diets, whereas CaPr-supplemented calves showed the opposite effect (interaction, p = 0.05). Supplementation of CaPr decreased total protein (TP, p = 0.03) and albumin (ALB, p < 0.01) serum concentrations, with lower concentrations observed in 20CaPr + 50. CaPr supplementation reduced (p = 0.01) total cholesterol (TCHO) levels. An interaction between CaPr and CON level (p = 0.02) was observed since TCHO levels remained consistently low at higher CON levels. Glucose was decreased with increasing levels of CON (p = 0.02) but not (p = 0.85) for CaPr-supplemented calves. NoCaPr + 50 and NoCaPr + 70 increased (p = 0.05) ALB concentration. Gamma glutamyltransferase levels increased (p = 0.05) with increasing CON levels irrespective of CaPr supplementation. Comparing the profit within the same CON level in the diet, CaPr treatments yielded higher income, with the largest difference in profit observed when CaPr was supplemented at 50% CON level (USD 29 more/calf). In conclusion, CaPr supplementation proves to be an effective strategy for enhancing growth performance and dietary energy among high-risk beef calves, resulting in greater economic returns. The groups that received CaPr demonstrated superior profitability, particularly in calves fed diets with lower CON levels. Under the conditions in which this experiment was carried out, the optimal response occurred when the low-CON diet (50%) was supplemented with CaPr.

Cellular Therapy in Experimental Autoimmune Encephalomyelitis as an Adjuvant Treatment to Translate for Multiple Sclerosis.

This study aims to evaluate and compare cellular therapy with human Wharton's jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund's complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 × 105. Moreover, the cells were placed in a 10 µL solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases.

Precursors of falls from height in two main contractor companies in the Chilean construction sector and their subcontractors: Shared vision and preventive prioritization.

BACKGROUND: Risk factors that can result in serious injuries or deaths are frequently not understood or prevented because of the traditional way in which organizations approach safety. This is especially true for falls from heights in the construction sector, which remain a leading safety hazard in construction globally. METHODS: A theoretical framework derived from a thorough review of international evidence provided the foundation for the conduct of 50 structured focus groups with a total of 209 participants representing construction workers and supervisors in two main Chilean construction contractor companies and their subcontractors. RESULTS: A total of 627 precursors (risk factors), 56 taxonomies (work tasks/activities), and 622 defenses (prevention actions) were identified. These were classified in three macro dimensions and 13 subdimensions in total, providing a comprehensive framework for the origin, manifestation, and neutralization of such precursors. DISCUSSION: The findings provide a useful framework for understanding of the most critical risks to which workers are exposed and actions to prevent them. This framework should form the basis for the development of practical safety programs and tools such as management and training checklists, and data analysis for early warning signs.

Amino acid profile behavior during the fermentation of Criollo cocoa beans.

The study investigated the behavior of seventeen amino acids during spontaneous (SF) and starter culture (SC) fermentation of Criollo cocoa beans from Copallín, Guadalupe and Tolopampa, Amazonas-Peru. For this purpose, liquid chromatography (UHPLC) was used to quantify amino acids. Multivariate analysis was used to differentiate the phases of the fermentation process. The percentage of essential amino acids during SC fermentation (63.4%) was higher than SF (61.8%); it was observed that the starter culture accelerated their presence and increased their concentration during the fermentation process. The multivariate analysis identified a first stage (day 0 to day 2), characterized by a low content of amino acids that increased due to protein hydrolysis. The study showed that adding the starter culture (Saccharomyces cerevisiae) to the fermentation mass increased the concentration of essential amino acids (63.0%) compared to the spontaneous process (61.8%). Moreover, this addition reduced the fermentation time (3-4 days less), demonstrating that the fermentation process with a starter culture allows obtaining a better profile of amino acids precursors of flavor and aroma.

Biomarkers in Alzheimer's Disease: Are Olfactory Neuronal Precursors Useful for Antemortem Biomarker Research?

Alzheimer's disease (AD), as the main cause of dementia, affects millions of people around the world, whose diagnosis is based mainly on clinical criteria. Unfortunately, the diagnosis is obtained very late, when the neurodegenerative damage is significant for most patients. Therefore, the exhaustive study of biomarkers is indispensable for diagnostic, prognostic, and even follow-up support. AD is a multifactorial disease, and knowing its underlying pathological mechanisms is crucial to propose new and valuable biomarkers. In this review, we summarize some of the main biomarkers described in AD, which have been evaluated mainly by imaging studies in cerebrospinal fluid and blood samples. Furthermore, we describe and propose neuronal precursors derived from the olfactory neuroepithelium as a potential resource to evaluate some of the widely known biomarkers of AD and to gear toward searching for new biomarkers. These neuronal lineage cells, which can be obtained directly from patients through a non-invasive and outpatient procedure, display several characteristics that validate them as a surrogate model to study the central nervous system, allowing the analysis of AD pathophysiological processes. Moreover, the ease of obtaining and harvesting endows them as an accessible and powerful resource to evaluate biomarkers in clinical practice.

Gene Signature Associated with Nervous System in an Experimental Radiation- and Estrogen-Induced Breast Cancer Model.

Breast cancer is frequently the most diagnosed female cancer in the world. The experimental studies on cancer seldom focus on the relationship between the central nervous system and cancer. Despite extensive research into the treatment of breast cancer, chemotherapy resistance is an important issue limiting the efficacy of treatment. Novel biomarkers to predict prognosis or sensitivity to chemotherapy are urgently needed. This study examined nervous-system-related genes. The profiling of differentially expressed genes indicated that high-LET radiation, such as that emitted by radon progeny, in the presence of estrogen, induced a cascade of events indicative of tumorigenicity in human breast epithelial cells. Bioinformatic tools allowed us to analyze the genes involved in breast cancer and associated with the nervous system. The results indicated that the gene expression of the Ephrin A1 gene (EFNA1), the roundabout guidance receptor 1 (ROBO1), and the kallikrein-related peptidase 6 (KLK6) was greater in T2 and A5 than in the A3 cell line; the LIM domain kinase 2 gene (LIMK2) was greater in T2 than A3 and A5; the kallikrein-related peptidase 7 (KLK7), the neuroligin 4 X-linked gene (NLGN4X), and myelin basic protein (MBP) were greater than A3 only in T2; and the neural precursor cell expressed, developmentally down-regulated 9 gene (NEDD9) was greater in A5 than in the A3 and E cell lines. Concerning the correlation, it was found a positive correlation between ESR1 and EFNA1 in BRCA-LumA patients; with ROBO1 in BRCA-Basal patients, but this correlation was negative with the kallikrein-related peptidase 6 (KLK6) in BRCA-LumA and -LumB, as well as with LIMK2 and ROBO1 in all BRCA. It was also positive with neuroligin 4 X-linked (NLGN4X) in BRCA-Her2 and BRCA-LumB, and with MBP in BRCA-LumA and -LumB, but negative with KLK7 in all BRCA and BRCA-LumA and NEDD9 in BRCA-Her2. The differential gene expression levels between the tumor and adjacent tissue indicated that the ROBO1, KLK6, LIMK2, KLK7, NLGN4X, MBP, and NEDD9 gene expression levels were higher in normal tissues than in tumors; however, EFNA1 was higher in the tumor than the normal ones. EFNA1, LIMK2, ROBO1, KLK6, KLK7, and MBP gene expression had a negative ER status, whereas NEDD9 and NLGN4X were not significant concerning ER status. In conclusion, important markers have been analyzed concerning genes related to the nervous system, opening up a new avenue of studies in breast cancer therapy.

Effects of Duration of Calcium Propionate Supplementation in Lambs Finished with Supplemental Zilpaterol Hydrochloride: Productive Performance, Carcass Characteristics, and Meat Quality.

Forty-five male non-castrated crossbred Dorper lambs (40.17 ± 0.35 kg body weight, BW) were employed in a completely randomized design with five treatments to investigate the effects of the duration of calcium propionate (CaPr) supplementation (10 g CaPr/lamb/d for 0, 14, 28, or 42 d before slaughter) on lambs finished with zilpaterol hydrochloride (ZH, 7.2 mg/lamb/d for a fixed period of 28 d before slaughter) regarding their productive performance, carcass characteristics, and meat quality. Treatments consisted of the following: (1) No additives (CTL), (2) 0 days on CaPr plus 28 d on ZH, (3) 14 days on CaPr plus 28 d on ZH, (4) 28 days on CaPr plus 28 d on ZH, and (5) 42 days on CaPr plus 28 d on ZH. When compared with CTL, ZH lambs exhibited a similar average daily gain (ADG) but had lower dry matter intake (DMI), leading to increased feed efficiency. Supplementing with ZH alone did not affect carcass traits, visceral mass, whole cuts, or meat quality. Lambs that received both CaPr 28 d and ZH exhibited quadratic increases (p < 0.05) in final body weight (FBW), ADG, and dressing percentage (D%). These increases were optimal at estimated inclusion durations of 26 d for FBW, 30 for ADG, and 39 d for D%. The ADG:DMI ratio and the longissimus muscle area (LMA) both exhibited quadratic increases (p < 0.05). The optimal duration of CaPr supplementation for ADG:DMI ratio was found to be 28 d, while for LMA, it was 14 d. As the period of CaPr supplementation increased, there was a linear increase (p < 0.05) in hot carcass weight, leg circumference, and whole cuts of breast IMPS209 and shoulder IMPS207. Cook loss percent increased quadratically (p < 0.05), and was higher when CaPr was included for an estimated duration of 26 d. As the duration of CaPr supplementation increased, the purge loss percentage (PRL) also increased linearly (p < 0.05). In conclusion, including CaPr in the diet for a duration of 28 d in lambs improved the response to ZH supplementation on the productive performance, carcass weight, and some whole cuts. However, it can also have a negative effect on PRL%.

The combined effects of binder addition and different sintering methods on the mechanical properties of bovine hydroxyapatite.

Hydroxyapatite (HA) from bovine bones has been used as a biomaterial in dentistry due to its biocompatibility and bioactivity. However, dense HA bioceramics still present inadequate properties for applications that require high mechanical performance, such as infrastructure. Microstructural reinforcements and control of ceramic processing steps are methods to improve these shortcomings. The present study assessed the effects of polyvinyl butyral (PVB) addition in combination with two sintering methodologies (2-step and conventional), on the mechanical properties of polycrystalline bovine HA bioceramics. The samples were divided into four groups (with 15 samples per group): conventional sintering with binder (HBC) and without binder (HWC) and 2-step sintering with (HB2) and without binder (HW2). HA was extracted from bovine bones, turned into nanoparticles in a ball mill, and subjected to uniaxial and isostatic pressing into discs, according to ISO 6872 standards. All groups were characterized by x-ray diffractometry (XRD), differential thermal analysis (DTA) and Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and relative density. Besides, mechanical analyses (biaxial flexural strength (BFS) and modulus of elasticity) were also performed. The characterization results demonstrated that adding agglutinants or the sintering method did not affect HA's chemical and structural characteristics. Even so, the HWC group showed the highest mechanical values for BFS and modulus of elasticity being 109.0 (98.0; 117.0) MPa and 105.17 ± 14.65 GPa, respectively. The HA ceramics submitted to conventional sintering and without the addition of binders achieved better mechanical properties than the other groups. The impacts of each variable were discussed and correlated to the final microstructures and mechanical properties.

NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health.

PURPOSE OF REVIEW: NAD+ is a vital molecule that takes part as a redox cofactor in several metabolic reactions besides being used as a substrate in important cellular signaling in regulation pathways for energetic, genotoxic, and infectious stress. In stress conditions, NAD+ biosynthesis and levels decrease as well as the activity of consuming enzymes rises. Dietary precursors can promote NAD+ biosynthesis and increase intracellular levels, being a potential strategy for reversing physiological decline and preventing diseases. In this review, we will show the biochemistry and metabolism of NAD+ precursors NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide), the latest findings on their beneficial physiological effects, their interplay with gut microbiota, and the future perspectives for research in nutrition and food science fields. RECENT FINDINGS: NMN and NR demonstrated protect against diabetes, Alzheimer disease, endothelial dysfunction, and inflammation. They also reverse gut dysbiosis and promote beneficial effects at intestinal and extraintestinal levels. NR and NMN have been found in vegetables, meat, and milk, and microorganisms in fermented beverages can also produce them. NMN and NR can be obtained through the diet either in their free form or as metabolites derivate from the digestion of NAD+. The prospection of NR and NMN to find potential food sources and their dietary contribution in increasing NAD+ levels are still an unexplored field of research. Moreover, it could enable the development of new functional foods and processing strategies to maintain and enhance their physiological benefits, besides the studies of new raw materials for extraction and biotechnological development.

Citrus fruit residues as alternative precursors to developing H2O and CO2 activated carbons and its application for Cu(II) adsorption.

Due to its toxicity, the presence of Cu(II) ions released in aquatic environments presents a serious threat to the environment and human health. In search of sustainable and low-cost alternatives, there are citrus fruit residues, which are generated in large quantities by the juice industries and can be used to produce activated carbons. Therefore, the physical route was investigated for producing activated carbons to reuse citrus wastes. In this work, eight activated carbons were developed, varying the precursor (orange peel-OP, mandarine peel-MP, rangpur lime peel-RLP, and sweet lime peel-SLP) and the activating agent (CO2 and H2O) to remove Cu(II) ions of the aqueous medium. Results revealed promising activated carbons with a micro-mesoporous structure, a specific surface area of around 400 m2 g-1, and a pore volume of around 0.25 cm3 g-1. In addition, Cu (II) adsorption was favored at pH 5.5. The kinetic study showed that the equilibrium was reached within 60 min removing about 80% of Cu(II) ions. The Sips model was the most suitable for the equilibrium data, providing maximum adsorption capacities (qmS) values of 69.69, 70.27, 88.04, 67.83 mg g-1 for activated carbons (AC-CO2) from OP, MP, RLP, and SLP, respectively. The thermodynamic behavior showed that the adsorption process of Cu(II) ions was spontaneous, favorable, and endothermic. It was suggested that the mechanism was controlled by surface complexation and Cu2+-π interaction. Desorption was possible with an HCl solution (0.5 mol L-1). From the results obtained in this work, it is possible to infer that citrus residues could be successfully converted into efficient adsorbents to remove Cu(II) ions from aqueous solutions.

PFAS in fish from AFFF-impacted environments: Analytical method development and field application at a Canadian international civilian airport.

Methods targeting anionic per- and polyfluoroalkyl substances (PFAS) in aquatic biota are well established, but commonly overlook many PFAS classes present in aqueous film-forming foams (AFFFs). Here, we developed an analytical method for the expanded analysis of negative and positive ion mode PFAS in fish tissues. Eight variations of extraction solvents and clean-up protocols were first tested to recover 70 AFFF-derived PFAS from the fish matrix. Anionic, zwitterionic, and cationic PFAS displayed the best responses with methanol-based ultrasonication methods. The response of long-chain PFAS was improved for extracts submitted to graphite filtration alone compared with those involving solid-phase extraction. The validation included an assessment of linearity, absolute recovery, matrix effects, accuracy, intraday/interday precision, and trueness. The method was applied to a set of freshwater fish samples collected in 2020 in the immediate vicinity (creek, n = 15) and downstream (river, n = 15) of an active fire-training area at an international civilian airport in Ontario, Canada. While zwitterionic fluorotelomer betaines were major components of the subsurface AFFF source zone, they were rarely detected in fish, suggesting limited bioaccumulation potential. PFOS largely dominated the PFAS profile, with record-high concentrations in brook sticklebacks (Culaea inconstans) from the creek (16000-110,000 ng/g wet weight whole-body). These levels exceeded the Canadian Federal Environmental Quality Guidelines (FEQG) for PFOS pertaining to the Federal Fish Tissue Guideline (FFTG) for fish protection and Federal Wildlife Diet Guidelines (FWiDG) for the protection of mammalian and avian consumers of aquatic biota. Perfluorohexane sulfonamide and 6:2 fluorotelomer sulfonate were among the precursors detected at the highest levels (maximum of ∼340 ng/g and ∼1100 ng/g, respectively), likely reflecting extensive degradation and/or biotransformation of C6 precursors originally present in AFFF formulations.

Study of a set of reading precursors among Chilean children with Down syndrome.

Learning to read for children with Down syndrome is relevant because of the impact this ability has on learning and the development of autonomy. Previous research has described reading development in this population, but it is not clear if the process and precursors are the same in a transparent language like Spanish. This study explores performance in a set of precursors (phonological awareness, visual recognition, vocabulary, letter knowledge and verbal reasoning) in 42 children with Down syndrome between 6:0 and 10:11 years. We hypothesized that the participants would have a lower performance than previously reported with children with typical development, particularly in tasks of phonological awareness, because the method for reading instruction in Chile with this population is usually the global method. Our results show that the precursors improve with age, that there are differences in performance between the skills assessed, and the ceiling effect was not observed as would be expected for children with typical development for the abilities assessed at these ages, which suggests that in the children assessed the precursors are not consolidated at these ages. These results suggest that the stimulation of phonological awareness and other reading precursors in children with Down syndrome is important for reading development.

Chemical Characterization of Quality-Related Compounds in Cocoa Matrices: An Overview of Analytical Methods Applied for Their Analysis.

Cocoa currently faces differentiation processes toward niches of specialty products, leading to greater competitiveness for producers who must compete with products differentiated by their integral quality regarding their organoleptic characteristics, such as fine-flavor cocoa and their functional characteristics. Quality is influenced by the genetic variety of the cultivars on the one hand, and the correct postharvest processing operations of cocoa seeds, on the other. During the transformation operations, the native chemical compounds of the seeds, especially proteins, carbohydrates, and polyphenols, are transformed and generate other compounds called flavor precursors, which are responsible for defining the product quality. In this sense, the analysis of the most relevant chemical compounds in cocoa is essential to guarantee higher overall quality. Similarly, understanding the fundamental aspects that affect fine-flavor cocoa production is crucial for improving transformation processes. Therefore, reliable and robust analytical techniques are required to detect and quantify these chemical compounds. This review highlights the main techniques used to analyze essential cocoa metabolites and derived products throughout all postharvest transformation stages: from cocoa seeds to chocolate bar, offering an overview of the sample preparation methods and the analytical and imaging methodologies often employed to characterize qualifying cocoa products.

Socio-Economic and Cultural Context in the Development of Early Mathematical Competencies: A Comparative Study of Specific Educational Contexts in Chile and Spain.

This research presents the findings of a comparative study of mathematical competence among 130 students (M = 54.08 months; SD = 2.57) from vulnerable school contexts in Chile and the Spanish public school system. The study analyses a set of general and specific domain precursors for which evidence of socioeconomic background exists. Using multivariate regression and discriminant analysis techniques, we calculated similarities and differences between groups by comparing these precursors. Significant differences were found between the Spanish and Chilean groups (p < .05); however, no differences were observed in non-symbolic comparison and receptive vocabulary. Possible reasons for the existence and extent of these differences are discussed in terms of socio-cultural and educational contexts.

Antidepressant Low Doses of Ketamine and Melatonin in Combination Produce Additive Neurogenesis in Human Olfactory Neuronal Precursors.

Melatonin (MEL), an indolamine with diverse functions in the brain, has been shown to produce antidepressant-like effects, presumably through stimulating neurogenesis. We recently showed that the combination of MEL with ketamine (KET), an NMDA receptor antagonist, has robust antidepressant-like effects in mice, at doses that, by themselves, are non-effective and have no adverse effects. Here, we show that the KET/MEL combination increases neurogenesis in a clone derived from human olfactory neuronal precursors, a translational pre-clinical model for effects in the human CNS. Neurogenesis was assessed by the formation of cell clusters > 50 µm in diameter, positively stained for nestin, doublecortin, BrdU and Ki67, markers of progenitor cells, neurogenesis, and proliferation. FGF, EGF and BDNF growth factors increased the number of cell clusters in cultured, cloned ONPs. Similarly, KET or MEL increased the number of clusters in a dose-dependent manner. The KET/MEL combination further increased the formation of clusters, with a maximal effect obtained after a triple administration schedule. Our results show that the combination of KET/MEL, at subeffective doses that do not produce adverse effects, stimulate neurogenesis in human neuronal precursors. Moreover, the mechanism by which the combination elicits neurogenesis is meditated by melatonin receptors, CaM Kinase II and CaM antagonism. This could have clinical advantages for the fast treatment of depression.

3,4-Dihydro-2(1H)-Pyridones as Building Blocks of Synthetic Relevance.

3,4-Dihydro-2(1H)-pyridones (3,4-DHPo) and their derivatives are privileged structures, which has increased their relevance due to their biological activity in front of a broad range of targets, but especially for their importance as synthetic precursors of a variety of compounds with marked biological activity. Taking into account the large number of contributions published over the years regarding this kind of heterocycle, here, we presented a current view of 3,4-dihydro-2(1H)-pyridones (3,4-DHPo). The review includes general aspects such as those related to nomenclature, synthesis, and biological activity, but also highlights the importance of DHPos as building blocks of other relevant structures. Additional to the conventional multicomponent synthesis of the mentioned heterocycle, nonconventional procedures are revised, demonstrating the increasing efficiency and allowing reactions to be carried out in the absence of the solvent, becoming an important contribution to green chemistry. Biological activities of 3,4-DHPo, such as vasorelaxant, anti-HIV, antitumor, antibacterial, and antifungal, have demonstrated this heterocycle's potential in medicinal chemistry.

Bioconversion of Glycosidic Precursors from Sour Guava (Psidium friedrichsthalianum Nied.) Fruit by the Oral Microbiota into Odor-Active Volatile Compounds.

The ability of the human oral microbiota to hydrolyze the glycosidic aroma precursor extract isolated from sour guava (Psidium friedrichsthalianum Nied.) fruits was studied herein. The glycosidic extract (GP) was incubated with a mixture of the oral microbiota isolated from three individuals' saliva to evaluate the hydrolytic capacity of oral bacteria in the generation of odor-active compounds. The oral microbiota was able to release 1-hexanol from GP, under both aerobic and anaerobic conditions. Additionally, the aroma precursor extracts showed a decrease in the growth of harmful oral bacteria (Streptococcus and Actinomyces). This effect can be considered beneficial to human health because these bacteria have been related to different diseases of the bucco-respiratory tract.

Valorization of Spent Coffee Grounds as Precursors for Biopolymers and Composite Production.

Spent coffee grounds (SCG) are a current subject in many works since coffee is the second most consumed beverage worldwide; however, coffee generates a high amount of waste (SCG) and can cause environmental problems if not discarded properly. Therefore, several studies on SCG valorization have been published, highlighting its waste as a valuable resource for different applications, such as biofuel, energy, biopolymer precursors, and composite production. This review provides an overview of the works using SCG as biopolymer precursors and for polymer composite production. SCG are rich in carbohydrates, lipids, proteins, and minerals. In particular, carbohydrates (polysaccharides) can be extracted and fermented to synthesize lactic acid, succinic acid, or polyhydroxyalkanoate (PHA). On the other hand, it is possible to extract the coffee oil and to synthesize PHA from lipids. Moreover, SCG have been successfully used as a filler for composite production using different polymer matrices. The results show the reasonable mechanical, thermal, and rheological properties of SCG to support their applications, from food packaging to the automotive industry.

Synthesis and characterization of experimental endodontic sealers containing bioactive glasses particles of NbG or 45S5.

OBJECTIVE: This study evaluated the influence of adding bioactive glasses particles [Niobophosphate (NbG) or bioglass (45S5)] into endodontic cements in relation to physical, chemical and biological properties. METHODS: The following commercial cements were used as comparison: AH Plus (Dentsply), Endofill (Dentsply), MTA Fillapex (Angelus) and EndoSequence (BC Sealer, Brasseler). Setting time, radiopacity, flow rate, weight loss/variation, alkaline capacity (pH) at different time-intervals (24h/48h/7d/14d/28d), bioactivity (assessed under SEM/EDS, FTIR/ATR and XDR) and cell viability were measured. Data were analyzed by One-way ANOVA/Holm-Sidak post-test (α = 5%) (normal distribution) and Kruskal-Wallis/Students-Newman-Keuls post-test (α = 5%) (non-normal distribution). RESULTS: Bioactive endodontic experimental cements (containing NbG or 45S5) had high alkalinization capacity. The experimental cements presented high weight loss/variation (p < 0.001). 45S5 experimental cement did not present radiopacity (p < 0.001). AH Plus had the lowest cell cytotoxicity when compared to the other tested cements (p < 0.001). Regarding bioactivity, SEM/EDS analyses showed precipitates with high concentrations of Ca/P for 45S5 and NbG, as well as for MTA Fillapex and BC Sealer. AH plus and Endofill did not present bioactive precipitates. FTIR/ATR and XDR analyses found hydroxyapatite precursors for NbG, 45S5, MTA Fillapex and BC Sealer. SIGNIFICANCE: The incorporation of bioactive particles (NbG or 45S5) into endodontic cements had potential to neutralize acidic environments and induced formation of hydroxyapatite precursors. Clinically, these would produce a cement that is bactericidal and have the potential to improve tissue healing. The improved radiopacity and flowability would facilitate the visualization of the material in the radiograph and the filling of anatomical complexities during root canal obturation. As drawbacks, the excessive weight loss and post-setting cytotoxicity could result in clinical degradation of the cement and adjacent tissue irritation for the patient.