Valorization of feather waste in Brazil: structure, methods of extraction, and applications of feather keratin.

This systematic review presents the potential of using feather waste as a ß-keratin source, including the Brazilian scenario in the generation of this byproduct. The structure and properties of α- and ß-keratin, the methods commonly reported to extract keratin from poultry feathers, and applications of feather keratin-based materials are also covered in this review. The literature search for poultry production data in Brazil was conducted for the last 2 years, for the period 2021-2022. A broad literature search for extraction methods and applications of feather keratin was done for the period 2001-2022. The poultry industry is one of the largest sectors of the food industry, and Brazil was the third-largest world producer of chicken meat with more than six billion chickens slaughtered in 2021. Poultry feathers constitute about 7% weight of broilers; thus, it can be estimated that about one million tons of poultry feathers were generated in Brazil in 2021, and the improper disposal of this byproduct contributes to environmental problems and disease transmission. The most common method of reusing feathers is the production of feather meal. From economic and environmental points of view, it is advantageous to develop processes to add value to this byproduct, including the extraction of keratin. Among natural biodegradable polymers, keratin-based materials have revolutionized the field of biomaterials due to their biocompatibility and biodegradability, allowing their application in biomedical, pharmaceutical, chemical, and engineering areas.

Eco-Friendly Polysaccharide-Based Synthesis of Nanostructured MgO: Application in the Removal of Cu2+ in Wastewater.

The present study described three synthesis routes using different natural polysaccharides as low-cost non-toxic fuels and complexing agents for obtaining MgO. Cassava starch, Aloe vera leaves (mainly acemannan) gel, and citric pectin powder were mixed with magnesium nitrate salt and calcined at 750 °C for 2 h. The samples were named according to the polysaccharide: cassava starch (MgO-St), citrus pectin (MgO-CP), and Aloe vera (MgO-Av). X-ray diffraction identified the formation of a monophasic periclase structure (FCC type) for the three samples. The N2 adsorption/desorption isotherms (B.E.T. method) showed an important difference in textural properties, with a higher pore volume (Vmax = 89.76 cc/g) and higher surface area (SA = 43.93 m2/g) obtained for MgO-St, followed by MgO-CP (Vmax = 11.01 cc/g; SA = 7.01 m2/g) and MgO-Av (Vmax = 6.44 cc/g; SA = 6.63 m2/g). These data were consistent with the porous appearance observed in SEM images. Porous solids are interesting as adsorbents for removing metallic and molecular ions from wastewater. The removal of copper ions from water was evaluated, and the experimental data at equilibrium were adjusted according to the Freundlich, Langmuir, and Temkin isotherms. According to the Langmuir model, the maximum adsorption capacity (qmax) was 6331.117, 5831.244, and 6726.623 mg·g-1 for the adsorbents MgO-St, MgO-Av, and MgO-CP, respectively. The results of the adsorption isotherms indicated that the synthesized magnesium oxides could be used to decrease the amount of Cu2+ ions in wastewater.

Alkaline pre-treatment (NAOH) as a strategy to increase the performance and feasibility of the anaerobic digestion of cattle slurry.

Dairy cattle manure with bedding (CB), including manure, urine, water, and shavings, is lignocellulosic biomass and needs to be pre-treated in anaerobic reactors to enhance biomass digestibility. This study analyzed the technical and economic feasibility of physical treatment (milling) and alkaline treatment of CB for biogas production. Pre-treatment included drying, milling, and alkaline hydrolysis at room temperature for 24 h. Maximum biogas production was determined using the biochemical methane potential (BMP) test. Physicochemical analyses were performed to characterise CB before and after pre-treatment and the BMP test. The characteristics of the lignocellulosic material were examined by scanning electron microscopy. The economic feasibility (return on investment) of each treatment (USD per ton of CB) was determined. Treatment with 3% NaOH achieved the highest biogas production (771 mL per kg of volatile solids) and was 104.5% higher than that of milling and 124.7% higher than that of chemical pre-treatment with 4% NaOH. The analysis of economic feasibility showed that the payback period of treatment with 3% NaOH was 1.4 years for scenario 1 (continuous stirred tank reactor - CSTR) and 3 years for scenario 2 (covered lagoon digester). These results demonstrate the feasibility of producing biogas as a renewable energy source via the anaerobic digestion of CB.

Role of Oxysterols in the Activation of the NLRP3 Inflammasome as a Potential Pharmacological Approach in Alzheimer's Disease.

Alzheimer's disease (AD), the most prevalent form of dementia, is a complex clinical condition with multifactorial origin posing a major burden to health care systems across the world. Even though the pathophysiological mechanisms underlying the disease are still unclear, both central and peripheral inflammation has been implicated in the process. Piling evidence shows that the nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated in AD. As dyslipidemia is a risk factor for dementia, and cholesterol can also activate the inflammasome, a possible link between lipid levels and the NLRP3 inflammasome has been proposed in Alzheimer's. It is also speculated that not only cholesterol but also its metabolites, the oxysterols, may be involved in AD pathology. In this context, mounting data suggest that NLRP3 inflammasome activity can be modulated by different peripheral nuclear receptors, including liver-X receptors, which present oxysterols as endogenous ligands. In light of this, the current review explores whether the activation of NLRP3 by nuclear receptors, mediated by oxysterols, may also be involved in AD and could serve as a potential pharmacological avenue in dementia.

Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington's disease.

Obesity represents a global health problem and is characterized by metabolic dysfunctions and a low-grade chronic inflammatory state, which can increase the risk of comorbidities, such as atherosclerosis, diabetes and insulin resistance. Here we tested the hypothesis that the genetic deletion of metabotropic glutamate receptor 5 (mGluR5) may rescue metabolic and inflammatory features present in BACHD mice, a mouse model of Huntington's disease (HD) with an obese phenotype. For that, we crossed BACHD and mGluR5 knockout mice (mGluR5-/-) in order to obtain the following groups: Wild type (WT), mGluR5-/-, BACHD and BACHD/mGluR5-/- (double mutant mice). Our results showed that the double mutant mice present decreased body weight as compared to BACHD mice in all tested ages and reduced visceral adiposity as compared to BACHD at 6 months of age. Additionally, 12-month-old double mutant mice present increased adipose tissue levels of adiponectin, decreased leptin levels, and increased IL-10/TNF ratio as compared to BACHD mice. Taken together, our preliminary data propose that the absence of mGluR5 reduce weight gain and visceral adiposity in BACHD mice, along with a decrease in the inflammatory state in the visceral adipose tissue (VAT), which may indicate that mGluR5 may play a role in adiposity modulation.

Neurochemical abnormalities in the hippocampus of male rats displaying audiogenic seizures, a genetic model of epilepsy.

BACKGROUND: Epilepsy is a disorder characterized by recurrent seizures that affects 1% of the population. However, the neurochemical alterations observed in epilepsy are not fully understood. There are different animal models of epilepsy, such as genetic or drug induced. In the present study, we utilize Wistar Audiogenic Rats (WAR), a murine strain that develops seizures in response to high intensity audio stimulation, in order to investigate abnormalities in glutamatergic and GABAergic systems. METHODS: Synaptosomes and glial plasmalemmal vesicles were prepared from hippocampus and cortex, respectively. Glutamate and GABA release and uptake were assayed by monitoring the fluorescence and using L-[3H]-radiolabeled compounds. Glutamate and calcium concentration in the synaptosomes were also measured. The expression of neuronal calcium sensor 1 (NCS-1) was determined by western blot. RESULTS: Glutamate and GABA release evoked by KCl was decreased in WAR compared to control Wistar rats. Calcium independent release was not considerably different in both groups. The total amount of glutamate of synaptosomes, as well as glutamate uptake by synaptosomes and GPV were also decreased in WAR in comparison with the controls. In addition, [Ca2+]i of hippocampal synaptosomes, as well as NCS-1 expression in the hippocampus, were increased in WAR in comparison with controls. CONCLUSION: In conclusion, our results suggest that WAR have important alterations in the glutamatergic and GABAergic pathways, as well as an increased expression of NCS-1 in the hippocampus and inferior colliculus. These alterations may be linked to the spreading of hyperexcitability and recruitment of various brain regions.

Negative Modulation of the Metabotropic Glutamate Receptor Type 5 as a Potential Therapeutic Strategy in Obesity and Binge-Like Eating Behavior.

Obesity is a multifactorial disease, which in turn contributes to the onset of comorbidities, such as diabetes and atherosclerosis. Moreover, there are only few options available for treating obesity, and most current pharmacotherapy causes severe adverse effects, while offering minimal weight loss. Literature shows that metabotropic glutamate receptor 5 (mGluR5) modulates central reward pathways. Herein, we evaluated the effect of VU0409106, a negative allosteric modulator (NAM) of mGluR5 in regulating feeding and obesity parameters. Diet-induced obese C57BL/6 mice were treated for 14 days with VU0409106, and food intake, body weight, inflammatory/hormonal levels, and behavioral tests were performed. Our data suggest reduction of feeding, body weight, and adipose tissue inflammation in mice treated with high-fat diet (HFD) after chronic treatment with VU0409106. Furthermore, a negative modulation of mGluR5 also reduces binge-like eating, the most common type of eating disorder. Altogether, our results pointed out mGluR5 as a potential target for treating obesity, as well as related disorders.

Effects of Transplanted Umbilical Cord Blood Mononuclear Cells Overexpressing GDNF on Spatial Memory and Hippocampal Synaptic Proteins in a Mouse Model of Alzheimer's Disease.

BACKGROUND/OBJECTIVE: Alzheimer's disease (AD) is a progressive incurable neurodegenerative disorder. Glial cell line-derived neurotrophic factor (GDNF) is a prominent regulator of brain tissue and has an impressive potential for use in AD therapy. While its metabolism is still not fully understood, delivering neuropeptides such as GDNF via umbilical cord blood mononuclear cells (UCBMCs) to the sites of neurodegeneration is a promising approach in the development of innovative therapeutic avenues. METHODS: UCBMCs were transduced with adenoviral vectors expressing GDNF and injected into AD transgenic mice. Various parameters including homing and survival of transplanted cells, expression of GDNF and synaptic proteins, as well as spatial memory were evaluated. RESULTS: UCBMCs were observed in the hippocampus and cortex several weeks after transplantation, and their long-term presence was associated with improved spatial memory. Post-synaptic density protein 95 (PSD-95) and synaptophysin levels in the hippocampus were also effectively restored following the procedure in AD mice. CONCLUSIONS: Our data indicate that gene-cell therapy with GDNF-overexpressing UCBMCs may produce long-lasting neuroprotection and stimulation of synaptogenesis. Such adenoviral constructs could potentially possess a high therapeutic potential for the treatment of AD.

Evaluation of PCSK9 levels and its genetic polymorphisms in women with polycystic ovary syndrome.

Dyslipidemia is one of the common metabolic disorders in Polycystic Ovary Syndrome (PCOS). Proprotein convertase subtilisin kexin type 9 (PCSK9) is a new component of lipid metabolism and correlated to the development of dyslipidemia and atherosclerosis. This protein acts by preventing the recycling of LDL receptors (LDL-r) back to the cell surface and thus generates higher levels of LDLc. The objective of this study was to evaluate the PCSK9 polymorphisms rs505151 (c.2009A>G), rs562556 (c.1420A>G) and rs11206510 (T>C) and plasma PCSK9 levels in PCOS. A group of women with PCOS (n=97), and a group of healthy women (control, n=99) were selected. Biochemical parameters were determined by using Vitros system and polymorphisms were assessed by TaqMan SNP Genotyping Assays. Plasma PCSK9 levels or PCSK9 polymorphisms were not associated with PCOS. The genotype rs11206510TT was associated with higher levels of PCSK9 in both groups. The population investigated (PCOS+control groups) with the rs505151AA genotype presented higher HDLc levels. The GG genotype regarding rs562556 polymorphism was associated with higher HDLc in PCOS group, while the AA genotype carriers had higher plasma testosterone levels when evaluated all women in a same group. The results were the same by comparing recessive and dominant model despite PCOS or both groups altogether. Our results suggest that PCSK9 is not altered specifically in PCOS, but it could be associated with in lipid and androgen metabolism in Brazilian women.

Transcriptional Analysis of Blood Lymphocytes and Skin Fibroblasts, Keratinocytes, and Endothelial Cells as a Potential Biomarker for Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating and progressive form of dementia that is typically associated with a build-up of amyloid-ß plaques and hyperphosphorylated and misfolded tau protein in the brain. Presently, there is no single test that confirms AD; therefore, a definitive diagnosis is only made after a comprehensive medical evaluation, which includes medical history, cognitive tests, and a neurological examination and/or brain imaging. Additionally, the protracted prodromal phase of the disease makes selection of control subjects for clinical trials challenging. In this study we have utilized a gene-expression array to screen blood and skin punch biopsy (fibroblasts, keratinocytes, and endothelial cells) for transcriptional differences that may lead to a greater understanding of AD as well as identify potential biomarkers. Our analysis identified 129 differentially expressed genes from blood of dementia cases when compared to healthy individuals, and four differentially expressed punch biopsy genes between AD subjects and controls. Additionally, we identified a set of genes in both tissue compartments that showed transcriptional variation in AD but were largely stable in controls. The translational products of these variable genes are involved in the maintenance of the Golgi structure, regulation of lipid metabolism, DNA repair, and chromatin remodeling. Our analysis potentially identifies specific genes in both tissue compartments that may ultimately lead to useful biomarkers and may provide new insight into the pathophysiology of AD.

Human adipose-derived stem cells stimulate neuroregeneration.

Traumatic brain injuries and degenerative neurological disorders such as Alzheimer's dementia, Parkinson's disease, amyotrophic lateral sclerosis and many others are characterized by loss of brain cells and supporting structures. Restoring microanatomy and function using stem cells is a promising therapeutic approach. Among the many various sources, adipose-derived stem cells (ADSCs) are one of the most easily harvested alternatives, they multiply rapidly, and they demonstrate low immunogenicity with an ability to differentiate into several cell types. The objective of this study was to evaluate the effect of xenotransplanted human ADSCs on post-traumatic regeneration of rat sciatic nerve. Peripheral reconstruction following complete sciatic transection and autonerve grafting was complemented by intra-operative injection of hADSCs into the proximal and distal stumps. The injury caused gliosis and apoptosis of sensory neurons in the lumbar 5 (L5) ganglia in the control rodents; however, animals treated with hADSCs demonstrated a smaller amount of cellular loss. Formation of amputation neuroma, which hinders axonal repair, was less prominent in the experimental group, and immunohistochemical analysis of myelin basic protein showed good myelination 65 days after surgery. At this point, control groups still exhibited high levels of microglia/macrophage-specific marker Iba-1 and proliferating cell nuclear antigen, the mark of an ongoing inflammation and incomplete axonal growth 2 months after the injury. This report demonstrates that hADSCs promote neuronal survival in the spinal ganglion, fuel axonal repair and stimulate the regeneration of peripheral nerves.

Topological Magnon Bands in a Kagome Lattice Ferromagnet.

There is great interest in finding materials possessing quasiparticles with topological properties. Such materials may have novel excitations that exist on their boundaries which are protected against disorder. We report experimental evidence that magnons in an insulating kagome ferromagnet can have a topological band structure. Our neutron scattering measurements further reveal that one of the bands is flat due to the unique geometry of the kagome lattice. Spin wave calculations show that the measured band structure follows from a simple Heisenberg Hamiltonian with a Dzyaloshinkii-Moriya interaction. This serves as the first realization of an effectively two-dimensional topological magnon insulator--a new class of magnetic material that should display both a magnon Hall effect and protected chiral edge modes.

Apolipoprotein polymorphism is associated with pro-thrombotic profile in non-demented dyslipidemic subjects.

Apolipoprotein gene polymorphism has an important role in lipid metabolism and in the development of cerebro- and cardio-vascular disease (CCVD), including dementia. Dyslipidemia and hemostatic abnormalities are key risk factors associated with athero-sclerotic events preceding CCVD. The aim of this study was to evaluate the possible relationships of various apolipoprotein-species with hemostatic parameters and cognitive function. Lipid profile, gene polymorphism, coagulation markers, and mini-mental state examination (MMSE) scores were assessed in 109 dys-lipidemic subjects and in 107 healthy control volunteers. Thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels were significantly higher in apolipoprotein-E2 (apoE2) patients when compared to other apoE forms. The apoA5 -1131T>C polymorphism was associated with elevated D-dimer concentration in dyslipidemic TT homozygous individuals. MMSE did not correlate with lipid or coagulation profile. These data suggest that apoE and apoA5 variants have an effect on hemostatic parameters, but they neither influence nor predict cognitive performance in non-demented individuals.

Hyper-coagulable profile with elevated pro-thrombotic biomarkers and increased cerebro- and cardio-vascular disease risk exist among healthy dyslipidemic women.

Dyslipidemia is one of the pathognomonic elements of athero-genesis, as well as cerebro- and cardio-vascular disease (CCVD). Hemostatic factors are also involved in athero-sclerosis and ischemic changes, however their relationship with disrupted lipid homeostasis is not well characterized. The aim of this study was to determine the coagulation state of dyslipidemic patients and to evaluate their association with CCVD risk factors. Biochemical and hematological parameters, as well as neuro-psychiatric profile of 109 dyslipidemic subjects and 107 normo-lipidic healthy volunteers were assessed. Serum bio-marker levels and cognitive performance generally did not differ in the groups, but prothrombin fragment 1+2 (F1+2) and D-dimer concentrations were markedly higher among women. Hyper-coagulability was not associated with dyslipidemia, but was correlated with the female gender, which might pose an increased thromboembolic risk in asymptomatic women.

Carrier localization and electronic phase separation in a doped spin-orbit-driven Mott phase in Sr3(Ir(1-x)Ru(x))2O7.

Interest in many strongly spin-orbit-coupled 5d-transition metal oxide insulators stems from mapping their electronic structures to a J(eff)=1/2 Mott phase. One of the hopes is to establish their Mott parent states and explore these systems' potential of realizing novel electronic states upon carrier doping. However, once doped, little is understood regarding the role of their reduced Coulomb interaction U relative to their strongly correlated 3d-electron cousins. Here we show that, upon hole-doping a candidate J(eff)=1/2 Mott insulator, carriers remain localized within a nanoscale phase-separated ground state. A percolative metal-insulator transition occurs with interplay between localized and itinerant regions, stabilizing an antiferromagnetic metallic phase beyond the critical region. Our results demonstrate a surprising parallel between doped 5d- and 3d-electron Mott systems and suggest either through the near-degeneracy of nearby electronic phases or direct carrier localization that U is essential to the carrier response of this doped spin-orbit Mott insulator.

Reduced frequency of T lymphocytes expressing CTLA-4 in frontotemporal dementia compared to Alzheimer's disease.

Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia.

Structural and thermodynamic studies of two centrin isoforms from Blastocladiella emersonii upon calcium binding.

Centrins are calcium-binding proteins associated with microtubules organizing centers. Members of two divergent subfamilies of centrins were found in the aquatic fungus Blastocladiella emersonii, contrasting with the occurrence of only one member known for the better explored terrestrial fungi. BeCen1 shows greatest identity with human centrins HsCen1, HsCen2 and green algae centrin CrCenp, while BeCen3 records largest identity with human centrin HsCen3 and yeast centrin Cdc31p. Following the discovery of this unique feature, BeCen1 and BeCen3 centrins were produced to study whether these proteins had distinct features upon calcium binding. Circular dichroism showed opposite calcium binding effects on the α-helix arrangement of the secondary structure. The spectra indicated a decrease in α-helix signal for holo-BeCen1 contrasting with an increase for holo-BeCen3. In addition, only BeCen1 refolds after being de-natured. The fluorescence emission of the hydrophobic probe ANS increases for both proteins likely due to hydrophobic exposure, however, only BeCen1 presents a clear blue shift when calcium is added. ITC experiments identified four calcium binding sites for both proteins. In contrast to calcium binding to BeCen1, which is mainly endothermic, binding to BeCen3 is mainly exothermic. Light-scattering evidenced the formation of large particles in solution for BeCen1 and BeCen3 at temperatures above 30°C and 40°C, respectively. Atomic force microscopy confirmed the presence of supramolecular structures, which differ in the compactness and branching degree. Binding of calcium leads to different structural changes in BeCen1 and BeCen3 and the thermodynamic characteristics of the interaction also differ.

Coexistence of half-metallic itinerant ferromagnetism with local-moment antiferromagnetism in Ba0.60K0.40Mn2As2.

Magnetization, nuclear magnetic resonance, high-resolution x-ray diffraction, and magnetic field-dependent neutron diffraction measurements reveal a novel magnetic ground state of Ba0.60K0.40Mn2As2 in which itinerant ferromagnetism (FM) below a Curie temperature TC≈100 K arising from the doped conduction holes coexists with collinear antiferromagnetism (AFM) of the Mn local moments that order below a Néel temperature TN=480 K. The FM ordered moments are aligned in the tetragonal ab plane and are orthogonal to the AFM ordered Mn moments that are aligned along the c axis. The magnitude and nature of the low-T FM ordered moment correspond to complete polarization of the doped-hole spins (half-metallic itinerant FM) as deduced from magnetization and ab-plane electrical resistivity measurements.

Non-peptidic cruzain inhibitors with trypanocidal activity discovered by virtual screening and in vitro assay.

A multi-step cascade strategy using integrated ligand- and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected compounds, 12 non-covalent binding cruzain inhibitors with affinity values (K i) in the low micromolar range (3-60 µM) acting through a competitive inhibition mechanism were identified. This mechanism has been confirmed by determining the binding mode of the cruzain inhibitor Nequimed176 through X-ray crystallographic studies. Cruzain, a validated therapeutic target for new chemotherapy for Chagas disease, also shares high similarity with the mammalian homolog cathepsin L. Because increased activity of cathepsin L is related to invasive properties and has been linked to metastatic cancer cells, cruzain inhibitors from the same library were assayed against it. Affinity values were in a similar range (4-80 µM), yielding poor selectivity towards cruzain but raising the possibility of investigating such inhibitors for their effect on cell proliferation. In order to select the most promising enzyme inhibitors retaining trypanocidal activity for structure-activity relationship (SAR) studies, the most potent cruzain inhibitors were assayed against T. cruzi-infected cells. Two compounds were found to have trypanocidal activity. Using compound Nequimed42 as precursor, an SAR was established in which the 2-acetamidothiophene-3-carboxamide group was identified as essential for enzyme and parasite inhibition activities. The IC50 value for compound Nequimed42 acting against the trypomastigote form of the Tulahuen lacZ strain was found to be 10.6±0.1 µM, tenfold lower than that obtained for benznidazole, which was taken as positive control. In addition, by employing the strategy of molecular simplification, a smaller compound derived from Nequimed42 with a ligand efficiency (LE) of 0.33 kcal mol(-1) atom(-1) (compound Nequimed176) is highlighted as a novel non-peptidic, non-covalent cruzain inhibitor as a trypanocidal agent candidate for optimization.