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1.
J Autism Dev Disord ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568367

RESUMO

Research has shown video modeling to be effective for training adult service providers to administer evidence-based practices to children with autism. This study examined the effects of video modeling training (VMT) on neurotypical adolescents' performance of peer mediated social interaction (PMSI), a 10-step procedure of simplified behavioral practices, during roleplay with an adult actor. A multiple probe design across participants evaluated the effects of VMT on delivery of PMSI by five neurotypical adolescents. All participants demonstrated immediate increases and generalized delivery of PMSI to four adolescents with autism following VMT. Social interaction for two additional youths with autism also improved when evaluated within a peer mediated setting, as a measure of social validity, before and after VMT.

3.
Microb Biotechnol ; 17(3): e14442, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465728

RESUMO

The human microbiome comprises an ample set of organisms that inhabit and interact within the human body, contributing both positively and negatively to our health. In recent years, several research groups have described the presence of microorganisms in organs or tissues traditionally considered as 'sterile' under healthy and pathological conditions. In this sense, microorganisms have been detected in several types of cancer, including those in 'sterile' organs. But how can the presence of microorganisms be detected? In most studies, 16S and internal transcribed spacer (ITS) ribosomal DNA (rDNA) sequencing has led to the identification of prokaryotes and fungi. However, a major limitation of this technique is that it cannot distinguish between living and dead organisms. RNA-based methods have been proposed to overcome this limitation, as the shorter half-life of the RNA would identify only the transcriptionally active microorganisms, although perhaps not all the viable ones. In this sense, metaproteomic techniques or the search for molecular metabolic signatures could be interesting alternatives for the identification of living microorganisms. In summary, new technological advances are challenging the notion of 'sterile' organs in our body. However, to date, evidence for a structured living microbiome in most of these organs is scarce or non-existent. The implementation of new technological approaches will be necessary to fully understand the importance of the microbiome in these organs, which could pave the way for the development of a wide range of new therapeutic strategies.


Assuntos
Corpo Humano , Infertilidade , Humanos , Análise de Sequência de DNA , DNA Ribossômico/genética , RNA/genética , RNA Ribossômico 16S/genética
4.
J Org Chem ; 89(1): 163-173, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38087461

RESUMO

We report the synthesis of a new set of amphiphilic saddle-shaped heptagon-containing polycyclic aromatic hydrocarbons (PAHs) functionalized with tetraethylene glycol chains and their self-assembly into large two-dimensional (2D) polymers. An in-depth analysis of the self-assembly mechanism at the air/water interface has been carried out, and the proposed arrangement models are in good agreement with the molecular dynamics simulations. Quite remarkably, the number and disposition of the tetraethylene glycol chains significantly influence the disposition of the PAHs at the interface and conditionate their packing under pressure. For the three compounds studied, we observed three different behaviors in which the aromatic core is parallel, perpendicular, and tilted with respect to the water surface. We also show that these curved PAHs are able to self-assemble in solution into remarkably large sheets of up to 150 µm2. These results show the relationship, within a family of curved nanographenes, between the monomer configuration and their self-assembly capacity in air/water interfaces and organic-water mixtures.

5.
Exp Hematol Oncol ; 12(1): 102, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066554

RESUMO

Pseudomyxoma peritonei (PMP) is a rare disease characterized by a massive accumulation of mucus in the peritoneal cavity. The only effective treatment is aggressive surgery, aimed at removing all visible tumors. However, a high percentage of patients relapse, with subsequent progression and death. Recently, there has been an increase in therapies that target mutated oncogenic proteins. In this sense, KRAS has been reported to be highly mutated in PMP, with KRASG12D being the most common subtype. Here, we tested the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in a high-grade PMP xenograft mouse model carrying a KRASG12D mutation. The results obtained in this work showed a profound inhibition of tumor growth, which was associated with a reduction in cell proliferation, an increase in apoptosis, and a reduction in the MAPK and PI3K/AKT/mTOR signaling pathways. In conclusion, these results demonstrate the high potency and efficacy of MRTX1133 in KRASG12D-PMP tumors and provide a rationale for clinical trials.

6.
Food Nutr Res ; 672023.
Artigo em Inglês | MEDLINE | ID: mdl-38084155

RESUMO

Antioxidants are a collection of substances that may prevent or delay the oxidation of cellular components. The antioxidant defense system includes both endogenously produced antioxidants and dietary antioxidants. The consumption of dietary antioxidants has long been speculated to be important for the defense against cellular oxidation, inflammation, and other disease-related processes. In addition to the well-known dietary antioxidants, such as vitamin C, vitamin E, ß-carotene, and selenium, whole plants and plant-products contain numerous compounds, called phytochemicals, with antioxidant properties. These phytochemicals are potentially important modulators of oxidative stress and have been linked to health beneficial effects. However, the mechanisms underlying these potential health beneficial effects are not well understood. Foods containing high levels of phytochemicals with antioxidant properties include berries, fruits, vegetables, whole grains, and nuts and seeds. The aim of this scoping review is to describe the evidence of the role of specific antioxidants and phytochemicals, but not foods rich in these substances, for health outcomes. Based on a literature search from 2011 to March 2022, we identified eight meta-analyses related to the current topic. These studies include evidence of the effect of resveratrol (present mainly in berries, grapes, and peanuts) on health outcomes related to cardiometabolic risk, blood pressure, obesity, oxidative stress, adipokines, inflammation, and bone quality. In summary, resveratrol did elicit several health beneficial effects. However, the magnitude of effects was low, and whether the effects are related to the redox properties of resveratrol is not known. Even though there is a large body of evidence linking a plant-based diet rich in antioxidants and phytochemicals to beneficial health effects, the role of specific antioxidants and phytochemicals is still unclear.

7.
Biochimie ; 219: 118-129, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37993054

RESUMO

Breast cancer is the most prevalent cancer in women. Metabolic abnormalities, particularly increased lipid synthesis and uptake, impact the onset and progression of the disease. However, the influence of lipid metabolism in breast cancer varies according to the disease stage and patient's hormone status. In postmenopausal patients, obesity is associated with a higher risk and poor prognosis of luminal tumors, while in premenopausal individuals, it is correlated to BRCA mutated tumors. In fact, the tumor's lipid profile may be used to distinguish between HER2+, luminal and BRCA-mutated tumors. Moreover, drug resistance was associated with increased fatty acid synthesis and alterations in membrane composition, impacting its fluidity and spatial subdomains such as lipid rafts. Here, we discuss the subtype-specific lipid metabolism alterations found in breast cancer and the potentiality of its modulation in a clinical setting.

8.
J Morphol ; 284(9): e21630, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37585233

RESUMO

In viviparous teleosts, intraovarian gestation occurs intrafollicularly, as in poeciliids, or intraluminally, as in goodeids and anablepids. Furthermore, there are two different forms of embryonic nutrition: lecithotrophy and matrotrophy; depending on the species, these can be exclusive or coexist during gestation. In matrotrophic species, nutrients are transmitted from the mother to the embryo and are especially important in species with intraluminal gestation. Jenynsia lineata is a South American viviparous teleost with intraluminal gestation, characterized by eggs with scarce yolk, which is resorbed when embryos are 6 mm long, thus developing a branchial placenta. Using histological, histochemical, and immunohistochemical techniques, the present study describes the characteristics and changes of the ovarian mucosa in J. lineata during gestational and nongestational phases, and analyzes the embryonic pharyngeal epithelium in the branchial placenta. The ovaries of 30 adult female specimens were processed using histological techniques and stained with hematoxylin-eosin, Masson's trichrome, and Alcian Blue pH 2.5/periodic acid Schiff reagent. To detect cell proliferation, we used antiproliferating cell nuclear antigen antibody. In nonpregnant females, eosinophilic granular cells (EGCs) and lymphocytes were identified in the lamina propria of the tunica mucosa, and melanomacrophage centers (MMCs) and fibroblasts were identified adjacent to tissue debris in the ovarian folds'. In the cellular debris, an embryo in resorption was observed. In pregnant females, the ovarian mucosa has thin vascularization branches entering the opercular chamber of the embryos, in close contact with the forming gill processes, thereby establishing a branchial placenta. Active cell replacement was observed in these ovarian branches. The identification of fibroblasts, lymphocytes, EGCs, and MMCs adjacent to tissue debris could indicate that these cell types are involved in the embryonic resorption process. Considering the new data obtained in this study on the branchial placenta of J. lineata, we conclude that cell proliferation could be involved in the development of maternal-embryonic interaction.


Assuntos
Ciprinodontiformes , Ovário , Feminino , Animais , Gravidez , Placenta , Núcleo Celular , Proliferação de Células
9.
Mol Genet Genomic Med ; 11(9): e2234, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37498300

RESUMO

BACKGROUND: Opitz GBBB syndrome (GBBB) is an X-linked disease characterized by midline defects, including congenital heart defects. We present our diagnostic approach to the identification of GBBB in a consanguineous family in which two males siblings were concordant for a total anomalous connection of pulmonary veins and minor facial dysmorphias. METHODS: Targeted exome sequencing analysis of a 380-gene panel associated with cardiovascular disease was performed on the propositus. Interpretative analysis of the exome results was conducted, and 3D models of the protein changes were generated. RESULTS: We identified a NM_000381.4:c.608G>A;p.(Arg203Gln) change in MID1, affecting the conformation of the B-box 2 domain of the protein, with a zinc finger structure and associated protein interactions. This clinical phenotype is consistent with GBBB; however, the type of congenital heart disease observed in this case has not been previously reported. CONCLUSION: A new likely pathogenic variant on MID1 c.608G>A was found to be associated with Opitz GBBB syndrome.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X , Hipertelorismo , Hipospadia , Humanos , Masculino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Hipertelorismo/genética , Hipospadia/genética
10.
ACS Appl Mater Interfaces ; 15(27): 32597-32609, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37390355

RESUMO

The development of bio-MOFs or MOF biocomposites through the combination of MOFs with biopolymers offers the possibility of expanding the potential applications of MOFs, making use of more environmentally benign processes and reagents and giving rise to a new generation of greener and more bio-oriented composite materials. Now, with the increasing use of MOFs for biotechnological applications, the development of new protocols and materials to obtain novel bio-MOFs compatible with biomedical or biotechnological uses is needed. Herein, and as a proof of concept, we have explored the possibility of using short-peptide supramolecular hydrogels as media to promote the growth of MOF particles, giving rise to a new family of bio-MOFs. Short-peptide supramolecular hydrogels are very versatile materials that have shown excellent in vitro and in vivo biomedical applications such as tissue engineering and drug delivery vehicles, among others. These peptides self-assemble by noncovalent interactions, and, as such, these hydrogels are easily reversible, being more biocompatible and biodegradable. These peptides can self-assemble by a multitude of stimuli, such as changes in pH, temperature, solvent, adding salts, enzymatic activity, and so forth. In this work, we have taken advantage of this ability to promote peptide self-assembly with some of the components required to form MOF particles, giving rise to more homogeneous and well-integrated composite materials. Hydrogel formation has been triggered using Zn2+ salts, required to form ZIF-8, and formic acid, required to form MOF-808. Two different protocols for the in situ MOF growth have been developed. Finally, the MOF-808 composite hydrogel has been tested for the decontamination of water polluted with phosphate ions as well as for the catalytic degradation of toxic organophosphate methyl paraoxon in an unbuffered solution.


Assuntos
Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Hidrogéis/química , Sais , Peptídeos , Sistemas de Liberação de Medicamentos
11.
Metabolism ; 144: 155589, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37182789

RESUMO

BACKGROUND: Evidence is accumulating that growth hormone (GH) protects against the development of steatosis and progression of non-alcoholic fatty liver disease (NAFLD). GH may control steatosis indirectly by altering systemic insulin sensitivity and substrate delivery to the liver and/or by the direct actions of GH on hepatocyte function. APPROACH: To better define the hepatocyte-specific role of GH receptor (GHR) signaling on regulating steatosis, we used a mouse model with adult-onset, hepatocyte-specific GHR knockdown (aHepGHRkd). To prevent the reduction in circulating insulin-like growth factor 1 (IGF1) and the subsequent increase in GH observed after aHepGHRkd, subsets of aHepGHRkd mice were treated with adeno-associated viral vectors (AAV) driving hepatocyte-specific expression of IGF1 or a constitutively active form of STAT5b (STAT5bCA). The impact of hepatocyte-specific modulation of GHR, IGF1 and STAT5b on carbohydrate and lipid metabolism was studied across multiple nutritional states and in the context of hyperinsulinemic:euglycemic clamps. RESULTS: Chow-fed male aHepGHRkd mice developed steatosis associated with an increase in hepatic glucokinase (GCK) and ketohexokinase (KHK) expression and de novo lipogenesis (DNL) rate, in the post-absorptive state and in response to refeeding after an overnight fast. The aHepGHRkd-associated increase in hepatic KHK, but not GCK and steatosis, was dependent on hepatocyte expression of carbohydrate response element binding protein (ChREBP), in re-fed mice. Interestingly, under clamp conditions, aHepGHRkd also increased the rate of DNL and expression of GCK and KHK, but impaired insulin-mediated suppression of hepatic glucose production, without altering plasma NEFA levels. These effects were normalized with AAV-mediated hepatocyte expression of IGF1 or STAT5bCA. Comparison of the impact of AAV-mediated hepatocyte IGF1 versus STAT5bCA in aHepGHRkd mice across multiple nutritional states, indicated the restorative actions of IGF1 are indirect, by improving systemic insulin sensitivity, independent of changes in the liver transcriptome. In contrast, the actions of STAT5b are due to the combined effects of raising IGF1 and direct alterations in the hepatocyte gene program that may involve suppression of BCL6 and FOXO1 activity. However, the direct and IGF1-dependent actions of STAT5b cannot fully account for enhanced GCK activity and lipogenic gene expression observed after aHepGHRkd, suggesting other GHR-mediated signals are involved. CONCLUSION: These studies demonstrate hepatocyte GHR-signaling controls hepatic glycolysis, DNL, steatosis and hepatic insulin sensitivity indirectly (via IGF1) and directly (via STAT5b). The relative contribution of these indirect and direct actions of GH on hepatocytes is modified by insulin and nutrient availability. These results improve our understanding of the physiologic actions of GH on regulating adult metabolism to protect against NAFLD progression.


Assuntos
Hormônio do Crescimento Humano , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Masculino , Camundongos , Animais , Lipogênese/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores da Somatotropina/genética , Receptores da Somatotropina/metabolismo , Resistência à Insulina/fisiologia , Fígado/metabolismo , Hormônio do Crescimento/metabolismo , Insulina/metabolismo , Glicólise , Glucose/metabolismo , Hormônio do Crescimento Humano/metabolismo
12.
Front Oncol ; 13: 1076500, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36776312

RESUMO

Introduction: Pseudomyxoma peritonei (PMP) is a rare malignant disease characterized by a massive multifocal accumulation of mucin within the peritoneal cavity. The current treatment option is based on complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. However, the recurrence is frequent with subsequent progression and death. To date, most of the studies published in PMP are related to histological and genomic analyses. Thus, the need for further studies unveiling the underlying PMP molecular mechanisms is urgent. In this regard, hypoxia and oxidative stress have been extensively related to tumoral pathologies, although their contribution to PMP has not been elucidated. Methods: In this manuscript, we have evaluated, for the first time, the intratumoral real-time oxygen microtension (pO2mt) in the tumor (soft and hard mucin) and surrounding healthy tissue from five PMP patients during surgery. In addition, we measured hypoxia (Hypoxia Inducible Factor-1a; HIF-1α) and oxidative stress (catalase; CAT) markers in soft and hard mucin from the same five PMP patient samples and in five control samples. Results: The results showed low intratumoral oxygen levels, which were associated with increased HIF-1α protein levels, suggesting the presence of a hypoxic environment in these tumors. We also found a significant reduction in CAT activity levels in soft and hard mucin compared with healthy tissue samples. Discussion: In conclusion, our study provides the first evidence of low intratumoral oxygen levels in PMP patients associated with hypoxia and oxidative stress markers. However, further investigation is required to understand the potential role of oxidative stress in PMP in order to find new therapeutic strategies.

13.
Nutr Neurosci ; 26(1): 25-39, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34905445

RESUMO

BACKGROUND: Obesity results from an unbalance in the ingested and burned calories. Energy balance (EB) is critically regulated by the hypothalamic arcuate nucleus (ARC) by promoting appetite or anorectic actions. Hypothalamic inflammation, driven by high activation of the microglia, has been reported as a key mechanism involved in the development of diet-induced obesity. Kaempferol (KF), a flavonoid-type polyphenol present in a large number of fruits and vegetables, was shown to regulate both energy metabolism and inflammation. OBJECTIVES: In this work, we studied the effects of both the central and peripheral treatment with KF on hypothalamic inflammation and EB regulation in mice with obesity. METHODS: Obese adult mice were chronically (40 days) treated with KF (0.5 mg/kg/day, intraperitoneally). During the treatment, body weight, food intake (FI), feed efficiency (FE), glucose tolerance, and insulin sensitivity were determined. Analysis of microglia activation in the ARC of the hypothalamus at the end of the treatment was also performed. Body weight, FI, and FE changes were also evaluated in response to 5µg KF, centrally administrated. RESULTS: Chronic administration of KF decreased ∼43% of the density, and ∼30% of the ratio, of activated microglia in the arcuate nucleus. These changes were accompanied by body weight loss, decreased FE, reduced fasting blood glucose, and a tendency to improve insulin sensitivity. Finally, acute central administration of KF reproduced the effects on EB triggered by peripheral administration. CONCLUSION: These findings suggest that KF might fight obesity by regulating central processes related to EB regulation and hypothalamic inflammation.


Assuntos
Resistência à Insulina , Microglia , Camundongos , Animais , Quempferóis/metabolismo , Quempferóis/farmacologia , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Hipotálamo/metabolismo , Peso Corporal , Núcleo Arqueado do Hipotálamo/metabolismo , Polifenóis/farmacologia , Inflamação/metabolismo , Redução de Peso , Camundongos Endogâmicos C57BL
14.
Retina ; 43(2): 263-274, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36223778

RESUMO

PURPOSE: To assess the safety of injecting human embryonic stem cell retinal pigment epithelial cell dose to treat Stargardt disease. METHODS: In this prospective, Phase I clinical trial, human embryonic stem cell retinal pigment epithelial cells in suspension were injected into the subretinal space in eyes with the worse best-corrected visual acuity (BCVA). After vitrectomy/posterior hyaloid removal, a partial retinal detachment was created and the human embryonic stem cell retinal pigment epithelial cells were administered. Phacoemulsification with intraocular lens implantation was performed in eyes with lens opacity. All procedures were optical coherence tomography-guided. The 12-month follow-up included retinal imaging, optical coherence tomography, visual field/electrophysiologic testing, and systemic evaluation. The main outcome was the absence of ocular/systemic inflammation or rejection, tumor formation, or toxicity during follow-up. RESULTS: The mean baseline BCVAs in the phacoemulsification and no phacoemulsification groups were similar (1.950 ± 0.446 and 1.575 ± 0.303, respectively). One year postoperatively, treated eyes showed a nonsignificant increase in BCVA. No adverse effects occurred during follow-up. Intraoperative optical coherence tomography was important for guiding all procedures. CONCLUSION: This surgical procedure was feasible and safe without cellular migration, rejection, inflammation, or development of ocular or systemic tumors during follow-up.


Assuntos
Descolamento Retiniano , Epitélio Pigmentado da Retina , Humanos , Epitélio Pigmentado da Retina/patologia , Doença de Stargardt , Estudos Prospectivos , Descolamento Retiniano/patologia , Células-Tronco , Inflamação , Pigmentos da Retina , Tomografia de Coerência Óptica
15.
Foods ; 12(23)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38231857

RESUMO

BACKGROUND: Whole-grain bread can be an important source of fibre for people with coeliac disease (CeD) who must adhere to a gluten-free diet and avoid consuming wheat, rye and barley. Gluten-free bread frequently has a lower nutritional quality and different texture relative to gluten-containing counterparts. OBJECTIVE: The aim was to investigate experiences with gluten-free bread amongst people with CeD prior to and during a randomised controlled trial (RCT). DESIGN: We conducted individual interviews with 10 people with CeD participating in a RCT that aimed to investigate the effects of fibre-rich gluten-free products on metabolic regulation in people with CeD compared with benchmark gluten-free products. Five participants were in the control group (benchmark gluten-free bread) and five participants in the intervention group (fibre-rich gluten-free bread). The fibre-rich gluten free bread was formulated and prepared by the project group. The benchmark gluten-free bread was commercially available. The RCT lasted for four weeks. Interviews were conducted digitally between October 2021 and January 2022 and were thematically analysed. RESULTS: Participants in both groups appeared to avoid bread prior to the study, primarily due to the poor taste and chewy consistency of the available bread in food stores and bakeries. Participants preferred the fibre-rich intervention bread as opposed to the available bread in the food market. However, participants had to become accustomed to eating the fibre-rich whole-grain bread during the study, since they avoided eating store-bought bread that they experienced chewy and not filling. CONCLUSIONS: Participants asked for fibre-rich gluten-free bread products that are satiating and have a good texture. Palatable gluten-free bread products might be an important source of fibre for people with CeD.

16.
Food Nutr Res ; 662022.
Artigo em Inglês | MEDLINE | ID: mdl-36340917

RESUMO

Background: Bread is an important source of dietary fibre. However, an increasing number of individuals exclude bread from their habitual diet for various reasons. In recent years, sourdough bread has increased in popularity, and clinical studies have indicated that sourdough bread may decrease gastrointestinal symptoms. Objective: To investigate attitudes towards and experiences with sourdough and baker's yeast bread amongst participants in a randomised controlled trial (RCT), the health effects and consumer aspects of bread (HELFAB) study. Design: We conducted individual interviews with 10 participants who stated to be sceptical about bread and who participated in an RCT to investigate the health effects of sourdough bread versus baker's yeast bread. The participants were interviewed on two occasions (before and after the RCT). Interviews were conducted digitally between September and December 2020 and were thematically analysed. Results: Half of the interviewed participants experienced gastrointestinal symptoms, such as pain in the stomach, when they consumed bread prior to the RCT. They often preferred sourdough bread to baker's yeast bread both before and after the study, since they found that sourdough bread was easier to digest. Participants who were sceptical about bread prior to the study became more positive about bread because of their experiences with the intervention breads. This finding was mainly related to the taste and consistency of sourdough bread. The participants often associated bread with healthiness, mainly due to the dietary fibre content in bread. Conclusions: Sourdough bread with increased dietary fibre may be an important source of dietary fibre for those who perceive gastrointestinal problems from baker's yeast bread. Participants in this qualitative study stated to change their attitudes towards bread, mainly due to perceived healthiness of the intervention bread.

17.
ACS Nano ; 16(10): 16941-16953, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36219724

RESUMO

Supramolecular short-peptide assemblies have been widely used for the development of biomaterials with potential biomedical applications. These peptides can self-assemble in a multitude of chiral hierarchical structures triggered by the application of different stimuli, such as changes in temperature, pH, solvent, etc. The self-assembly process is sensitive to the chemical composition of the peptides, being affected by specific amino acid sequence, type, and chirality. The resulting supramolecular chirality of these materials has been explored to modulate protein and cell interactions. Recently, significant attention has been focused on the development of chiral materials with potential spintronic applications, as it has been shown that transport of charge carriers through a chiral environment polarizes the carrier spins. This effect, named chirality-induced spin selectivity or CISS, has been studied in different chiral organic molecules and materials, as well as carbon nanotubes functionalized with chiral molecules. Nevertheless, this effect has been primarily explored in homochiral systems in which the chirality of the medium, and hence the resulting spin polarization, is defined by the chirality of the molecule, with limited options for tunability. Herein, we have developed heterochiral carbon-nanotube-short-peptide materials made by the combination of two different chiral sources: that is, homochiral peptides (l/d) + glucono-δ-lactone. We show that the presence of a small amount of glucono-δ-lactone with fixed chirality can alter the supramolecular chirality of the medium, thereby modulating the sign of the spin signal from "up" to "down" and vice versa. In addition, small amounts of glucono-δ-lactone can even induce nonzero spin polarization in an otherwise achiral and spin-inactive peptide-nanotube composite. Such "chiral doping" strategies could allow the development of complementary CISS-based spintronic devices and circuits on a single material platform.


Assuntos
Nanotubos de Carbono , Nanotubos de Peptídeos , Peptídeos , Solventes/química , Materiais Biocompatíveis
18.
Lipids Health Dis ; 21(1): 92, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36163070

RESUMO

BACKGROUND: Improving dietary fat quality strongly affects serum cholesterol levels and hence the risk of cardiovascular diseases (CVDs). Recent studies have identified dietary fat as a potential modulator of the gut microbiota, a central regulator of host metabolism including lipid metabolism. We have previously shown a significant reduction in total cholesterol levels after replacing saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFAs). The aim of the present study was to investigate the effect of dietary fat quality on gut microbiota, short-chain fatty acids (SCFAs), and bile acids in healthy individuals. In addition, to investigate how changes in gut microbiota correlate with blood lipids, bile acids, and fatty acids. METHODS: Seventeen participants completed a randomized, controlled dietary crossover study. The participants received products with SFAs (control) or PUFAs in random order for three days. Fecal samples for gut microbiota analyses and fasting blood samples (lipids, fatty acids, and bile acids) were measured before and after the three-day intervention. RESULTS: Of a panel of 40 bacteria, Lachnospiraceae and Bifidobacterium spp. were significantly increased after intervention with PUFAs compared with SFAs. Interestingly, changes in Lachnospiraceae, as well as Phascolarlactobacterium sp. and Eubacterium hallii, was also found to be negatively correlated with changes in total cholesterol levels after replacing the intake of SFAs with PUFAs for three days. No significant differences in SCFAs or bile acids were found after the intervention. CONCLUSION: Replacing SFAs with PUFAs increased the abundance of the gut microbiota family of Lachnospiraceae and Bifidobacterium spp. Furthermore, the reduction in total cholesterol after improving dietary fat quality correlated with changes in the gut microbiota family Lachnospiraceae. Future studies are needed to reveal whether Lachnospiraceae may be targeted to reduce total cholesterol levels. TRIAL REGISTRATION: The study was registered at Clinical Trials ( https://clinicaltrials.gov/ , registration identification number: NCT03658681).


Assuntos
Ácidos Graxos Insaturados , Ácidos Graxos , Ácidos e Sais Biliares , Colesterol , Estudos Cross-Over , Gorduras na Dieta , Humanos , Lipídeos
19.
Food Nutr Res ; 662022.
Artigo em Inglês | MEDLINE | ID: mdl-35844956

RESUMO

Background: Metabolic diseases have been related to gut microbiota, and new knowledge indicates that diet impacts host metabolism through the gut microbiota. Identifying specific gut bacteria associated with both diet and metabolic risk markers may be a potential strategy for future dietary disease prevention. However, studies investigating the association between the gut microbiota, diet, and metabolic markers in healthy individuals are scarce. Objective: We explored the relationship between a panel of gut bacteria, dietary intake, and metabolic and anthropometric markers in healthy adults. Design: Forty-nine volunteers were included in this cross-sectional study. Measures of glucose, serum triglyceride, total cholesterol, hemoglobin A1c (HbA1c), blood pressure (BP), and body mass index (BMI) were collected after an overnight fast, in addition to fecal samples for gut microbiota analyzes using a targeted approach with a panel of 48 bacterial DNA probes and assessment of dietary intake by a Food Frequency Questionnaire (FFQ). Correlations between gut bacteria, dietary intake, and metabolic and anthropometric markers were assessed by Pearson's correlation. Gut bacteria varying according to dietary intake and metabolic markers were assessed by a linear regression model and adjusted for age, sex, and BMI. Results: Of the 48 gut bacteria measured, 24 and 16 bacteria correlated significantly with dietary intake and metabolic and/or anthropometric markers, respectively. Gut bacteria including Alistipes, Lactobacillus spp., and Bacteroides stercoris differed according to the intake of the food components, fiber, sodium, saturated fatty acids, and dietary indices, and metabolic markers (BP and total cholesterol) after adjustments. Notably, Bacteroides stercoris correlated positively with the intake of fiber, grain products, and vegetables, and higher Bacteroides stercoris abundance was associated with higher adherence to Healthy Nordic Food Index (HNFI) and lower diastolic BP after adjustment. Conclusion: Our findings highlight the relationship between the gut microbiota, diet, and metabolic markers in healthy individuals. Further investigations are needed to address whether these findings are causally linked and whether targeting these gut bacteria can prevent metabolic diseases.

20.
Medicine (Baltimore) ; 101(27): e29228, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35801794

RESUMO

Point-of-care (PoC) testing facilitates early infant diagnosis (EID) and treatment initiation, which improves outcome. We present a field evaluation of a new PoC test (Cepheid Xpert® HIV-1 Qual XC RUO) to determine whether this test improves EID and assists the management of children living with human immunodeficiency virus (HIV) infection. We compared 2 PoC tests with the standard-of-care (SoC) test used to detect HIV infection from dry blood spots in newborn infants at high risk of in utero infection. We also evaluated the ability of the PoC tests to detect HIV total nucleic acid (TNA) in children living with HIV infection who had maintained undetectable plasma viremia following very early combination antiretroviral therapy (cART) initiation. Qualitative (Qual) detection of HIV using the Xpert® HIV-1 Qual XC RUO ("RUO") and Xpert® HIV-1 Qual ("Qual") PoC tests was compared in 224 infants with the SoC DBS Roche COBAS® HIV-1/HIV-2 qualitative test. The same 2 PoC tests were also evaluated in 35 older children who had initiated cART before 21 days of age and maintained undetectable plasma viremia for a mean of 25 months. No discrepancies were observed in detection of HIV infection via the 2 PoC tests or the SoC test in the 224 neonates studied, but only 95% of the SoC test results were generated compared with 100% of the PoC test results (P = .0009). The cycle threshold values for the research use only (RUO) assay were the lowest of the 3 assays (P < .0001 in each case). In 6 of the 35 early-treated aviremic children, HIV TNA was detected by RUO but not Qual. The RUO assay outperforms Qual in detecting HIV-1 infection. RUO would therefore potentially improve EID and assist in identifying cART-adherent early-treated children with the lowest HIV TNA levels and the highest HIV cure potential.


Assuntos
Infecções por HIV , HIV-1 , Adolescente , Criança , Diagnóstico Precoce , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Sensibilidade e Especificidade , Viremia/diagnóstico , Viremia/tratamento farmacológico
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