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1.
Artigo em Inglês | MEDLINE | ID: mdl-35912644

RESUMO

Increasing awareness of the health benefits of specific constituents in fruits, vegetables, cereals, and other whole foods has sparked a broader interest in the potential health benefits of nutraceuticals. Many nutraceuticals are hydrophobic substances, which means they must be encapsulated in colloidal delivery systems. Oil-in-water emulsions are one of the most widely used delivery systems for improving the bioavailability and bioactivity of these nutraceuticals. The composition and structure of emulsions can be designed to improve the water dispersibility, physicochemical stability, and bioavailability of the encapsulated nutraceuticals. The nature of the emulsion used influences the interfacial area and properties of the nutraceutical-loaded oil droplets in the gastrointestinal tract, which influences their digestion, as well as the bioaccessibility, metabolism, and absorption of the nutraceuticals. In this article, we review recent in vitro and in vivo studies on the utilization of emulsions to improve the bioavailability of nutraceuticals. The findings from this review should facilitate the design of more efficacious nutraceutical-loaded emulsions with increased bioactivity.

2.
Inorg Chem ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913725

RESUMO

Metal-organic frameworks (MOFs) have been a focus of research because of their unique porous structure, but they are usually not directly for electrocatalysis. Herein, we prepared a special class of Fe/Zn/Mo-based trimetallic hybrid zeolitic imidazolate frameworks by in situ solvothermal synthesis that have the potential to act directly as highly efficient oxygen evolution reaction electrocatalysts. This work provides a foundation for the preparation of multimetal MOFs and expands the investigation of electrocatalysts.

3.
J Biomol Struct Dyn ; : 1-10, 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35950523

RESUMO

Transient receptor potential vanilloid subfamily member 6 (TRPV6) is an epithelial calcium channel that regulates the initial step of the transcellular calcium transport pathway. TRPV6 is expressed in the kidney, intestine, placenta, and other tissues, and the dysregulation of the channel is implicated in several human cancers. It has been reported that phosphatidylinositol 4,5-bisphosphate (PIP2) activates TRPV6 and its close homologue TRPV5; however, the underlying molecular mechanism is less clear. Recently, a structure of rabbit TRPV5 in complex with dioctanoyl (diC8) PIP2, a soluble form of PIP2, was determined by cryo-electron microscopy. Based on this structure, the structural model of human TRPV6 with PIP2 was set up, and then molecular dynamics simulations were performed for TRPV6 with and without PIP2. Simulation results show that the positively charged residues responsible for TRPV5 binding of diC8 PIP2 are conserved in the interactions between TRPV6 and PIP2. The binding of PIP2 to TRPV6 increases the distance between the diagonally opposed residues D542 in the selectivity filter and that between the diagonally opposed M578 residues in the lower gate of TRPV6. A secondary structural analysis reveals that residues M578 in TRPV6 undergo structural and position changes during the binding of PIP2 with TRPV6. In addition, principal component analysis indicates that the binding of PIP2 increases the dynamical motions of both the selectivity filter and the lower gate of TRPV6. These changes induced by PIP2 favor the channel opening. Thus, this study provides a basis for understanding the mechanism underlying the PIP2-induced TRPV6 channel activation.Communicated by Ramaswamy H. Sarma.

4.
Int J Food Microbiol ; 379: 109869, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35963080

RESUMO

Pickles are typical traditional Chinese fermented vegetables. Complex microbiota interacts throughout the fermentation and deterioration process. Minimal studies are available involving quorum sensing (QS) signaling in pickles. This study investigated the changes in the general pickle properties and microbial diversity at 4 d, 31 d, and 79 d. The QS signaling activity of various strains isolated at these key time points was screened using biosensor strains, while the types of signal molecules were further identified using UHPLC/QTOF-MS/MS. At 4 d, Lactobacillus represented the dominant genus, while Lactobacillus plantarum was identified as the bacteria with AI-2-producing ability. At 31 d, the dominant genus was also Lactobacillus, while the relative abundance of Pediococcus displayed a distinct increase. At this time point, L. plantarum represented the AI-2-producing bacteria, followed by Lactobacillus brevis, Pediococcus sp., Enterobacter sp., and Bacillus megaterium. At 79 d, Lactobacillus was displaced by Enterobacter as the dominant microorganisms, while the AI-2-producing bacteria were identified as L. plantarum, Enterobacter sp., B. megaterium, Klebsiella sp., and Staphylococcus sp. Moreover, AHL activity was only present in isolates from the 79-d brine and was identified as C4-HSL and C6-HSL. In addition, the luxS gene was amplified via cDNA reversely transcription from the total RNA extracted from the brine at all three time points using the L. plantarum luxS primers. The AHL-related genes were only amplified in the RNA of 79-d brine samples using Klebsiella pneumoniae- and Bacillus cereus-related primers. This study presented theoretical references for QS during pickle fermentation and deterioration.

5.
Ecol Evol ; 12(8): e9166, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35919390

RESUMO

Understanding the roles of ecological drivers in shaping biodiversity is fundamental for conservation practice. In this study, we explored the effects of elevation, conservation status, primary productivity, habitat diversity and anthropogenic disturbance (represented by human population density and birding history) on taxonomic, phylogenetic and functional avian diversity in a subtropical landscape in southeastern China. We conducted bird surveys using 1-km transects across a total of 30 sites, of which 10 sites were located within a natural reserve. Metrics of functional diversity were calculated based on six functional traits (body mass, clutch size, dispersal ratio, sociality, diet and foraging stratum). We built simultaneous autoregression models to assess the association between the ecological factors and diversity of the local avian communities. Local avian diversity generally increased with increasing habitat diversity, human population density and primary productivity. We also detected phylogenetic and functional clustering in these communities, suggesting that the avian assemblages were structured mainly by environmental filtering, rather than interspecific competition. Compared with sites outside the natural reserve, sites within the natural reserve had relatively lower avian diversity but a higher level of phylogenetic heterogeneity.

6.
Front Neurol ; 13: 891283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911919

RESUMO

Somatosensory deficits after stroke are a major health problem, which can impair patients' health status and quality of life. With the developments in human brain mapping techniques, particularly magnetic resonance imaging (MRI), many studies have applied those techniques to unravel neural substrates linked to apoplexy sequelae. Multi-parametric MRI is a vital method for the measurement of stroke and has been applied to diagnose stroke severity, predict outcome and visualize changes in activation patterns during stroke recovery. However, relatively little is known about the somatosensory deficits after stroke and their recovery. This review aims to highlight the utility and importance of MRI techniques in the field of somatosensory deficits and synthesizes corresponding articles to elucidate the mechanisms underlying the occurrence and recovery of somatosensory symptoms. Here, we start by reviewing the anatomic and functional features of the somatosensory system. And then, we provide a discussion of MRI techniques and analysis methods. Meanwhile, we present the application of those techniques and methods in clinical studies, focusing on recent research advances and the potential for clinical translation. Finally, we identify some limitations and open questions of current imaging studies that need to be addressed in future research.

7.
J Biol Chem ; : 102341, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35931119

RESUMO

Human papillomaviruses (HPVs) cause a subset of cases of head and neck squamous cell carcinomas (HNSCCs). Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked GlcNAcylation (O-GlcNAc) transferase (OGT), but the OGT substrates and cellular pathways affected by this increase are unclear. Here, we focus on the effects of O-GlcNAcylation on HPV-positive HNSCCs. We found that upon HPV infection, ULK1, an autophagy-initiating kinase, is hyper-O-GlcNAcylated, stabilized, and linked with autophagy elevation. Through mass spectrometry, we identified that ULK1 is O-GlcNAcylated at Ser409, which is distinct from the previously reported Thr635/Thr754 sites. It has been demonstrated that PKCαmediates phosphorylation of ULK1 at Ser423, which attenuates its stability by shunting ULK1 to the chaperone-mediated autophagy (CMA) pathway. Using biochemical assays, we demonstrate that ULK1 Ser409Ser410 O-GlcNAcylation antagonizes its phosphorylation at Ser423. Moreover, we found that mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone Hsc70. Further, we determined that ULK1-2A mutants attenuate the association of ULK1 with STX17, which is vital for the fusion between autophagosomes and lysosomes. Analysis of The Cancer Genome Atlas (TCGA) database reveals that ULK1 is upregulated in HPV-positive HNSCCs and its level positively correlates with HNSCC patient survival. Overall, our work demonstrates that O-GlcNAcylation of ULK1 is altered in response to environmental changes. O-GlcNAcylation of ULK1 at Ser409 and perhaps at its neighboring Ser410 stabilizes ULK1, and this might underlie the molecular mechanism of HPV-positive HNSCC patient survival.

8.
Iran J Basic Med Sci ; 25(6): 755-761, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35949310

RESUMO

Objectives: Cigarette smoke may play a direct role in proliferation of human pulmonary artery smooth muscle cells (HPASMCs). However, the mechanism involved and the effect of interventions remain unclear. We aimed to evaluate the effect of cigarette smoke extract (CSE) on HPASMCs, explore the role of inflammation and oxidative stress, and the effects of Tempol and PDTC in this process. Materials and Methods: HPASMCs were subjected to normal control (NC), CSE, CSE+Tempol (CSE+T), and CSE+PDTC (CSE+P) groups. Proliferation of HPASMCs was measured by CCK-8 and Western blot. TNF-α, IL-6, MDA, and SOD levels were determined by ELISA and commercial kits. Nuclear translocation of NF-κB p65 was evaluated by western blot. Results: 1%, 2.5%, and 5% CSE all promoted proliferation of HPASMCs, and effect of 1% CSE was the most significant, however, 7.5% and 10% CSE inhibited viability of cells (all P<0.05). Compared with the NC group, TNF-α, IL-6, and MDA levels increased, SOD activity decreased (all P<0.05), and NF-κB p65 expression in nuclei increased (P=0.04) in the CSE group. Tempol and PDTC inhibited the proliferation of HPASMCs induced by CSE (all P<0.05). And compared with the CSE group, TNF-α, IL-6, and MDA levels in CSE+T and CSE+P groups decreased, while SOD activity increased (all P<0.05). Tempol reduced the expression of NF-κB p65 in nuclei but did not achieve a significant difference (P=0.08). PDTC inhibited the nuclear translocation of NF-κB p65 (P=0.03). Conclusion: CSE stimulates HPASMCs proliferation in a certain concentration range. The CSE-induced proliferation of HPASMCs involved excessive inflammatory response and oxidative stress. Tempol and PDTC attenuate these effects of CSE on HPASMCs.

9.
Front Oncol ; 12: 965088, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957889

RESUMO

Nasopharyngeal carcinoma is a type of head and neck cancer with a high incidence in men. In the past decades, the survival rate of NPC has remained around 70%, but it often leads to treatment failure due to its distant metastasis or recurrence. The lncRNA-mRNA regulatory network has not been fully elucidated. We downloaded the NPC-related gene expression datasets GSE53819 and GSE12452 from the Gene Expression Omnibus database; GSE53819 included 18 NPC tissues and 18 normal tissues, and GSE12452 included 31 NPC tissues and 10 normal tissues. Weighted gene co-expression network analysis was performed on mRNA and lncRNA to screen out modules that were highly correlated with tumor progression. The two datasets were subjected to differential analysis after removing batch effects, and then Venn diagrams were used to screen for overlapping genes in the module genes and differential genes. The lncRNA-mRNA co-expression network was then constructed, and key mRNAs were identified by MCODE analysis and expression analysis. GSEA analysis and qRT-PCR were performed on key mRNAs. Through a series of analyses, we speculated that BTK, CD72, PTPN6, and VAV1 may be independent predictors of the prognosis of NPC patients.Taken together, our study provides potential candidate biomarkers for NPC diagnosis, prognosis, or precise treatment.

10.
Ann Surg Oncol ; 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35829796

RESUMO

BACKGROUND: Metabolic disorders are significant in the occurrence and development of malignant tumors. Changes of specific metabolites and metabolic pathways are molecular therapeutic targets. This study aims to determine the metabolic differences between oral squamous cell carcinoma (OSCC) tissues and paired adjacent noncancerous tissues (ANT) through liquid chromatography-mass spectrometry (LC-MS). SPHK1 is a key enzyme in sphingolipid metabolism. This study also investigates the potential role of SPHK1 in OSCC. MATERIALS AND METHODS: This study used LC-MS to analyze metabolic differences between OSCC tissues and paired ANT. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were applied to explain the significance of phospholipid metabolism pathways in the occurrence and development of OSCC. Through further experiments, we confirmed the oncogenic phenotypes of SPHK1 in vitro and in vivo, including proliferation, migration, and invasion. RESULTS: The sphingolipid metabolic pathway was significantly activated in OSCC, and the key enzyme SPHK1 was significantly upregulated in oral cancer tissues, predicting poor OSCC prognosis. In this study, SPHK1 overexpression was associated with high-grade malignancy and poor OSCC prognosis. SPHK1 targeted NF-κB by facilitating p65 expression to regulate OSCC tumor progression and promote metastasis. CONCLUSIONS: This study identified metabolic differences between OSCC and paired ANT, explored the carcinogenic role of overexpressed SPHK1, and revealed the association of SPHK1 with poor OSCC prognosis. SPHK1 targets NF-κB signaling by facilitating p65 expression to regulate tumor progression and promote tumor metastasis, providing potential therapeutic targets for diagnosing and treating oral tumors.

11.
Neurosci Bull ; 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35819574

RESUMO

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b+ pericytes after TBI. These CD11b+ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.

12.
Front Hum Neurosci ; 16: 882114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865354

RESUMO

Purpose: Thyroid-associated ophthalmopathy (TAO) is a vision threatening autoimmune and inflammatory orbital disease, and has been reported to be associated with a wide range of structural and functional abnormalities of bilateral hemispheres. However, whether the interhemisphere functional connectivity (FC) of TAO patients is altered still remain unclear. A new technique called voxel-mirrored homotopic connectivity (VMHC) combined with support vector machine (SVM) method was used in the present study to explore interhemispheric homotopic functional connectivity alterations in patients with TAO. Methods: A total of 21 TAO patients (14 males and 7 females) and 21 wellmatched healthy controls (HCs, 14 males and 7 females), respectively, underwent functional magnetic resonance imaging (fMRI) scanning in the resting state. We evaluated alterations in the resting state functional connectivity between hemispheres by applying VMHC method and then selected these abnormal brain regions as seed areas for subsequent study using FC method. Furthermore, the observed changes of regions in the VMHC analysis were chosen as classification features to differentiate patients with TAO from HCs through support vector machine (SVM) method. Results: The results showed that compared with HCs, TAO patients showed significantly lower VMHC values in the bilateral postcentral gyrus, lingual gyrus, calcarine, middle temporal gyrus, middle occipital gyrus and angular. Moreover, significantly decreased FC values were found between the right postcentral gyrus/lingual gyrus/calcarine and left lingual gyrus/cuneus/superior occipital gyrus, left postcentral gyrus/lingual gyrus/calcarine and right lingual gyrus/ middle temporal gyrus, right middle temporal gyrus and left cerebellum-8/lingual gyrus/middle occipital gyrus/supplementary motor area, left middle temporal gyrus and right middle occipital gyrus, right middle occipital gyrus/angular and left middle temporal pole (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). The SVM classification model achieved good performance in differentiating TAO patients from HCs (total accuracy: 73.81%; area under the curve: 0.79). Conclusion: The present study revealed that the altered interhemisphere interaction and integration of information involved in cognitive and visual information processing pathways including the postcentral gyrus, cuneus, cerebellum, angular, widespread visual cortex and temporal cortex in patients with TAO relative to HC group. VMHC variability had potential value for accurately and specifically distinguishing patients with TAO from HCs. The new findings may provide novel insights into the neurological mechanisms underlying visual and cognitive disorders in patients with TAO.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35882668

RESUMO

The transient receptor potential (TRP) channels, classified into six (-A, -V, -P, -C, -M, -ML, -N and -Y) subfamilies, are important membrane sensors and mediators of diverse stimuli including pH, light, mechano-force, temperature, pain, taste, and smell. The mammalian TRP superfamily of 28 members share similar membrane topology with six membrane-spanning helices (S1-S6) and cytosolic N-/C-terminus. Abnormal function or expression of TRP channels is associated with cancer, skeletal dysplasia, immunodeficiency, and cardiac, renal, and neuronal diseases. The majority of TRP members share common functional regulators such as phospholipid PIP2, 2-aminoethoxydiphenyl borate (2-APB), and cannabinoid, while other ligands are more specific, such as allyl isothiocyanate (TRPA1), vanilloids (TRPV1), menthol (TRPM8), ADP-ribose (TRPM2), and ML-SA1 (TRPML1). The mechanisms underlying the gating and regulation of TRP channels remain largely unclear. Recent advances in cryogenic electron microscopy provided structural insights into 19 different TRP channels which all revealed close proximity of the C-terminus with the N-terminus and intracellular S4-S5 linker. Further studies found that some highly conserved residues in these regions of TRPV, -P, -C and -M members mediate functionally critical intramolecular interactions (i.e., within one subunit) between these regions. This review provides an overview on (1) intramolecular interactions in TRP channels and their effect on channel function; (2) functional roles of interplays between PIP2 (and other ligands) and TRP intramolecular interactions; and (3) relevance of the ligand-induced modulation of intramolecular interaction to diseases.

14.
Crit Rev Oncol Hematol ; 176: 103756, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35809794

RESUMO

BACKGROUND: Secondary central nervous system (CNS) relapses are an uncommon yet devastating complication in diffuse large B cell lymphoma (DLBCL). Although several prophylaxis attempts were employed clinically in order to reduce the CNS relapse rate, the optimal management remained uncertain. METHODS: We employed conventional meta-analysis along with Network meta-analysis to investigate an optimal prophylactic strategy. The primary outcome was CNS relapse rate. RESULTS: A total of thirty-six studies comprising 5 RCTs, one clinical trial and 30 observational studies were included. Rituximab overall was superior in reducing CNS relapse rate, and the statistical significance exists (RR 0.79(0.68-0.93), p = 0.004). In rituximab era, none of intravenous, intrathecal administration or novel target agents could significantly decrease CNS relapse rate in high CNS risk patients. Intensive chemotherapy regimen containing HD-MTX with HD-Ara-C (SUCRA 93.4 %) was ranked as the first in reducing CNS relapse rate followed by no prophylaxis (SUCRA 57.5 %), HD-MTX (SUCRA 53.1 %), IT (SUCRA 34.5 %) and lenalidomide maintenance (SUCRA 11.5 %). In addition, intercalated HD-MTX had a trend of reducing CNS relapse but without statistical significance (RR 0.86(0.44-1.68), p = 0.67). However, i-HD-MTX was associated with increased grade 3-4 toxicities and prolonged inpatient stay. Early HD-MTX exposure also increased the treatment related death. CONCLUSION: Our network meta-analysis provides an overview of the relative efficacy of all available CNS prophylaxis strategies in DLBCL. In rituximab era, none of intravenous, intrathecal administration or novel target agents could significantly decrease CNS relapse rate in high CNS risk patients. Further studies with prospective, randomized clinical trials as well as with more focus on novel target agents that could spread blood-brain barriers are suggested.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/prevenção & controle , Ciclofosfamida , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Metanálise em Rede , Estudos Prospectivos , Rituximab/uso terapêutico , Vincristina
15.
Nature ; 607(7920): 677-681, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35896646

RESUMO

Ultracold polar molecules offer strong electric dipole moments and rich internal structure, which makes them ideal building blocks to explore exotic quantum matter1-9, implement quantum information schemes10-12 and test the fundamental symmetries of nature13. Realizing their full potential requires cooling interacting molecular gases deeply into the quantum-degenerate regime. However, the intrinsically unstable collisions between molecules at short range have so far prevented direct cooling through elastic collisions to quantum degeneracy in three dimensions. Here we demonstrate evaporative cooling of a three-dimensional gas of fermionic sodium-potassium molecules to well below the Fermi temperature using microwave shielding. The molecules are protected from reaching short range with a repulsive barrier engineered by coupling rotational states with a blue-detuned circularly polarized microwave. The microwave dressing induces strong tunable dipolar interactions between the molecules, leading to high elastic collision rates that can exceed the inelastic ones by at least a factor of 460. This large elastic-to-inelastic collision ratio allows us to cool the molecular gas to 21 nanokelvin, corresponding to 0.36 times the Fermi temperature. Such cold and dense samples of polar molecules open the path to the exploration of many-body phenomena with strong dipolar interactions.

16.
ACS Nano ; 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35848623

RESUMO

2H-1T' MoTe2 van der Waals heterostructures (vdWHs) have promising applications in optoelectronics due to a seamlessly homogeneous semiconductor-metal coupled interface. However, the existing methods to fabricate such vdWHs involved complicated steps that may deteriorate the interfacial coupling and are also lacking precise thickness control capability. Here, a one-step growth method was developed to controllably grow bilayer 2H-1T' MoTe2 vdWHs in the small growth window overlapped for both phases. Atomic-resolution low-voltage transmission electron microscopy shows the distinct moiré patterns in the bilayer vdWHs, revealing the epitaxial nature of the top 2H phase with the lattice parameters regulated by the underneath 1T' phase. Such epitaxially stacked bilayer vdWHs modulate the interlayer coupling by resonating their vibration modes, as unveiled by the angle-resolved polarized Raman spectroscopy and first-principles calculations.

17.
Biochem Biophys Res Commun ; 621: 122-129, 2022 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-35820282

RESUMO

With an increasing prevalence of obesity related kidney disease, exploring the mechanisms of therapeutic method is of critical importance. Empagliflozin is a new antidiabetic agent with broad clinical application prospect in cardiovascular and renal diseases. However, a metabonomics-based renoprotective mechanism of empagliflozin in obesity remains unclear. Our results showed that empagliflozin significantly alleviated the deposition of lipid droplet, glomerular and tubular injury. The innovation lied in detection of empagliflozin-targeted differential metabolites in kidneys. Compared with normal control mice, obese mice showed higher levels of All-trans-heptaprenyl diphosphate, Biliverdin, Galabiose, Galabiosylceramide (d18:1/16:0), Inosine, Methylisocitric acid, Uric acid, Xanthosine, O-glutarylcarnitine, PG(20:3(8Z,11Z,14Z)/0:0), PG(20:4(5Z,8Z,11Z,14Z)/0:0), PE(O-16:0/0:0), PG(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0), and lower level of Adenosine. Empagliflozin regulated these metabolites in the opposite direction. Associated metabolic pathways were Phospholipids metabolism, Purine metabolism, and Biliverdin metabolism. Most of metabolites were associated with inflammatory response and oxidative stress. Empagliflozin improved the oxidative stress and inflammation imbalance. Our study revealed the metabonomics-based renoprotective mechanism of empagliflozin in obese mice for the first time. Empagliflozin may be a promising tool to delay the progression of obesity-related kidney disease.


Assuntos
Biliverdina , Metabolômica , Animais , Compostos Benzidrílicos , Glucosídeos , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico
18.
Neurochem Int ; 159: 105385, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35843421

RESUMO

Resveratrol (RES) is a polyphenol with diverse beneficial pharmacological activities, and our previous results have demonstrated its neuroprotective potential. The purpose of this study was to investigate the therapeutic effect of RES in Alzheimer's disease (AD)-like behavioral dysfunction induced by streptozotocin (STZ) and explore it's potential mechanism of action. STZ was microinjected bilaterally into the dorsal hippocampus of C57BL/6J mice at a dose of 3 mg/kg, and RES was administered intragastrically at a dose of 25 mg/kg for 5 weeks. Neurobehavioral performance was observed, and serum concentrations of insulin and Nesfatin-1 were measured. Moreover, the protein expression of amyloid beta 1-42 (Aß1-42), Tau, phosphorylated Tau (p-Tau) (Ser396), synaptic ras GTPase activation protein (SynGAP), postsynaptic density protein 95 (PSD95), synapsin-1, synaptogomin-1, and key molecules of the Wnt/ß-catenin signaling pathway in the hippocampus and prefrontal cortex (PFC) were assessed. Finally, pathological damage to hippocampal tissue was examined by Nissl and immunofluorescence staining. The results showed that compared with the controls, bilateral hippocampal microinjections of STZ induced task-specific learning and memory impairments, as indicated by the disadvantaged performances in the novel object recognition test (NOR) and Morris water maze (MWM), but not the contextual fear conditioning test (CFC). Treatment with RES could improve these behavioral disadvantages. The serum concentrations of insulin and Nesfatin-1 in the model group were remarkably higher than those of the control group. In addition, protein expression of Aß1-42, Tau, and p-Tau (Ser396) was increased but expression of SynGAP, PSD95, brain-derived neurotrophic factor (BDNF), and p-GSK-3ß/GSK-3ß were decreased in the hippocampus. Although the protein expression of BDNF and SynGAP was also markedly decreased in the PFC of the model mice, there was no significant difference among groups in the protein expression of PSD95, BDNF, synapsin-1, synaptogomin-1, and p-GSK-3ß/GSK-3ß. RES (25 mg/kg) reversed the enhanced insulin level, the abnormal protein expression of Aß1-42, Tau, and p-Tau (Ser396) in the hippocampus and PFC, and the hippocampal protein expression of SynGAP, PSD95 and BDNF. In addition, RES reversed the STZ-induced decrease in the number of Nissl bodies and the increase in fluorescence intensity of IBA1 in the hippocampal CA1 region. These findings indicate that RES could ameliorate STZ-induced AD-like neuropathological injuries, the mechanism of which could be partly related to its regulation of BDNF expression and synaptic plasticity-associated proteins in the hippocampus.

19.
Clin Immunol ; 242: 109082, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35901921

RESUMO

Although C-type lectin domain family 9A (Clec9A) on conventional type 1 dendritic cells (cDC1s) plays a critical role in cytotoxic CD8+ T cell response in cancers and viral infections, its role in chronic obstructive pulmonary disease (COPD) is unknown. We measured the expression of Clec9A in sera, bronchoalveolar lavage fluid (BALF), and peripheral blood mononuclear cells (PBMCs) from controls and COPD patients. The percentages of Clec9A+ DC and cytotoxic CD8+ T cell in the BALF were determined by flow cytometry between patients with COPD and non-obstructive chronic bronchitis (NOCB). Compared with healthy individuals, the serum levels of Clec9A were increased at different stages of COPD patients, and the mRNA and protein levels of Clec9A were both increased in COPD patients at GOLD stages III-IV. The percentage of Clec9A+ DCs was also increased in the BALF of COPD patients compared with NOCB patients. Moreover, enhanced Clec9A+ DCs recruitment was positively correlated with cytotoxic CD8+ T cell response in the BALF of COPD patients. This study suggests that Clec9A+ DCs participate in the CD8+ T cell-mediated chronic airway inflammation in COPD.

20.
Behav Brain Res ; 433: 113997, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35803544

RESUMO

Effective treatment for cognitive dysfunction after traumatic brain injury (TBI) is lacking in clinical practice. Increased brain-derived neurotrophic factor (BDNF) expression in cognitive circuits can significantly alleviate cognitive dysfunction in animal models of TBI. Selective 5-hydroxytryptamine receptor 6 (5-HT6R) agonists significantly increase BDNF expression and improve cognitive function. Therefore, we evaluated the protective effect of a highly selective 5-HT6R agonist, WAY-181187, on cognitive dysfunction after TBI. We established a controlled cortical impact model of moderate TBI in rats and performed drug intervention for five consecutive days. Rats had spatial reference memory impairment in the Morris water maze one and four weeks after TBI. BDNF expression in the medial prefrontal cortex (mPFC) and hippocampus decreased two and five weeks after TBI. Additionally, five weeks after TBI, decreases in neuronal dendritic spine density and the proportion of thin, mushroom-shaped dendritic spines and an increased proportion of stubby-type dendritic spines were observed. WAY-181187 administration (3 mg/kg) for five consecutive days after TBI significantly alleviated cognitive dysfunction at one and four weeks (P < 0.001 and P < 0.01), upregulated BDNF expression in the mPFC and hippocampus at two (P < 0.01 and P < 0.05) and five (P < 0.01 and P < 0.001) weeks and increased the dendritic spine density and the proportions of thin, mushroom-shaped dendrites in the mPFC (P < 0.05, P < 0.001 and P < 0.01) and hippocampus (P < 0.05, P < 0.001 and P < 0.05) at five weeks after TBI. Our results confirm that WAY-181187 administration (3 mg/kg) in the acute phase alleviated cognitive dysfunction after TBI, possibly by upregulating BDNF expression in the mPFC and hippocampus, enhancing neuroplasticity.


Assuntos
Lesões Encefálicas Traumáticas , Disfunção Cognitiva , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Aprendizagem em Labirinto , Ratos , Serotonina/metabolismo
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