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1.
Nano Lett ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34213911

RESUMO

Nanocarbon materials, such as graphene, carbon nanotubes, and their derivatives, are considered highly effective reinforcing agents in metals. Copious experimental and computational observations suggest that the nature of the interfaces may significantly affect the mechanical behavior of nanocarbon-metal composites, while the exact correlation between the interfacial structure and the deformation and failure mechanisms of the composite remains elusive. Using a nanolaminated graphene-aluminum (Al) composite as the model material, we designed and created composites with distinct interfacial structures and bonding states via graphene functionalization. The mechanical behavior of the composites was strongly affected by the structure of the functionalized graphene (FG)/Al interface, and the optimum strength-ductility synergy came from the composite with the intermediate extent of functionalization. Complementing experimental results with molecular dynamics and phase-field simulation efforts, we interpreted these results by the combined effects of the intrinsic strength of FG nanosheets and the FG/Al interfacial bonding state.

2.
Int Immunopharmacol ; : 107892, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34215553

RESUMO

Differentiated embryo-chondrocyte expressed gene 1 (DEC1) belongs to the family of basic helix-loop-helix (bHLH)-type transcription factors. DEC1 is expressed in various mammalian cells, but early studies focused on its roles outside the immune system. In recent years, relevant studies have found that DEC1 plays an important role in the immunotherapy of tumors, the functional regulation of the immune system, and the onset of autoimmune diseases. DEC1 promotes interferon (IFN)-γand granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion through the production of CD4+ T cells, which promotes inflammatory defense responses and autoimmune diseases. Additionally, DEC1 can inhibit the expression of interleukin (IL)-10 to further strengthen the immune response. In this review, we summarized recent advances in our understanding of the roles of DEC1 in animal models and human cells, including regulating immune cell differentiation, controlling cytokine production, and maintaining the balance of pro- and anti-inflammatory signals.

3.
Nutrients ; 13(7)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206629

RESUMO

A perinatal high-salt (HS) diet was reported to elevate plasma triglycerides. This study aimed to investigate the hypothesis that a perinatal HS diet predisposed offspring to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of abnormal lipid metabolism, and the possible mechanism. Female C57BL/6 mice were fed a control diet (0.5% NaCl) or HS diet (4% NaCl) during pregnancy and lactation and their offspring were sacrificed at weaning. The perinatal HS diet induced greater variation in fecal microbial beta-diversity (ß-diversity) and increased bacteria abundance of Proteobacteria and Bacteroides. The gut microbiota dysbiosis promoted bile acid homeostasis disbalance, characterized by the accumulation of lithocholic acid (LCA) and deoxycholic acid (DCA) in feces. These alterations disturbed gut barrier by increasing the expression of tight junction protein (Tjp) and occludin (Ocln), and increased systemic lipopolysaccharide (LPS) levels and hepatic inflammatory cytokine secretion (TNF-α and IL-6) in the liver. The perinatal HS diet also inhibited hepatic expression of hepatic FXR signaling (CYP7A1 and FXR), thus triggering increased hepatic expression of pro-inflammatory cytokines (TNF-α and IL-6) and hepatic lipid metabolism-associated genes (SREBP-1c, FAS, ACC), leading to unique characteristics of NAFLD. In conclusion, a perinatal HS diet induced NAFLD in weanling mice offspring; the possible mechanism was related to increased bacteria abundance of Proteobacteria and Bacteroides, increased levels of LCA and DCA in feces, and increased expressions of hepatic FXR signaling.

4.
J Diabetes ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259386

RESUMO

BACKGROUND: Type 2 diabetes is increasingly diagnosed at a younger age worldwide and in China. Limited data are available regarding the association between age at diabetes diagnosis and risks of albuminuria. This study sought to examine the independent effect of age at diagnosis of type 2 diabetes on the risk of albuminuria. METHODS: We used data from a nationwide multicenter study with 207,961 participants in mainland China. Age, sex, and study site were matched for 31,366 screen-detected type 2 diabetes and 31,366 normal controls. Age, sex, study site, and diabetes duration were matched for 7,490 self-reported type 2 diabetes and 7,490 normal controls. Risks of having albuminuria in matched type 2 diabetes vs. controls were examined using multivariable logistic regression analysis in strata of age at diabetes diagnosis. RESULTS: Although the absolute rate of albuminuria is higher in older adults, the odds ratio of albuminuria in type 2 diabetes vs. matched controls decreased with increasing age at diagnosis. For participants with diabetes diagnosed at an age of <50, 50-59, 60-69, or ≥70 years, the multivariable adjusted risk of albuminuria increased by 81%, 60%, 45%, and 33% for screen-detected diabetes, and 135%, 121%, 90%, and 58% for self-reported diabetes compared with their normal controls, respectively. CONCLUSIONS: A younger age at diagnosis of type 2 diabetes is associated with a more significantly elevated risk of albuminuria than an older age at diagnosis in Chinese adults.

5.
J Biomed Mater Res A ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34260157

RESUMO

Alveolar ridge augmentation can be used to obtain appropriate alveolar ridge for dental implantation. A variety of bone graft materials including autogenous bone, allograft, xenograft, and alloplastic material are used in alveolar ridge augmentation. Autogenous tooth-derived bone graft material has received much attention for the past few years, because the structure and physicochemical characteristics of tooth are similar to those of bones. Compared to autogenous tooth, allogenic tooth has the advantage of extensive resources. However, the problem of cell-derived immunological rejection of allogenic tooth remains unresolved. In the present study, acellular tooth root (ATR) is obtained by an innovative combination procedure. The biocompatibility of ATR is assessed using cytotoxicity test, hemolysis test, intracutaneous reactivity test, and acute systemic toxicity test. Osseointegration is evaluated in vivo by implanting ATR into the rat tibia defect as an allograft material. The results show that the ATR has fine biocompatibility, and there is an osseointegration between ATR and bone bed at 8 weeks post operation. This study demonstrates that the ATR could be used in alveolar ridge augmentation as a kind of new tooth-derived bone graft material.

6.
Stem Cell Res Ther ; 12(1): 376, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215315

RESUMO

BACKGROUND: There is a huge controversy about whether xenograft or allograft in the "immune-privileged" brain needs immunosuppression. In animal studies, the prevailing sophisticated use of immunosuppression or immunodeficient animal is detrimental for the recipients, which results in a short lifespan of animals, confounds functional behavioral readout of the graft benefits, and discourages long-term follow-up. METHODS: Neuron-restricted neural progenitor cells (NPCs) were derived from human embryonic stem cells (ESCs, including H1, its gene-modified cell lines for better visualization, and HN4), propagated for different passages, and then transplanted into the brain of immunocompetent rats without immunosuppressants. The graft survivals, their cell fates, and HLA expression levels were examined over time (up to 4 months after transplantation). We compared the survival capability of NPCs from different passages and in different transplantation sites (intra-parenchyma vs. para- and intra-cerebroventricle). The host responses to the grafts were also investigated. RESULTS: Our results show that human ESC-derived neuron-restricted NPCs survive extendedly in adult rat brain parenchyma with no need of immunosuppression whereas a late-onset graft rejection seems inevitable. Both donor HLA antigens and host MHC-II expression level remain relatively low with little change over time and cannot predict the late-onset rejection. The intra-/para-cerebroventricular human grafts are more vulnerable to the immune attack than the intrastriatal counterparts. Prevention of graft hyperplasia by using hypoproliferative late passaged human NPCs further significantly extends the graft survival time. Our new data also shows that a subpopulation of host microglia upregulate MHC-II expression in response to the human graft, but fail to present the human antigen to the host immune system, suggestive of the immune-isolation role of the blood-brain barrier (BBB). CONCLUSIONS: The present study confirms the "immune privilege" of the brain parenchyma and, more importantly, unveils that choosing hypoproliferative NPCs for transplantation can benefit graft outcome in terms of both lower tumor-genic risk and the prolonged survival time without immunosuppression.


Assuntos
Transplante de Tecido Encefálico , Células-Tronco Neurais , Animais , Encéfalo , Rejeição de Enxerto , Sobrevivência de Enxerto , Xenoenxertos , Humanos , Ratos , Ratos Sprague-Dawley
7.
J Headache Pain ; 22(1): 72, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261444

RESUMO

BACKGROUND: Migraine constitutes a global health burden, and its pathophysiology is not well-understood; research evaluating cerebral perfusion and altered blood flow between brain areas using non-invasive imaging techniques, such as arterial spin labeling, have been scarce. This study aimed to assess cerebral blood flow (CBF) and its connectivity of migraine. METHODS: This study enrolled 40 patients with episodic migraine without aura (MwoA), as well as 42 healthy patients as control (HC). Two groups of normalized CBF and CBF connectivity were compared, and the relationship between CBF variation and clinical scale assessment was further evaluated. RESULTS: In comparison to HC subjects, MwoA patients exhibited higher CBF in the right middle frontal orbital gyrus (ORBmid.R) and the right middle frontal gyrus, while that in Vermis_6 declined. The increased CBF of ORBmid.R was positively correlated with both the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the monthly attack frequency score. In MwoA, significantly decreased CBF connectivity was detected between ORBmid.R and the left superior frontal gyrus, the right putamen, the right caudate, as well as the right angular gyrus. In addition, increased CBF connectivity was observed between the left calcarine cortex and ORBmid.R. CONCLUSIONS: Our results indicate that migraine patients exhibit abnormalities in regional CBF and feature CBF connection defects at the resting state. The affected areas involve information perception, information integration, and emotional, pain and visual processing. Our findings might provide important clues for the pathophysiology of migraine.


Assuntos
Mapeamento Encefálico , Epilepsia , Encéfalo , Circulação Cerebrovascular , Humanos , Imageamento por Ressonância Magnética , Marcadores de Spin
8.
Vet Microbiol ; 260: 109167, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34274763

RESUMO

Virulent Newcastle disease virus (NDV) is a violent infection in avian species. The understanding of its pathogenic mechanism is consistently evolving along with the development of molecular biological advancement. Exosomes derived from NDV infected cells (NDV Ex) were reported to promote virus replication through transportation of viral proteins and miRNAs. However, the function of mRNAs in NDV Ex remains unknown. In this study, a novel mechanism of NDV Ex to facilitate NDV infection was explored. Through transcriptome analysis, seven immune related genes were found to up-regulate in NDV Ex. Among them, NLRX1 mRNA was notably enriched in NDV Ex, and decreased inside the cells after virulent NDV infection. Further investigation suggested that NLRX1 mRNA decrease was in accordance with the NLRX1 protein expression reduction. This process can be reversed by the inhibition of exosome release. Therefore, NDV infection could utilize NDV Ex to export NLRX1 mRNA and reduce cellular NLRX1 protein. As NLRX1 is a crucial anti-viral protein of MAVS signal pathway, and NDV Ex transported NLRX1 cannot counteract its function in recipient cells, it can be concluded that NDV could benefit its replication through exporting NLRX1 mRNA to relieve the anti-viral pressure on its survival.

9.
Poult Sci ; 100(9): 101228, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34293615

RESUMO

In order to explore the mechanism of liver injury induced by florfenicol (FFC) in broilers. Sixty broilers were randomly divided into 2 groups: control group: normal drinking water and feed were given every d; FFC group: tap water containing FFC (0.15g/L) was given every d and feed was taken freely; each group was given 5 dd of continuous medication and feed was taken freely. The results showed that compared with the control group, FFC could significantly inhibit the weight gain of broilers (P < 0.05), and significantly inhibit the expression of CYP1A1 and CYP2H1 in liver tissue (P < 0.05). It was found that the expression of genes related to the effect of cytochrome P450 on the metabolism of exogenous substances, the peroxisome proliferators-activated receptors signal pathway, peroxisome pathway and glutathione metabolic pathway in the liver of broilers. The results of qPCR of UDP glucuronosyltransferase family 2A1 (UGT2A1), glutathione S-transferase-like 2 (GSTAL2), hematopoietic prostaglandin D synthase (HPGDS), glutathione S-transferase theta 1(GSTT1), isocitrate dehydrogenase (NADP(+)) 1 (IDH1), acyl-CoA oxidase 2 (ACOX2), fatty acid binding protein 1 (FABP1), adenylosuccinate lyase (ADSL), and phosphoribosyl aminoim idazolesuccino carboxamide synthase (PAICS) genes which were randomly selected from the most significant genes were consistent with those of RNA-seq. The results showed that FFC can affect the drug metabolism and lipid synthesis in the liver of broiler, thus impairing the normal function of liver and the growth and development of broiler.

10.
Ann Palliat Med ; 10(6): 6694-6705, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34237972

RESUMO

BACKGROUND: To explore the feasibility and efficiency of posterior wedge osteotomy assisted by O-arm navigation treatment of ankylosing spondylitis (AS) patients with thoracolumbar fracture. METHODS: This is a case series study. A total of 16 cases of AS accompanied by thoracolumbar fractures from January 2012 to July 2015 were retrospectively analyzed. All patients underwent "posterior wedge osteotomy assisted by O-arm navigation". The operation time, blood loss volume, preoperative and postoperative visual analogue scale (VAS), American Spinal Injury Association (ASIA) classification, and spinal imaging parameters [Cobb angle, C7 plumb line (C7PL), and jaw-brow angle] were collected and analyzed. RESULTS: The operative time consumption was 120-350 mins and the intra-operative blood loss volume was 200-800 mL. No obvious postoperative complications occurred in any participants. The back pain of all participants was relieved, and the neurological functions of eight participants with spinal cord injury (SCI) were recovered in varying degrees except for one patient with severe SCI. The spinal deformities of the participants were corrected to varying degrees. The fracture sites of 16 participants were all healed, and there was no loosening or detachment of internal fixation during the 6-month follow-up period. CONCLUSIONS: Posterior wedge osteotomy assisted by O-arm navigation was shown to be a safe and effective method to treat AS accompanied by thoracolumbar fractures. This treatment strategy can accurately decompress and reduce the fracture and significantly correct the kyphosis, with good surgical effect.


Assuntos
Espondilite Anquilosante , Cirurgia Assistida por Computador , Humanos , Imageamento Tridimensional , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Osteotomia , Estudos Retrospectivos , Espondilite Anquilosante/cirurgia , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Anatol J Cardiol ; 25(7): 476-483, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34236322

RESUMO

OBJECTIVE: Severe right ventricular hypertrophy (SRVH) in hypertrophic cardiomyopathy (HCM) is rare. We studied the clinical characteristics and prognosis of 36 patients with HCM and SRVH in a Chinese cohort. METHODS: Patients with HCM and SRVH were enrolled between 2013 and 2017. The clinical characteristics, treatment therapies, and clinical outcomes of the 36 patients were retrospectively studied and compared with those of 128 patients without SRVH. RESULTS: Patients in the group with SRVH were younger than those in the group without SRVH (27.58±15.09 years vs 40.34±13.21 years, respectively; p<0.001). Patients with SRVH had more serious clinical symptoms and a higher New York Heart Association functional class than those without SRVH. Most patients in the group with SRVH exhibited diffuse RV hypertrophy, and 13 patients presented with biventricular outflow tract obstruction. Maximal left ventricular (LV) wall thickness (27.29±7.95 mm vs 24.33±5.85 mm, respectively; p=0.027) and LV outflow tract gradient (80.83±24.41 mm Hg vs 42.3±5.7 mm Hg, respectively; p=0.000) were significantly greater in patients with SRVH than in those without SRVH. A total of 30 patients in the group with SRVH underwent surgical correction. During a median follow-up period of 48 months, six patients with SRVH reached primary clinical endpoints (four sudden cardiac deaths, one heart failure-related death, and one heart transplantation), whereas only two deaths occurred in the patients without SRVH. CONCLUSION: We conclude that patients with HCM and SRVH exhibit serious symptoms and have complex surgical requirements and poor clinical outcomes.

12.
Oncogene ; 40(27): 4615-4624, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34131285

RESUMO

Mini-chromosome maintenance (MCM) proteins are critical components of DNA-replication-licensing factors. MCM8 is an MCM protein that exhibits oncogenic functions in several human malignancies. However, the role of MCM8 in glioblastomas (GBMs) has remained unclear. In the present study, we investigated the biological functions and mechanisms of MCM8 in glioma stem cells (GSCs). The clinical relevance of MCM8 mRNA expression was explored via TCGA and REMBRANDT datasets. The effects of MCM8 on the self-renewal and tumorigenicity of GSCs were examined both in vitro and in vivo. The regulation of MCM8 expression and its interacting proteins were also evaluated. We found that the expression of MCM8 was elevated in high-grade gliomas and classical molecular subtypes and was inversely correlated with patient prognosis. GSCs had a significantly higher expression of MCM8 compared with that in normal glioma cells. Silencing of MCM8 induced G0/G1 arrest and apoptosis, as well as inhibited the proliferation and self-renewal of GSCs. Forced expression of MCM8 enhanced clonogenicity of GSCs both in vitro and in vivo. MCM8 expression was regulated by EGFR signaling, which was mediated by NF-κB (p65). MCM8 interacted with DNA-replication-initiating factors-including EZH2, CDC6, and CDCA2-and influenced these factors to associate with chromatin. In addition, MCM8 knockdown increased the sensitivity of GSCs to radiation and TMZ treatments. Our findings suggest that MCM8, regulated by the EGFR pathway, maintains the clonogenic and tumorigenic potential of GSCs through interaction with DNA-replication-initiating factors; hence, MCM8 may represent a novel therapeutic target in GBMs.

13.
Food Chem ; 363: 130340, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34144416

RESUMO

This study sought to explore the antibacterial mechanism associated with membrane damage in Yersinia enterocolitica by protocatechualdehyde (PCA), thus providing improved knowledge of whether PCA is suitable for pork preservation. The minimum inhibitory concentration (MIC) of PCA was determined by micro-broth dilution. We then characterized functional and morphological changes of Y. enterocolitica treated with PCA. Finally, the growth inhibition model of PCA against Y. enterocolitica in pork was established using the response surface method. Accordingly, the MIC of PCA against Y. enterocolitica was found to be 0.3125 mg/mL. Significant observations incorporated membrane depolarization, a markedly decreased intracellular ATP and pH, and morphological changes induced by PCA treatment. After PCA treatment under low temperatures, the average Y. enterocolitica count in pork decreased by two log cycles. According to the obtained findings, PCA exhibited satisfactory performances as a food preservative to control the growth and reproduction of Y. enterocolitica in pork.

14.
Soft Matter ; 17(26): 6477-6485, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34137771

RESUMO

Structural and pigment colorations are omnipresent in insects, producing a range of colors for camouflage, warning, mimicry and other strategies necessary for survival. Structural coloration has attracted a lot of attention due to its significance in biophotonics, biomimetics and even esthetic appeal. The coupling of structural and pigment colorations has been largely unnoticed. Herein we show how pigments, scattering and interference work together in two-dimensional waveguiding structures to produce the coloration of Jordanita globulariae (Huebner, 1793), a moth whose forewings sparkle with slightly iridescent green scales. We show that subwavelength structures scatter and couple light into a concave multilayered structure to enhance the absorption of pigments. A finite element method (FEM) model, adequately describing the photonic properties of J. globulariae, was developed based on the nanoscale architecture of the insect's wing scales. The principle of absorption enhanced by scattering and waveguiding is present in many insect species and might be imitated to tailor the spectral properties of optical devices.


Assuntos
Mariposas , Animais , Biomimética , Pigmentação , Asas de Animais
15.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067635

RESUMO

The color of bracts generally turns yellow or black from green during cereal grain development. However, the impact of these phenotypic changes on photosynthetic physiology during black bract formation remains unclear. Two oat cultivars (Avena sativa L.), 'Triple Crown' and 'Qinghai 444', with yellow and black bracts, respectively, were found to both have green bracts at the heading stage, but started to turn black at the flowering stage and become blackened at the milk stage for 'Qinghai 444'. Their photosynthetic characteristics were analyzed and compared, and the key genes, proteins and regulatory pathways affecting photosynthetic physiology were determined in 'Triple Crown' and 'Qinghai 444' bracts. The results show that the actual PSII photochemical efficiency and PSII electron transfer rate of 'Qinghai 444' bracts had no significant changes at the heading and milk stages but decreased significantly (p < 0.05) at the flowering stage compared with 'Triple Crown'. The chlorophyll content decreased, the LHCII involved in the assembly of supercomplexes in the thylakoid membrane was inhibited, and the expression of Lhcb1 and Lhcb5 was downregulated at the flowering stage. During this critical stage, the expression of Bh4 and C4H was upregulated, and the biosynthetic pathway of p-coumaric acid using tyrosine and phenylalanine as precursors was also enhanced. Moreover, the key upregulated genes (CHS, CHI and F3H) of anthocyanin biosynthesis might complement the impaired PSII activity until recovered at the milk stage. These findings provide a new insight into how photosynthesis alters during the process of oat bract color transition to black.


Assuntos
Avena/metabolismo , Flores/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Antocianinas/genética , Antocianinas/metabolismo , Clorofila/metabolismo , Expressão Gênica/genética , Regulação da Expressão Gênica de Plantas/genética , Fotossíntese/fisiologia , Complexo de Proteína do Fotossistema II/fisiologia , Tilacoides/metabolismo
16.
Stem Cell Res Ther ; 12(1): 345, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34116709

RESUMO

BACKGROUND: Adult hippocampal neurogenesis (AHN) is restricted under the pathological conditions of neurodegenerative diseases, especially in Alzheimer's disease (AD). The drop of AHN reduces neural circuit plasticity, resulting in the decrease of the generation of newborn neurons in dentate gyrus (DG), which makes it difficult to recover from learning/memory dysfunction in AD, therefore, it is imperative to find a therapeutic strategy to promote neurogenesis and clarify its underlying mechanism involved. METHODS: Amyloid precursor protein/presenilin 1 (APP/PS1) mice were treated with photobiomodulation therapy (PBMT) for 0.1 mW/mm2 per day in the dark for 1 month (10 min for each day). The neural stem cells (NSCs) were isolated from hippocampus of APP/PS1 transgenic mice at E14, and the cells were treated with PBMT for 0.667 mW/mm2 in the dark (5 min for each time). RESULTS: In this study, photobiomodulation therapy (PBMT) is found to promote AHN in APP/PS1 mice. The latent transforming growth factor-ß1 (LTGFß1) was activated in vitro and in vivo during PBMT-induced AHN, which promoted the differentiation of hippocampal APP/PS1 NSCs into newborn neurons. In particular, behavioral experiments showed that PBMT enhanced the spatial learning/memory ability of APP/PS1 mice. Mechanistically, PBMT-stimulated reactive oxygen species (ROS) activates TGFß/Smad signaling pathway to increase the interaction of the transcription factors Smad2/3 with Smad4 and competitively reduce the association of Smad1/5/9 with Smad4, thereby significantly upregulating the expression of doublecortin (Dcx)/neuronal class-III ß-tubulin (Tuj1) and downregulating the expression of glial fibrillary acidic protein (GFAP). These in vitro effects were abrogated when eliminating ROS. Furthermore, specific inhibition of TGFß receptor I (TGFßR I) attenuates the DNA-binding efficiency of Smad2/3 to the Dcx promotor triggered by PBMT. CONCLUSION: Our study demonstrates that PBMT, as a viable therapeutic strategy, directs the adult hippocampal APP/PS1 NSCs differentiate towards neurons, which has great potential value for ameliorating the drop of AHN in Alzheimer's disease mice.


Assuntos
Doença de Alzheimer , Transdução de Sinais , Proteínas Smad , Fator de Crescimento Transformador beta , Doença de Alzheimer/terapia , Precursor de Proteína beta-Amiloide/genética , Animais , Modelos Animais de Doenças , Hipocampo , Camundongos , Camundongos Transgênicos , Neurogênese , Presenilina-1/genética
17.
Neuropharmacology ; 196: 108685, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34175325

RESUMO

Targeting the common molecular mechanism of type 2 diabetes mellitus and Alzheimer's disease (AD), including dysregulation of glucose metabolism, insulin resistance, and neuroinflammation, might be an efficient treatment strategy for AD. Previous studies have shown that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous PPARγ agonist, has anti-inflammatory, insulin sensitizing and anti-diabetic effects. However, whether 15d-PGJ2 has beneficial effects on AD remains to be elucidated. In the present study, we found that intranasal administration of 15d-PGJ2 (300 ng/30 µL/day) for 3 months significantly inhibited Aß plaques, suppressed neuroinflammation, and attenuated cognitive deficits in APP/PS1 transgenic mice. Interestingly, 15d-PGJ2 treatment could increase brain glucose uptake, as detected by 18F-FDG microPET imaging, and co-localization of GLUT4 and NeuN in the hippocampus of APP/PS1 mice. Furthermore, 15d-PGJ2 markedly increased the expression of PPARγ and PGC-1α, upregulated GLUT4, and decreased the phosphorylation of IRS-1 (Ser616) in the hippocampus of APP/PS1 mice. Importantly, co-administration of a PPARγ antagonist GW9662 abrogated these protective effects of 15d-PGJ2. Collectively, intranasal 15d-PGJ2 conferred protective effects against AD by activating PPARγ-dependent PGC-1α/GLUT4 signalling. The PPARγ agonist 15d-PGJ2 might be a potential therapeutic drug for AD.

18.
Adv Pharmacol ; 91: 141-183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34099107

RESUMO

The discovery of nuclear receptors, particularly retinoid X receptors (RXR), and their involvement in numerous pathways related to development sparked interest in their immunomodulatory properties. Genetic models using deletion or overexpression of RXR and the subsequent development of several small molecules that are agonists or antagonists of this receptor support a promising therapeutic role for these receptors in immunology. Bexarotene was approved in 1999 for the treatment of cutaneous T cell lymphoma. Several other small molecule RXR agonists have since been synthesized with limited preclinical development, but none have yet achieved FDA approval. Cancer treatment has recently been revolutionized with the introduction of immune checkpoint inhibitors, but their success has been restricted to a minority of patients. This review showcases the emerging immunomodulatory effects of RXR and the potential of small molecules that target this receptor as therapies for cancer and other diseases. Here we describe the essential roles that RXR and partner receptors play in T cells, dendritic cells, macrophages and epithelial cells, especially within the tumor microenvironment. Most of these effects are site and cancer type dependent but skew immune cells toward an anti-inflammatory and anti-tumor effect. This beneficial effect on immune cells supports the promise of combining rexinoids with approved checkpoint blockade therapies in order to enhance efficacy of the latter and to delay or potentially eliminate drug resistance. The data compiled in this review strongly suggest that targeting RXR nuclear receptors is a promising new avenue in immunomodulation for cancer and other chronic inflammatory diseases.

19.
J Ultrasound Med ; 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34101225

RESUMO

Cystic renal masses are often encountered during abdominal imaging. Although most of them are benign simple cysts, some cystic masses have malignant characteristics. The Bosniak classification system provides a useful way to classify cystic masses. The Bosniak classification is based on the results of a well-established computed tomography protocol. Over the past 30 years, the classification system has been refined and improved. This paper reviews the literature on this topic and compares the advantages and disadvantages of different screening and classification methods. Patients will benefit from multimodal diagnosis for lesions that are difficult to classify after a single examination.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34125886

RESUMO

CONTEXT: Little is known about the link between nonalcoholic fatty liver disease (NAFLD) evolution and incident chronic kidney disease (CKD). OBJECTIVE: We aim to assess the associations of NALFD status changes and NAFLD fibrosis progression with the risk of incident CKD. METHODS: We conducted a community-based prospective study including participants aged 40 years or older and free of CKD at baseline in 2010, and followed up after a mean of 4.4 years. NAFLD was diagnosed by ultrasonography. NAFLD fibrosis score (NFS) was used to evaluate fibrosis stage and progression. CKD was defined by estimated glomerular filtration rate (eGFR) or urine albumin-to-creatinine ratio (UACR). All the measurements were performed at baseline and follow-up examination. RESULTS: Among 4,042 participants with four NAFLD status change groups, incident NAFLD was associated with an increased risk of incident CKD (Odds Ratio, OR = 1.44, 95% Confidence Interval [CI] 1.003 - 2.06; P = 0.048) compared to non-NAFLD after adjustments for the confounders including evolution of diabetes, hypertension and obesity in addition to the baseline levels. However, the risk of incident CKD was not significantly different between NAFLD resolution and persistent NAFLD. Among 534 participants in persistent NAFLD group, those with fibrosis progression from low NFS to intermediate or high NFS was associated with a significantly increased risk of incident CKD compared to those with fibrosis stable in low NFS (OR = 2.82, 95% CI 1.22 - 6.56; P = 0.016). CONCLUSIONS: NAFLD development and fibrosis progression are associated with increased risk of incident CKD.

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