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1.
Mol Biol Evol ; 41(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38225175

RESUMO

Speciation in the face of gene flow is usually associated with a heterogeneous genomic landscape of divergence in nascent species pairs. However, multiple factors, such as divergent selection and local recombination rate variation, can influence the formation of these genomic islands. Examination of the genomic landscapes of species pairs that are still in the early stages of speciation provides an insight into this conundrum. In this study, population genomic analyses were undertaken using a wide range of sampling and whole-genome resequencing data from 96 unrelated individuals of Kentish plover (Charadrius alexandrinus) and white-faced plover (Charadrius dealbatus). We suggest that the two species exhibit varying levels of population admixture along the Chinese coast and on the Taiwan Island. Genome-wide analyses for introgression indicate that ancient introgression had occurred in Taiwan population, and gene flow is still ongoing in mainland coastal populations. Furthermore, we identified a few genomic regions with significant levels of interspecific differentiation and local recombination suppression, which contain several genes potentially associated with disease resistance, coloration, and regulation of plumage molting and thus may be relevant to the phenotypic and ecological divergence of the two nascent species. Overall, our findings suggest that divergent selection in low recombination regions may be a main force in shaping the genomic islands in two incipient shorebird species.


Assuntos
Estudo de Associação Genômica Ampla , Ilhas Genômicas , Humanos , Especiação Genética , Genoma , Fluxo Gênico , Recombinação Genética , Seleção Genética
2.
J Am Chem Soc ; 146(20): 13934-13948, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38741463

RESUMO

Double perovskite films have been extensively studied for ferroelectric order, ferromagnetic order, and photovoltaic effects. The customized ion combinations and ordered ionic arrangements provide unique opportunities for bandgap engineering. Here, a synergistic strategy to induce chemical strain and charge compensation through inequivalent element substitution is proposed. A-site substitution of the barium ion is used to modify the chemical valence and defect density of the two B-site elements in Bi2FeMnO6 double perovskite epitaxial thin films. We dramatically increased the ferroelectric photovoltaic effect to ∼135.67 µA/cm2 from 30.62 µA/cm2, which is the highest in ferroelectric thin films with a thickness of less than 100 nm under white-light LED irradiation. More importantly, the ferroelectric polarization can effectively improve the photovoltaic efficiency of more than 5 times. High-resolution HAADF-STEM, synchrotron-based X-ray diffraction and absorption spectroscopy, and DFT calculations collectively demonstrate that inequivalent ion plays a dual role of chemical strain (+1.92 and -1.04 GPa) and charge balance, thereby introducing lattice distortion effects. The reduction of the oxygen vacancy density and the competing Jahn-Teller distortion of the oxygen octahedron are the main phenomena of the change in electron-orbital hybridization, which also leads to enhanced ferroelectric polarization values and optical absorption. The inequivalent strategy can be extended to other double perovskite systems and applied to other functional materials, such as photocatalysis for efficient defect control.

3.
World J Urol ; 42(1): 300, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710872

RESUMO

OBJECTIVE: To observe the effect of acupuncture Zhibian (BL54) on the function of the bladder in controlling urine in women under ultrasound. METHOD: 74 healthy subjects were randomly divided into deep acupuncture group of 37 cases and shallow acupuncture group of 37 cases. Under the guidance of ultrasound, the two groups of subjects were acupunctured at bilateral BL54. The deep acupuncture group was acupunctured to the pudendal nerve, and the shallow acupuncture group was acupunctured to the superficial fascia. Ultrasound was used to observe the peak systolic velocity (PSV), time average maximum velocity (TAMX), end diastolic velocity (EDV), pulsation index (PI), resistance index (RI) of the pudendal arteries, and bladder volume of two groups of subjects before and after acupuncture. The anatomical hierarchical structure of bilateral BL54 and score of Chinese version of the Massachusetts General Hospital Acupuncture Sensation Scale (C-MASS) of all subjects was measured. RESULT: After acupuncture, the PSV, TMAX of the pudendal artery, bladder volume, and the Score of C-MASS Scale in the deep acupuncture group were higher than in the shallow acupuncture group (P < 0.05). The RI of the pudendal arteries in the shallow acupuncture group decreased compared to before acupuncture (P < 0.05). CONCLUSION: Acupuncture at the BL54 can increase the blood flow velocity of the pudendal artery, improve the function of the bladder in controlling urine in women, and different depths of acupuncture will have different therapeutic effects.


Assuntos
Terapia por Acupuntura , Bexiga Urinária , Humanos , Feminino , Terapia por Acupuntura/métodos , Bexiga Urinária/diagnóstico por imagem , Adulto , Ultrassonografia de Intervenção , Adulto Jovem , Pessoa de Meia-Idade , Pontos de Acupuntura
4.
Int Urogynecol J ; 35(3): 599-608, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38236284

RESUMO

INTRODUCTION AND HYPOTHESIS: The objective was to observe the clinical efficacy of warm acupuncture combined with Kegel exercise in treating postpartum pelvic floor dysfunction in women. METHODS: A total of 70 primiparous women with postpartum pelvic floor muscle (PFM) injury were randomly divided into a combination group (n = 35, receiving warm acupuncture at Zhibian (BL54) acupoint and Kegel exercise) and a sham control group (n = 35, receiving sham warm acupuncture and Kegel exercise). Both groups were treated three times a week for 4 consecutive weeks. The recovery of PFM strength and changes in Urethral Rotation Angle (URA), Bladder Neck Descent (BND), and Retrovesical Angle (RVA) in pelvic floor ultrasound reports, the scores of pelvic floor dysfunction-related questionnaires, and the efficacy of urinary incontinence treatment of the two groups were compared before and after treatment. RESULTS: After treatment, the recovery rates of type I and II PFM strength, pelvic floor ultrasound parameters, pelvic floor dysfunction-related scale scores, and urinary incontinence treatment efficacy in the combination group were significantly better than those in the sham control group (p < 0.05). CONCLUSION: Warm acupuncture combined with Kegel exercise can significantly improve PFM strength and promote the recovery of postpartum pelvic floor function in women.


Assuntos
Terapia por Acupuntura , Incontinência Urinária , Feminino , Humanos , Diafragma da Pelve , Período Pós-Parto/fisiologia , Terapia por Exercício
5.
Biochem Biophys Res Commun ; 587: 107-112, 2022 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-34871997

RESUMO

It is very important to maintain normal levels of risk avoidance in daily life. We found that DISC1-NTM mice, which are a model for mental disorders, had a phenotype marked by a risk-avoidance impairment as measured in an open-field test (OFT). We used optogenetic methods to modulate glutamatergic neurons in the basolateral amygdala (BLA) in an attempt to rescue this risk-avoidance impairment. We found that photostimulation of BLA neurons at 20 Hz modified DISC1-NTM mouse behavior from low risk avoidance to high risk avoidance. We observed following photostimulation that, compared to controls, the number of entries to the center of the open field was lower and less time was spent in the central area. We also found that the time spent immobile was higher during photostimulation compared with WT mice. We also used a lower photostimulation frequency of 5 Hz, which activated BLA glutamatergic neurons and rescued the risk-avoidance impairment in DISC1-NTM mice. Our findings confirm that the BLA participates in diverse risk-avoidance behavior. Our results are also a reminder that differences in neuronal firing patterns within the same pathway may lead to different physiological functions.


Assuntos
Aprendizagem da Esquiva/fisiologia , Complexo Nuclear Basolateral da Amígdala/metabolismo , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Potenciais de Ação/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/patologia , Feminino , Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/deficiência , Neurônios/patologia , Optogenética/métodos , Técnicas de Patch-Clamp , Estimulação Luminosa/métodos , Assunção de Riscos
6.
Mol Psychiatry ; 26(9): 4719-4741, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32555286

RESUMO

The prevailing view is that parvalbumin (PV) interneurons play modulatory roles in emotional response through local medium spiny projection neurons (MSNs). Here, we show that PV activity within the nucleus accumbens shell (sNAc) is required for producing anxiety-like avoidance when mice are under anxiogenic situations. Firing rates of sNAcPV neurons were negatively correlated to exploration time in open arms (threatening environment). In addition, sNAcPV neurons exhibited high excitability in a chronic stress mouse model, which generated excessive maladaptive avoidance behavior in an anxiogenic context. We also discovered a novel GABAergic pathway from the anterior dorsal bed nuclei of stria terminalis (adBNST) to sNAcPV neurons. Optogenetic activation of these afferent terminals in sNAc produced an anxiolytic effect via GABA transmission. Next, we further demonstrated that chronic stressors attenuated the inhibitory synaptic transmission at adBNSTGABA → sNAcPV synapses, which in turn explains the hyperexcitability of sNAc PV neurons on stressed models. Therefore, activation of these GABAergic afferents in sNAc rescued the excessive avoidance behavior related to an anxious state. Finally, we identified that the majority GABAergic input neurons, which innervate sNAcPV cells, were expressing somatostatin (SOM), and also revealed that coordination between SOM- and PV- cells functioning in the BNST → NAc circuit has an inhibitory influence on anxiety-like responses. Our findings provide a potentially neurobiological basis for therapeutic interventions in pathological anxiety.


Assuntos
Interneurônios , Parvalbuminas , Animais , Ansiedade , Neurônios GABAérgicos , Camundongos , Somatostatina
7.
Int J Mol Sci ; 23(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36293510

RESUMO

Evidence shows that stress can promote the occurrence and development of tumors. In recent years, many studies have shown that stress-related hormones or peripheral neurotransmitters can promote the proliferation, survival, and angiogenesis of tumor cells and impair the body's immune response, causing tumor cells to escape the "surveillance" of the immune system. However, the perception of stress occurs in the central nervous system (CNS) and the role of the central nervous system in tumor progression is still unclear, as are the underlying mechanisms. This review summarizes what is known of stress-related CNS-network activation during the stress response and the influence of the CNS on tumors and discusses available adjuvant treatment methods for cancer patients with negative emotional states, such as anxiety and depression.


Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Sistema Imunitário/patologia , Sistema Nervoso Central/patologia , Hormônios , Neurotransmissores , Sistema Hipotálamo-Hipofisário/patologia , Sistema Hipófise-Suprarrenal/patologia , Estresse Psicológico
8.
Int J Mol Sci ; 24(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36614104

RESUMO

Chronically stressed individuals are reported to overconsume tasty, palatable foods like sucrose to blunt the psychological and physiological impacts of stress. Negative consequences of high-sugar intake on feeding behavior include increased metabolic disease burdens like obesity. However, the neural basis underlying long-term high-sugar intake-induced overeating during stress is not fully understood. To investigate this question, we used the two-bottle sucrose choice paradigm in mice exposed to chronic unpredictable mild stressors (CUMS) that mimic those of daily life stressors. After 21 days of CUMS paralleled by consecutive sucrose drinking, we explored anxiety-like behavior using the elevated plus maze and open field tests. The normal water-drinking stressed mice displayed more anxiety than the sucrose-drinking stressed mice. Although sucrose-drinking displayed anxiolytic effects, the sucrose-drinking mice exhibited binge eating (chow) and a compulsive eating phenotype. The sucrose-drinking mice also showed a significant body-weight gain compared to the water-drinking control mice during stress. We further found that c-Fos expression was significantly increased in the ventral part of the lateral septum (vLS) of the sucrose-treated stressed mice after compulsive eating. Pharmacogenetic activation of the vLS glutamate decarboxylase 2(GAD2) neurons maintained plain chow intake but induced a compulsive eating phenotype in the naïve GAD2-Cre mice when mice feeding was challenged by flash stimulus, mimicking the negative consequences of excessive sucrose drinking during chronic stress. Further, pharmacogenetic activation of the vLSGAD2 neurons aggravated anxiety of the stressed GAD2-Cre mice but did not alter the basal anxiety level of the naïve ones. These findings indicate the GABAergic neurons within the vLS may be a potential intervention target for anxiety comorbid eating disorders during stress.


Assuntos
Dependência de Alimentos , Açúcares , Camundongos , Animais , Açúcares/farmacologia , Ansiedade/metabolismo , Sacarose/efeitos adversos , Bebidas , Neurônios , Fenótipo , Estresse Psicológico/metabolismo , Ingestão de Alimentos
9.
Nat Chem Biol ; 15(6): 615-622, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31101915

RESUMO

A uracil DNA glycosylase (UDG) from Mycobacterium smegmatis (MsmUdgX) shares sequence similarity with family 4 UDGs and forms exceedingly stable complexes with single-stranded uracil-containing DNAs (ssDNA-Us) that are resistant to denaturants. However, MsmUdgX has been reported to be inactive in excising uracil from ssDNA-Us and the underlying structural basis is unclear. Here, we report high-resolution crystal structures of MsmUdgX in the free, uracil- and DNA-bound forms, respectively. The structural information, supported by mutational and biochemical analyses, indicates that the conserved residue His109 located on a characteristic loop forms an irreversible covalent linkage with the deoxyribose at the apyrimidinic site of ssDNA-U, thus rendering the enzyme unable to regenerate. By proposing the catalytic pathway and molecular mechanism for MsmUdgX, our studies provide an insight into family 4 UDGs and UDGs in general.


Assuntos
Mycobacterium smegmatis/enzimologia , Uracila-DNA Glicosidase/metabolismo , Biocatálise , Morte Celular , Modelos Moleculares , Conformação Proteica , Uracila-DNA Glicosidase/química , Uracila-DNA Glicosidase/genética
10.
Biochem Biophys Res Commun ; 533(4): 657-664, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33019977

RESUMO

Chronic exposure to stressors can disrupt normal brain function and induce anxiety-like behavior and neurobiological alterations in the basolateral amygdala (BLA). Here, we showed that unpredictable chronic mild stress (UCMS) induced anxiety-like behavior, lowered glutamatergic neuronal activity and reactive astrocytes in the BLA. Using optogenetic tools, we found that activation of BLA glutamatergic neurons did not rescue anxiety-like behavior in stressed mice. In contrast, however, optogenetic activation of the BLA astrocytes relieved stress-induced anxiety, and, interestingly, chronic optogenetic manipulation fully restored the UCMS-induced behavioral and neurobiological dysfunctions, including anxiety-like behavior, lower c-Fos expression in the BLA, S100 overexpression in the BLA, and higher serum corticosterone concentration. Thus, our findings suggest that chronic manipulation of BLA astrocytes is a potential therapeutic intervention target for pathological anxiety.


Assuntos
Ansiedade/fisiopatologia , Astrócitos/efeitos da radiação , Complexo Nuclear Basolateral da Amígdala/efeitos da radiação , Neurônios/fisiologia , Optogenética/métodos , Estresse Psicológico/fisiopatologia , Animais , Astrócitos/metabolismo , Complexo Nuclear Basolateral da Amígdala/citologia , Complexo Nuclear Basolateral da Amígdala/metabolismo , Complexo Nuclear Basolateral da Amígdala/patologia , Corticosterona/sangue , Camundongos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas S100/metabolismo
11.
J Clin Ultrasound ; 48(9): 522-526, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32757278

RESUMO

PURPOSE: The aim of this study was to evaluate the applicability of bedside ultrasonography for the diagnosis of deep venous thrombosis (DVT) in patients infected with corona virus disease 2019 (COVID-19) with and without treatment with low molecular weight heparin (LMWH). METHODS: We retrospectively analyzed the records of deceased and surviving patients in whom ultrasonography detected or not a DVT, and in whom LMWH was or not prescribed. RESULTS: The incidence of DVT is higher in the deceased (33/35) than in the surviving (22/46) patients. LMWH was administered in a larger proportion of surviving (18/22) than of deceased (18/33) patients. D-dimer concentrations decreased in patients who received LMWH in both groups. CONCLUSIONS: There was a high incidence of DVT in patients who succumbed to COVID-19. Bedside ultrasonography can detect the presence of DVT as early as possible and help assessing the risk of venous thromboembolism, allowing early and reasonable use of LMWH.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/patologia , Heparina de Baixo Peso Molecular/administração & dosagem , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/patologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/virologia , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Betacoronavirus/isolamento & purificação , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Esquema de Medicação , Feminino , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Testes Imediatos , Estudos Retrospectivos , SARS-CoV-2 , Ultrassonografia/métodos , Trombose Venosa/tratamento farmacológico
12.
Bioorg Med Chem ; 27(5): 832-840, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30711309

RESUMO

Cryptococcus neoformans is the leading cause of cryptococcal meningitis, which is associated with high mortality due to lack of effective treatment. Herein a series of tricyclic isoxazole derivatives with excellent anti-cryptococcal activities were identified by structural simplification and scaffold hopping of antifungal natural product sampangine. Particularly, compound 8a showed promising features as an anti-cryptococcal lead compound. It was highly active against C. neoformans (MIC80 = 0.031 µg/mL), which was more potent than fluconazole and voriconazole. Moreover, compound 8a showed potent fungicidal activity and had potent inhibitory effects against important virulence factors (i.e. biofilm, melanin and urease) of C. neoformans. Preliminary antifungal mechanism investigation revealed that compound 8a induced apoptosis of C. neoformans cells and arrested the cell cycle at the G1/S phase.


Assuntos
Alcaloides/farmacologia , Antifúngicos/farmacologia , Cryptococcus neoformans/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Isoxazóis/farmacologia , Naftiridinas/farmacologia , Alcaloides/síntese química , Alcaloides/química , Antifúngicos/síntese química , Antifúngicos/química , Apoptose/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Descoberta de Drogas , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Isoxazóis/síntese química , Isoxazóis/química , Melaninas/antagonistas & inibidores , Testes de Sensibilidade Microbiana , Estrutura Molecular , Naftiridinas/síntese química , Naftiridinas/química , Relação Estrutura-Atividade , Urease/antagonistas & inibidores
13.
Biochem Biophys Res Commun ; 486(3): 804-810, 2017 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-28351618

RESUMO

Tuberculosis (TB) is a severe disease caused by Mycobacterium tuberculosis (M. tb) and the well-characterized M. tb MazE/F proteins play important roles in stress adaptation. Recently, the MazF-mt9 toxin has been found to display endonuclease activities towards tRNAs but the mechanism is unknown. We hereby present the crystal structure of apo-MazF-mt9. The enzyme recognizes tRNALys with a central UUU motif within the anticodon loop, but is insensitive to the sequence context outside of the loop. Based on our crystallographic and biochemical studies, we identified key residues for catalysis and proposed the potential tRNA-binding site.


Assuntos
Anticódon/química , Apoproteínas/química , Proteínas de Bactérias/química , Toxinas Bacterianas/química , Endorribonucleases/química , Mycobacterium tuberculosis/química , RNA de Transferência de Lisina/química , Sequência de Aminoácidos , Apoproteínas/genética , Apoproteínas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Sequência de Bases , Sítios de Ligação , Clonagem Molecular , Endorribonucleases/genética , Endorribonucleases/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Modelos Moleculares , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/patogenicidade , Conformação de Ácido Nucleico , Ligação Proteica , Domínios Proteicos , Estrutura Secundária de Proteína , RNA de Transferência de Lisina/genética , RNA de Transferência de Lisina/metabolismo , Proteínas Recombinantes , Alinhamento de Sequência , Homologia Estrutural de Proteína , Relação Estrutura-Atividade
14.
BMC Cancer ; 17(1): 360, 2017 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28532481

RESUMO

BACKGROUND: Endonuclease domain containing 1 (ENDOD1) is implicated in tumorigenesis and aggressiveness of multiple tumors. In this study, we aimed to investigate the role of ENDOD1 in prostate cancer (PCa). METHODS: Immunohistochemistry were performed in 30 cases of benign prostatic hyperplasia (BPH) and 50 cases of PCa to identify its association with clinicopathological characteristics. Real-time PCR and western blot were used to detect ENDOD1 mRNA and protein expression in normal prostatic epithelial and PCa cell lines. MTT assays were employed to determine the effect of cell proliferation. Flow cytometry was used to explore the cell cycle distribution and apoptotic effects. Transwell migration and invasion assays were done to evaluate changes in the ability of cell migration and invasion. RESULTS: Immunoreactivity scores of ENDOD1 showed no statistical difference between BPH and low-grade PCa, whereas lower immunostaining scores were observed in high-grade compared with low-grade PCa. Real-time PCR data indicated that ENDOD1 mRNA expression was markedly increased in LNCaP and 22Rv1 cells and decreased in PC3 and DU145 cells compared to the normal epithelial cells RWPE1. Western blot showed that androgen-sensitive LNCaP cells had the highest protein expression level of ENDOD1, whereas castration-resistant PCa cell lines PC3 and DU145 had significantly lower protein levels. Meanwhile, overexpression of ENDOD1 suppressed cell proliferation, induced G0/G1 cell cycle arrest and inhibited cell migration and invasion. Conversely, siRNA-mediated silencing of ENDOD1 promoted cell proliferation, migration and invasion. No apoptotic effects occurred upon manipulation of ENDOD1 expression. CONCLUSION: Our results indicate that ENDOD1 is a novel tumor suppressor in PCa, which may be employed as a new drug target of preventing progression to metastatic castration-resistant prostate cancer.


Assuntos
Endonucleases/genética , Neoplasias da Próstata/metabolismo , Idoso , Apoptose , Estudos de Casos e Controles , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Endonucleases/metabolismo , Expressão Gênica , Genes Supressores de Tumor , Humanos , Masculino , Gradação de Tumores , Invasividade Neoplásica , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
15.
Biomed Environ Sci ; 30(9): 623-631, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29081336

RESUMO

OBJECTIVE: In the present study, we investigated the antioxidant and anti-aging effects of Silybum marianum protein hydrolysate (SMPH) in D-galactose-treated mice. METHODS: D-galactose (500 mg/kg body weight) was intraperitoneally injected daily for 7 weeks to accelerate aging, and SMPH (400, 800, 1,200 mg/kg body weight, respectively) was simultaneously administered orally. The antioxidant and anti-aging effects of SMPH in the liver and brain were measured by biochemical assays. Transmission electron microscopy (TEM) was performed to study the ultrastructure of liver mitochondri. RESULTS: SMPH decreased triglyceride and cholesterol levels in the D-galactose-treated mice. It significantly elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC), which were suppressed by D-galactose. Monoamine oxidase (MAO) and malondialdehyde (MDA) levels as well as the concentrations of caspase-3 and 8-OHdG in the liver and brain were significantly reduced by SMPH. Moreover, it increased Bcl-2 levels in the liver and brain. Furthermore, SMPH significantly attenuated D-galactose-induced liver mitochondrial dysfunction by improving the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase as well as mitochondrial membrane potential (ΔΨm) and fluidity. TEM showed that the degree of liver mitochondrial damage was significantly decreased by SMPH. CONCLUSION: The results indicated that SMPH protects against D-galactose-induced accelerated aging in mice through its antioxidant and anti-aging activities.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Galactose/toxicidade , Proteínas de Plantas/farmacologia , Hidrolisados de Proteína/farmacologia , Silybum marianum/química , Animais , Encéfalo/efeitos dos fármacos , Caspase 3/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Mitocôndrias Hepáticas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Plantas/química , Substâncias Protetoras/farmacologia , Hidrolisados de Proteína/química , Superóxido Dismutase/metabolismo
16.
Fish Shellfish Immunol ; 49: 16-23, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26706223

RESUMO

The adenine nucleotide translocases (ANTs) play a vital role in energy metabolism via ADP/ATP exchange in eukaryotic cells. Apostichopus japonicus (Echinodermata: Holothuroidea) is an important economic species in China. Here, a cDNA representing an ANT gene of A. japonicus was isolated and characterized from respiratory tree and named AjANT. The full-length AjANT cDNA is 1924 bp, including a 5'-untranslated region (UTR) of 38 bp, 3'-UTR of 980 bp and an open reading frame (ORF) of 906 bp encoding a polypeptide of 301 amino acids. The protein contains three homologous repeat Mito_carr domains (Pfam00153). The deduced AjANT protein sequence has 49-81% in comparison to ANT proteins from other individuals. The predicted tertiary structure of AjANT protein is highly similar to animal ANT proteins. Phylogenetic analysis showed that the AjANT is closely related to Holothuroidea ANT genes. Real-time quantitative reverse transcription-PCR (qPCR) analysis showed that AjANT expression is higher in the respiratory tree than in other examined tissues. After thermal stress or LPS challenge, expression of AjANT was significantly fluctuant compared to the control. These results suggested that changes in the expression of ANT gene might be involved in immune defense and in protecting A. japonicus against thermal stress.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Temperatura Alta , Imunidade Inata/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Translocases Mitocondriais de ADP e ATP/genética , Stichopus/genética , Stichopus/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Perfilação da Expressão Gênica , Translocases Mitocondriais de ADP e ATP/química , Translocases Mitocondriais de ADP e ATP/metabolismo , Dados de Sequência Molecular , Filogenia , Estrutura Terciária de Proteína , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Stichopus/metabolismo , Distribuição Tecidual
17.
Glia ; 62(1): 106-21, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24272706

RESUMO

Astrocytes are key components of the central nervous system (CNS) and release factors to support neural stem cell proliferation, differentiation, and migration. Adenosine 5'-triphosphate (ATP) is one of the key factors released upon activation of astrocytes that regulates the neural stem cell's function. However, it is not clear whether ATP derived from the depolarized astrocytes plays a vital role in promoting the neuronal differentiation of mesenchymal stem cells (MSCs) in vitro and in vivo. Herein, for the first time, we co-cultured MSCs with light-stimulated-channelrhodopsin-2 (ChR2)-astrocytes, and observed that the neuronal differentiation of MSCs was enhanced by expressing more neuronal markers, Tuj1 and NeuN. The ChR2-astrocyte-conditioned medium also stimulated MSCs differentiating into neuronal lineage cells by expressing more Tuj1 and Pax6, which was blocked by the P2X receptor antagonist, TNP-ATP. Then we found that light-depolarization of astrocytes significantly increased ATP accumulation in their bathing medium without impairing the cell membrane. We further found that ATP up-regulated the Tuj1, Pax6, FZD8 and ß-catenin mRNA levels of MSCs, which could be reversed by application of TNP-ATP. Together these in vitro data provided convergent evidence that ATP from light-depolarized-astrocytes activated the wnt/ß-catenin signaling of MSCs through binding to the P2X receptors, and promoted the neuronal differentiation of MSCs. Finally but importantly, our study also demonstrated in stroke rats that light-controlled astrocytes stimulated endogenous ATP release into the ischemic area to influence the transplanted MSCs, resulting in promoting the MSCs towards neuronal differentiation and improvements of neurological deficit.


Assuntos
Astrócitos/fisiologia , Diferenciação Celular , Terapia Baseada em Transplante de Células e Tecidos , Células-Tronco Mesenquimais/citologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Animais , Animais Recém-Nascidos , Proliferação de Células , Células Cultivadas , Channelrhodopsins , Corpo Estriado/citologia , Modelos Animais de Doenças , Humanos , Masculino , Células-Tronco Mesenquimais/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução Genética
18.
J Med Chem ; 67(6): 4726-4738, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38489247

RESUMO

Cryptococcus neoformans (C. neoformans) and Candida albicans (C. albicans) are classified as the critical priority groups among the pathogenic fungi, highlighting the urgent need for developing more effective antifungal therapies. On the basis of antifungal natural product sampangine, herein, a series of tricyclic oxime and oxime ether derivatives were designed. Among them, compound WZ-2 showed excellent inhibitory activity against C. neoformans (MIC80 = 0.016 µg/mL) and synergized with fluconazole to treat resistant C. albicans (FICI = 0.078). Interestingly, compound WZ-2 effectively inhibited virulence factors (e.g., capsule, biofilm, and yeast-to-hypha morphological transition), suggesting the potential to overcome drug resistance. In a mouse model of cryptococcal meningitis, compound WZ-2 (5 mg/kg) effectively reduced the brain C. neoformans H99 burden. Furthermore, compound WZ-2 alone and its combination with fluconazole also significantly reduced the kidney burden of the drug-resistant strain (0304103) and sensitive strain (SC5314) of C. albicans.


Assuntos
Alcaloides , Candidíase , Criptococose , Cryptococcus neoformans , Compostos Heterocíclicos de 4 ou mais Anéis , Naftiridinas , Animais , Camundongos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Candidíase/tratamento farmacológico , Candida albicans , Testes de Sensibilidade Microbiana
19.
Sci Total Environ ; 954: 176215, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276998

RESUMO

The deleterious health impacts of polycyclic aromatic hydrocarbons (PAHs) on the population have been extensively substantiated and acknowledged. Mounting evidence underscores that PAH exposure is closely linked to an elevated risk of mental disorders, particularly in populations experiencing occupational and high-level exposure. In this study, we aimed to investigate the mechanisms underlying anxiety-like behaviors induced by different dosages of PAHs, with a concentrated focus on brain region-specific metabolic alterations in mice using various metabolomics approaches. Male C57BL/6 mice were exposed to benzo[a]pyrene (B[a]P), a typical PAH, through gavage at occupational exposure and EPA toxicologically relevant dosages (2.0 and 20.0 mg/kg/day) for 21 days, respectively. Behavioral assessments revealed that occupational exposure to B[a]P induced anxiety-like behaviors in C57BL/6 mice. Meanwhile, elevated serum norepinephrine and corticotropin-releasing hormone further confirmed the anxiety-inducing effects of B[a]P exposure. Metabolomics analysis uncovered dysregulation across various metabolic pathways following B[a]P exposure, encompassing brain neurotransmitter, organic acid, amino acid, lipid, fatty acid, and cholesterol. Anxiety levels and lipid metabolic abnormalities were notably exacerbated at the higher dosage, despite being only a 10-fold increase. Of particular significance, a decrease in lysophosphatidic acid (LPA) and lysophosphatidylserine (LPS) emerged as pivotal indicators of B[a]P neurotoxicity. Spatial-resolved metabolomics further demonstrated distinctive lipid and metabolite profiles across different brain subregions after exposure to B[a]P. Remarkably, alterations were specifically observed in the anxiety-related brain regions, such as the hippocampus, cortex, white matter, and thalamus, varying with exposure dosages. These findings underscore the significance of brain metabolic abnormalities in the development of mental disorders triggered by B[a]P exposure and highlight the need for establishing precise exposure limits of B[a]P to safeguard public mental health.

20.
Nanomaterials (Basel) ; 14(17)2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39269118

RESUMO

Strontium aluminate, with suitable lattice parameters and environmentally friendly water solubility, has been strongly sought for use as a sacrificial layer in the preparation of freestanding perovskite oxide thin films in recent years. However, due to this material's inherent water solubility, the methods used for the preparation of epitaxial films have mainly been limited to high-vacuum techniques, which greatly limits these films' development. In this study, we prepared freestanding single-crystal perovskite oxide thin films on strontium aluminate using a simple, easy-to-develop, and low-cost chemical full-solution deposition technique. We demonstrate that a reasonable choice of solvent molecules can effectively reduce the damage to the strontium aluminate layer, allowing successful epitaxy of perovskite oxide thin films, such as 2-methoxyethanol and acetic acid. Molecular dynamics simulations further demonstrated that this is because of their stronger adsorption capacity on the strontium aluminate surface, which enables them to form an effective protective layer to inhibit the hydration reaction of strontium aluminate. Moreover, the freestanding film can still maintain stable ferroelectricity after release from the substrate, which provides an idea for the development of single-crystal perovskite oxide films and creates an opportunity for their development in the field of flexible electronic devices.

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