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1.
Medicine (Baltimore) ; 100(31): e26757, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397819

RESUMO

ABSTRACT: The role of cognitive, social and biological factors in the etiology of chronic periodontitis has been reported.The aim of this study was to evaluate the salivary cortisol level and interleukin-1 B level in patients of Chronic periodontitis in smokers and stress and nonsmokers without stress.The design of study randomized, prospective, double-blinded, and prospective study.The total sample size was comprised of 600 subjects between the ages of 20 and 50 years. The sample size was divided into 300 males and 300 females. Out of 600 subjects, 200 subjects comprised of subjects with chronic periodontitis with positive depression level with a history of smoking (Group I), 200 subjects comprised of subjects with chronic periodontitis without depression and without smoking (Group II), and 200 subjects who were taken as the control group comprised of healthy subjects without chronic periodontitis, without depression level, and no smoking history (Group III). Salivary cortisol levels were determined by enzyme-linked immunosorbent assay (ELISA).The result showed that there was a positive correlation between morning and evening salivary cortisol level in all the groups with correlation coefficient. There was significant higher value of salivary cortisol in Group I patients when compared with Group II and Group III. However, when the comparison of salivary cortisol levels was done between the Group II and Control group, the result showed nonsignificant P value.It is suggested that stress is positively correlated with the salivary cortisol levels in smokers and nonsmokers.


Assuntos
Periodontite Crônica/sangue , Hidrocortisona/análise , Interleucina-1beta/análise , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Periodontite Crônica/diagnóstico , Periodontite Crônica/epidemiologia , Feminino , Voluntários Saudáveis , Humanos , Hidrocortisona/sangue , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Saliva/enzimologia , Fumar/efeitos adversos , Fumar/epidemiologia , Fumar/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia
2.
Cancer Commun (Lond) ; 41(8): 726-746, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34268906

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most malignant tumors with high incidence, yet its molecular mechanism is not fully understood, hindering the development of targeted therapy. Metabolic abnormalities are a hallmark of cancer. Targeting dysregulated metabolic features has become an important direction for modern anticancer therapy. In this study, we aimed to identify a new metabolic enzyme that promotes proliferation of CRC and to examine the related molecular mechanisms. METHODS: We performed RNA sequencing and tissue microarray analyses of human CRC samples to identify new genes involved in CRC. Squalene epoxidase (SQLE) was identified to be highly upregulated in CRC patients. The regulatory function of SQLE in CRC progression and the therapeutic effect of SQLE inhibitors were determined by measuring CRC cell viability, colony and organoid formation, intracellular cholesterol concentration and xenograft tumor growth. The molecular mechanism of SQLE function was explored by combining transcriptome and untargeted metabolomics analysis. Western blotting and real-time PCR were used to assess MAPK signaling activation by SQLE. RESULTS: SQLE-related control of cholesterol biosynthesis was highly upregulated in CRC patients and associated with poor prognosis. SQLE promoted CRC growth in vitro and in vivo. Inhibition of SQLE reduced the levels of calcitriol (active form of vitamin D3) and CYP24A1, followed by an increase in intracellular Ca2+ concentration. Subsequently, MAPK signaling was suppressed, resulting in the inhibition of CRC cell growth. Consistently, terbinafine, an SQLE inhibitor, suppressed CRC cell proliferation and organoid and xenograft tumor growth. CONCLUSIONS: Our findings demonstrate that SQLE promotes CRC through the accumulation of calcitriol and stimulation of CYP24A1-mediated MAPK signaling, highlighting SQLE as a potential therapeutic target for CRC treatment.

3.
Mol Immunol ; 134: 202-209, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33813201

RESUMO

Accruing research shows the implications of long non-coding RNAs (lncRNAs) in the progression of various autoimmune diseases including systemic lupus erythematosus (SLE). The present study aimed to identify the expression pattern of LINC00176 in SLE and to explore its effects on CD4+T cell adhesion in this context. The biological functions of LINC00176, WIF1 and WNT5a on CD4+T cells in SLE were evaluated via gain- and loss-of-function experiments, following delivery of pcDNA3-LINC00176, siRNA-LINC00176, pcDNA3-WIF1 and WNT-sFRP5 (an inhibitor for the WNT5a signaling pathway). High LINC00176 expression was evident in the CD4+T cells of SLE patients. Additionally, WIF1 was identified as a potential target gene of LINC00176, and was negatively regulated by LINC00176. The overexpression of LINC00176 could promote proliferation and adhesion of CD4+T cells in SLE. Such alternations were reversed following up-regulation of WIF1 or inhibition of the WNT5a signaling pathway. Taken together, the key findings of our study highlight the ability of LINC00176 to potentially promote the proliferation and adhesion of CD4+T cells in SLE by down-regulating WIF1 and activating the WNT5a signaling pathway, providing new insight and a theoretical basis for translation in SLE therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Linfócitos T CD4-Positivos/imunologia , Regulação da Expressão Gênica/fisiologia , Lúpus Eritematoso Sistêmico/imunologia , RNA Longo não Codificante/imunologia , Proteína Wnt-5a/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Linfócitos T CD4-Positivos/metabolismo , Adesão Celular/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , RNA Longo não Codificante/metabolismo , Transdução de Sinais/fisiologia , Proteína Wnt-5a/metabolismo , Adulto Jovem
4.
Chem Commun (Camb) ; 56(83): 12546-12549, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32940282

RESUMO

Herein, we disclose the first set of unique selenium-containing SLAP (SiLicon Amine Protocol) reagents for the direct synthesis of C3/C5-substituted selenomorpholines and 1,4-selenazepanes from diverse (hetero)aldehydes under mild photocatalytic conditions. Enantiomerically pure 1,2-amino alcohol/α-amino acid versions of these heterocycles were also synthesized. Further, we have shown the late-stage modification of certain biologically active agents using the developed seleno-SLAP reagents.

5.
Mol Ther Nucleic Acids ; 21: 983-990, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32818922

RESUMO

Subarachnoid hemorrhage (SAH) patients' surgery is performed to prevent extravasation of blood into the subarachnoid space. Cerebral vasospasm (CVS; narrowing of cerebral arteries) occurs following SAH and represents a major cause of associated mortality and morbidity. To improve postsurgery care of SAH patients and their prognosis, the ability to predict CVS onset is critical. We report a long noncoding RNA (lncRNA) signature to distinguish SAH patients with CVS from SAH patients without CVS. Cerebrospinal fluid (CSF) was obtained from SAH patients without CVS (n = 10) and SAH patients with CVS (n = 10). lncRNAs ZFAS1 and MALAT1 were significantly upregulated (p < 0.05), whereas lncRNAs LINC00261 and LINC01619 were significantly downregulated in SAH patients with CVS (p < 0.05) compared to SAH patients without CVS. We applied this lncRNA signature to retrospectively predict CVS in SAH patients (n = 38 for SAH patients without CVS, and n = 27 for SAH patients with CVS). The 4-lncRNA signature was found to be predictive in >40% of samples and the 2-lncRNA comprising MALAT1 and LINC01619 accurately predicted CVS in ∼90% cases. These results are initial steps toward personalized management of SAH patients in clinics and provide novel CSF biomarkers that can substantially improve the clinical management of SAH patients.

6.
Crit Rev Food Sci Nutr ; 59(12): 1976-1985, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29727198

RESUMO

Effectiveness of using visual approaches in health education and its influential factors were still in debate. This study aimed to asess the effects of visualized nutrition education on dietary knowledge and behavioral changes, and factors influencing them. A comprehensive search of PubMed, EMBASE, Scopus, and Cochrane Library was conducted. Eligible studies were trials assessed effects of visualized nutrition education on dietary knowledge or behavior changes, compared with non-visualized or no education group. Fourteen studies (n = 7,259) were qualitatively analyzed and 7 of them were included in the meta-analysis. We found a higher fiber intake in both short term (1.59 g/1000 kcals, 95% CI 0.90-2.27) and long term (1.36 g/1000 kcals, 95% CI 0.64-2.09). A marginal advantage was shown in short-term fruits and vegetables consumption (F&V consumption) (standardized mean difference [SMD] = 0.08, 95% CI -0.00 to 0.16). The education effects were more pronounced when education was delivered in series (SMDF&V consumption = 0.09, 95% CI 0.00-0.17), avoiding loss-framing (SMDFat intake = 0.31, 95% CI 0.10-0.51) and video modeling (SMDF&V consumption = 0.23, 95% CI 0.03-0.43), with short length plus cultural adaptation. Visualized nutrition education was overall promising in improving dietary behaviors. Delivering in series, short in length, with cultural adaptation were features tended to enlarge the benefits of visualized education while loss-framing and video modeling might be avoided.


Assuntos
Dieta , Comportamento Alimentar , Educação em Saúde , Terapia Nutricional , Bases de Dados Factuais , Dieta Saudável , Frutas , Humanos , Fatores de Risco , Verduras
8.
J Mol Cell Biol ; 10(5): 437-447, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29432547

RESUMO

The Hedgehog (Hh) signaling pathway plays important roles in both embryonic development and adult tissue homeostasis. Such biological functions are mediated by the transcription factor Cubitus interruptus (Ci). Yet the transcriptional regulation of the effector Ci itself is poorly investigated. Through an RNAi-based genetic screen, we identified that female sterile (1) homeotic (Fsh), a transcription co-activator, directly activates Ci transcription. Biochemistry assays demonstrated physical interactions among Fsh, Sex combs extra (Sce), and Polycomb (Pc). Functional assays further showed that both Pc and Sce are required for Ci expression, which is not likely mediated by the derepression of Engrailed (En), a repressor of Ci, in Pc or Sce mutant cells. Finally, we provide evidence showing that Pc/Sce facilitates the binding of Fsh at Ci locus and that the physical interaction between Fsh and Pc is essential for Fsh-mediated Ci transcription. Taken together, we not only uncover that Ci is transcriptionally regulated by Fsh-Pc-Sce complex but also provide evidence for the coordination between Fsh and PcG proteins in transcriptional regulation.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Animais , Animais Geneticamente Modificados , Proteínas de Ligação a DNA/metabolismo , Drosophila melanogaster/genética , Epigênese Genética , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Mutação , Complexo Repressor Polycomb 1/genética , Transcrição Genética , Asas de Animais/crescimento & desenvolvimento
9.
EMBO Rep ; 18(11): 1922-1934, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28887318

RESUMO

The Hh pathway controls many morphogenetic processes in metazoans and plays important roles in numerous pathologies and in cancer. Hh signaling is mediated by the activity of the Gli/Ci family of transcription factors. Several studies in Drosophila have shown that ubiquitination by the ubiquitin E3 ligases Slimb and Rdx(Hib) plays a crucial role in controlling Ci stability dependent on the levels of Hh signals. If Hh levels are low, Slimb adds K11- and K48-linked poly-ubiquitin chains on Ci resulting in partial degradation. Ubiquitin E2 enzymes are pivotal in determining the topologies of ubiquitin chains. However, which E2 enzymes participate in the selective ubiquitination-degradation of Ci remains elusive. Here, we find that the E2 enzyme UbcD1 negatively regulates Hh signaling activity in Drosophila wing disks. Genetic and biochemical analyses in wing disks and in cultured cells reveal that UbcD1 directly controls Ci stability. Interestingly, UbcD1 is found to be selectively involved in Slimb-mediated Ci degradation. Finally, we show that the homologs of UbcD1 play a conserved role in modulating Hh signaling in vertebrates.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Hedgehog/genética , Processamento de Proteína Pós-Traducional , Enzimas de Conjugação de Ubiquitina/genética , Peixe-Zebra/genética , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Sequência Conservada , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Embrião não Mamífero , Proteínas Hedgehog/metabolismo , Discos Imaginais/crescimento & desenvolvimento , Discos Imaginais/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Receptor Patched-2/genética , Receptor Patched-2/metabolismo , Poliubiquitina/genética , Poliubiquitina/metabolismo , Estabilidade Proteica , Proteólise , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
10.
Sci Rep ; 7(1): 5101, 2017 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-28698559

RESUMO

Hox genes play a fundamental role in regulating animal development. However, less is known about their functions on homeostasis maintenance in adult stem cells. Here, we report that the repression of an important axial Hox gene, Abdominal-B (Abd-B), in cyst stem cells (CySCs) is essential for the homeostasis and cell identity maintenance in the adult Drosophila testis. Derepression of Abd-B in CySCs disrupts the proper self-renewal of both germline stem cells (GSCs) and CySCs, and leads to an excessive expansion of early stage somatic cells, which originate from both lineages. We further demonstrate that canonical Polycomb (Pc) and functional pathway of Polycomb group (PcG) proteins are responsible for maintaining the germline cell identity non-autonomously via repressing Abd-B in CySCs in the adult Drosophila testis.


Assuntos
Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila/citologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Testículo/citologia , Animais , Linhagem da Célula , Células Cultivadas , Drosophila/genética , Drosophila/metabolismo , Histonas/metabolismo , Masculino , Complexo Repressor Polycomb 1/genética , Proteínas do Grupo Polycomb/metabolismo , Espermatozoides/citologia , Espermatozoides/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Testículo/metabolismo
11.
Oxid Med Cell Longev ; 2017: 3172692, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28698767

RESUMO

Activation of nuclear factor erythroid 2-related factor 2 (NRF2) has been found to ameliorate diabetic testicular damage (DTD) in rodents. However, it was unclear whether NRF2 is required for these approaches in DTD. Epigallocatechin gallate (EGCG) is a potent activator of NRF2 and has shown beneficial effects on multiple diabetic complications. However, the effect of EGCG has not been studied in DTD. The present study aims to explore the role of NRF2 in both self and EGCG protection against DTD. Therefore, streptozotocin-induced diabetic C57BL/6 wild type (WT) and Nrf2 knockout (KO) mice were treated in the presence or absence of EGCG, for 24 weeks. The Nrf2 KO mice exhibited more significant diabetes-induced loss in testicular weight and spermatozoa count, and increase in testicular apoptotic cell death, as compared with the WT mice. EGCG activated NRF2 expression and function, preserved testicular weight and spermatozoa count, and attenuated testicular apoptotic cell death, endoplasmic reticulum stress, inflammation, and oxidative damage in the WT diabetic mice, but not the Nrf2 KO diabetic mice. The present study demonstrated for the first time that NRF2 plays a critical role in both self and EGCG protection against DTD.


Assuntos
Catequina/análogos & derivados , Fator 2 Relacionado a NF-E2/metabolismo , Testículo/metabolismo , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Catequina/uso terapêutico , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Experimental , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio , Testículo/efeitos dos fármacos
13.
Cell Res ; 26(5): 529-42, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27002220

RESUMO

The highly conserved polycomb group (PcG) proteins maintain heritable transcription repression of the genes essential for development from fly to mammals. However, sporadic reports imply a potential role of PcGs in positive regulation of gene transcription, although systematic investigation of such function and the underlying mechanism has rarely been reported. Here, we report a Pc-mediated, H3K27me3-dependent positive transcriptional regulation of Senseless (Sens), a key transcription factor required for development. Mechanistic studies show that Pc regulates Sens expression by promoting H4K20me1 at the Sens locus. Further bioinformatic analysis at genome-wide level indicates that the existence of H4K20me1 acts as a selective mark for positive transcriptional regulation by Pc/H3K27me3. Both the intensities and specific patterns of Pc and H3K27me3 are important for the fates of target gene transcription. Moreover, binding of transcription factor Broad (Br), which physically interacts with Pc and positively regulates the transcription of Sens, is observed in Pc(+)H3K27me3(+)H4K20me1(+) genes, but not in Pc(+)H3K27me3(+)H4K20me1(-) genes. Taken together, our study reveals that, coupling with the transcription factor Br, Pc positively regulates transcription of Pc(+)H3K27me3(+)H4K20me1(+) genes in developing Drosophila wing disc.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Histonas/metabolismo , Lisina/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Animais , Sequência de Bases , Biomarcadores/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Metilação , Proteínas Nucleares/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/genética , Transcrição Genética , Asas de Animais/metabolismo
14.
Development ; 143(10): 1655-62, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-27013244

RESUMO

SUMO (Small ubiquitin-related modifier) modification (SUMOylation) is a highly dynamic post-translational modification (PTM) that plays important roles in tissue development and disease progression. However, its function in adult stem cell maintenance is largely unknown. Here, we report the function of SUMOylation in somatic cyst stem cell (CySC) self-renewal in adult Drosophila testis. The SUMO pathway cell-autonomously regulates CySC maintenance. Reduction of SUMOylation promotes premature differentiation of CySCs and impedes the proliferation of CySCs, which leads to a reduction in the number of CySCs. Consistent with this, CySC clones carrying a mutation of the SUMO-conjugating enzyme are rapidly lost. Furthermore, inhibition of the SUMO pathway phenocopies disruption of the Hedgehog (Hh) pathway, and can block the proliferation of CySCs induced by Hh activation. Importantly, the SUMO pathway directly regulates the SUMOylation of Hh pathway transcription factor Cubitus interruptus (Ci), which is required for promoting CySC proliferation. Thus, we conclude that SUMO directly targets the Hh pathway and regulates CySC maintenance in adult Drosophila testis.


Assuntos
Envelhecimento/fisiologia , Proteínas de Drosophila/metabolismo , Proteínas Hedgehog/metabolismo , Transdução de Sinais , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Testículo/citologia , Animais , Diferenciação Celular , Proliferação de Células , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Epistasia Genética , Masculino , Sumoilação , Testículo/metabolismo
15.
Development ; 143(3): 530-9, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26718004

RESUMO

In eukaryotes, aberrant expression of transposable elements (TEs) is detrimental to the host genome. Piwi-interacting RNAs (piRNAs) of ∼23 to 30 nucleotides bound to PIWI clade Argonaute proteins silence transposons in a manner that is strictly dependent on their sequence complementarity. Hence, a key goal in understanding piRNA pathways is to determine mechanisms that modulate piRNA sequences. Here, we identify a protein-protein interaction between the 3'-to-5' exoribonuclease Nibbler (Nbr) and Piwi that links Nbr activity with piRNA pathways. We show that there is a delicate balance in the interplay between Nbr and Hen1, a methyltransferase involved in 2'-O-methylation at the 3' terminal nucleotides of piRNAs, thus connecting two genes with opposing activities in the biogenesis of piRNA 3' ends. With age, piRNAs become shorter and fewer in number, which is coupled with the derepression of select TEs. We demonstrate that activities of Nbr and Hen1 inherently contribute to TE silencing and age-dependent profiles of piRNAs. We propose that antagonistic roles of Nbr and Hen1 define a mechanism to modulate piRNA 3' ends.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Exorribonucleases/metabolismo , Metiltransferases/metabolismo , RNA Interferente Pequeno/metabolismo , Envelhecimento/genética , Alelos , Animais , Sequência de Bases , Elementos de DNA Transponíveis/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Inativação Gênica , Genoma de Inseto , Células Germinativas/metabolismo , Modelos Biológicos , Dados de Sequência Molecular , Ovário/metabolismo
16.
Cell Discov ; 1: 15006, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27462407

RESUMO

Intestinal homeostasis is maintained by intestinal stem cells (ISCs) and their progenies. A complex autonomic nervous system spreads over posterior intestine. However, whether and how neurons regulate posterior intestinal homeostasis is largely unknown. Here we report that neurons regulate Drosophila posterior intestinal homeostasis. Specifically, downregulation of neuronal Hedgehog (Hh) signaling inhibits the differentiation of ISCs toward enterocytes (ECs), whereas upregulated neuronal Hh signaling promotes such process. We demonstrate that, among multiple sources of Hh ligand, those secreted by ECs induces similar phenotypes as does neuronal Hh. In addition, intestinal JAK/STAT signaling responds to activated neuronal Hh signaling, suggesting that JAK/STAT signaling acts downstream of neuronal Hh signaling in intestine. Collectively, our results indicate that neuronal Hh signaling is essential for the determination of ISC fate.

17.
PLoS One ; 8(7): e69868, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23894554

RESUMO

The objective of this study was to evaluate the functional properties of lactic acid bacteria (LAB) isolated from Tibetan kefir grains. Three Lactobacillus isolates identified as Lactobacillus acidophilus LA15, Lactobacillus plantarum B23 and Lactobacillus kefiri D17 that showed resistance to acid and bile salts were selected for further evaluation of their probiotic properties. The 3 selected strains expressed high in vitro adherence to Caco-2 cells. They were sensitive to gentamicin, erythromycin and chloramphenicol and resistant to vancomycin with MIC values of 26 µg/ml. All 3 strains showed potential bile salt hydrolase (BSH) activity, cholesterol assimilation and cholesterol co-precipitation ability. Additionally, the potential effect of these strains on plasma cholesterol levels was evaluated in Sprague-Dawley (SD) rats. Rats in 4 treatment groups were fed the following experimental diets for 4 weeks: a high-cholesterol diet, a high-cholesterol diet plus LA15, a high-cholesterol diet plus B23 or a high-cholesterol diet plus D17. The total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in the serum were significantly (P<0.05) decreased in the LAB-treated rats compared with rats fed a high-cholesterol diet without LAB supplementation. The high-density lipoprotein cholesterol levels in groups B23 and D17 were significantly (P<0.05) higher than those in the control and LA15 groups. Additionally, both fecal cholesterol and bile acid levels were significantly (P<0.05) increased after LAB administration. Fecal lactobacilli counts were significantly (P<0.05) higher in the LAB treatment groups than in the control groups. Furthermore, the 3 strains were detected in the rat small intestine, colon and feces during the feeding trial. The bacteria levels remained high even after the LAB administration had been stopped for 2 weeks. These results suggest that these strains may be used in the future as probiotic starter cultures for manufacturing novel fermented foods.


Assuntos
Produtos Fermentados do Leite/microbiologia , Grão Comestível/microbiologia , Lactobacillus/isolamento & purificação , Lactobacillus/fisiologia , Probióticos/farmacologia , Animais , Antibacterianos/farmacologia , Aderência Bacteriana , Ácidos e Sais Biliares/metabolismo , Peso Corporal/efeitos dos fármacos , Células CACO-2 , Colesterol/sangue , Colesterol/metabolismo , Farmacorresistência Bacteriana , Ingestão de Alimentos/efeitos dos fármacos , Fezes/microbiologia , Humanos , Concentração de Íons de Hidrogênio , Hipolipemiantes/metabolismo , Hipolipemiantes/farmacologia , Intestinos/microbiologia , Lactobacillus/efeitos dos fármacos , Lactobacillus/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Probióticos/metabolismo , Ratos , Ratos Sprague-Dawley , Especificidade da Espécie , Tibet
18.
Protein Cell ; 4(9): 650-5, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23807635

RESUMO

Stem cell niche is a specialized microenvironment crucial to self-renewal. The testis in Drosophila contains two different types of stem cells, the germline stem cells and the somatic cyst stem cells that are sustained by their respective niche signals, thus is a good system for studying the interaction between the stem cells and their hosting niche. The JAK-STAT and BMP pathways are known to play critical roles in the self-renewal of different kinds of stem cells, but the roles of several other pathways have emerged recently in a complex signaling network in the testis niche. Reports of independent observations from three research groups have uncovered an important role of Hedgehog (Hh) in the Drosophila testis niche. In this review, we summarize these recent findings and discuss the interplay between the Hh signaling mechanisms and those of the JAK-STAT and BMP pathways. We also discuss directions for further investigation.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Proteínas Hedgehog/metabolismo , Testículo/metabolismo , Células-Tronco Germinativas Adultas/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Drosophila/citologia , Feminino , Janus Quinases/metabolismo , Masculino , Ovário/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Nicho de Células-Tronco , Testículo/citologia , Fatores de Transcrição/metabolismo
19.
J Cell Biol ; 203(4): 575-83, 2013 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-24385484

RESUMO

The evolutionarily conserved Hedgehog (Hh) signaling pathway is transduced by the Cubitus interruptus (Ci)/Gli family of transcription factors that exist in two distinct repressor (Ci(R)/Gli(R)) and activator (Ci(A)/Gli(A)) forms. Aberrant activation of Hh signaling is associated with various human cancers, but the mechanism through which Ci(R)/Gli(R) properly represses target gene expression is poorly understood. Here, we used Drosophila melanogaster and zebrafish models to define a repressor function of Atrophin (Atro) in Hh signaling. Atro directly bound to Ci through its C terminus. The N terminus of Atro interacted with a histone deacetylase, Rpd3, to recruit it to a Ci-binding site at the decapentaplegic (dpp) locus and reduce dpp transcription through histone acetylation regulation. The repressor function of Atro in Hh signaling was dependent on Ci. Furthermore, Rerea, a homologue of Atro in zebrafish, repressed the expression of Hh-responsive genes. We propose that the Atro-Rpd3 complex plays a conserved role to function as a Ci(R) corepressor.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas Hedgehog/metabolismo , Histona Desacetilase 1/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Acetilação , Animais , Sítios de Ligação , Proteínas Correpressoras/metabolismo , Drosophila melanogaster/metabolismo , Evolução Molecular , Loci Gênicos/genética , Histonas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Ligação Proteica , Peixe-Zebra/metabolismo
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