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1.
Anim Biosci ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38665075

RESUMO

Objective: In this study, the effects of dietary ferulic acid (FA) on the growth traits, antioxidant capacity, and intestinal barrier function of broilers were investigated. Methods: In total, 192 male Arbor Acres broilers were randomly allocated to one of three dietary groups (8 replicates of 8 birds each): control (CON) group (basal diet), FA100 group (basal diet + 100 mg/kg FA), or FA200 group (basal diet + 200 mg/kg FA). The duration of the feeding trial was 42 days. Results: higher average daily gain (ADG) and lower feed to gain (F/G) ratio during day 0 to day 21 were found in the FA100 and FA200 groups, while higher ADG and lower F/G during day 21 to day 42 were only found in FA200 group, compared to the CON group (p < 0.05). Serum levels of MDA and DAO on day 21 were lower in the FA100 and FA200 groups and those on day 42 were lower in the FA200 group, while GSH-Px level in the FA100 and FA200 groups on day 21 and that in the FA200 group on day 42 were increased (p < 0.05). On day 21, jejunal GSS expression was upregulated in the FA200 group (p < 0.05), while jejunal and ileal expression of NRF2 and Occludin as well as ileal expression of GPX1 and ZO1 were increased in the FA100 and FA200 groups compared to the CON group (p < 0.05). On day 42, mRNA expression of GSS, NRF2, SOD1, and GPX1 in the jejunum and ileum as well as Claudin2 in the jejunum and Occludin in the ileum were increased in the FA200 group (p < 0.05). Conclusion: Dietary FA addition could improve the growth performance, antioxidant capacity, and gut integrity of broilers. The current findings provided evidences that the adoption of FA can be as nutrition intervention measure to achieve high-efficient broiler production for poultry farmers.

2.
MedComm (2020) ; 5(4): e507, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38525107

RESUMO

Meibomian gland dysfunction (MGD)-related dry eye disease (DED) is a significant subtype of DED. In this research, we investigate the effectiveness of far infrared (FIR) functional glasses in the treatment of MGD-related DED. According to the TFO DEWS II diagnostic criteria, 61 eyes with MGD-related DED were included. All participants wore functional FIR glasses throughout the day for a period of 4 weeks and were followed up three times during the treatment. All subjects were followed up thoroughly in accordance with the DED clinical examination procedure. Ultimately, the treatment's impact was assessed. We found the Visual Analogue Scale and Ocular Surface Disease Index scores after FIR treatment were significantly lower than the baseline values (p < 0.05). Compared with the baseline, fluorescein tear breakup time and corneal fluorescein staining score after FIR treatment were significantly improved (p < 0.05). The eyelid margin signs, meibum quality, and meibomian gland expressibility after the 4-week treatment were significantly better than those at baseline (p < 0.05). We can see that wearing the FIR functional glasses significantly relieves the symptoms and signs of patients. We believe FIR therapy could be considered as a new method of MGD-related DED.

3.
Mol Ecol ; 33(5): e17279, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38308460

RESUMO

In this issue of Molecular Ecology, Salter et al. (2023) discovered that the Cuban Northern Bobwhite subspecies, Colinus virginianus cubanensis (Gould, 1850), is an ancient hybrid population formed due to historical hybridization potentially brought by waves of historical human migration. This study revealed a complex mixture of gene flow from distinct spatiotemporal origins underlying a seemingly semi-independent evolutionary trajectory. Hybridization can be more common and complex than we thought.


Assuntos
Colinus , Fluxo Gênico , Animais , Humanos , Colinus/genética , Evolução Biológica , Hibridização Genética
4.
World J Pediatr ; 20(1): 64-72, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37389785

RESUMO

BACKGROUND: The aim of this study was to review current delivery room (DR) resuscitation intensity in Chinese tertiary neonatal intensive care units and to investigate the association between DR resuscitation intensity and short-term outcomes in preterm infants born at 24+0-31+6 weeks' gestation age (GA). METHODS: This was a retrospective cross-sectional study. The source population was infants born at 24+0-31+6 weeks' GA who were enrolled in the Chinese Neonatal Network 2019 cohort. Eligible infants were categorized into five groups: (1) regular care; (2) oxygen supplementation and/or continuous positive airway pressure (O2/CPAP); (3) mask ventilation; (4) endotracheal intubation; and (5) cardiopulmonary resuscitation (CPR). The association between DR resuscitation and short-term outcomes was evaluated by inverse propensity score-weighted logistic regression. RESULTS: Of 7939 infants included in this cohort, 2419 (30.5%) received regular care, 1994 (25.1%) received O2/CPAP, 1436 (18.1%) received mask ventilation, 1769 (22.3%) received endotracheal intubation, and 321 (4.0%) received CPR in the DR. Advanced maternal age and maternal hypertension correlated with a higher need for resuscitation, and antenatal steroid use tended to be associated with a lower need for resuscitation (P < 0.001). Severe brain impairment increased significantly with increasing amounts of resuscitation in DR after adjusting for perinatal factors. Resuscitation strategies vary widely between centers, with over 50% of preterm infants in eight centers requiring higher intensity resuscitation. CONCLUSIONS: Increased intensity of DR interventions was associated with increased mortality and morbidities in very preterm infants in China. There is wide variation in resuscitative approaches across delivery centers, and ongoing quality improvement to standardize resuscitation practices is needed.


Assuntos
Salas de Parto , Recém-Nascido Prematuro , Recém-Nascido , Gravidez , Lactente , Humanos , Feminino , Estudos Retrospectivos , Estudos Transversais , China/epidemiologia , Idade Gestacional
5.
BMC Ophthalmol ; 23(1): 498, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062441

RESUMO

BACKGROUND: To investigate the validation of phenol red thread (PRT) test in a Chinese population by evaluating the intraobserver repeatability and interobserver reproducibility, determining correlations between the PRT test and other dry eye disease (DED) parameters including tear meniscus height (TMH) and Schirmer I test, and testing the accuracy of diagnosing DED when using the PRT test alone. METHODS: A total of 108 eyes were involved in this prospective and diagnostic study, and were divided into two groups (with and without DED). Each subject underwent a series of ocular surface examinations, including Ocular Surface Disease Index (OSDI) questionnaire, non-invasive tear breakup time (NIBUT), tear meniscus height (TMH) assessment, PRT test, fluorescein tear breakup time (FBUT), corneal fluorescein staining and Schirmer I test. RESULTS: In the experimental group and the control group, the intra-class correlation coefficients (ICCs) of the repeatability were 0.747 and 0.723, respectively (all P < 0.05). The ICCs of the reproducibility in both groups were 0.588 and 0.610, respectively (all P < 0.05). The PRT test correlated weakly with the Schirmer I test and the tear meniscus height, with Spearman coefficients of 0.385 and 0.306, respectively (all P < 0.05). The PRT test is available to diagnose DED, with an area under the curve of 0.806 and a Youden index of 0.556 at the cutoff point of 8.83 mm. CONCLUSIONS: The PRT test can provide patients a comfortable, timesaving and less irritating approach to screening and diagnosing DED compared to Schirmer I test.


Assuntos
Síndromes do Olho Seco , Fenolsulfonaftaleína , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Lágrimas , Síndromes do Olho Seco/diagnóstico , Fluoresceína , China
6.
Adv Sci (Weinh) ; 10(27): e2206380, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37541303

RESUMO

Tumor cells often overexpress immune checkpoint proteins, including CD47, for immune evasion. However, whether or how oncogenic activation of receptor tyrosine kinases, which are crucial drivers in tumor development, regulates CD47 expression is unknown. Here, it is demonstrated that epidermal growth factor receptor (EGFR) activation induces CD47 expression by increasing the binding of c-Src to CD47, leading to c-Src-mediated CD47 Y288 phosphorylation. This phosphorylation inhibits the interaction between the ubiquitin E3 ligase TRIM21 and CD47, thereby abrogating TRIM21-mediated CD47 K99/102 polyubiquitylation and CD47 degradation. Knock-in expression of CD47 Y288F reduces CD47 expression, increases macrophage phagocytosis of tumor cells, and inhibits brain tumor growth in mice. In contrast, knock-in expression of CD47 K99/102R elicits the opposite effects compared to CD47 Y288F expression. Importantly, CD47-SIRPα blockade with an anti-CD47 antibody treatment significantly enhances EGFR-targeted cancer therapy. In addition, CD47 expression levels in human glioblastoma (GBM) specimens correlate with EGFR and c-Src activation and aggravation of human GBM. These findings elucidate a novel mechanism underlying CD47 upregulation in EGFR-activated tumor cells and underscore the role of the EGFR-c-Src-TRIM21-CD47 signaling axis in tumor evasion and the potential to improve the current cancer therapy with a combination of CD47 blockade with EGFR-targeted remedy.


Assuntos
Antígeno CD47 , Glioblastoma , Evasão Tumoral , Animais , Humanos , Camundongos , Antígeno CD47/metabolismo , Linhagem Celular Tumoral , Receptores ErbB , Glioblastoma/metabolismo , Fosforilação
7.
Animals (Basel) ; 13(13)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37443996

RESUMO

The purpose of this study was to investigate the effects of dried blueberry pomace (BP) and pineapple pomace (PP) on the growth performance and meat quality of broiler chickens. A total of 240 1-day-old Ross 308 broiler chickens were randomly divided into 3 groups, with 10 replicates per treatment group and 8 birds per replicate (4 males and 4 females). The three groups were the control (CON) group, the 3% BP group, and 3% PP group. The entire trial period lasted 42 days. The results show that the average daily feed intake, average daily gain, and feed-to-gain ratio of the BP group and the PP group were not significantly different from those in the CON group (p > 0.05). Adding BP to the diet significantly reduced the proportion of liver and giblets (p < 0.05). Adding PP to the diet significantly reduced the proportion of liver, while the proportion of gizzard significantly increased (p < 0.05). The pH24h and L* of breast muscles were significantly lower in the PP group than in the CON group (p < 0.05). The water-holding capacity of the leg muscles in the BP group and the PP group was significantly lower than that in the CON group (p < 0.05). The crude protein content of breast muscle and the ether extract content of leg muscle in the BP group were significantly lower than those in the CON group (p < 0.05). In conclusion, the addition of 3% BP and PP to broiler chickens' diets had no adverse effects on growth performance or meat quality.

8.
Ecol Evol ; 13(7): e10323, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37492456

RESUMO

Social interactions can drive distinct gene expression profiles which may vary by social context. Here we use female sailfin molly fish (Poecilia latipinna) to identify genomic profiles associated with preference behavior in distinct social contexts: male interactions (mate choice) versus female interactions (shoaling partner preference). We measured the behavior of 15 females interacting in a non-contact environment with either two males or two females for 30 min followed by whole-brain transcriptomic profiling by RNA sequencing. We profiled females that exhibited high levels of social affiliation and great variation in preference behavior to identify an order of magnitude more differentially expressed genes associated with behavioral variation than by differences in social context. Using a linear model (limma), we took advantage of the individual variation in preference behavior to identify unique gene sets that exhibited distinct correlational patterns of expression with preference behavior in each social context. By combining limma and weighted gene co-expression network analyses (WGCNA) approaches we identified a refined set of 401 genes robustly associated with mate preference that is independent of shoaling partner preference or general social affiliation. While our refined gene set confirmed neural plasticity pathways involvement in moderating female preference behavior, we also identified a significant proportion of discovered that our preference-associated genes were enriched for 'immune system' gene ontology categories. We hypothesize that the association between mate preference and transcriptomic immune function is driven by the less well-known role of these genes in neural plasticity which is likely involved in higher-order learning and processing during mate choice decisions.

9.
Evolution ; 77(8): 1874-1881, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37179462

RESUMO

The divergence of reproductive traits frequently underpins the evolution of reproductive isolation. Here we investigated whether tinamou (Tinamidae) egg colorations function as mating signals that diverged as character displacement (mating signal character displacement hypothesis). We tested three evolutionary predictions behind the hypothesis: (a) egg colors coevolve with known mating signals; (b) signal divergence is associated with divergent habitat adaptation; and (c) sympatric tinamou species with similar songs have different egg colors as character displacement during speciation. We found support for all three predictions. In particular, egg colors coevolved with songs; songs and egg colors coevolved with habitat partitioning; and tinamou species that were likely sympatric with similar songs tended to have different egg colors. In conclusion, the mating signal character displacement hypothesis is well supported in which egg colors serve as mating signals that undergo character displacement during tinamou speciation.


Assuntos
Evolução Biológica , Especiação Genética , Cor , Fenótipo
10.
Food Chem ; 424: 136409, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37220684

RESUMO

The dynamic variations in key contributing odorants, amino acids and reducing sugars in shiitake mushrooms during hot-air drying were determined by gas chromatography-mass spectrometry (GC-MS), high performance liquid chromatography-tandem mass (HPLC-MS/MS) and ion chromatography (IC). The potential precursors were explored by the partial least squares-discriminant analysis and Pearson correlation analysis, and Met, Cys, and ribose were considered as the possible precursors of dimethyl trisulfide and lenthionine. The verification experiments in the absence and presence of shiitake mushroom matrix further confirmed that Met and its interaction with ribose both contributed to generating dimethyl trisulfide. The polynomial nonlinear fitting curve could better represent the dose-effect relationships of Met and Met-ribose to produce dimethyl trisulfide with R2 of 0.9579 and 0.9957. Conversely, ribose, Cys or Cys-ribose were verified to be unable to form the key contributing odorants. Collectively, the results provided a method to reveal precursors and generation pathway of odorants.


Assuntos
Cogumelos Shiitake , Compostos Orgânicos Voláteis , Espectrometria de Massas em Tandem , Aminoácidos/análise , Cogumelos Shiitake/química , Odorantes/análise , Ribose
11.
Talanta ; 259: 124491, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37023672

RESUMO

The construction of sensors with specific recognition functions can easily, sensitively and efficiently detect heavy metal ions, which is a demand in the field of electrochemical sensing and an important topic in the detection of environmental pollutants. An electrochemical sensor based on MOFs composites was developed for sensing of multiplex metal ions. The large surface area, adjustable porosities and channels in MOFs facilitate successful loading of sufficient quantities highly active units. The active units and pore structures of MOFs are regulated and synergetic with each other to enhance the electrochemical activity of MOFs composites. Thus, the selectivity, sensitivity and reproducibility of MOFs composites have been improved. Fortunately, after characterization, Fe@YAU-101/GCE sensor with strong signal was successfully constructed. In the presence of target metal ions in solution, the Fe@YAU-101/GCE can efficiently and synchronously identify Hg2+, Pb2+, and Cd2+. The detection limits (LOD) are 6.67 × 10-10 M(Cd2+), 3.33 × 10-10 M(Pb2+) and 1.33 × 10-8 M (Hg2+), and are superior to the permissible limits set by the National Environmental Protection Agency. The electrochemical sensor is simple without sophisticated instrumentation and testing processes, hence promising for practical applications.

12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(5): 834-841, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36224686

RESUMO

Objective: To investigate the effects of using Bifidobacterium bifidum TMC3115 in early life on intestinal microbiota and immune functions and the long-term impact on inflammatory bowel disease. Methods: Fourteen pregnant BALB/c mice were purchased and 84 newborn BALB/c mice were subsequently obtained. Then, the newborn mice were randomly assigned to a normal saline (NS) group and a TMC3115 group, given via oral gavage normal saline and TMC3115, respectively, at a daily volume of 0.2 mL for each mouse. About 42 mice were assigned to each group. The gavage was stopped after 3 weeks. At this point, half of the mice in each group were sacrificed, and then the remaining mice in each group were randomly divided into NS-water group, NS-DSS group, TMC3115-water group, and TMC3115-DSS group, with about 10 mice in each group. The mice were given regular feed until the end of week 6 when they were given 3% dextran sulphate sodium (DSS) ad libitum for 4 days to establish the enteritis model, while the non-modeling groups were given pure water ad libitum. The experiment ended after 6 weeks and 4 days. The weekly body mass changes of the mice were documented. The intestinal tissue at the end of the experiment and the fecal samples, spleen and serum of the mice at 3 weeks and at the end of the experiment were collected to determine the pathology scores of colonic inflammation, the composition of fecal gut microbiota, spleen organ index and the mass concentration of serum cytokines. Results: 1) At the end of the experiment, the inflammatory pathology score was significantly lower in the TMC3115-DSS group compared with that of the Saline-DSS group ( P<0.05), with less disruption of colonic crypt structures and other structures, less inflammatory infiltration, and more intact epithelial structures. 2) At 3 weeks, in comparison with those of the NS group, the relative abundance of Bifidobacteriumwas significantly higher in the feces of the TMC3115 ( P<0.05), the relative abundance of both Enterococcusand Staphylococcuswas lower ( P<0.05), the splenic organ index was significantly higher ( P<0.05), and interleukin (IL)-10 was significantly decreased ( P<0.05), while there was no significant change in IL-6 or TNF-α ( P>0.05). At the end of the experiment, in comparison with those of the NS-DSS group that undergone DSS induction, the TMC3115-DSS group had reduced relative abundance of Staphylococcus, Staphylococcus tumefaciens and Escherichia/ Shigellain the feces ( P<0.05), while the splenic organ index was significantly higher ( P<0.05), and there were no significant changes in IL-6 or TNF-α ( P>0.05). Conclusion: The use of TMC3115 in early life promotes the construction of gut microbiota in neonatal mice, thereby producing a long-term effect that alleviates colitis in mice, but the mechanisms involved are still not fully understood.


Assuntos
Bifidobacterium bifidum , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Colite/microbiologia , Colo , Citocinas , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Interleucina-6 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Solução Salina/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Água/farmacologia
13.
Wei Sheng Yan Jiu ; 51(4): 624-644, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36047269

RESUMO

OBJECTIVE: To explore the protective effect and mechanism of Bifidobacterium bifidum TMC3115 of improving the gut microbiota disorder caused by antibiotic exposurein early life, and the possible protection of inflammatory bowel disease in adulthood in mice. METHODS: 80 newborn mice were randomly divided into 3 groups, a blank control group(n=40), a ceftriaxone exposure group(n=20), a Bifidobacterium bifidum TMC3115 intervention group(n=20). After birth, they were respectively treated with saline, ceftriaxone(100 mg/kg), and ceftriaxone(100 mg/kg) + TMC3115(1×10~9CFU/d) for 3 weeks. After 3 weeks, half of each group was randomly sacrificed, and the rest were normally fed to 6 weeks. At 6 weeks, the blank control group was randomly divided into a negative control group(n=10) and a colitis model group(n=10). The negative control group drunk pure water freely, and the other three groups were added 3% DSS to the drinking water for 4 days to induce colitis. At 6 weeks and 4 days, the remaining mice were sacrificed. The weight change, spleen coefficient, gut microbiota analysis based on second-generation sequencing and serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-10(IL-10)levels of the mice at 3 weeks and after DSS intervention were recorded. In addition, the colon length and inflammation pathology score of the mice after DSS intervention were also measured. RESULTS: At 3 weeks, compared with the control, antibiotic exposure in the early life inhibited the weight gain and reduced the diversity and uniformity of the gut microbiota of the mice(P<0.05). The intervention of TMC3115 under antibiotic exposure during this period increased the relative abundance of Bifidobacterium in the intestines(P<0.05), and the effect still existed after DSS stimulation in adulthood, laying the foundation for TMC3115 to exert long-term benefits. After DSS stimulation in adulthood, mice showed significant weight gain inhibition, colon length shorteningand inflammation pathology scoreincrease compared with the negative control(P<0.05), showed the inflammatory bowel disease(IBD)model was successfully constructed. The relative abundance of beneficial bacteria such as Lactobacillus in the Bifidobacterium bifidum TMC3115 intervention group increased compared with the ceftriaxone exposure group(P<0.05), while the relative abundance of harmful bacteria such as Staphylococcus, Clostridium, and Desulfovibrio decreased(P<0.05). Furthermore, the mice exposed to antibiotic in early life produced a stronger immune response, but the mice which received TMC3115 intervention at the same time had a significant decrease in serum TNF-α and IL-6 levels and increase in IL-10 level compared with the mice which only interfered with antibiotics(P<0.05). CONCLUSION: Antibiotic exposure in early life is a negative factor for long-term inflammatory bowel disease, and TMC3115 has preventive significance for long-term inflammatory bowel disease under the background of antibiotic exposure. The mechanism of TMC3115 may be to adjust the gut microbiota and balance the immune system.


Assuntos
Bifidobacterium bifidum , Colite , Doenças Inflamatórias Intestinais , Animais , Antibacterianos , Bifidobacterium bifidum/fisiologia , Ceftriaxona , Colite/induzido quimicamente , Colite/microbiologia , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação , Doenças Inflamatórias Intestinais/patologia , Interleucina-10 , Interleucina-6 , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa , Aumento de Peso
14.
Nutrients ; 14(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36079908

RESUMO

Commensal microorganisms in the human gut are a good source of candidate probiotics, particularly those with immunomodulatory effects that may improve health outcomes by regulating interactions between the gut microbiome and distal organs. Previously, we used an immune-based screening strategy to select two potential probiotic strains from infant feces in China, Bifidobacterium breve 207-1 (207-1) and Lacticaseibacillus paracasei 207-27 (207-27). In this study, the in vitro immunological effects and potential in vivo general health benefits of these two strains were evaluated using Lacticaseibacillus rhamnosus GG (LGG) as the control. The results showed that 207-1 and 207-27 significantly and differentially modulated the cytokine profiles of primary splenic cells, while did not induce abnormal systemic immune responses in healthy mice. They also modulated the gut microbiota composition in a strain-dependent manner, thus decreasing Gram-negative bacteria and increasing health-promoting taxa and short-chain fatty acid levels, particularly butyric acid. Conclusively, 207-1 and 207-27 shaped a robust gut environment in healthy mice in a strain-specific manner. Their potential immunomodulatory effects and other elite properties will be further explored using animal models of disease and subsequent clinical trials. This immune-based screening strategy is promising in efficiently and economically identifying elite candidate probiotics.


Assuntos
Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Probióticos , Animais , Ácidos Graxos Voláteis , Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , Humanos , Lactente , Camundongos , Probióticos/farmacologia , Probióticos/uso terapêutico
15.
Genes Genomics ; 44(12): 1509-1517, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35917090

RESUMO

BACKGROUND: Overexpression of PD-L1 is observed in many types of human cancer, including glioblastoma (GBM) and contributes to tumor immune evasion. In addition, GBM shows highly-activated aerobic glycolysis due to overexpression of phosphofructokinase 1 platelet isoform (PFKP), which the key enzyme in the glycolysis. However, it remains unclear whether the metabolic enzyme PFKP plays a role in the regulation of PD-L1 expression and GBM immune evasion. OBJECTIVE: We aimed to investigate the non-metabolic role of PFKP in PD-L1 expression-induced GBM immune evasion. METHODS: The mechanisms of PFKP-induced PD-L1 expression were studied by several experiments, including real-time PCR, immunoblot analysis, and ATP production. The coculture experiments using GBM cell and T cells were performed to evaluate the effect of PFKP on T cell activation. The clinical relationship between PFKP and PD-L1 was analyzed in The Cancer Genome Atlas (TCGA) database and in human GBM specimens. RESULTS: We showed that PFKP promotes EGFR activation-induced PD-L1 expression in human GBM cells. Importantly, we demonstrated that EGFR-phosphorylated PFKP Y64 plays an important role in AKT-mediated ß-catenin transactivation and subsequent PD-L1 transcriptional expression, thereby enhancing the GBM immune evasion. In addition, based on our findings, the levels of PFKP Y64 phosphorylation are positively correlated with PD-L1 expression in human GBM specimens, highlighting the clinical significance of PFKP Y64 phosphorylation in the GBM immune evasion. CONCLUSION: These findings provide new mechanistic insight into the regulation of PD-L1 expression by a non-metabolic function of PFKP on tumor cells.


Assuntos
Glioblastoma , Fosfofrutoquinase-1 Tipo C , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptores ErbB/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Evasão da Resposta Imune , Fosforilação , Isoformas de Proteínas/metabolismo , Fosfofrutoquinase-1 Tipo C/genética , Fosfofrutoquinase-1 Tipo C/metabolismo
16.
Front Microbiol ; 13: 916824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935215

RESUMO

Inflammatory bowel disease (IBD) is a chronic intestinal disease characterized by microbiota disturbance and intestinal mucosal damage. The current study aimed to investigate the preventive effects of Bifidobacterium bifidum BD-1 (BD-1) against long-term IBD and possible mechanism by which it alters the gut microbiota, immune response, and mucosal barrier. Our study found that early treatment of BD-1 + Ceftri (ceftriaxone followed by BD-1) and BD-1 confers a certain protective effect against the occurrence of long-term Dextran sulfate sodium-induced colitis, which manifests as a decrease in inflammation scores and MPO activity levels, as well as a relatively intact intestinal epithelial structure. Moreover, compared to BD-1, Ceftri, and NS, early treatment with BD-1 + Ceftri promoted greater expression levels of mucosal barrier-related proteins [KI67, MUC2, ZO-1, secretory immunoglobulin A (slgA), Clauding-1, and Occludin], better local immune responses activation, and moderately better modulation of systemic immune responses during long-term colitis. This may be due to the fact that BD-1 + Ceftri can deliberately prolong the colonization time of some beneficial microbiota (e.g., Bifidobacterium) and reduce the relative abundance of inflammation-related microbiota (e.g., Escherichia/Shigella and Ruminococcus). Interestingly, we found that the changes in the gut barrier and immunity were already present immediately after early intervention with BD-1 + Ceftri, implying that early effects can persist with appropriate intervention. Furthermore, intervention with BD-1 alone in early life confers an anti-inflammatory effect to a certain degree in the long-term, which may be due to the interaction between BD-1 and the host's native gut microbiota affecting intestinal metabolites. In conclusion, BD-1 was not as effective as BD-1 + Ceftri in early life, perhaps due to its failure to fully play the role of the strain itself under the influence of the host's complex microbiota. Therefore, further research is needed to explore specific mechanisms for single strain and native microbiota or the combination between probiotics and antibiotics.

17.
Am Nat ; 200(1): E1-E15, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35737992

RESUMO

AbstractPopulation genomic analysis of hybrid zones is instrumental to our understanding of the evolution of reproductive isolation. Many temperate hybrid zones are formed by the secondary contact between two parental populations that have undergone postglacial range expansion. Here, we show that explicitly accounting for historical parental isolation followed by range expansion prior to secondary contact is fundamental to explaining genetic and fitness patterns in these hybrid zones. Specifically, ancestral population expansion can result in allele surfing, where neutral or slightly deleterious mutations drift to high frequency at the expansion front. If these surfed deleterious alleles are recessive, they can contribute to substantial heterosis in hybrids produced at secondary contact, counteracting negative effects of Bateson-Dobzhansky-Muller incompatibilities (BDMIs) and hence weakening reproductive isolation. When BDMIs are linked to such recessive deleterious alleles, the fitness benefit of introgression at these loci can facilitate introgression at the BDMIs. The extent to which this occurs depends on the strength of selection against the linked deleterious alleles and the distribution of recombination across the chromosome. Finally, surfing of neutral loci can alter the expected pattern of population ancestry; thus, accounting for historical population expansion is necessary to develop accurate null genomic models of secondary contact hybrid zones.


Assuntos
Especiação Genética , Vigor Híbrido , Alelos , Genética Populacional , Hibridização Genética , Modelos Genéticos
18.
Proc Natl Acad Sci U S A ; 119(19): e2119382119, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35512091

RESUMO

Sex chromosomes play a special role in the evolution of reproductive barriers between species. Here we describe conflicting roles of nascent sex chromosomes on patterns of introgression in an experimental hybrid swarm. Drosophila nasuta and Drosophila albomicans are recently diverged, fully fertile sister species that have different sex chromosome systems. The fusion between an autosome (Muller CD) with the ancestral X and Y gave rise to neo-sex chromosomes in D. albomicans, while Muller CD remains unfused in D. nasuta. We found that a large block containing overlapping inversions on the neo-sex chromosome stood out as the strongest barrier to introgression. Intriguingly, the neo-sex chromosome introgression barrier is asymmetrical and sex-dependent. Female hybrids showed significant D. albomicans­biased introgression on Muller CD (neo-X excess), while males showed heterosis with excessive (neo-X, D. nasuta Muller CD) genotypes. We used a population genetic model to dissect the interplay of sex chromosome drive, heterospecific pairing incompatibility between the neo-sex chromosomes and unfused Muller CD, neo-Y disadvantage, and neo-X advantage in generating the observed sex chromosome genotypes in females and males. We show that moderate neo-Y disadvantage and D. albomicans specific meiotic drive are required to observe female-specific D. albomicans­biased introgression in this system, together with pairing incompatibility and neo-X advantage. In conclusion, this hybrid swarm between a young species pair sheds light onto the multifaceted roles of neo-sex chromosomes in a sex-dependent asymmetrical introgression barrier at a species boundary.


Assuntos
Cromossomos Sexuais , Cromossomo Y , Animais , Drosophila/genética , Evolução Molecular , Cromossomos Sexuais/genética
19.
Neurobiol Dis ; 170: 105757, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35588989

RESUMO

Gut microbiota depletion may result in cognitive impairment and emotional disorder. This study aimed to determine the possible association between host gut microbiota, cognitive function, and emotion in various life stages and its related underlying mechanisms. Seventy-five neonatal mice were randomly divided into five groups (n = 15 per group). Mice in the vehicle group were administered distilled water from birth to death, and those in the last four groups were administered antibiotic cocktail from birth to death, from birth to postnatal day (PND) 21 (infancy), from PND 21 to 56 (adolescence), and from PND 57 to 84 (adulthood), respectively. Antibiotic exposure consistently altered the gut microbiota composition and decreased the diversity of gut microbiota. Proteobacteria were the predominant bacteria instead of Firmicutes and Bacteroidetes after antibiotic exposure in different life stages. Long-term and infant gut microbiota depletion resulted in anxiety- and depression-like behaviors, memory impairments, and increased expression of γ-aminobutyric acid type A receptor α1 of adult mice. Long-term antibiotic exposure also significantly decreased serum interleukin (IL)-1ß, IL-10, and corticosterone of adult mice. Gut microbiota depletion in adolescence resulted in anxiety-like behaviors, short-term memory decline, decreased serum interferon-γ (IFN-γ), mRNA expression of 5-hydroxytryptamine receptor 1A, and neuropeptide Y receptor Y2 in the prefrontal cortex of adult mice. Antibiotic exposure in adulthood damaged short-term memory and decreased serum IL-10, IFN-γ, and increased γ-aminobutyric acid type B receptor 1 mRNA expression of adult mice. These results suggest that antibiotic-induced gut microbiota depletion in the long term and infancy resulted in the most severe cognitive and emotional disorders followed by depletion in adolescence and adulthood. These results also suggest that gut microbes could influence host cognitive function and emotion in a life stage-dependent manner by affecting the function of the immune system, hypothalamic-pituitary-adrenal axis, and the expression of neurochemicals in the brain.


Assuntos
Disfunção Cognitiva , Microbioma Gastrointestinal , Animais , Antibacterianos/farmacologia , Comportamento Animal/fisiologia , Disfunção Cognitiva/induzido quimicamente , Microbioma Gastrointestinal/fisiologia , Sistema Hipotálamo-Hipofisário , Interleucina-10 , Camundongos , Sistema Hipófise-Suprarrenal , RNA Mensageiro , Ácido gama-Aminobutírico
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