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1.
J Cell Mol Med ; 26(14): 3995-4006, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35713152

RESUMO

Mounting evidence indicates that hepatic de novo lipogenesis is a common abnormality in non-alcoholic fatty liver disease (NAFLD) patients. We investigated whether a selective COX-2 inhibitor, celecoxib, alleviates hepatic steatosis by targeting an Akt-driven lipogenic pathway. We estimated the efficacy of celecoxib in a novel Akt-driven NAFLD mouse model established via hydrodynamic transfection of activated forms of AKT and in fructose-fed NAFLD mice that exhibited increased insulin-independent hepatic lipogenesis. AKT-transfected and insulin-stimulated human hepatoma cells were used for the in vitro experiments. Haematoxylin and eosin staining, immunohistochemistry and immunoblotting were performed for mechanistic studies. The results revealed that celecoxib ameliorated hepatic steatosis in the AKT-triggered NAFLD mice. Mechanistically, celecoxib effectively suppressed AKT/mTORC1 signalling and its downstream lipogenic cascade in the Akt-driven NAFLD mice and in vitro. Furthermore, celecoxib had limited efficacy in alleviating hepatic lipid accumulation and showed no influence on lipogenic proteins associated with hepatic lipogenesis in fructose-administered mice. This study suggests that celecoxib may be favourable for the treatment of NAFLD, especially in the subset with Akt-triggered hepatic lipogenesis.


Assuntos
Insulinas , Hepatopatia Gordurosa não Alcoólica , Animais , Celecoxib/farmacologia , Frutose/metabolismo , Frutose/farmacologia , Humanos , Insulinas/metabolismo , Lipogênese , Fígado/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
2.
J Biol Chem ; 294(26): 10172-10181, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31088910

RESUMO

The Toll signaling pathway in Drosophila melanogaster regulates several immune-related functions, including the expression of antimicrobial peptide (AMP) genes. The canonical Toll receptor (Toll-1) is activated by the cytokine Spätzle (Spz-1), but Drosophila encodes eight other Toll genes and five other Spz genes whose interactions with one another and associated functions are less well-understood. Here, we conducted in vitro assays in the Drosophila S2 cell line with the Toll/interleukin-1 receptor (TIR) homology domains of each Toll family member to determine whether they can activate a known target of Toll-1, the promoter of the antifungal peptide gene drosomycin. All TIR family members activated the drosomycin promoter, with Toll-1 and Toll-7 TIRs producing the highest activation. We found that the Toll-1 and Toll-7 ectodomains bind Spz-1, -2, and -5, and also vesicular stomatitis virus (VSV) virions, and that Spz-1, -2, -5, and VSV all activated the promoters of drosomycin and several other AMP genes in S2 cells expressing full-length Toll-1 or Toll-7. In vivo experiments indicated that Toll-1 and Toll-7 mutants could be systemically infected with two bacterial species (Enterococcus faecalis and Pseudomonas aeruginosa), the opportunistic fungal pathogen Candida albicans, and VSV with different survival times in adult females and males compared with WT fly survival. Our results suggest that all Toll family members can activate several AMP genes. Our results further indicate that Toll-1 and Toll-7 bind multiple Spz proteins and also VSV, but they differentially affect adult survival after systemic infection, potentially because of sex-specific differences in Toll-1 and Toll-7 expression.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Infecções Bacterianas/microbiologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica , Receptores Toll-Like/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/genética , Infecções Bacterianas/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/microbiologia , Feminino , Masculino , Regiões Promotoras Genéticas , Transdução de Sinais , Receptores Toll-Like/genética
3.
PLoS Pathog ; 13(9): e1006604, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28873459

RESUMO

The lysin motif (LysM) containing proteins can bind chitin and are ubiquitous in various organisms including fungi. In plant pathogenic fungi, a few LysM proteins have been characterized as effectors to suppress chitin-induced immunity in plant hosts and therefore contribute to fungal virulence. The effector mechanism is still questioned in fungus-animal interactions. In this study, we found that LysM proteins are also present in animal pathogenic fungi and have evolved divergently. The genome of the insect pathogen Beauveria bassiana encodes 12 LysM proteins, and the genes were differentially transcribed by the fungus when grown in different conditions. Deletion of six genes that were expressed by the fungus growing in insects revealed that two, Blys2 and Blys5, were required for full fungal virulence. Both proteins could bind chitin and Blys5 (containing two LysM domains) could additionally bind chitosan and cellulose. Truncation analysis of Blys2 (containing five LysM domains) indicated that the combination of LysM domains could determine protein-binding affinity and specificity for different carbohydrates. Relative to the wild-type strain, loss of Blys2 or Blys5 could impair fungal propagation in insect hemocoels and lead to the upregulation of antifungal gene in insects. Interestingly, the virulence defects of ΔBlys2 and ΔBlys5 could be fully restored by complementation with the Slp1 effector from the rice blast fungus Magnaporthe oryzae. In contrast to Slp1 and Blys2, Blys5 could potentially protect fungal hyphae against chitinase hydrolysis. The results of this study not only advance the understanding of LysM protein evolution but also establish the effector mechanism of fungus-animal interactions.


Assuntos
Beauveria/imunologia , Genes Fúngicos/imunologia , Magnaporthe/imunologia , Mucoproteínas/isolamento & purificação , Magnaporthe/genética , Virulência
4.
Environ Microbiol ; 20(1): 293-304, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29159973

RESUMO

Phosphatidylcholine (PC) plays an important role in maintaining membrane integrity and functionality. In this study, two key genes (Mrpct and Mrpem) putatively involved in the cytidine diphosphate (CDP)-choline and phosphatidylethanolamine N-methyltransferase (PEMT) pathways for PC biosynthesis were characterized in the insect pathogenic fungus Metarhizium robertsii. The results indicated that disruption of Mrpct did not lead to any reduction of total PC content but impaired fungal virulence and increased cellular accumulation of triacylglycerol. Deletion of Mrpem reduced PC content and impaired fungal conidiation and infection structure differentiation but did not result in virulence defects. Lipidomic analysis revealed that deletion of Mrpct and Mrpem resulted in dissimilar effects on increase and decrease of PC moieties and other phospholipid species accumulations. Interestingly, we found that these two genes played opposite roles in activation of cell autophagy when the fungi were grown in a nutrient-rich medium. The connection between PC metabolism and autophagy was confirmed because PC content was drastically reduced in Mratg8Δ and that the addition of PC could rescue null mutant sporulation defect. The results of this study facilitate the understanding of PC metabolism on fungal physiology.


Assuntos
Autofagia/genética , Citidina Difosfato Colina/genética , Metarhizium/genética , Metarhizium/metabolismo , Fosfatidilcolinas/biossíntese , Fosfatidiletanolamina N-Metiltransferase/genética , Animais , Citidina Difosfato Colina/metabolismo , Proteínas Fúngicas/genética , Deleção de Genes , Genes Fúngicos/genética , Homeostase , Insetos/microbiologia , Metabolismo dos Lipídeos/genética , Fosfatidiletanolamina N-Metiltransferase/metabolismo , Fosfolipídeos/metabolismo , Virulência/genética
5.
Hu Li Za Zhi ; 65(4): 94-101, 2018 Aug.
Artigo em Zh | MEDLINE | ID: mdl-30066327

RESUMO

BACKGROUND & PROBLEMS: Patients undergoing percutaneous coronary interventions (PCIs) are restricted to bedrest and immobilization of the affected leg for sheath retention. These result in high incidences of back pain and emotional irritation, which may negatively affect cardiac rehabilitation. One-hundred percent of the post-transfemoral PCI patients in our unit had a back-pain score of 3 or higher, with an average pain score of 6. Analysis showed the main causes to be: poor awareness of nurses regarding back pain and physical activity; lack of physical activity guidelines and no regular auditing of physical activity; and lack of education and related materials. PURPOSE: To increase the completion rate of instruction for physical activity to over 90.0% and to reduce the incidence of back pain (score of 3 or higher) among post-PCIs to 35.0% or less. RESOLUTIONS: We conducted in-service education, revised related instruction materials, filmed the recommended physical activity for post-PCIs, and conducted a quality assurance audit. RESULTS: The completion rate among post-PCIs for the instructions for physical activity increased from 32.5% to 90.0%. The incidence of back pain (score >3) reduced from 100% to 26.8%. CONCLUSIONS: Implementing a physical activity education program with multimedia materials and regular audits effectively reduces the discomfort of patients following PCIs.


Assuntos
Dor nas Costas/prevenção & controle , Intervenção Coronária Percutânea/efeitos adversos , Dor nas Costas/epidemiologia , Exercício Físico , Humanos , Incidência , Capacitação em Serviço , Recursos Humanos de Enfermagem Hospitalar/educação
6.
BMC Genomics ; 18(1): 668, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28854898

RESUMO

BACKGROUND: Ascomycete Cordyceps species have been using as valued traditional Chinese medicines. Particularly, the fruiting bodies of Cordyceps cicadae (syn. Isaria cicadae) have long been utilized for the treatment of chronic kidney disease. However, the genetics and bioactive chemicals in this fungus have been largely unexplored. RESULTS: In this study, we performed comprehensive omics analyses of C. cicadae, and found that, in contrast to other Cordyceps fungi, C. cicadae produces asexual fruiting bodies with the production of conidial spores instead of the meiotic ascospores. Genome sequencing and comparative genomic analysis indicate that the protein families encoded by C. cicadae are typical of entomopathogenic fungi, including the expansion of proteases and chitinases for targeting insect hosts. Interestingly, we found that the MAT1-2 mating-type locus of the sequenced strain contains an abnormally truncated MAT1-1-1 gene. Gene deletions revealed that asexual fruiting of C. cicadae is independent of the MAT locus control. RNA-seq transcriptome data also indicate that, compared to growth in a liquid culture, the putative genes involved in mating and meiosis processes were not up-regulated during fungal fruiting, further supporting asexual reproduction in this fungus. The genome of C. cicadae encodes an array of conservative and divergent gene clusters for secondary metabolisms. Based on our analysis, the production of known carcinogenic metabolites by this fungus could be potentially precluded. However, the confirmed production of oosporein raises health concerns about the frequent consumption of fungal fruiting bodies. CONCLUSIONS: The results of this study expand our knowledge of fungal genetics that asexual fruiting can occur independent of the MAT locus control. The obtained genomic and metabolomic data will benefit future investigations of this fungus for medicinal uses.


Assuntos
Cordyceps/genética , Cordyceps/metabolismo , Carpóforos/genética , Perfilação da Expressão Gênica , Metabolômica , Cordyceps/crescimento & desenvolvimento , Cordyceps/fisiologia , Evolução Molecular , Carpóforos/crescimento & desenvolvimento , Deleção de Genes , Loci Gênicos/genética , Família Multigênica/genética , Filogenia , Reprodução Assexuada/genética , Sintenia
7.
Environ Microbiol ; 18(11): 3976-3990, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27312218

RESUMO

The final product of the glycerol phosphate (GP) pathway is triacylglycerol (TAG) that regulates the homeostasis of energy, fatty acids and phospholipids in cells. The enzymes involved in this pathway have been characterized in many model organisms; however, their contributions to fungal infection are largely unclear. In this study, we performed serial deletion of genes in the GP pathway in the insect pathogenic fungus Metarhizium robertsii. The results indicated that a lysophosphatidate acyltransferase mrLPAAT1 was required for fungal growth, cell differentiation, maintenance of cell polarity and virulence. Lipidomic analysis indicated that deletion of mrLPAAT1 resulted in significant increases in TAG, fatty acids and phosphatidylcholine (PC) but decreased phosphatidic acid (PA), phosphatidylethanolamine (PE) and other species of phospholipids when compared to the wild type. Disruption of the isozymatic gene mrLPAAT2, however, resulted in a reduction in PC but not PA in the mutant cells. There were no changes in development and virulence in ΔmrLPAAT2. Phospholipid feeding assays verified that a PE supplement could rescue the cell differentiation defect in ΔmrLPAAT1. The results of this study reveal that cellular phospholipid homeostasis mediated by the GP pathway regulates fungal growth, cell polarity, differentiation and virulence.


Assuntos
Polaridade Celular , Metarhizium/metabolismo , Metarhizium/patogenicidade , Fosfolipídeos/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Animais , Ácidos Graxos/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Homeostase , Insetos/microbiologia , Metarhizium/citologia , Metarhizium/crescimento & desenvolvimento , Virulência
8.
Fungal Genet Biol ; 88: 35-43, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26812121

RESUMO

Fungal sexual lives are considerably diversified in terms of the types of mating systems and mating-control gene functions. Sexual fruiting bodies of the ascomycete fungus Cordyceps militaris have been widely consumed as edible and medicinal mushrooms, whereas the regulation of fruiting-body development and sex in this fungus remain elusive. Herein, we performed the comprehensive functional analyses of mating-type (MAT) genes in C. militaris. Interspecies functional convergence was evident that MAT1-1 and MAT1-2-1 null mutants were sterile and lost the ability to produce stromata in outcrosses with the opposite mating-type partner. In contrast to other fungal species, functional divergence of MAT1-1-1 and MAT1-1-2 was also observed that ΔMAT1-1-1 produced barren stromata in outcrosses, whereas ΔMAT1-1-2 generated fruiting bodies morphologically similar to that of the parental strain but with sterile perithecia. The homothallic-like transformants MAT1-2::MAT1-1-1 (haploidic MAT1-2 isolate transformed with the MAT1-1-1 gene) produced sterile stromata, whereas the MAT1-1::MAT1-2-1 (haploidic MAT1-1 isolate transformed with the MAT1-2-1 gene) mutant was determined to be completely fruitless. The findings relating to the fully fertile gene-complementation mutants suggest that the genomic location is not essential for the MAT genes to fulfill their functions in C. militaris. Comparison of the production of bioactive constituents cordycepin and adenosine provides experimental support that the fungal sexual cycle is an energy consuming process. The results of the present study enrich our knowledge of both convergent and divergent controls of fungal sex.


Assuntos
Cordyceps/genética , Cordyceps/fisiologia , Proteínas Fúngicas/genética , Genes Fúngicos Tipo Acasalamento , Adenosina/biossíntese , Desoxiadenosinas/biossíntese , Carpóforos/genética , Teste de Complementação Genética , Mutação , Receptores de Feromônios/genética
9.
Eukaryot Cell ; 14(4): 396-405, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25710964

RESUMO

Two-component signaling pathways generally include sensor histidine kinases and response regulators. We identified an ortholog of the response regulator protein Skn7 in the insect-pathogenic fungus Metarhizium robertsii, which we named MrSkn7. Gene deletion assays and functional characterizations indicated that MrSkn7 functions as a transcription factor. The MrSkn7 null mutant of M. robertsii lost the ability to sporulate and had defects in cell wall biosynthesis but was not sensitive to oxidative and osmotic stresses compared to the wild type. However, the mutant was able to produce spores under salt stress. Insect bioassays using these spores showed that the virulence of the mutant was significantly impaired compared to that of the wild type due to the failures to form the infection structure appressorium and evade host immunity. In particular, deletion of MrSkn7 triggered cell autolysis with typical features such as cell vacuolization, downregulation of repressor genes, and upregulation of autolysis-related genes such as extracellular chitinases and proteases. Promoter binding assays confirmed that MrSkn7 could directly or indirectly control different putative target genes. Taken together, the results of this study help us understand the functional divergence of Skn7 orthologs as well as the mechanisms underlying the development and control of virulence in insect-pathogenic fungi.


Assuntos
Autólise , Parede Celular/ultraestrutura , Proteínas Fúngicas/fisiologia , Metarhizium/fisiologia , Fatores de Transcrição/fisiologia , Animais , Quitinases/genética , Proteínas Fúngicas/genética , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Gafanhotos , Metarhizium/genética , Metarhizium/patogenicidade , Mariposas/microbiologia , Esporos Fúngicos/fisiologia , Fatores de Transcrição/genética , Ativação Transcricional , Virulência
10.
Appl Opt ; 55(25): 6866-73, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27607260

RESUMO

Structured illumination using sinusoidal patterns has been used for optical imaging of biological tissues in biomedical research, and of horticultural products in food quality evaluation. Implementation of structured-illumination imaging relies on retrieval of amplitude images, which is conventionally achieved by a phase-shifting technique that requires collecting a minimum of three phase-shifted images. In this study, we have proposed Gram-Schmidt orthonormalization (GSO) to retrieve amplitude component (AC) images using only two phase-shifted images. We have proposed two forms of GSO implementation, and prior to GSO processing, we eliminated the direct component (DC) background by subtracting a DC image we recovered using a spiral phase function (SPF) in the Fourier space. We demonstrated the GSO methods through numerical simulations and application examples of detection of bruise defects in apples by structured-illumination reflectance imaging (SIRI). GSO performed comparably to conventional three-phase-based demodulation. It is simple, fast and effective for amplitude retrieval and requires no prior phase information, which could facilitate fast implementation of structured-illumination imaging.

11.
Proc Natl Acad Sci U S A ; 109(4): 1287-92, 2012 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-22232661

RESUMO

Insect pathogenic fungi produce a plethora of insecticidally and pharmaceutically active compounds, including 39 cyclohexadepsipeptide destruxins (dtxs). Even though dtxs were first discovered more than 50 y ago, the genes responsible for their biosynthesis were unknown until this study. Based on our comparative genomic information and targeted gene disruptions, we report the gene cluster for dtx biosynthesis in the insect pathogen Metarhizium robertsii. The nonribosomal peptide synthetase DtxS1 has six adenylation domains, two of which are capable of selecting different amino acids to synthesize dtx B and its analogs. The cytochrome P450 enzyme DtxS2 converts dtx B into other dtxs by a chain of reactions, each producing a new derivative. The aldo-keto reductase DtxS3 and aspartic acid decarboxylase DtxS4 are responsible for the conversion and provision of the first and last substrates for the dtx assembly line, respectively. Insect bioassays showed that dtxs could suppress both cellular and humoral immune responses thereby assisting fungal propagation in insects. The differing abilities of Metarhizium species to produce toxins is dependent on the presence of the dtxS1 gene. The toxigenic species are capable of killing multiple orders of insects, whereas the nontoxigenic Metarhizium spp. have narrow host ranges. Thus, the acquisition or retention of the dtx biosynthesis gene cluster in Metarhizium lineages has been coordinated with the evolution of fungal host specificity. The data from this study will facilitate the development of dtxs as bioinsecticides or pharmaceuticals.


Assuntos
Depsipeptídeos/biossíntese , Genes Fúngicos/genética , Insetos/microbiologia , Metarhizium/genética , Família Multigênica/genética , Micotoxinas/biossíntese , Oxirredutases do Álcool/metabolismo , Aldeído Redutase , Aldo-Ceto Redutases , Animais , Bioensaio , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/metabolismo , Primers do DNA/genética , Depsipeptídeos/genética , Genômica/métodos , Interações Hospedeiro-Patógeno/genética , Insetos/imunologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Metarhizium/imunologia , Metarhizium/metabolismo , Micotoxinas/genética , Reação em Cadeia da Polimerase , Especificidade da Espécie
12.
J Sci Food Agric ; 94(11): 2239-45, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24374740

RESUMO

BACKGROUND: Fast and non-destructive determination of rapeseed protein content carries significant implications in rapeseed production. This study presented the first attempt of using Fourier transform mid-infrared photoacoustic spectroscopy (FTIR-PAS) to quantify protein content of rapeseed. The full-spectrum model was first built using partial least squares (PLS). Interval selection methods including interval partial least squares (iPLS), synergy interval partial least squares (siPLS), backward elimination interval partial least squares (biPLS) and dynamic backward elimination interval partial least squares (dyn-biPLS) were then employed to select the relevant band or band combination for PLS modeling. RESULTS: The full-spectrum PLS model achieved an ratio of prediction to deviation (RPD) of 2.047. In comparison, all interval selection methods produced better results than full-spectrum modeling. siPLS achieved the best predictive accuracy with an RPD of 3.215 when the spectrum was sectioned into 25 intervals, and two intervals (1198-1335 and 1614-1753 cm(-1) ) were selected. iPLS excelled biPLS and dyn-biPLS, and dyn-biPLS performed slightly better than biPLS. CONCLUSION: FTIR-PAS was verified as a promising analytical tool to quantify rapeseed protein content. Interval selection could extract the relevant individual band or synergy band associated with the sample constituent of interest, and then improve the prediction accuracy of the full-spectrum model.


Assuntos
Brassica napus/química , Brassica rapa/química , Proteínas Alimentares/análise , Técnicas Fotoacústicas/métodos , Sementes/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Espectral/métodos , Dieta , Humanos , Análise dos Mínimos Quadrados , Reprodutibilidade dos Testes
13.
Insect Sci ; 31(1): 79-90, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37465843

RESUMO

Spermatogenesis is a critical part of reproduction in insects; however, its molecular mechanism is still largely unknown. In this study, we identified a testis-specific gene CG3526 in Drosophila melanogaster. Bioinformatics analysis showed that CG3526 contains a zinc binding domain and 2 C2 H2 type zinc fingers, and it is clustered to the vertebrate really interesting new gene (RING) family E3 ubiquitin-protein ligases. When CG3526 was knocked down by RNA interference (RNAi), the testis became much smaller in size, and the apical tip exhibited a sharp and thin end instead of the blunt and round shape in the control testis. More importantly, compared to the control flies, only a few mature sperm were present in the seminal vesicle of C587-Gal4 > CG3526 RNAi flies. Immunofluorescence staining of the testis from CG3526 RNAi flies showed that the homeostasis of testis stem cell niche was disrupted, cell distribution in the apical tip was scattered, and the process of spermatogenesis was not completed. Furthermore, we found that the phenotype of CG3526 RNAi flies' testis was similar to that of testis of Stat92E RNAi flies, the expression level of CG3526 was significantly downregulated in the Stat92EF06346 mutant flies, and the promoter activity of CG3526 was upregulated by STAT92E. Taken together, our results indicated that CG3526 is a downstream effector gene in the JAK-STAT signaling pathway that plays a key role in the spermatogenesis of Drosophila.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Masculino , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Sêmen/metabolismo , Espermatogênese/genética , Testículo/metabolismo , Drosophila/metabolismo
14.
iScience ; 27(2): 108795, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38292423

RESUMO

Macroautophagy/autophagy is a conserved process in eukaryotic cells to degrade and recycle damaged intracellular components. Higher level of autophagy in the brain has been observed, and autophagy dysfunction has an impact on neuronal health, but the molecular mechanism is unclear. In this study, we showed that overexpression of Toll-1 and Toll-7 receptors, as well as active Spätzle proteins in Drosophila S2 cells enhanced autophagy, and Toll-1/Toll-7 activated autophagy was dependent on Tube-Pelle-PP2A. Interestingly, Toll-1 but not Toll-7 mediated autophagy was dMyd88 dependent. Importantly, we observed that loss of functions in Toll-1 and Toll-7 receptors and PP2A activity in flies decreased autophagy level, resulting in the loss of dopamine (DA) neurons and reduced fly motion. Our results indicated that proper activation of Toll-1 and Toll-7 pathways and PP2A activity in the brain are necessary to sustain autophagy level for DA neuron survival.

15.
Insect Sci ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38643371

RESUMO

Spermatogenesis is critical for insect reproduction and the process is regulated by multiple genes. Glycosyltransferases have been shown to participate in the development of Drosophila melanogaster; however, their role in spermatogenesis is still unclear. In this study, we found that α1,4-galactosyltransferase 1 (α4GT1) was expressed at a significantly higher level in the testis than in the ovary of Drosophila. Importantly, the hatching rate was significantly decreased when α4GT1 RNA interference (RNAi) males were crossed with w1118 females, with only a few mature sperm being present in the seminal vesicle of α4GT1 RNAi flies. Immunofluorescence staining further revealed that the individualization complex (IC) in the testes from α4GT1 RNAi flies was scattered and did not move synchronically, compared with the clustered IC observed in the control flies. Terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay showed that apoptosis signals in the sperm bundles of α4GT1 RNAi flies were significantly increased. Moreover, the expression of several individualization-related genes, such as Shrub, Obp44a and Hanabi, was significantly decreased, whereas the expression of several apoptosis-related genes, including Dronc and Drice, was significantly increased in the testes of α4GT1 RNAi flies. Together, these results suggest that α4GT1 may play dual roles in Drosophila spermatogenesis by regulating the sperm individualization process and maintaining the survival of sperm bundles.

16.
Front Pharmacol ; 14: 1196287, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37256232

RESUMO

Ferroptosis is an iron-dependently nonapoptotic cell death characterized by excessive accumulation of lipid peroxides and cellular iron metabolism disturbances. Impaired iron homeostasis and dysregulation of metabolic pathways are contributors to ferroptosis. As a major metabolic hub, the liver synthesizes and transports plasma proteins and endogenous fatty acids. Also, it acts as the primary location of iron storage for hepcidin generation and secretion. To date, although the intricate correlation between ferroptosis and liver disorders needs to be better defined, there is no doubt that ferroptosis participates in the pathogenesis of liver diseases. Accordingly, pharmacological induction and inhibition of ferroptosis show significant potential for the treatment of hepatic disorders involved in lipid peroxidation. In this review, we outline the prominent features, molecular mechanisms, and modulatory networks of ferroptosis and its physiopathologic functions in the progression of liver diseases. Further, this review summarizes the underlying mechanisms by which ferroptosis inducers and inhibitors ameliorate liver diseases. It is noteworthy that natural active ingredients show efficacy in preclinical liver disease models by regulating ferroptosis. Finally, we analyze crucial concepts and urgent issues concerning ferroptosis as a novel therapeutic target in the diagnosis and therapy of liver diseases.

17.
Sci Rep ; 13(1): 6314, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37072478

RESUMO

Fourier transform mid infrared (FT-MIR) spectroscopy combined with modeling techniques has been studied as a useful tool for multivariate chemical analysis in agricultural research. A drawback of this method is the sample preparation requirement, in which samples must be dried and fine ground for accurate model calibrations. For research involving large sample sets, this may dramatically increase the time and cost of analysis. This study investigates the effect of fine grinding on model performance using leaf tissue from a variety of crop species. Dried leaf samples (N = 300) from various environmental conditions were obtained with data on 11 nutrients measured using chemical methods. The samples were scanned with attenuated total reflectance (ATR) and diffuse reflectance (DRIFT) FT-MIR techniques. Scanning was repeated after fine grinding for 2, 5, and 10 min. The spectra were analyzed for the 11 nutrients using partial least squares regression with a 75%/25% split for calibration and validation and repeated for 50 iterations. All analytes except for boron, iron, and zinc were well-modeled (average R2 > 0.7), with higher R2 values on ATR spectra. The 5 min level of fine grinding was found to be most optimal considering overall model performance and sample preparation time.


Assuntos
Nutrientes , Folhas de Planta , Espectrofotometria Infravermelho/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise dos Mínimos Quadrados
18.
Eur J Pharmacol ; 940: 175457, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36529278

RESUMO

Accumulating evidence suggests that de novo lipogenesis is a typical characteristic facilitating nonalcoholic fatty liver disease (NAFLD) progression. Gallic acid (GA) is a naturally occurring phenolic acid with metabolic disease-related clinical significance and preclinical benefits. This study aimed to evaluate the anti-steatotic potentials of GA in a fructose-induced NAFLD mouse model featuring a hepatic lipogenic phenotype. The results revealed that GA alleviated hepatic steatosis, oxidative stress, and inflammatory response in fructose-fed mice. Mechanistically, GA treatment restored AMP-activated protein kinase α (AMPKα) phosphorylation, resulting in downregulations of pro-lipogenic factors, including sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FASN), and acetyl-CoA carboxylase (ACC), in hepatocytes of mice and in vitro. Furthermore, computational docking analysis indicated that GA could directly interact with AMPKα/ß subunits to stabilize its activation. These results suggest that GA ameliorates fructose-induced hepatosteatosis by restraining hepatic lipogenesis via AMPK-dependent suppression of the SREBP-1/ACC/FASN cascade. Altogether, this study demonstrates that GA supplement may be a promising therapeutic strategy in NAFLD, especially in the subset with enhanced hepatic lipogenesis.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Lipogênese/genética , Acetil-CoA Carboxilase/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Graxos/metabolismo , Ligases/metabolismo , Ácido Gálico/farmacologia , Ácido Gálico/uso terapêutico , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Frutose/efeitos adversos , Fígado/metabolismo , Ácido Graxo Sintase Tipo I/metabolismo
19.
Foods ; 11(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37430956

RESUMO

Fish and fishery products are among the most important sources of nutritional components for human health, including high-quality proteins, essential vitamins, minerals, and healthy polyunsaturated fatty acids. Fish farming and processing technologies are continuously evolving to improve and enhance the appearance, yield, and quality of fish and fish products from farm to fork throughout the fish supply chain, including growth, postharvest, treatment, storage, transportation, and distribution. Processing of fish involves a period of food withdrawal, collection and transportation, the process of stunning, bleeding, chilling, cutting, packaging, and byproduct recycling. Cutting is a set of crucial operations in fish processing to divide the whole fish into smaller pieces for producing fish products (e.g., fish fillets, steaks, etc.). Various techniques and machinery have been introduced in the field to advance and automate cutting operations. This review aims to provide a comprehensive review of fish cutting techniques, machine vision and artificial intelligence applications, and future directions in fish industries. This paper is expected to stimulate research on enhancing fish cutting yield, product diversity, safety and quality, as well as providing advanced solutions for engineering problems encountered in the fish industry.

20.
Insect Sci ; 29(4): 977-992, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34687267

RESUMO

Basic helix-loop-helix (bHLH) transcription factors play an important role in a wide range of metabolic and developmental processes in eukaryotes, and bHLH proteins also participate in immune responses, especially in plants. However, their roles in insects upon entomopathogen infection are unknown. In this study, 54 bHLH genes in 41 families were identified in a polyphagous pest, Spodoptera litura, including a new bHLH gene in group B, which is specifically present in Lepidoptera and was thus named Lep. The conserved amino acids in the bHLH domain, structural architecture, and chromosomal distribution of bHLH genes in S. litura were analyzed. The bHLH genes in Plutella xylostella and Apis mellifera were also updated, and genome-wide comparison and phylogenetic analysis of bHLH members in 5 holometabolous insects were performed. The expression profiles of S. litura bHLH (SlbHLH) genes in 3 tissues at different developmental stages and their responses to S. litura nucleopolyhedrovirus (SpltNPV), Nomuraea rileyi (Nr), and Bacillus thuringiensis (Bt) infection were investigated. More SlbHLHs in group B were expressed and differentially expressed during pathogen infections, and SlbHLHs tended to be downregulated in the midgut of S. litura larvae after B. thuringiensis treatment. Our study provides an overview of bHLH family members in S. litura and their responses to different pathogens used for pest biocontrol. These findings on bHLH members may contribute to uncovering the mechanism of host-pathogen interaction.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Nucleopoliedrovírus , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Abelhas , Larva/genética , Larva/metabolismo , Nucleopoliedrovírus/genética , Nucleopoliedrovírus/metabolismo , Filogenia , Spodoptera/genética , Spodoptera/metabolismo
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