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1.
Virology ; 565: 96-105, 2022 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-34768113

RESUMO

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered enteric coronavirus. We have previously shown that the caspase-dependent FASL-mediated and mitochondrion-mediated apoptotic pathways play a central role in SADS-CoV-induced apoptosis, which facilitates viral replication. However, the roles of intracellular signaling pathways in SADS-CoV-mediated cell apoptosis and the relative advantages that such pathways confer on the host or virus remain largely unknown. In this study, we show that SADS-CoV induces the activation of ERK during infection, irrespective of viral biosynthesis. The knockdown or chemical inhibition of ERK1/2 significantly suppressed viral protein expression and viral progeny production. The inhibition of ERK activation also circumvented SADS-CoV-induced apoptosis. Taken together, these data suggest that ERK activation is important for SADS-CoV replication, and contributes to the virus-mediated changes in host cells. Our findings demonstrate the takeover of a particular host signaling mechanism by SADS-CoV and identify a potential approach to inhibiting viral spread.


Assuntos
Alphacoronavirus/fisiologia , Sistema de Sinalização das MAP Quinases , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Replicação Viral , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/metabolismo , Chlorocebus aethiops , Técnicas de Silenciamento de Genes , Interações Hospedeiro-Patógeno , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/genética , Inibidores de Proteínas Quinases/farmacologia , Suínos , Células Vero , Replicação Viral/efeitos dos fármacos
2.
J Basic Microbiol ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34878177

RESUMO

Hot springs ecosystem is the most ancient continuously inhabited ecosystem on earth which harbors diverse thermophilic bacteria and archaea distributed worldwide. Life in extreme environments is very challenging so there is a great potential biological dark matter and their adaptation to harsh environments eventually producing thermostable enzymes which are very vital for the welfare of mankind. There is an enormous need for a new generation of stable enzymes that can endure harsh conditions in industrial processes and can either substitute or complement conventional chemical processes. Here, we review at the variety and distribution of thermophilic microbes, as well as the different thermostable enzymes that help them survive at high temperatures, such as proteases, amylases, lipases, cellulases, pullulanase, xylanases, and DNA polymerases, as well as their special properties, such as high-temperature stability. We have documented the novel isolated thermophilic and hyperthermophilic microorganisms, as well as the discovery of their enzymes, demonstrating their immense potential in the scientific community and in industry.

3.
Sci Rep ; 11(1): 22626, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799677

RESUMO

Yaks and Tibetan sheep are important and renowned livestock of the Qinghai-Tibetan Plateau (QTP). Both host genetics and environmental factors can shape the composition of gut microbiota, however, there is still no consensus on which is the more dominant factor. To investigate the influence of hosts and seasons on the gut microbiome diversity component, we collected fecal samples from yaks and Tibetan sheep across different seasons (summer and winter), during which they consumed different diets. Using 16S rRNA sequencing, principal component analysis (PCoA) data showed that PCo1 explained 57.4% of the observed variance (P = 0.001) and clearly divided winter samples from summer ones, while PCo2 explained 7.1% of observed variance (P = 0.001) and mainly highlighted differences in host species. Cluster analysis data revealed that the gut microbiota composition displayed a convergence caused by season and not by genetics. Further, we profiled the gut microbial community and found that the more dominant genera in yak and Tibetan sheep microbiota were influenced by seasonal diets factors rather than genetics. This study therefore indicated that seasonal diet can trump host genetics even at higher taxonomic levels, thus providing a cautionary note for the breeding and management of these two species.

4.
Physiol Mol Biol Plants ; 27(10): 2269-2282, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34744365

RESUMO

Genetic diversity of plants is the brace of biodiversity and diversity within species, between species, and of ecosystems. SSR markers are the most preferable molecular marker tool that has been successfully used to study the genetic diversity of plant species. Development of miRNA-SSR markers has been deed in animals but is still limited in plants. In this study, 365 precursors miRNA were extracted from Melilotus albus (Ma) genome and used to design Ma miRNA-SSR primers. 137 Ma primer pairs (79 from known and 58 from novel pre-miRNAs) were obtained. 66 pairs of Ma miRNA-SSR primers were selected with polymorphisms and expected fragment size. The polymorphisms of primers were evaluated in 60 individuals of 15 Ma accessions. A total of 66 primer pairs showed high polymorphism, with average polymorphic information content of 0.49 among 15 Ma accessions and 0.63 among 18 Melilotus species, indicating that these primers have high polymorphisms. The number of alleles produced per primer ranged from 2 to 6 with an average of 3.6 alleles per locus in Ma accessions, and 2 to 10 numbers of alleles with a mean of 5.24 alleles per locus in Melilotus spp. For further studies, the genetic relationship was examined and the cluster analysis showed that 15 Ma accessions were grouped in three groups, on the other hand, 18 Melilotus species clustered into two groups. The analysis of molecular variance (AMOVA) revealed that 64.82% of the variation was found within the species and 35.18% between the species. The population structure analysis showed similar results with PCA analysis in that 18 species were grouped in two groups. In addition, 16,450 miRNA target genes were identified and used for GO and KEGG analysis. This is the first study to develop miRNA-SSR molecular markers in Melilotus spp., which has a great potential for marker-assisted, genetic improvement, genotyping applications, QTL analysis, and molecular-assisted selection studies for plant breeders and other researchers. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-021-01086-z.

5.
Int J Mol Sci ; 22(19)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34639166

RESUMO

Coumarins, natural products abundant in Melilotus albus, confer features in response to abiotic stresses, and are mainly present as glycoconjugates. UGTs (UDP-glycosyltransferases) are responsible for glycosylation modification of coumarins. However, information regarding the relationship between coumarin biosynthesis and stress-responsive UGTs remains limited. Here, a total of 189 MaUGT genes were identified from the M. albus genome, which were distributed differentially among its eight chromosomes. According to the phylogenetic relationship, MaUGTs can be classified into 13 major groups. Sixteen MaUGT genes were differentially expressed between genotypes of Ma46 (low coumarin content) and Ma49 (high coumarin content), suggesting that these genes are likely involved in coumarin biosynthesis. About 73.55% and 66.67% of the MaUGT genes were differentially expressed under ABA or abiotic stress in the shoots and roots, respectively. Furthermore, the functions of MaUGT68 and MaUGT186, which were upregulated under stress and potentially involved in coumarin glycosylation, were characterized by heterologous expression in yeast and Escherichia coli. These results extend our knowledge of the UGT gene family along with MaUGT gene functions, and provide valuable findings for future studies on developmental regulation and comprehensive data on UGT genes in M. albus.


Assuntos
Cumarínicos/metabolismo , Genoma de Planta , Glucuronosiltransferase/metabolismo , Melilotus/metabolismo , Proteínas de Plantas/metabolismo , Estresse Fisiológico , Difosfato de Uridina/metabolismo , Cromossomos de Plantas/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Estudo de Associação Genômica Ampla , Glucuronosiltransferase/genética , Glicosilação , Melilotus/genética , Melilotus/crescimento & desenvolvimento , Filogenia , Proteínas de Plantas/genética , Transcriptoma
6.
Plant Biotechnol J ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717292

RESUMO

Melilotus species are used as green manure and rotation crops worldwide and contain abundant pharmacologically active coumarins. However, there is a paucity of information on its genome and coumarin production and function. Here, we reported a chromosome-scale assembly of Melilotus albus genome with 1.04 Gb in eight chromosomes, containing 71.42% repetitive elements. Long terminal repeat retrotransposon bursts coincided with declining of population sizes during the Quaternary glaciation. Resequencing of 94 accessions enabled insights into genetic diversity, population structure, and introgression. Melilotus officinalis had relatively larger genetic diversity than that of M. albus. The introgression existed between M. officinalis group and M. albus group, and gene flows was from M. albus to M. officinalis. Selection sweep analysis identified candidate genes associated with flower colour and coumarin biosynthesis. Combining genomics, BSA, transcriptomics, metabolomics, and biochemistry, we identified a ß-glucosidase (BGLU) gene cluster contributing to coumarin biosynthesis. MaBGLU1 function was verified by overexpression in M. albus, heterologous expression in Escherichia coli, and substrate feeding, revealing its role in scopoletin (coumarin derivative) production and showing that nonsynonymous variation drives BGLU enzyme activity divergence in Melilotus. Our work will accelerate the understanding of biologically active coumarins and their biosynthetic pathways, and contribute to genomics-enabled Melilotus breeding.

7.
J Appl Genet ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554437

RESUMO

Long terminal repeat retrotransposons (LTR-RTs) contribute a large fraction of many sequenced plant genomes and play important roles in genomic diversity and phenotypic variations. LTR-RTs are abundantly distributed in plant genomes, facilitating the development of markers based on LTR-RTs for a variety of genotyping purposes. Whole-genome analysis of LTR-RTs was performed in Cleistogenes songorica. A total of 299,079 LTR-RTs were identified and classified as Gypsy type, Copia type, or other type. LTR-RTs were widely distributed in the genome, enriched in the heterochromatic region of the chromosome, and negatively correlated with gene distribution. However, approximately one-fifth of genes were still interrupted by LTR-RTs, and these genes are annotated. Furthermore, four types of primer pairs (PPs) were designed, namely, retrotransposon-based insertion polymorphisms, inter-retrotransposon amplified polymorphisms, insertion site-based polymorphisms, and retrotransposon-microsatellite amplified polymorphisms. A total of 350 PPs were screened in 23 accessions of the genus Cleistogenes, of which 80 PPs showed polymorphism, and 72 PPs showed transferability among Gramineae and non-Gramineae species. In addition, a comparative analysis of homologous LTR-RTs was performed with other related grasses. Taken together, the study will serve as a valuable resource for genotyping applications for C. songorica and related grasses.

8.
Front Cell Infect Microbiol ; 11: 730222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540720

RESUMO

Toxoplasma gondii (T. gondii) is an important health problem in human and animals, and the highlighting side effects of launched therapeutic chemicals cannot be ignored. Thus, it is urgent to develop new drugs to against the infection. Myrislignan originated from nutmeg exhibited excellent anti-T. gondii activity in vitro and in vivo, and was able to destroy mitochondrial function. However, the exact mechanism of action is still unknown. In this study, combining RNAs deep-sequencing analysis and surface plasmon resonance (SPR) analysis, the differentially expressed genes (DEGs) and high affinity proteins suggested that myrislignan may affect the oxidation-reduction process of T. gondii. Furthermore, the upregulating ROS activity after myrislignan incubation verified that myrislignan destroyed the oxidant-antioxidant homeostasis of tachyzoites. Transmission electron microscopy (TEM) indicated that myrislignan induced the formation of autophagosome-like double-membrane structure. Moreover, monodansyl cadaverine (MDC) staining and western blot further illustrated autophagosome formation. Myrislignan treatment induced a significant reduction in T. gondii by flow cytometry analysis. Together, these findings demonstrated that myrislignan can induce the oxidation-reduction in T. gondii, lead to the autophagy, and cause the death of T. gondii.


Assuntos
Lignanas , Toxoplasma , Animais , Autofagia , Humanos , Oxirredução
9.
J Virol ; 95(21): e0124621, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34379449

RESUMO

Rotaviruses are the causative agents of severe and dehydrating gastroenteritis in children, piglets, and many other young animals. They replicate their genomes and assemble double-layered particles in cytoplasmic electron-dense inclusion bodies called "viroplasms." The formation of viroplasms is reportedly associated with the stability of microtubules. Although material transport is an important function of microtubules, whether and how microtubule-based transport influences the formation of viroplasms are still unclear. Here, we demonstrate that small viroplasms move and fuse in living cells. We show that microtubule-based dynein transport affects rotavirus infection, viroplasm formation, and the assembly of transient enveloped particles (TEPs) and triple-layered particles (TLPs). The dynein intermediate chain (DIC) is shown to localize in the viroplasm and to interact directly with nonstructural protein 2 (NSP2), indicating that the DIC is responsible for connecting the viroplasm to dynein. The WD40 repeat domain of the DIC regulates the interaction between the DIC and NSP2, and the knockdown of the DIC inhibited rotaviral infection, viroplasm formation, and the assembly of TEPs and TLPs. Our findings show that rotavirus viroplasms hijack dynein transport for fusion events, required for maximal assembly of infectious viral progeny. This study provides novel insights into the intracellular transport of viroplasms, which is involved in their biogenesis. IMPORTANCE Because the viroplasm is the viral factory for rotavirus replication, viroplasm formation undoubtedly determines the effective production of progeny rotavirus. Therefore, an understanding of the virus-host interactions involved in the biogenesis of the viroplasm is critical for the future development of prophylactic and therapeutic strategies. Previous studies have reported that the formation of viroplasms is associated with the stability of microtubules, whereas little is known about its specific mechanism. Here, we demonstrate that rotavirus viroplasm formation takes advantage of microtubule-based dynein transport mediated by an interaction between NSP2 and the DIC. These findings provide new insight into the intracellular transport of viroplasms.

10.
BMC Vet Res ; 17(1): 275, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399756

RESUMO

BACKGROUND: Myrislignan is a natural product from Myristica sp. with diverse pharmacological activities. Recently, the anti-Toxoplasma gondii (T. gondii) activity of myrislignan has been proposed, and in vivo studies of its pharmacokinetics in BALB/c mice are necessary to further evaluate the clinical effects of myrislignan. RESULTS: In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify myrislignan levels in mouse plasma using dehydrodiisoeugenol as an internal standard (IS) in positive ion mode. Chromatographic separation of the analytes was achieved using an ACE Ultracore Super C18 analytical column (2.5 µm, 2.1 × 50 mm) at 30 °C. A gradient mobile phase consisting of water (0.1 % formic acid) and acetonitrile (0.1 % formic acid) was delivered at a flow rate of 0.4 mL/min. Myrislignan and the IS eluted at 1.42 and 1.71 min, respectively. A good excellent linear response across the concentration range of 1-1000 ng/mL was achieved (r2 = 0.9973). The lower limit of quantification (LLOQ) was 1 ng/mL, and the inter- and intra-day accuracy and precision of the method showed relative standard deviations (RSDs) less than 10 %. The method was applied to examine the pharmacokinetics of myrislignan in mouse plasma following a single oral administration of 200 mg/kg or intraperitoneal administration of 50 mg/kg myrislignan, and the bioavailability (F) of orally administered myrislignan was only 1.97 % of the bioavailability of intraperitoneally administered myrislignan. CONCLUSIONS: A rapid and sensitive LC-MS/MS method has been was developed, validated and successfully used to determine myrislignan levels in mice after oral or intraperitoneal administration. This study is the first to report the pharmacokinetic parameters of myrislignan in mice and to compare its pharmacokinetics after oral and intraperitoneal administration, which will be useful for further research on the administration of myrislignan in animals and humans.


Assuntos
Cromatografia Líquida , Lignanas/sangue , Lignanas/farmacocinética , Espectrometria de Massas em Tandem , Administração Oral , Animais , Área Sob a Curva , Células 3T3 BALB , Disponibilidade Biológica , Meia-Vida , Injeções Intraperitoneais/veterinária , Lignanas/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Psychiatr Genet ; 31(6): 230-238, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34412081

RESUMO

OBJECTIVE: Emerging evidence suggests that vitamin D might protect from attempted suicide. The study aimed to investigate the associations between single-nucleotide polymorphisms (SNPs) related to vitamin D levels identified in a large genome-wide association study and attempted suicide in rural China. METHODS: This 1:1 matched case-control study included altogether 510 suicide attempters and 510 community controls. Genotypes of four target SNPs (DHCR7-rs12785878, CYP2R1-rs10741657, GC-rs2282679, and CYP24A1-rs6013897) were determined, and a genetic risk score (GRS) was constructed to evaluate the combined effect of them. Demographic and psychological information was acquired through face-to-face interviews. RESULTS: The A allele of CYP24A1-rs6013897 was significantly associated with attempted suicide (OR = 1.27, 95% CI, 1.03-1.58, P = 0.029), even after adjusting for demographic and psychological confounders (adjusted OR = 1.53, 95% CI, 1.01-2.30, P = 0.043). The GRS analyses revealed a significantly higher risk of attempted suicide with a greater number of low vitamin D alleles (adjusted OR = 1.33, 95% CI, 1.13-1.58, P < 0.001). Subgroup analyses stratified by sex indicated that the genetic associations were only significant among males with adjusted ORs of 3.77 (95% CI, 1.56-9.10) for the A allele of rs6013897 and 2.04 (95% CI, 1.32-3.17) for GRS. CONCLUSIONS: Our findings identity CYP24A1-rs6013897 as a potential biomarker for attempted suicide and indicate that a genetic predisposition to lower vitamin D levels may contribute to attempted suicide. It suggests the possibility that vitamin D may have the preventive potential for attempted suicide.

13.
BMC Microbiol ; 21(1): 214, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271864

RESUMO

BACKGROUND: The natural hosts of Shigella are typically humans and other primates, but it has been shown that the host range of Shigella has expanded to many animals. Although Shigella is becoming a major threat to animals, there is limited information on the genetic background of local strains. The purpose of this study was to assess the presence of virulence factors and the molecular characteristics of S. flexneri isolated from calves with diarrhea. RESULTS: Fifty-four S. flexneri isolates from Gansun, Shanxi, Qinghai, Xinjiang and Tibet obtained during 2014 to 2016 possessed four typical biochemical characteristics of Shigella. The prevalences of ipaH, virA, ipaBCD, ial, sen, set1A, set1B and stx were 100 %, 100 %, 77.78 %, 79.63 %, 48.15 %, 48.15 and 0 %, respectively. Multilocus variable number tandem repeat analysis (MLVA) based on 8 variable number of tandem repeat (VNTR) loci discriminated the isolates into 39 different MLVA types (MTs), pulsed field gel electrophoresis (PFGE) based on NotI digestion divided the 54 isolates into 31 PFGE types (PTs), and multilocus sequence typing (MLST) based on 15 housekeeping genes differentiated the isolates into 7 MLST sequence types (STs). CONCLUSIONS: The findings from this study enrich our knowledge of the molecular characteristics of S. flexneri collected from calves with diarrhea, which will be important for addressing clinical and epidemiological issues regarding shigellosis.

14.
Front Cell Dev Biol ; 9: 684393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34179016

RESUMO

Toxoplasma gondii is an obligate intracellular pathogen that infects warm-blooded animals and humans. However, side effects limit toxoplasmosis treatment, and new drugs with high efficiency and low toxicity need to be developed. Natural products found in plants have become a useful source of drugs for toxoplasmosis. In this study, twenty natural compounds were screened for anti-T. gondii activity by Giemsa staining or real-time fluorescence quantitative polymerase chain reaction (qPCR) in vitro. Among these, licarin-B from nutmeg exhibited excellent anti-T. gondii activity, inhibiting T. gondii invasion and proliferation in a dose-dependent manner, with an EC50 of 14.05 ± 3.96 µg/mL. In the in vivo, licarin-B treatment significantly reduced the parasite burden in tissues compared to no treatment, protected the 90% infected mice from to death at 50 mg/kg.bw. Flow cytometry analysis suggested a significant reduction in T. gondii survival after licarin-B treatment. Ultrastructural changes in T. gondii were observed by transmission electron microscopy (TEM), as licarin-B induced mitochondrial swelling and formation of cytoplasmic vacuoles, an autophagosome-like double-membrane structure and extensive clefts around the T. gondii nucleus. Furthermore, MitoTracker Red CMXRos, MDC, and DAPI staining showed that licarin-B promoted mitochondrial damage, autophagosome formation, and nuclear disintegration, which were consistent with the TEM observations. Together, these findings indicate that licarin-B is a promising anti-T. gondii agent that potentially functions by damaging mitochondria and activating autophagy, leading to T. gondii death.

15.
Vet Parasitol ; 296: 109498, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34139615

RESUMO

In our previous studies, we found that as the active gradients of Adonis coerulea, cardenolides and cardiac glycosides presented toxicity against mites by inhibiting Na+-K+-ATPase. In this paper, after evaluating the acaricidal activity of the commercial cardiac aglycones/glycosides, serials of novel strophanthidin derivatives were designed and synthesized with an efficient and simple route under mild conditions, and their toxicity against mites, the cytotoxicity and inhibitory effect on Na+-K+-ATP enzyme in PC12 cells were investigated. Results showed among of all compounds, including 9 commercial agent and 32 synthesized strophanthidin derivatives, QXG-1 presented the strongest toxicity against mites with the LC50 value of 320.0 µg/mL. C-19 group of strophanthidin substituted with glycinemethylester would increase the toxicity against mites, and the hydroxyl group at C-5 play the vital role in terms of the toxicity. At the given concentration, QXG-1 displayed the safety against PC12 (10.0 µg/mL) in vitro and mice (3.2 mg/kg) in acute toxicity test, and strong inhibitory effect on Na+-K+-ATPase. It could be used as a promising acaricidal agent. This study lays the foundation to develop of QXG-1 as a relatively safe and alternative acaricidal agent.


Assuntos
Acaricidas , Psoroptidae , Estrofantidina , Acaricidas/farmacologia , Adenosina Trifosfatases/metabolismo , Adonis/química , Animais , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Camundongos , Psoroptidae/efeitos dos fármacos , Estrofantidina/farmacologia
16.
J Antibiot (Tokyo) ; 74(8): 508-518, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103703

RESUMO

Drug resistance has been partly driven by the overuse of antimicrobials in agricultural animal feed. Better understanding of antibiotic resistance in bovine gut is needed to assess its potential effects based on metagenomic approach and analysis. In this study, we collected 40 fecal samples to explore drug resistance derived from antibiotic use in the bacterial community by an analysis of the diversities and differences of antibiotic-resistant genes (ARGs) in the gut microbiota from yak, beef, and dairy cattle. Overall, 1688 genes were annotated, including 734 ARG subtypes. The ARGs were related to tetracyclines, quinolones, ß-lactam, and aminoglycosides, in accordance with the antibiotics widely used in the clinic for humans or animals. The emergence, prevalence, and differences in resistance genes in the intestines of yaks, beef, and dairy cattle may be caused by the selective pressure of different feeding patterns, where yaks were raised without antibiotics for growth promotion. In addition, the abundance of ARGs in yak was lower than in beef and dairy cattle, whereas the abundance of integron, a kind of mobile genetic elements (MGEs) was higher in yaks than those in beef and dairy cattle. Furthermore, the results of this study could provide the basis for a comprehensive profile of various ARGs among yak, beef, and dairy cattle in future.


Assuntos
Bovinos/microbiologia , Farmacorresistência Bacteriana/genética , Metagenômica/métodos , Microbiota/genética , Ração Animal , Animais , Laticínios , Fezes/microbiologia , Humanos , Integrons/genética , Sequências Repetitivas Dispersas/genética , Carne , Microbiologia do Solo , Especificidade da Espécie
17.
J Agric Food Chem ; 69(23): 6455-6464, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34075744

RESUMO

Rhizoctonia solani causes serious plant diseases. Neocryptolepine presented the significant antifungal activity against R. solani, however the mode of action is unclear. In this paper, we investigated the potential mode of action of neocryptolepine against R. solani integrated the proteomics and transcriptomics. Results showed that after treatment with neocryptolepine, 1012 differentially expressed proteins and 10 920 differentially expressed genes of R. solani were found, most of them were enriched in mitochondrial respiratory chain. It affected oxidative phosphorylation led to the enrichment of ROS and the decrease of MMP, and inhibited complex III activity with the inhibition rate of 63.51% at 10 µg/mL. The mitochondrial structural and function were damaged. Cytochrome b-c1 complex subunit Rieske (UQCRFS1) with the high binding score to neocryptolepine was found as a potential target. In addition, it inhibited the sclerotia formation and presented antifungal efficacy by decreasing the diameter of a wound in potato in a concentration-dependent manner. Above results indicated that neocryptolepine inhibited the complex III activity by binding UQCRFS1 and blocked the ion transfer to cause the death of R. solani mycelia. This study laid the foundation for the future development of neocryptolepine as an alternative biofungicide.


Assuntos
Alcaloides , Rhizoctonia , Alcaloides/farmacologia , Antifúngicos/farmacologia , Doenças das Plantas , Proteômica , Quinolinas , Rhizoctonia/genética , Transcriptoma
18.
Vet Med Sci ; 7(5): 2061-2067, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33949142

RESUMO

Aloe vera is reputed to have medicinal properties. For centuries, it has been used for an array of ailments such as mild fever, wounds and burns, gastrointestinal disorders, diabetes, sexual vitality and fertility problems to cancer, immune modulation, AIDS and various skin infections. In present study, antibacterial activity of aloe vera gel extracts was tested against some common skin infection pathogens, that is, Escherichia coli, Shigella, Salmonella spp. and Staphylococcus aureus all were recorded positive. Antibiotic resistance and susceptibility pattern of above isolates were also studied against 10 clinically significant antibiotics (ampicillin [AMC], amoxicillin, augmentin, cefotaxime, ceftazidime [CAZ], cefuroxime [CXM], ciprofloxaci, tetracycline, cefpodoxime and imipenem). AMC and CXM were found to be most effective antibiotic followed by CXM with highest efficacy against Gram-negative bacteria. In case of CAZ showed highest efficacy was showed against Gram-positive bacteria. Aloe vera leave gel was extracted with four different solvent-like aloe vera leaf extract, root extract, leaf ethanol extract and root ethanol extract; however, Gram-negative as well Gram-positive isolates was found highest susceptibility with aloe leaf and aloe root ethanol extract. Moderate sensitivity observed with aloe leaf extract and aloe root extract against both Gram-positive as well as Gram-negative bacterial isolates. This result showed that ethanol extracts of aloe vera both leaf and root can be used alongside conventional antibiotics to fight agents of infections that are so prevalent in the skin infection.

19.
Aging (Albany NY) ; 13(11): 15336-15352, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34047714

RESUMO

Histone acetylation which regulates about 2-10% of genes has been demonstrated to be involved in tumorigenesis of esophageal squamous cell carcinoma (ESCC). In this study, we investigated the treatment response of ESCC to selective histone deacetylase inhibitor (HDACi) LMK-235 and potential biomarker predicting the treatment sensitivity. We identified tensin-3 (TNS3) which was highly over-expressed in ESCC as one of the down-regulated genes in response to LMK-235 treatment. TNS3 was found positively correlated with the tumor malignancy and poor prognosis in the patients. Silencing TNS3 significantly inhibited ESCC cell proliferation both in vitro and in vivo, sensitizing the treatment response to LMK-235. Our findings provide an insight into understanding the oncogenic role of TNS3 in ESCC and its clinical application for HDAC targeted therapy of ESCC.


Assuntos
Benzamidas/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Tensinas/metabolismo , Animais , Benzamidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Bases de Dados como Assunto , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oncogenes , Fenótipo , RNA Interferente Pequeno/metabolismo
20.
J Virol ; 95(16): e0018721, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34037422

RESUMO

Subversion of the host cell cycle to facilitate viral replication is a common feature of coronavirus infections. Coronavirus nucleocapsid (N) protein can modulate the host cell cycle, but the mechanistic details remain largely unknown. Here, we investigated the effects of manipulation of porcine epidemic diarrhea virus (PEDV) N protein on the cell cycle and the influence on viral replication. Results indicated that PEDV N induced Vero E6 cell cycle arrest at S-phase, which promoted viral replication (P < 0.05). S-phase arrest was dependent on the N protein nuclear localization signal S71NWHFYYLGTGPHADLRYRT90 and the interaction between N protein and p53. In the nucleus, the binding of N protein to p53 maintained consistently high-level expression of p53, which activated the p53-DREAM pathway. The key domain of the N protein interacting with p53 was revealed to be S171RGNSQNRGNNQGRGASQNRGGNN194 (NS171-N194), in which G183RG185 are core residues. NS171-N194 and G183RG185 were essential for N-induced S-phase arrest. Moreover, small molecular drugs targeting the NS171-N194 domain of the PEDV N protein were screened through molecular docking. Hyperoside could antagonize N protein-induced S-phase arrest by interfering with interaction between N protein and p53 and inhibit viral replication (P < 0.05). The above-described experiments were also validated in porcine intestinal cells, and data were in line with results in Vero E6 cells. Therefore, these results reveal the PEDV N protein interacts with p53 to activate the p53-DREAM pathway, and subsequently induces S-phase arrest to create a favorable environment for virus replication. These findings provide new insight into the PEDV-host interaction and the design of novel antiviral strategies against PEDV. IMPORTANCE Many viruses subvert the host cell cycle to create a cellular environment that promotes viral growth. PEDV, an emerging and reemerging coronavirus, has led to substantial economic loss in the global swine industry. Our study is the first to demonstrate that PEDV N-induced cell cycle arrest during the S-phase promotes viral replication. We identified a novel mechanism of PEDV N-induced S-phase arrest, where the binding of PEDV N protein to p53 maintains consistently high levels of p53 expression in the nucleus to mediate S-phase arrest by activating the p53-DREAM pathway. Furthermore, a small molecular compound, hyperoside, targeted the PEDV N protein, interfering with the interaction between the N protein and p53 and, importantly, inhibited PEDV replication by antagonizing cell cycle arrest. This study reveals a new mechanism of PEDV-host interaction and also provides a novel antiviral strategy for PEDV. These data provide a foundation for further research into coronavirus-host interactions.


Assuntos
Antivirais/farmacologia , Proteínas do Nucleocapsídeo de Coronavírus/química , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Vírus da Diarreia Epidêmica Suína/efeitos dos fármacos , Quercetina/análogos & derivados , Proteína Supressora de Tumor p53/química , Sequência de Aminoácidos , Animais , Antivirais/química , Sítios de Ligação , Linhagem Celular , Chlorocebus aethiops , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Proteínas do Nucleocapsídeo de Coronavírus/antagonistas & inibidores , Proteínas do Nucleocapsídeo de Coronavírus/genética , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Regulação da Expressão Gênica , Ensaios de Triagem em Larga Escala , Interações Hospedeiro-Patógeno/genética , Simulação de Acoplamento Molecular , Sinais de Localização Nuclear , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/metabolismo , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Quercetina/química , Quercetina/farmacologia , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase S do Ciclo Celular/genética , Transdução de Sinais , Suínos , Doenças dos Suínos/tratamento farmacológico , Doenças dos Suínos/genética , Doenças dos Suínos/metabolismo , Doenças dos Suínos/virologia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Células Vero , Replicação Viral/efeitos dos fármacos
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