RESUMO
BACKGROUND: It is unclear whether acetabular reconstruction techniques have any impact on clinical outcomes. This study aimed to determine (1) whether acetabular reconstruction techniques influenced the position of the acetabular cup and (2) whether clinical outcomes based on the acetabular reconstruction techniques differ in patients undergoing total hip arthroplasty (THA) with Crowe II to III developmental dysplasia of the hip. METHODS: This was a retrospective analysis of prospectively collected data from 69 patients (74 hips) who were treated with cementless THA using medial protrusio technique (MPT) or structural autologous bone-grafting technique (SABT). There were 39 patients (41 hips) included in the MPT group and 30 patients (33 hips) in the SABT group. Clinical and radiographic outcomes were evaluated. RESULTS: All patients were followed up for at least 3 years. There were similar results between the 2 groups in terms of blood loss, Harris hip score, leg length discrepancy, cup inclination, cup anteversion, and proportion of cup coverage (P > .05). The operative time was significantly longer in the SABT group compared with the MPT group (P < .001). The postoperative vertical center of rotation was significantly higher in the MPT group compared with the SABT group (P = .001), and postoperative horizontal center of rotation was significantly shallower in the SABT group compared with the MPT group (P < .001). CONCLUSION: The MPT and SABT provide similar clinical and radiographic outcomes in the management of Crowe II to III developmental dysplasia of the hip by cementless THA. However, the MPT has the advantage of a shorter operative time, whereas the SABT is more conducive to placing the acetabular cup in an anatomic position. LEVEL OF EVIDENCE: Level III, Therapeutic, Case-Control Study.
Assuntos
Artroplastia de Quadril , Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Luxação do Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Luxação do Quadril/etiologia , Estudos Retrospectivos , Estudos de Casos e Controles , Displasia do Desenvolvimento do Quadril/cirurgia , Displasia do Desenvolvimento do Quadril/etiologia , Resultado do Tratamento , Luxação Congênita de Quadril/cirurgia , Acetábulo/cirurgiaRESUMO
Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in young women, but its pathogenesis remains unclear. The primary pathogenic factors contributing to its development include genetics, abnormal bone metabolism, and endocrine factors. Bone marrow stem cells (BMSCs) play a crucial role in the pathogenesis of AIS by regulating its occurrence and progression. Noncoding RNAs (ncRNAs) are also involved in the pathogenesis of AIS, and their role in regulating BMSCs in patients with AIS requires further evaluation. In this review, we discuss the relevant literature regarding the osteogenic, chondrogenic, and lipogenic differentiation of BMSCs. The corresponding mechanisms of ncRNA-mediated BMSC regulation in patients with AIS, recent advancements in AIS and ncRNA research, and the importance of ncRNA translation profiling and multiomics are highlighted.
RESUMO
Adolescent idiopathic scoliosis (AIS) is a complex disease characterized by three-dimensional structural deformities of the spine. Its pathogenesis is associated with osteopenia. Bone-marrow-derived mesenchymal stem cells (BMSCs) play an important role in bone metabolism. We detected 1919 differentially expressed mRNAs and 744 differentially expressed lncRNAs in BMSCs from seven patients with AIS and five patients without AIS via high-throughput sequencing. Multiple analyses identified bone morphogenetic protein-6 (BMP6) as a hub gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS. BMP6 expression was found to be decreased in AIS and its knockdown in human BMSCs significantly altered the degree of osteogenic differentiation. Additionally, CAP1-217 has been shown to be a potential upstream regulatory molecule of BMP6. We showed that CAP1-217 knockdown downregulated the expression of BMP6 and the osteogenic differentiation of BMSCs. Simultaneously, knockout of BMP6 in zebrafish embryos significantly increased the deformity rate. The findings of this study suggest that BMP6 is a key gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS via the CAP1-217/BMP6/RUNX2 axis.
Assuntos
Doenças Ósseas Metabólicas , Escoliose , Humanos , Adolescente , Animais , Escoliose/genética , Escoliose/patologia , Osteogênese/genética , Peixe-Zebra/genética , Coluna Vertebral/metabolismo , Diferenciação Celular/genética , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/metabolismo , Células Cultivadas , Células da Medula Óssea/metabolismo , Proteína Morfogenética Óssea 6/genéticaRESUMO
Adolescent idiopathic scoliosis (AIS) is a common spinal deformity characterized by changes in the three-dimensional structure of the spine. It usually initiates during puberty, the peak period of human growth when the secretion of numerous hormones is changing, and it is more common in females than in males. Accumulating evidence shows that the abnormal levels of many hormones including estrogen, melatonin, growth hormone, leptin, adiponectin and ghrelin, may be related to the occurrence and development of AIS. The purpose of this review is to provide a summary and critique of the research published on each hormone over the past 20 years, and to highlight areas for future study. It is hoped that the presentation will help provide a better understanding of the role of endocrine hormones in the pathogenesis of AIS.
Assuntos
Células Endócrinas/metabolismo , Hormônios/metabolismo , Escoliose/metabolismo , Adolescente , Animais , HumanosRESUMO
The invasion and colonization of host plants by the destructive pathogen Ralstonia solanacearum rely on its cell motility, which is controlled by multiple factors. Here, we report that the LysR-type transcriptional regulator CrgA (RS_RS16695) represses cell motility in R. solanacearum GMI1000. CrgA possesses common features of a LysR-type transcriptional regulator and contains an N-terminal helix-turn-helix motif as well as a C-terminal LysR substrate-binding domain. Deletion of crgA results in an enhanced swim ring and increased transcription of flhDC In addition, the ΔcrgA mutant possesses more polar flagella than wild-type GMI1000 and exhibits higher expression of the flagellin gene fliC Despite these alterations, the ΔcrgA mutant did not have a detectable growth defect in culture. Yeast one-hybrid and electrophoretic mobility shift assays revealed that CrgA interacts directly with the flhDC promoter. Expressing the ß-glucuronidase (GUS) reporter under the control of the crgA promoter showed that crgA transcription is dependent on cell density. Soil-soaking inoculation with the crgA mutant caused wilt symptoms on tomato (Solanum lycopersicum L. cv. Hong yangli) plants earlier than inoculation with the wild-type GMI1000 but resulted in lower disease severity. We conclude that the R. solanacearum regulator CrgA represses flhDC expression and consequently affects the expression of fliC to modulate cell motility, thereby conditioning disease development in host plants.IMPORTANCERalstonia solanacearum is a widely distributed soilborne plant pathogen that causes bacterial wilt disease on diverse plant species. Motility is a critical virulence attribute of R. solanacearum because it allows this pathogen to efficiently invade and colonize host plants. In R. solanacearum, motility-defective strains are markedly affected in pathogenicity, which is coregulated with multiple virulence factors. In this study, we identified a new LysR-type transcriptional regulator (LTTR), CrgA, that negatively regulates motility. The mutation of the corresponding gene leads to the precocious appearance of wilt symptoms on tomato plants when the pathogen is introduced using soil-soaking inoculation. This study indicates that the regulation of R. solanacearum motility is more complex than previously thought and enhances our understanding of flagellum regulation in R. solanacearum.
Assuntos
Proteínas de Bactérias/fisiologia , Flagelos/fisiologia , Ralstonia solanacearum/fisiologia , Transativadores/fisiologia , Fatores de Transcrição/fisiologia , Ensaio de Desvio de Mobilidade Eletroforética , Solanum lycopersicum/microbiologia , Microscopia Eletrônica de Transmissão , Regiões Promotoras Genéticas/fisiologia , Ralstonia solanacearum/genética , Ralstonia solanacearum/patogenicidade , Ralstonia solanacearum/ultraestrutura , Reação em Cadeia da Polimerase em Tempo Real , Elementos Reguladores de Transcrição/fisiologia , Microbiologia do Solo , Técnicas do Sistema de Duplo-Híbrido , VirulênciaRESUMO
RipX of Ralstonia solanacearum is translocated into host cells by a type III secretion system and acts as a harpin-like protein to induce a hypersensitive response in tobacco plants. The molecular events in association with RipX-induced signaling transduction have not been fully elucidated. This work reports that transient expression of RipX induced a yellowing phenotype in Nicotiana benthamiana, coupled with activation of the defense reaction. Using yeast two-hybrid and split-luciferase complementation assays, mitochondrial ATP synthase F1 subunit α (ATPA) was identified as an interaction partner of RipX from N. benthamiana. Although a certain proportion was found in mitochondria, the YFP-ATPA fusion was able to localize to the cell membrane, cytoplasm, and nucleus. RFP-RipX fusion was found from the cell membrane and cytoplasm. Moreover, ATPA interacted with RipX at both the cell membrane and cytoplasm in vivo. Silencing of the atpA gene had no effect on the appearance of yellowing phenotype induced by RipX. However, the silenced plants improved the resistance to R. solanacearum. Moreover, qRT-PCR and promoter GUS fusion experiments revealed that the transcript levels of atpA were evidently reduced in response to expression of RipX. These data demonstrated that RipX exerts a suppressive effect on the transcription of atpA gene, to induce defense reaction in N. benthamiana.
Assuntos
Proteínas de Bactérias , Resistência à Doença/genética , Nicotiana , Proteínas de Plantas , ATPases Translocadoras de Prótons , Ralstonia solanacearum , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , ATPases Translocadoras de Prótons/genética , ATPases Translocadoras de Prótons/metabolismo , Ralstonia solanacearum/genética , Ralstonia solanacearum/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/microbiologiaRESUMO
To counteract host antiviral RNA silencing, plant viruses encode numerous viral suppressors of RNA silencing (VSRs). P0 proteins have been identified as VSRs in many poleroviruses. However, their suppressor function has not been fully characterized. Here, we investigated the function of P0 from pea mild chlorosis virus (PMCV) in the suppression of local and systemic RNA silencing via green fluorescent protein (GFP) co-infiltration assays in wild-type and GFP-transgenic Nicotiana benthamiana (line 16c). Amino acid deletion analysis showed that N-terminal residues Asn 2 and Val 3, but not the C-terminus residues from 230-270 aa, were necessary for PMCV P0 (P0PM) VSR activity. P0PM acted as an F-box protein, and triple LPP mutation (62LPxx79P) at the F-box-like motif abolished its VSR activity. In addition, P0PM failed to interact with S-phase kinase-associated protein 1 (SKP1), which was consistent with previous findings of P0 from potato leafroll virus. These data further support the notion that VSR activity of P0 is independent of P0-SKP1 interaction. Furthermore, we examined the effect of P0PM on ARGONAUTE1 (AGO1) protein stability, and co-expression analysis showed that P0PM triggered AGO1 degradation. Taken together, our findings suggest that P0PM promotes degradation of AGO1 to suppress RNA silencing independent of SKP1 interaction.
Assuntos
Proteínas F-Box/metabolismo , Luteoviridae/metabolismo , Proteína P0 da Mielina/metabolismo , Nicotiana/genética , Nicotiana/virologia , Necrose e Clorose das Plantas/virologia , Interferência de RNA , Proteínas Virais/metabolismo , Proteínas Argonautas/metabolismo , Proteínas de Fluorescência Verde/genética , Mutação , Organismos Geneticamente Modificados , Necrose e Clorose das Plantas/genética , Proteínas de Plantas/metabolismo , Proteólise , Proteínas Quinases Associadas a Fase S/metabolismoRESUMO
Ralstonia solanacearum is the causal agent of bacterial wilt disease. Here, we report that a large FAD-linked oxidase encoded by RSc0454 in GMI1000 is required for pathogenicity. The FAD-linked oxidase encoded by RSc0454 is composed of 1,345 amino acids, including DUF3683, lactate dehydrogenase (LDH), and succinate dehydrogenase (SDH) domains. The RSc0454 protein showed both LDH and SDH activities. To investigate its role in pathogenicity, a deletion mutant of the RSc0454 gene was constructed in GMI1000, which was impaired in its ability to cause bacterial wilt disease in tomato. A single DUF3683, LDH, or SDH domain was insufficient to restore bacterial pathogenicity. Mutagenesis of the RSc0454 gene did not affect growth rate but caused cell aggregation at the bottom of the liquid nutrient medium, which was reversed by exogenous applications of lactate, fumarate, pyruvate, and succinate. qRT-PCR and promoter LacZ fusion experiments demonstrated that RSc0454 gene transcription was induced by lactate and fumarate (both substrates of LDH). Compared with the downregulation of the succinate dehydrogenase gene sdhBADC and the lactate dehydrogenase gene ldh, RSc0454 gene transcription was enhanced in planta. This suggests that the oxidase encoded by RSc0454 was involved in a redox balance, which is in line with the different living conditions of R. solanacearum.
Assuntos
Oxirredutases , Ralstonia solanacearum , Virulência , Flavina-Adenina Dinucleotídeo/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Doenças das Plantas/microbiologia , Ralstonia solanacearum/enzimologia , Ralstonia solanacearum/genética , Ralstonia solanacearum/patogenicidade , Deleção de Sequência , Virulência/genéticaRESUMO
Adolescent idiopathic scoliosis (AIS) is a severe spinal deformity that often occurs during puberty. The occurrence of AIS is suggested to be related to abnormal development of cartilage. Our previous study found increased serum ghrelin levels in AIS patients that may linked to the development of AIS. However, whether ghrelin affects cartilage in AIS patients is unclear. We used quantitative real-time PCR (qRT-PCR) and immunohistochemistry to detect the expression of cartilage-specific genes and the ghrelin receptor, growth hormone secretagogue receptor (GHSR). The mRNA and protein levels of collagen II (COLII), SOX9, AGGRECAN (ACAN) and GHSR were higher in AIS patients than in controls. In addition, the protein levels of GHSR downstream signaling pathway members p-STAT3 (Ser727), and p-ERK1/2 were increased. Furthermore, we treated chondrocytes from AIS patients with 100 nM ghrelin, the cell proliferation assay and Western blotting showed that ghrelin promotes chondrocyte proliferation and enhances COLII, SOX9, ACAN, p-ERK1/2 and p-STAT3 expression, respectively. Interestingly, all these observed alterations were abolished by ghrelin + [D-Lys3]-GHRP-6 (a ghrelin receptor inhibitor) treatment. And after U0126 (an inhibitor of ERK1/2 phosphorylation) treatment, ERK1/2 and STAT3 (Ser727) phosphorylation was simultaneously suppressed indicating that ERK1/2 is an upstream pathway protein of STAT3 (Ser727). In conclusion, ghrelin plays an important role in upregulating cartilage-specific genes on AIS primary chondrocytes by activating ERK/STAT3 signaling pathway.
Assuntos
Condrócitos/efeitos dos fármacos , Grelina/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Escoliose/tratamento farmacológico , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Adolescente , Agrecanas/genética , Agrecanas/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Criança , Condrócitos/metabolismo , Condrócitos/patologia , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Humanos , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Escoliose/metabolismo , Escoliose/patologiaRESUMO
Xanthomonas citri subsp. citri (Xcc) is the causal agent of citrus canker, a serious bacterial disease that affects citrus trees worldwide. The ectopic expression of TAL effector AvrXa7 in Xcc suppressed canker development. The Xcc strain expressing avrXa7 induced a yellow symptom around the inoculation site. Transcriptome analysis revealed 315 differentially expressed genes, which were categorized into several functional groups. The more interesting genes were those involved in the biosynthesis of terpene and ethylene. In particular, the linoleate 13â¯S-lipoxygenase gene CsLOX2-1 was found to possess the AvrXa7 binding sequence in the promoter region. The recognition of AvrXa7 to the CsLOX2-1 promoter was subsequently confirmed by yeast one-hybrid and electrophoretic mobility shift experiments. This demonstrated that the TALE effector AvrXa7 promotes CsLOX2-1 expression by directly binding to the promoter sequence. Our findings contribute a valuable clue to identifying the potential genes that can be used to prevent citrus canker.
Assuntos
Proteínas de Bactérias/genética , Citrus/genética , Citrus/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Efetores Semelhantes a Ativadores de Transcrição/genética , Xanthomonas/genética , Xanthomonas/patogenicidade , Proteínas de Bactérias/metabolismo , Agentes de Controle Biológico , Citrus/metabolismo , Expressão Ectópica do Gene , Genes de Plantas , Lipoxigenase/genética , Lipoxigenase/metabolismo , Doenças das Plantas/prevenção & controle , Regiões Promotoras Genéticas , Efetores Semelhantes a Ativadores de Transcrição/metabolismo , TranscriptomaRESUMO
Jasmine virus H (JaVH) is a novel virus associated with symptoms of yellow mosaic on jasmine. The JaVH genome is 3,867 nt in length with five open reading frames (ORFs) encoding a 27-kDa protein (ORF 1), an 87-kDa replicase protein (ORF 2), two centrally located movement proteins (ORF 3 and 4), and a 37-kDa capsid protein (ORF 5). Based on genomic and phylogenetic analysis, JaVH is predicted to be a member of the genus Pelarspovirus in the family Tombusviridae.
Assuntos
Genoma Viral , Jasminum/virologia , Filogenia , RNA Viral/genética , Tombusviridae/genética , Sequência de Bases , Proteínas do Capsídeo/genética , Sequenciamento de Nucleotídeos em Larga Escala , Fases de Leitura Aberta , RNA Polimerase Dependente de RNA/genética , Tombusviridae/classificação , Tombusviridae/isolamento & purificaçãoRESUMO
To evaluate the effect of Chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque. Eight SIV rhesus macaques of the same age were randomly divided into Chinese medicine of invigorating spleen and kidney detoxification group(hereinafter referred to as Chinese medicine group) and anti-virus drug(HAART) group. The traditional Chinese medicine and antiviral therapy were given for 8 weeks, and peripheral blood was collected for detection in every 4 weeks. The results showed that Chinese medicine of invigorating spleen and kidney detoxification could not obviously decrease plasma viral load as HAART, but it can increase CD4 number in peripheral blood, especially the CD4 naive cells, and increase the number of CD4 and CD8 cells, enhance the immune response to pathogens. Therefore, it delayed the occurrence and development of spleen deficiency to a certain extent, indicating that the medicine had immune regulation effect, with considerable clinical value and application prospects.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Animais , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Macaca mulatta , Vírus da Imunodeficiência Símia , Carga ViralRESUMO
Recent evidence indicates that mesenchymal stem cells (MSC) derived from early embryonic tissues have better therapeutic ability as compared with adult tissue-derived stem cells. In the present study, we transplanted human early embryonic MSC (hMSC) into MRL/Lpr mice via tail vein injection to observe the therapeutic efficacy of hMSC and their impact on T helper 17 (Th17) cell differentiation in MRL/Lpr mice. Animals in hMSC treatment group received hMSC (1 × 106/200 µL) via the tail vein at the age of 16 and 19 weeks. We found that hMSC treatment prolonged the survival of MRL/Lpr mice without inducing tumorigenesis, reduced urine protein, and alleviated the renal pathologic changes. In addition, it reduced the proportion of Th17 cells in the spleen of MRL/Lpr mice and the serum interleukin 17 (IL-17) concentration. Our in vitro experiment also demonstrated that hMSC could secrete Th17 differentiation-related cytokines of PGE2, IL-10 and TGF-ß, and IFN-γ stimulation up-regulated the secretion of these immune regulating factors. The results of the present study suggest that hMSC therapy could alleviate systemic and local renal lesions in MRL/Lpr mice, probably by secreting immune regulating factors and regulating Th17 cell differentiation in MRL/Lpr mice.
Assuntos
Células-Tronco Embrionárias/citologia , Imunidade Celular , Rim/patologia , Lúpus Eritematoso Sistêmico/prevenção & controle , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Células Th17/imunologia , Animais , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Interleucina-17/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos MRL lpr , Células Th17/patologiaRESUMO
BACKGROUND: The carA and carB genes code the small and large subunits of carbamoyl-phosphate synthase (CPS) that responsible for arginine and pyrimidine production. The purpose of this work was to study the gene organization and expression pattern of carAB operon, and the biological functions of carA and carB genes in Xanthomonas citri subsp. citri. METHODS: RT-PCR method was employed to identify the full length of carAB operon transcript in X. citri subsp. citri. The promoter of carAB operon was predicted and analyzed its activity by fusing a GUS reporter gene. The swimming motility was tested on 0.25% agar NY plates with 1% glucose. Biofilm was measured by cell adhesion to polyvinyl chloride 96-well plate. RESULTS: The results indicated that carAB operon was composed of five gene members carA-orf-carB-greA-rpfE. A single promoter was predicted from the nucleotide sequence upstream of carAB operon, and its sensitivity to glutamic acid, uracil and arginine was confirmed by fusing a GUS reporter gene. Deletion mutagenesis of carB gene resulted in reduced abilities in swimming on soft solid media and in forming biofilm on polystyrene microtiter plates. CONCLUSIONS: From these results, we concluded that carAB operon was involved in multiple biological processes in X. citri subsp. citri.
Assuntos
Biofilmes/crescimento & desenvolvimento , Carbamoil-Fosfato Sintase (Amônia)/genética , Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Locomoção , Óperon , Xanthomonas/genética , Xanthomonas/fisiologia , Análise Mutacional de DNA , Perfilação da Expressão Gênica , Ordem dos Genes , Genes Bacterianos , Genes Reporter , Glucuronidase/análise , Glucuronidase/genética , Regiões Promotoras Genéticas , Deleção de Sequência , Transcrição GênicaRESUMO
Polerovirus P0 suppressors of host gene silencing contain a consensus F-box-like motif with Leu/Pro (L/P) requirements for suppressor activity. The Inner Mongolian Potato leafroll virus (PLRV) P0 protein (P0(PL-IM)) has an unusual F-box-like motif that contains a Trp/Gly (W/G) sequence and an additional GW/WG-like motif (G139/W140/G141) that is lacking in other P0 proteins. We used Agrobacterium infiltration-mediated RNA silencing assays to establish that P0(PL-IM) has a strong suppressor activity. Mutagenesis experiments demonstrated that the P0(PL-IM) F-box-like motif encompasses amino acids 76-LPRHLHYECLEWGLLCG THP-95, and that the suppressor activity is abolished by L76A, W87A, or G88A substitution. The suppressor activity is also weakened substantially by mutations within the G139/W140/G141 region and is eliminated by a mutation (F220R) in a C-terminal conserved sequence of P0(PL-IM). As has been observed with other P0 proteins, P0(PL-IM) suppression is correlated with reduced accumulation of the host AGO1-silencing complex protein. However, P0(PL-IM) fails to bind SKP1, which functions in a proteasome pathway that may be involved in AGO1 degradation. These results suggest that P0(PL-IM) may suppress RNA silencing by using an alternative pathway to target AGO1 for degradation. Our results help improve our understanding of the molecular mechanisms involved in PLRV infection.
Assuntos
Luteoviridae/metabolismo , Nicotiana/virologia , Doenças das Plantas/virologia , RNA Interferente Pequeno/metabolismo , Solanum tuberosum/virologia , Proteínas Virais/genética , Sequência de Aminoácidos , Proteínas Argonautas , China , Sequência Conservada , Motivos F-Box , Regulação da Expressão Gênica de Plantas , Luteoviridae/genética , Dados de Sequência Molecular , Mutação , Folhas de Planta/genética , Folhas de Planta/metabolismo , Folhas de Planta/virologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Interferência de RNA , Proteínas Quinases Associadas a Fase S/genética , Proteínas Quinases Associadas a Fase S/metabolismo , Alinhamento de Sequência , Nicotiana/genética , Nicotiana/metabolismo , Técnicas do Sistema de Duplo-Híbrido , Proteínas Virais/metabolismoRESUMO
Xanthomonas citri subsp. citri (Xcc), the causal agent of citrus canker, elicits canker symptoms in citrus plants because of the transcriptional activator-like (TAL) effector PthA4, which activates the expression of the citrus susceptibility gene CsLOB1. This study reports the regulation of the putative carbohydrate-binding protein gene Cs9g12620 by PthA4-mediated induction of CsLOB1 during Xcc infection. We found that the transcription of Cs9g12620 was induced by infection with Xcc in a PthA4-dependent manner. Even though it specifically bound to a putative TAL effector-binding element in the Cs9g12620 promoter, PthA4 exerted a suppressive effect on the promoter activity. In contrast, CsLOB1 bound to the Cs9g12620 promoter to activate its expression. The silencing of CsLOB1 significantly reduced the level of expression of Cs9g12620, which demonstrated that Cs9g12620 was directly regulated by CsLOB1. Intriguingly, PhtA4 interacted with CsLOB1 and exerted feedback control that suppressed the induction of expression of Cs9g12620 by CsLOB1. Transient overexpression and gene silencing revealed that Cs9g12620 was required for the optimal development of canker symptoms. These results support the hypothesis that the expression of Cs9g12620 is dynamically directed by PthA4 for canker formation through the PthA4-mediated induction of CsLOB1.
Assuntos
Proteínas de Bactérias , Citrus , Doenças das Plantas , Xanthomonas , Xanthomonas/genética , Xanthomonas/metabolismo , Doenças das Plantas/microbiologia , Citrus/microbiologia , Citrus/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Regiões Promotoras GenéticasRESUMO
Ralstonia solanacearum (Rso) causes destructive bacterial wilt across a broad range of host plants by delivering a repertoire of type III effectors. In the present study, we determined that the deletion of the type III effector RipAF1 resulted in increased virulence on Nicotiana benthamiana, Solanum lycopersicum, and Capsicum annuum plants. RipAF1 showed ADP-ribosylation activity in vivo and in vitro. Transient overexpression of RipAF1 suppressed jasmonic acid (JA) signaling and induced salicylic acid (SA) signaling. The ADP-ribosylation activity of RipAF1 was essential for JA and SA signaling mediation. Host fibrillin FBN1 was identified as a RipAF1-interactor that is ADP-ribosylated by RipAF1 directly. Most importantly, the ADP-ribosylation of conserved residues of FBN1 contributes to its localization to the plasma membrane and leads to the suppression of JA signaling and induction of SA signaling. We concluded that RipAF1 mediates antagonistic crosstalk between JA and SA signaling pathways by ADP-ribosylation of FBN1.
RESUMO
Background: Metabolic syndrome (MetS) has been shown to have a negative impact on prostate cancer (PCa). However, there is limited research on the effects of MetS on testosterone levels in metastatic prostate cancer (mPCa). Objective: This study aims to investigate the influence of MetS, its individual components, and composite metabolic score on the prognosis of mPCa patients, as well as the impact on testosterone levels. Additionally, it seeks to identify MetS-related risk factors that could impact the time of decline in testosterone levels among mPCa patients. Methods: A total of 212 patients with mPCa were included in the study. The study included 94 patients in the Non-MetS group and 118 patients in the combined MetS group. To analyze the relationship between MetS and testosterone levels in patients with mPCa. Additionally, the study aimed to identify independent risk factors that affect the time for testosterone levels decline through multifactor logistic regression analysis. Survival curves were plotted by the Kaplan-Meier method. Results: Compared to the Non-MetS group, the combined MetS group had a higher proportion of patients with high tumor burden, T stage ≥ 4, and Gleason score ≥ 8 points (P < 0.05). Patients in the combined MetS group also had higher lowest testosterone values and it took longer for their testosterone to reach the lowest level (P < 0.05). The median progression-free survival (PFS) time for patients in the Non-MetS group was 21 months, while for those in the combined MetS group it was 18 months (P = 0.001). Additionally, the median overall survival (OS) time for the Non-MetS group was 62 months, whereas for the combined MetS group it was 38 months (P < 0.001). The median PFS for patients with a composite metabolic score of 0-2 points was 21 months, 3 points was 18 months, and 4-5 points was 15 months (P = 0.002). The median OS was 62 months, 42 months, and 29 months respectively (P < 0.001). MetS was found to be an independent risk factor for testosterone levels falling to the lowest value for more than 6 months. The risk of testosterone levels falling to the lowest value for more than 6 months in patients with MetS was 2.157 times higher than that of patients with Non-MetS group (P = 0.031). Patients with hyperglycemia had a significantly higher lowest values of testosterone (P = 0.015). Additionally, patients with a BMI ≥ 25 kg/m2 exhibited lower initial testosterone levels (P = 0.007). Furthermore, patients with TG ≥ 1.7 mmol/L experienced a longer time for testosterone levels to drop to the nadir (P = 0.023). The lowest value of testosterone in the group with a composite metabolic score of 3 or 4-5 was higher than that in the 0-2 group, and the time required for testosterone levels to decrease to the lowest value was also longer (P < 0.05). Conclusion: When monitoring testosterone levels in mPCa patients, it is important to consider the impact of MetS and its components, and make timely adjustments to individualized treatment strategies.
Assuntos
Síndrome Metabólica , Neoplasias da Próstata , Testosterona , Humanos , Masculino , Síndrome Metabólica/sangue , Testosterona/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/metabolismo , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Prognóstico , Gradação de Tumores , Metástase NeoplásicaRESUMO
Osteosarcoma (OS) is the most common malignancy in children and adolescents and has a high probability of recurrence and metastasis. A growing number of studies have shown that neutrophil extracellular traps (NETs) are strongly associated with cancer metastasis, but in osteosarcoma, genes associated with NETs that promote osteosarcoma recurrence and metastasis remain to be explored. We systematically investigated the gene expression patterns of NETs in OS samples from the GEO database. NETs molecular typing was evaluated based on NETs expression profiles, and the association between NETs molecular subtypes and immune microenvironment and metastatic features were explored. Ultimately, we constructed a signature model and column line graph associated with metastasis prediction and screened possible potential drugs for metastatic osteosarcoma. We established two different molecular subtypes of NETs, which showed significant differences in metastatic status, metastasis time, tumor immune microenvironment, and biological effects. We also constructed a NETs-related gene metastasis signature(NRGMS) to assess the expression pattern of NETs in patients to predict metastatic recurrence in osteosarcoma patients. We screened for TOMM40 and FH associated with metastatic recurrence in osteosarcoma patients. Overall, this study constructs a predictive model for osteosarcoma metastasis of NETs-related genes, which is expected to provide new insights into the metastasis of osteosarcoma.
Assuntos
Neoplasias Ósseas , Armadilhas Extracelulares , Segunda Neoplasia Primária , Osteossarcoma , Adolescente , Criança , Humanos , Armadilhas Extracelulares/genética , Osteossarcoma/genética , Bases de Dados Factuais , Neoplasias Ósseas/genética , Microambiente Tumoral/genéticaRESUMO
Bone is the third most common metastatic site for all primary tumors, the common primary focus of bone metastases include breast cancer, prostate cancer, and so on. And the median survival time of patients with bone metastases is only 2-3 years. Therefore, it is urgent to develop new targets to diagnose and treat bone metastases. Based on two data sets GSE146661 and GSE77930 associated with bone metastases, it was found that 209 genes differentially expressed in bone metastases group and control group. PECAM1 was selected as hub-gene for the follow-up research after constructing protein-protein interaction (PPI) network and enrichment analysis. Moreover, q-PCR analysis verified that the expression of PECAM1 decreased in bone metastatic tumor tissues. PECAM1 was believed to be possibly related to the function of osteoclasts, we knocked down the expression of PECAM1 with shRNA in lymphocytes extracted from bone marrow nailed blood. The results indicated that sh-PECAM1 treatment could promote osteoclast differentiation, and the sh-PECAM1-treated osteoclast culture medium could significantly promote the proliferation and migration of tumor cells. These results suggested that PECAM1 may be a potential biomarker for the diagnosis and treatment of bone metastases of tumor.