RESUMO
Introduction: The etiology of esophageal squamous papilloma (ESP) is largely unknown. Previous studies have shown a variable association with human papillomavirus (HPV) with conflicting data. The aim of this study was to further investigate the possible association of HPV in our ESP series using RNA in-situ hybridization (ISH) and compare study groups from the United States of America and China. Methods: Demographic and clinical data of patients with ESP were retrieved from the University of California Los Angeles (UCLA) (1/2016-3/2019) and Peking Union Medical College Hospital (PUMCH) (9/2014-3/2019) pathology databases. Hematoxylin and eosin slides were reexamined. Confirmed cases were examined by high- and low-risk HPV RNA ISH. Results: For the UCLA cohort, 13â 429 upper endoscopies were performed and 78 biopsies from 72 patients were identified as ESP (F:M = 45:27, 66.7% > 45 years). Seventy-four (94.9%) biopsies were designated as polyps or nodules and 46.6% were located in the mid-esophagus. Other abnormal findings included gastroesophageal reflux disease (48.6%), hiatal hernia (38.9%), and esophagitis (36.1%). For the PUMCH cohort, 63â 754 upper endoscopies were performed and 73 biopsies from 71 patients were identified as ESP (F:M = 48:23, 71.8% > 45 years). Sixty-four (87.7%) biopsies were designated as polyps or nodules and 57.5% were located in the mid-esophagus. Other abnormal findings included esophagitis (19.7%), and hiatal hernia (8.5%). No features of conventional cytologic dysplasia or viral cytopathic change were found. None of the cases was associated with squamous cell carcinoma, and none showed positive HPV RNA ISH results. Conclusions: No association was found between ESP and active HPV infection in our 2 cohorts. Other etiopathogenetic mechanisms, such as aging, might contribute to the development of these innocent lesions.
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Exquisitely regulated plastid-to-nucleus communication by retrograde signaling pathways is essential for fine-tuning of responses to the prevailing environmental conditions. The plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) has emerged as a stress signal transduced into a diverse ensemble of response outputs. Here, we demonstrate enhanced phytochrome B protein abundance in red light-grown MEcPP-accumulating ceh1 mutant Arabidopsis (Arabidopsis thaliana) plants relative to wild-type seedlings. We further establish MEcPP-mediated coordination of phytochrome B with auxin and ethylene signaling pathways and uncover differential hypocotyl growth of red light-grown seedlings in response to these phytohormones. Genetic and pharmacological interference with ethylene and auxin pathways outlines the hierarchy of responses, placing ethylene epistatic to the auxin signaling pathway. Collectively, our findings establish a key role of a plastidial retrograde metabolite in orchestrating the transduction of a repertoire of signaling cascades. This work positions plastids at the zenith of relaying information coordinating external signals and internal regulatory circuitry to secure organismal integrity.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Etilenos/metabolismo , Ácidos Indolacéticos/metabolismo , Fitocromo B/metabolismo , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/efeitos da radiação , Arabidopsis/efeitos dos fármacos , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/efeitos da radiação , Vias Biossintéticas/efeitos dos fármacos , Vias Biossintéticas/genética , Vias Biossintéticas/efeitos da radiação , Epistasia Genética/efeitos dos fármacos , Epistasia Genética/efeitos da radiação , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Genes de Plantas , Hipocótilo/efeitos dos fármacos , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/efeitos da radiação , Ácidos Indolacéticos/farmacologia , Luz , Mutação/genética , Fitocromo B/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiaçãoRESUMO
The present study investigated the pharmacodynamic role and therapeutic mechanism of demethylzeylasteral in the suppression of inflammation in a rat model of unilateral ureteral obstruction and reduction in nuclear factor (NF)κB pathway activity. The rats in the unilateral ureteral obstruction model were treated with 30120 mg/kg demethylzeylasteral for 8 weeks. The activities of tumor necrosis factor (TNF)α, interleukin (IL)6 and caspase3/9, and the protein expression levels of cyclooxygenase (COX)2 and intercellular adhesion molecule1 (ICAM1) and NFκB p65 were analyzed using ELISA kits and western blot analyses, respectively. Compared with the rats in the unilateral ureteral obstruction model group, demethylzeylasteral treatment markedly inhibited the increased concentrations of serum creatinine and blood urea nitrogen, urinary protein/creatinine ratio, and concentrations of highdensity lipoprotein and lowdensity lipoprotein cholesterol, and prevented kidney damage. In addition, demethylzeylasteral inhibited the levels of TNFα andIL6 and suppressed the protein expression levels of COX2 and ICAM1 in the kidneys of the rats in the unilateral ureteral obstruction model. Demethylzeylasteral also significantly suppressed the protein expression of NFκB p65. The results of the present study suggested that demethylzeylasteral unilateral ureteral obstruction and inhibited inflammation via inhibiting the activation of COX2, ICAM1 and NFκB p65, and suppressing the activities of caspase3/9 in rats with unilateral ureteral obstruction.
Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/etiologia , Inflamação/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Obstrução Ureteral/complicações , Obstrução Ureteral/patologia , Animais , Biomarcadores , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , RatosRESUMO
To maintain homeostasis in the face of intrinsic and extrinsic insults, cells have evolved elaborate quality control networks to resolve damage at multiple levels. Interorganellar communication is a key requirement for this maintenance, however the underlying mechanisms of this communication have remained an enigma. Here we integrate the outcome of transcriptomic, proteomic, and metabolomics analyses of genotypes including ceh1, a mutant with constitutively elevated levels of both the stress-specific plastidial retrograde signaling metabolite methyl-erythritol cyclodiphosphate (MEcPP) and the defense hormone salicylic acid (SA), as well as the high MEcPP but SA deficient genotype ceh1/eds16, along with corresponding controls. Integration of multi-omic analyses enabled us to delineate the function of MEcPP from SA, and expose the compartmentalized role of this retrograde signaling metabolite in induction of distinct but interdependent signaling cascades instrumental in adaptive responses. Specifically, here we identify strata of MEcPP-sensitive stress-response cascades, among which we focus on selected pathways including organelle-specific regulation of jasmonate biosynthesis; simultaneous induction of synthesis and breakdown of SA; and MEcPP-mediated alteration of cellular redox status in particular glutathione redox balance. Collectively, these integrated multi-omic analyses provided a vehicle to gain an in-depth knowledge of genome-metabolism interactions, and to further probe the extent of these interactions and delineate their functional contributions. Through this approach we were able to pinpoint stress-mediated transcriptional and metabolic signatures and identify the downstream processes modulated by the independent or overlapping functions of MEcPP and SA in adaptive responses.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Glutationa/metabolismo , Metabolômica/métodos , Oxilipinas/metabolismo , Proteômica/métodos , Ácido Salicílico/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Transcriptoma/genéticaRESUMO
Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.