RESUMEN
N6-methyladenosine (m6A) methylation is a vital epigenetic mechanism associated with drug addiction. However, the relationship between m6A modification and oxycodone rewarding is less well explored. Based on an open field test, the present study evaluated oxycodone rewarding using chromatin immunoprecipitation PCR, immunofluorescence, and RNA sequencing. A marked increase in METTL14 protein and a decrease in PP1α protein due to oxycodone abundance in the striatal neurons were observed in a dose- and time-dependent manner. Oxycodone markedly increased LSD1 expression, and decreased H3K4me1 expression in the striatum. In the open field test, intra-striatal injection of METTL14 siRNA, HOTAIR siRNA, or LSD1 shRNA blocked oxycodone-induced increase in locomotor activity. The downregulation of PP1α was also inhibited after treatment with METTL14/HOTAIR siRNA and LSD1 shRNA. Enhanced binding of LSD1 with CoRest and of CoRest with the PP1α gene induced by oxycodone was also reversed by LSD1 shRNA. In addition, H3K4me1 demethylation was also blocked by the treatment. In summary, the investigation confirmed that METTL14-mediated upregulation of HOTAIR resulted in the repression of PP1α, which in turn facilitated the recruitment of LSD1, thus catalyzing H3K4me1 demethylation and promoting oxycodone addiction.
Asunto(s)
Metiltransferasas , Oxicodona , ARN Largo no Codificante , Animales , Masculino , Ratones , Cuerpo Estriado/metabolismo , Cuerpo Estriado/efectos de los fármacos , Desmetilación , Histona Demetilasas/metabolismo , Histona Demetilasas/genética , Histonas/metabolismo , Lisina/análogos & derivados , Metiltransferasas/metabolismo , Metiltransferasas/genética , Ratones Endogámicos C57BL , Oxicodona/farmacología , Proteína Fosfatasa 1/metabolismo , Proteína Fosfatasa 1/genética , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/genética , Regulación hacia ArribaRESUMEN
The lysine-specific demethylase 1 (KDM1A) is reported to be a regulator in learning and memory. However, the effect of KDM1A in oxycodone rewarding memory has yet to be studied. In our study, rewarding memory was assessed by using conditioned place preference (CPP) in male mice. Next generation sequencing and chromatin immunoprecipitation-PCR were used to explore the molecular mechanisms. Oxycodone significantly decreased PP1α mRNA and protein levels in hippocampal neurons. Oxycodone significantly increased KDM1A and H3K4me1 levels, while significantly decreased H3K4me2 levels in a time- and dose-dependent manner. Behavioral data demonstrated that intraperitoneal injection of ORY-1001 (KDM1A inhibitor) or intra-hippocampal injection of KDM1A siRNA/shRNA blocked the acquisition and expression of oxycodone CPP and facilitated the extinction of oxycodone CPP. The decrease of PP1α was markedly blocked by the injection of ORY-1001 or KDM1A siRNA/shRNA. Oxycodone-induced enhanced binding of CoRest with KDM1A and binding of CoRest with the PP1α promoter was blocked by ORY-1001. The level of H3K4me2 demethylation was also decreased by the treatment. The results suggest that oxycodone-induced upregulation of KDM1A via demethylation of H3K4me2 promotes the binding of CoRest with the PP1α promoter, and the subsequent decrease in PP1α expression in hippocampal neurons may contribute to oxycodone reward.
Asunto(s)
Epigénesis Genética , Histona Demetilasas , Oxicodona , Animales , Masculino , Epigénesis Genética/efectos de los fármacos , Ratones , Oxicodona/farmacología , Histona Demetilasas/metabolismo , Histona Demetilasas/genética , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Recompensa , Condicionamiento Psicológico/efectos de los fármacos , Ratones Endogámicos C57BL , Histonas/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Memoria/efectos de los fármacosRESUMEN
Uridine diphosphate glycosyltransferase(UGT) is involved in the glycosylation of a variety of secondary metabolites in plants and plays an important role in plant growth and development and regulation of secondary metabolism. Based on the genome of a diploid Chrysanthemum indicum, the UGT gene family from Ch. indicum was identified by bioinformatics methods, and the physical and chemical properties, subcellular localization prediction, conserved motif, phylogeny, chromosome location, gene structure, and gene replication events of UGT protein were analyzed. Transcriptome and real-time fluorescence quantitative polymerase chain reaction(PCR) were used to analyze the expression pattern of the UGT gene in flowers and leaves of Ch. indicum. Quasi-targeted metabolomics was used to analyze the differential metabolites in flowers and leaves. The results showed that a total of 279 UGT genes were identified in the Ch. indicum genome. Phylogenetic analysis showed that these UGT genes were divided into 8 subfamilies. Members of the same subfamily were distributed in clusters on the chromosomes. Tandem duplications were the main driver of the expansion of the UGT gene family from Ch. indicum. Structural domain analysis showed that 262 UGT genes had complete plant secondary metabolism signal sequences(PSPG box). The analysis of cis-acting elements indicated that light-responsive elements were the most ubiquitous elements in the promoter regions of UGT gene family members. Quasi-targeted metabolome analysis of floral and leaf tissue revealed that most of the flavonoid metabolites, including luteolin-7-O-glucoside and kaempferol-7-O-glucoside, had higher accumulation in flowers. Comparative transcriptome analysis of flower and leaf tissue showed that there were 72 differentially expressed UGT genes, of which 29 genes were up-regulated in flowers, and 43 genes were up-regulated in leaves. Correlation network and phylogenetic analysis showed that CindChr9G00614970.1, CindChr2G00092510.1, and CindChr2G00092490.1 may be involved in the synthesis of 7-O-flavonoid glycosides in Ch. indicum, and real-time fluorescence quantitative PCR analysis further confirmed the reliability of transcriptome data. The results of this study are helpful to understand the function of the UGT gene family from Ch. indicum and provide data reference and theoretical basis for further study on the molecular regulation mechanism of flavonoid glycosides synthesis in Ch. indicum.
Asunto(s)
Chrysanthemum , Glicosiltransferasas , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Chrysanthemum/genética , Uridina Difosfato , Filogenia , Reproducibilidad de los Resultados , Plantas/metabolismo , Flavonoides , Glicósidos , Regulación de la Expresión Génica de las PlantasRESUMEN
Based on the record of Miu Ci theory from Huangdi Neijing (The Yellow Emperor's Internal Classic), and incorporating the relevant discussions of medical scholars from various dynasties, this article interprets and analyzes the Miu Ci technique, the points to be needled, and the diseases can be treated. The following innovative understandings are proposedï¼ 1) The original meaning of "Miu" in Miu Ci is "to prick in a different way from the meridians (needle the major collaterals)", not "needle left and right interchangeably". Needle left and right interchangeably is not a necessary operation in Miu Ci. 2) The stimulation sites of Miu Ci are the "four extremities" of the human body, referred to as the "major collaterals of qi", and the nail bed of the four extremities is not equivalent to the commonly reco-gnized "Jing-well points". 3) Miu Ci can treat critical illnesses, not just limited to musculoskeletal pain or mild conditions at the early stage of a disease. 4) Miu Ci is not equivalent to Luo Ci needling (pricking bloodletting therapy).
Asunto(s)
Terapia por Acupuntura , Meridianos , Humanos , Medicina Tradicional China , Terapia por Acupuntura/métodos , Venodisección , Agujas , Puntos de AcupunturaRESUMEN
The gut-brain axis plays a vital role in Parkinson's disease (PD). The mechanisms of gut-brain transmission mainly focus on α-synuclein deposition, intestinal inflammation and microbiota function. A few studies have shown the trigger of PD pathology in the gut. α-Synuclein is highly conserved in food products, which was able to form ß-folded aggregates and to infect the intestinal mucosa. In this study we investigated whether α-synuclein-preformed fibril (PFF) exposure could modulate the intestinal environment and induce rodent models replicating PD pathology. We first showed that PFF could be internalized into co-cultured Caco-2/HT29/Raji b cells in vitro. Furthermore, we demonstrated that PFF perfusion caused the intestinal inflammation and activation of enteric glial cells in an ex vivo intestinal organ culture and in an in vivo intestinal mouse coloclysis model. Moreover, we found that PFF exposure through regular coloclysis induced PD pathology in wild-type (WT) and A53T α-synuclein transgenic mice with various phenotypes. Particularly in A53T mice, PFF induced significant behavioral disorders, intestinal inflammation, α-synuclein deposition, microbiota dysbiosis, glial activation as well as degeneration of dopaminergic neurons in the substantia nigra. In WT mice, however, the PFF induced only mild behavioral abnormalities, intestinal inflammation, α-synuclein deposition, and glial activation, without significant changes in microbiota and dopaminergic neurons. Our results reveal the possibility of α-synuclein aggregates binding to the intestinal mucosa and modeling PD in mice. This study may shed light on the investigation and early intervention of the gut-origin hypothesis in neurodegenerative diseases.
Asunto(s)
Enfermedad de Parkinson , Trastornos Parkinsonianos , Humanos , Ratones , Animales , alfa-Sinucleína/metabolismo , Células CACO-2 , Trastornos Parkinsonianos/metabolismo , Enfermedad de Parkinson/metabolismo , Ratones Transgénicos , Neuronas Dopaminérgicas/metabolismo , Inflamación/metabolismoRESUMEN
OBJECTIVE: SNRPA1, a subunit of spliceosome complex, has been implicated in diverse cancers, while its biological effect in LUAD remains elusive. Therefore, we sought to decipher the relationship between SNRPA1 expression and the prognosis of patients with LUAD and reveal the underlying molecular mechanism. MATERIALS AND METHODS: Based on the clinical data from TCGA databases, the multivariate Cox model was constructed to screen the prognostic value of SNRPA1. qRT-PCR and immunohistochemical staining were used to examine SNRPA1 mRNA and protein expression in LUAD. The effect of SNRPA1 on LUAD cell proliferation, migration, and epithelial mesenchymal transformation were examined using colony formation assays, wound healing, and western blot assays, respectively. Finally, the influence of SNRPA1 on LUAD immune microenvironment were validated from the Tumor Immune Estimation Resource database. RESULTS: SNRPA1 was significantly upregulated in both LUAD tissues and cell lines, and highly expressed SNRPA1 contributed to poor prognosis of LUAD patients. In vitro, SNRPA1 knockdown inhibited the proliferation and migration, as well as delayed the EMT differentiation of LUAD cells. Lastly, SNRPA1 was found to be positively associated with immune infiltration and some immune-check-point markers. CONCLUSIONS: Our findings indicate that SNRPA1 may be a new biomarker for prognostic prediction and a potential therapeutic target in the treatment of LUAD.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Western Blotting , Proliferación Celular/genética , Bases de Datos Factuales , Neoplasias Pulmonares/genética , Pronóstico , Microambiente TumoralRESUMEN
Tubular epithelial cells (TECs) play critical roles in the development of diabetic nephropathy (DN), and can activate macrophages through the secretion of exosomes. However, the mechanism(s) of TEC-exosomes in macrophage activation under DN remains unknown. By mass spectrometry, 1,644 differentially expressed proteins, especially Dll4, were detected in the urine exosomes of DN patients compared with controls, which was confirmed by western blot assay. Elevated Epsin1 and Dll4/N1ICD expression was observed in kidney tissues in both DN patients and db/db mice and was positively associated with tubulointerstitial damage. Exosomes from high glucose (HG)-treated tubular cells (HK-2) with Epsin1 knockdown (KD) ameliorated macrophage activation, TNF-α, and IL-6 expression, and tubulointerstitial damage in C57BL/6 mice in vivo. In an in vitro study, enriched Dll4 was confirmed in HK-2 cells stimulated with HG, which was captured by THP-1 cells and promoted M1 macrophage activation. In addition, Epsin1 modulated the content of Dll4 in TEC-exosomes stimulated with HG. TEC-exosomes with Epsin1-KD significantly inhibited N1ICD activation and iNOS expression in THP-1 cells compared with incubation with HG alone. These findings suggested that Epsin1 could modulate tubular-macrophage crosstalk in DN by mediating exosomal sorting of Dll4 and Notch1 activation.
Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Animales , Ratones , Movimiento Celular , Diabetes Mellitus/metabolismo , Nefropatías Diabéticas/metabolismo , Células Epiteliales/metabolismo , Glucosa/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BLRESUMEN
Background: Breast cancer has the highest incidence among malignant tumors in women, and its prevalence ranks first in global cancer morbidity. Aim: This study aimed to explore the feasibility of a prognostic model for patients with breast cancer based on the differential expression of genes related to fatty acid metabolism. Methods: The mRNA expression matrix of breast cancer and paracancer tissues was downloaded from The Cancer Genome Atlas database. The differentially expressed genes related to fatty acid metabolism were screened in R language. The TRRUST database was used to predict transcriptional regulators related to hub genes and construct an mRNA-transcription factor interaction network. A consensus clustering approach was used to identify different fatty acid regulatory patterns. In combination with patient survival data, Lasso and multivariate Cox proportional risk regression models were used to establish polygenic prognostic models based on fatty acid metabolism. The median risk score was used to categorize patients into high- and low-risk groups. Kaplan-Meier survival curves were used to analyze the survival differences between both groups. The Cox regression analysis included risk score and clinicopathological factors to determine whether risk score was an independent risk factor. Models based on genes associated with fatty acid metabolism were evaluated using receiver operating characteristic curves. A comparison was made between risk score levels and the fatty acid metabolism-associated genes in different subtypes of breast cancer. The differential gene sets of the Kyoto Encyclopedia of Genes and Genomes for screening high- and low-risk populations were compared using a gene set enrichment analysis. Furthermore, we utilized CIBERSORT to examine the abundance of immune cells in breast cancer in different clustering models. Results: High expression levels of ALDH1A1 and UBE2L6 prevented breast cancer, whereas high RDH16 expression levels increased its risk. Our comprehensive assessment of the association between prognostic risk scoring models and tumor microenvironment characteristics showed significant differences in the abundance of various immune cells between high- and low-risk breast cancer patients. Conclusions: By assessing fatty acid metabolism patterns, we gained a better understanding of the infiltration characteristics of the tumor microenvironment. Our findings are valuable for prognosis prediction and treatment of patients with breast cancer based on their clinicopathological characteristics.
RESUMEN
How cell-to-cell copy number alterations that underpin genomic instability1 in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer2, remains understudied. Here, by applying scaled single-cell whole-genome sequencing3 to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct 'foreground' mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment length variation (serrate structural variations) had measurable phenotypic and evolutionary consequences. In TNBC and HGSC, clone-specific high-level amplifications in known oncogenes were highly prevalent in tumours bearing fold-back inversions, relative to tumours with homologous recombination deficiency, and were associated with increased clone-to-clone phenotypic variation. Parallel haplotype-specific alterations were also commonly observed, leading to phylogenetic evolutionary diversity and clone-specific mono-allelic expression. Serrate variants were increased in tumours with fold-back inversions and were highly correlated with increased genomic diversity of cellular populations. Together, our findings show that cell-to-cell structural variation contributes to the origins of phenotypic and evolutionary diversity in TNBC and HGSC, and provide insight into the genomic and mutational states of individual cancer cells.
Asunto(s)
Genómica , Mutación , Neoplasias Ováricas , Análisis de la Célula Individual , Neoplasias de la Mama Triple Negativas , Femenino , Humanos , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Filogenia , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Uncontrolled lithium dendrites seriously hinder the commercialization of lithium metal batteries in comparison to the durable lithium-ion batteries. Herein, inspired by squashy pomegranate structure, a novel loading strategy of metallic lithium (Li) is introduced to construct dendrite-free Li metal anodes through porous reduced graphene oxide/Au (PRGO/Au) composite microrods (MRs) as unique storage parcels. The abundant internal voids and robust host structure are capable of achieving high mass loading of Li metal and effectively alleviating the conceivable volume change during cycling, accompanied by the preferential selective plating/stripping of Li inside the graphene-based MRs with the embedded Au nanonuclei. As a result, the obtained PRGO/Au-Li anodes deliver a long-lifespan stable cycling up to 600 h with a high specific capacity of ≈2140 mA h g-1 and voltage hysteresis as low as 20 mV in the absence of dendrites. The assembled full cells exhibit excellent rate capability and cycling stability. This work provides an alternative strategy to construct advanced high-energy-density lithium batteries via the unique 1D bioinspired graphene-based packaging strategy.
RESUMEN
Ultrafine Pd nanoparticles are prepared using a single-ion precursor on a MOF-808 carrier. The ligand 2,3-pyrazinedicarboxylic acid (Pza) is dispersed in porous MOF-808 via grafting on formic acid sites, and thus Pd2+ ions are chelated by Pza to form a new single-ion precursor Pd@MOF-808-Pza. Then a Pd-nano@MOF-808-Pza catalyst is prepared by direct reduction of this precursor using NaBH4. Material characterization reveals the homogeneous dispersion of 3-6 nm Pd nanoparticles within the MOF-808 matrix. Pd-nano@MOF-808-Pza exhibits excellent catalytic activity in the hydrogenation of unsaturated nitrogen-containing compounds, and other typical reactions, such as the Knoevenagel condensation, Suzuki/Heck cross-coupling, and hydrogen tandem reactions. In addition, density functional theory (DFT) calculations are carried out to elucidate the chelation of Pd2+ ions by Pza on MOF-808 and propose mechanisms of hydrogenation reactions. This work provides an effective reduction catalyst, and more importantly, a single-ion chelation strategy for design and synthesis of metal supported catalysts.
RESUMEN
The ancient and modern discussions on the treatment of acupoints of the pericardium meridian of hand jueyin and non-acupoints along the meridian for stomach diseases were summarized, and the treatment principle of pericardium meridian for stomach diseases was explored. The relationship between pericardium meridian and stomach was discussed from the three perspectives of heart-stomach correlation, organ-meridian correlation and qi-position correlation. Based on these discussions, the guiding significance of the thoughts of selection effective treatment parts and the theoretical construction for clinical practice was considered and examined.
Asunto(s)
Terapia por Acupuntura , Meridianos , Gastropatías , Puntos de Acupuntura , Humanos , Pericardio , Gastropatías/terapiaRESUMEN
The sudden outbreak of coronavirus disease 2019 (COVID-19) has deep and wide negative mental impacts on the public, and studies on the impact of COVID-19 on social and mental well-being are necessary. This study aimed to evaluate mental distress, including anxiety, depression, and post-traumatic stress disorder (PTSD), and its related risk factors in Chinese adults in the early stages of the COVID-19 pandemic. This study used a large-scale cross-sectional design. A total of 2067 adult participants completed the online survey via REDcap from 1st to 15th of March 2020 during the COVID-19 outbreak in China. Anxiety, depression, PTSD, and related risk factors, including self-efficacy, coping style, and social support, were measured using valid and reliable instruments. The data were analyzed using multiple linear regression. We found that 201 (9.7%) participants reported moderate-to-severe anxiety, 669 (33.8%) reported depression, and 368 (17.8%) reported symptoms of PTSD. Self-efficacy, coping style, and social support significantly affected anxiety, depression, and PTSD symptoms. Participants' sociodemographic characteristics, COVID-19 pandemic-related factors, low self-efficacy, low social support, and negative coping were predictors of mental distress during the COVID-19 pandemic. Our study will help healthcare professionals carry out early predictions and identification of high-risk groups and provide appropriate interventions to target groups during public health emergencies that plague the world.
Asunto(s)
COVID-19 , Trastornos por Estrés Postraumático , Adulto , Humanos , COVID-19/epidemiología , Trastornos por Estrés Postraumático/epidemiología , Estudios Transversales , Depresión/epidemiología , Depresión/etiología , Pandemias , Pueblos del Este de Asia , SARS-CoV-2 , Ansiedad/epidemiología , Ansiedad/etiologíaRESUMEN
Paeoniflorin (PF), a bioactive monoterpene glucoside, has shown a variety of pharmacological effects such as anti-inflammation and autophagy modulation etc. In this study, we investigated whether and how PF exerted a protective effect against ischemic brain injury in vivo and in vitro. Primary rat cortical neurons underwent oxygen/glucose deprivation/reperfusion (OGD/R) for 90 min. We showed that after OGD/R, a short fragment of histone deacetylase 4 (HDAC4) produced by caspase3-mediated degradation was markedly accumulated in the nucleus and the activity of caspase3 was increased. Treatment with PF (100 nM, 1 µM) significantly improved the viability of cortical neurons after OGD/R. Furthermore, PF treatment could maintain HDAC4 intrinsic subcellular localization and reduce the caspase3 activity without changing the HDAC4 at the transcriptional level. PF treatment significantly reduced OGD/R-caused inhibition of transcriptional factor MEF2 expression and increased the expression of downstream proteins such as GDNF, BDNF, and Bcl-xl, thus exerting a great anti-apoptosis effect as revealed by TUNEL staining. The beneficial effects of PF were almost canceled in HDAC4 (D289E)-transfected PC12 cells after OGD/R. In addition, PF treatment reduced the caspase9 activity, rescued the release of cytochrome c from mitochondria, and maintained the integrity of mitochondria membrane. We conducted in vivo experiments in 90-min-middle cerebral artery occlusion (MCAO) rat model. The rats were administered PF (20, 40 mg/kg, ip, 3 times at the reperfusion, 24 h and 48 h after the surgery). We showed that PF administration dose-dependently reduced infarction area, improved neurological symptoms, and maintained HDAC4 localization in rats after MCAO. These results demonstrate that PF is effective in protecting against ischemic brain injury and inhibit apoptosis through inhibiting the cytochrome c/caspase3/HDAC4 pathway.
Asunto(s)
Antiinflamatorios/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Citocromos c/metabolismo , Glucósidos/uso terapéutico , Histona Desacetilasas/metabolismo , Monoterpenos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Animales , Isquemia Encefálica/metabolismo , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Masculino , Prueba del Laberinto Acuático de Morris , Prueba de Campo Abierto , Ratas , Ratas Sprague-Dawley , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
Tubulointerstitial inflammation plays an important role in the progression of diabetic nephropathy (DN), and tubular epithelial cells (TECs) are crucial promoters of the inflammatory cascade. Exchange protein activated by cAMP (Epac) has been shown to suppress the angiotensin II (Ang-II)-induced release of inflammatory cytokines in tubular cells. However, the role of Epac in TEC-mediated tubulointerstitial inflammation in DN remains unknown. We found that administering the Epac agonist 8-pCPT-2'-O-Me-cAMP (8-O-cAMP) to db/db mice inhibited tubulointerstitial inflammation characterized by macrophage infiltration and increased inflammatory cytokine release and consequently alleviated tubulointerstitial fibrosis in the kidney. Furthermore, 8-O-cAMP administration restored CCAAT/enhancer binding protein ß (C/EBP-ß) expression and further upregulated the expression of Suppressor of cytokine signaling 3 (SOCS3), while inhibiting p-STAT3, MCP-1, IL-6, and TNF-α expression in the kidney cortex in db/db mice. And in vitro study showed that macrophage migration and MCP-1 expression induced by high glucose (HG, 30 mM) were notably reduced by 8-O-cAMP in human renal proximal tubule epithelial (HK-2) cells. In addition, 8-O-cAMP treatment restored C/EBP-ß expression in HK-2 cells and promoted C/EBP-ß translocation to the nucleus, where it transcriptionally upregulated SOCS3 expression, subsequently inhibiting STAT3 phosphorylation. Under HG conditions, siRNA-mediated knockdown of C/EBP-ß or SOCS3 in HK-2 cells partially blocked the inhibitory effect of Epac activation on the release of MCP-1. In contrast, SOCS3 overexpression inhibited HG-induced activation of STAT3 and MCP-1 expression in HK-2 cells. These findings indicate that Epac activation via 8-O-cAMP ameliorates tubulointerstitial inflammation in DN through the C/EBP-ß/SOCS3/STAT3 pathway.
Asunto(s)
Nefropatías Diabéticas/patología , Factores de Intercambio de Guanina Nucleótido/agonistas , Inflamación/patología , Túbulos Renales/efectos de los fármacos , Animales , Proteína beta Potenciadora de Unión a CCAAT/efectos de los fármacos , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacología , Citocinas/efectos de los fármacos , Humanos , Mediadores de Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , Factor de Transcripción STAT3/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteína 3 Supresora de la Señalización de Citocinas/efectos de los fármacos , Regulación hacia ArribaRESUMEN
OBJECTIVES: We aimed to construct an induction system for polyploid giant cancer cells (PGCCs), as well as to investigate PGCC features and clinical significance. METHODS: A laryngeal neoplasm-PGCC induction system was constructed using paclitaxel liposomes (PTX). We used western blots to compare expression of epithelial-mesenchymal transition-related proteins, stem cell interrelated proteins, and cyclin-associated proteins. We then measured PGCC count in tissue samples of patients with laryngeal neoplasms and analyzed its relationship with prognosis. Statistical significance was determined using t-tests. RESULTS: PTX successfully induced PGCCs. Western blotting showed that CyclinB1, CDC25C, CDK1, E-cadherin, and EIF-4A expression decreased in PGCCs compared with normal cancer cells, whereas vimentin and CD133 expression increased. Number of PGCCs in laryngeal cancer tissues and overall survival time were inversely correlated (P < .05). CONCLUSIONS: PTX successfully induces PGCC formation in laryngeal carcinoma, which may be the cause of poor prognosis in patients with laryngeal cancer.Level of Evidence: 4.
RESUMEN
A cellulose-producing bacterium Komagataeibacter rhaeticus K15 was isolated from kombucha tea, and its metabolic pathways and cellulose synthesis operon were analyzed by genome sequencing. Different from the reported K. rhaeticus, the K15 produced little gluconic acid (2.26 g/L) when glucose was the sole carbon source and has the capacity for high cellulose production (4.76 g/L) with other carbon sources. Furthermore, six nitrogen-fixing genes were found to be responsible for the survival of K15 on a nitrogen-free medium. Based on its fermentation characteristics, K15 was cultured in a kitchen waste medium as a strategy for green and sustainable bacterial cellulose production. The SEM, XRD, and FTIR results indicated that synthesized cellulose has a mean diameter of 40-50 nm nanofiber, good crystallinity, and the same chemical structure. The K15 strain provides a highly viable alternative strategy to reduce the costs of bacterial cellulose production using agro-industrial residues as nutrient sources.
Asunto(s)
Acetobacteraceae/metabolismo , Celulosa/biosíntesis , Fermentación , Genes Bacterianos , Microbiología Industrial/métodos , Eliminación de Residuos/métodos , Acetobacteraceae/genética , Culinaria , Fijación del Nitrógeno/genética , ResiduosRESUMEN
Both cadmium (Cd) contamination and boron (B) deficiency in farmland soils pose a threat to the yield and quality of crops in Southern China. The present study investigated the mechanisms by which B reduces Cd accumulation in rice (Oryza sativa) seedlings. Boron supplementation partially restored the decline in shoot and root biomass caused by Cd treatment (26% and 33%, respectively), with no significant difference between the B+Cd and control groups. We also found that B significantly reduced shoot and root Cd concentrations (by 64% and 25%, respectively) but increased Cd concentration (by 43%) and proportion (from 38% to 55%) in root cell walls. Transcriptome analysis and biochemical tests suggested that B supplementation enhanced lignin and pectin biosynthesis, pectin demethylation, and sulfur and glutathione metabolism. Moreover, B decreased the expression of some Cd-induced transporter-related genes (i.e., HMA2, Nramp1, and several ABC genes). These results indicate that B relieved Cd toxicity and reduced Cd accumulation in rice seedlings by restraining Cd uptake and translocation from root to shoot by improving Cd tolerance and chelation ability. These novel findings would benefit further investigations into how B influences Cd uptake, translocation, detoxification, and accumulation in crops.
Asunto(s)
Oryza , Plantones , Boro/toxicidad , Cadmio/toxicidad , Productos Agrícolas , Oryza/genéticaRESUMEN
Objective: To investigate the difference in the expression of Ras-associated protein 1 (Rap1) in necrotic and healthy areas of non-traumatic osteonecrosis of femoral head (NONFH) patients. Methods: Femoral head tissue samples from 30 cases of NONFH and 30 cases of traumatic osteonecrosis of the femoral head (TONFH) were collected after hip replacement surgery, respectively. No significant difference of Association Research Circulation Osseous (ARCO) staging was found between the NONFH and the TONFH groups ( Z=-0.769, P=0.442). In the NONFH group, 8 patients were ARCO stage IIIb, 10 were stage IV, and 12 were stage V, while in the TONFH ground, 11 patients were ARCO stage IIIb, 9 were stage IV, and 10 were stage V. There were 19 males and 11 females in the NONFH group, with an average age of 49.6 yr. (26-69 yr.), and 16 males and 14 females in the TONFH group, with an average age of 54.2 yr. (37-68 yr.). There was no significant difference in gender or age between the two groups ( P>0.05). Specimens were collected from different bone areas, including those from the necrotic areas (area A) and the healthy areas (area B) of the NONFH group, and those from the healthy areas (area B') of the TONFH group, i.e., the control group. Western blot and quantitative real-time reverse transcription PCR (qRT-PCR) were used to analyze the different expression of Rap1, vascular endothelial growth factor (VEGF) protein, phosphoinositide 3-kinase (PI3K), and Akt protein and their corresponding mRNA in the three areas of bone tissue. HE staining and immunohistochemisty staining were done in order to observe the morphological changes of each area. Results: Western blot results indicated that there was no statistical difference in the relative expression of Rap1, VEGF, PI3K, and Akt proteins ( P>0.05). The relative expressions of Rap1, VEGF, PI3K, and Akt proteins in the area A were lower than those in the area B and the difference was statistically significant ( P<0.05). qRT-PCR results showed that the relative expressions of Rap1, VEGF, PI3 K and Akt mRNA in area A were lower than those of area B, and a statistical difference was found ( P<0.05). The relative expression of the mRNA of Rap1, VEGF , PI3 K and Akt in area B and area B' were not significantly different ( P>0.05). HE staining and immunohistochemisty staining showed that chondrocytes decreased in the necrotic area (area A) of NONFH, chondrocytes nucleus disappeared, subchondral bone trabeculae were broken, bone trabeculae thickened, and empty bone lacunae appeared. Granulation tissues composed of new capillaries and fibrous cells have proliferated and crawled around the necrotic area. Positive expressions of the Rap1, VEGF, PI3K and Akt proteins in area A were weaker than those of the normal area. In addition, there were positive expressions of Rap1, PI3K and Akt on the trabecular bone of both area A and area B at similar intensity of expression. There were strong positive expressions of Rap1, VEGF, PI3K and Akt on the intima of arterioles and venules, and on the peripheral stromal cell membrane, but the positive expression in area A was significantly lower than that in area B. However, the positive expression positions and intensity of all indicators were similar in area B and area B'. Conclusion: The necrosis in NONFH may be related to vascular endothelial damages caused by the inhibition of the Rap1-PI3K/Akt signaling pathways and the subsequent decline in the protein expression.
Asunto(s)
Necrosis de la Cabeza Femoral , Cabeza Femoral , Adulto , Anciano , Endotelio Vascular , Femenino , Necrosis de la Cabeza Femoral/genética , Humanos , Masculino , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas , Complejo Shelterina , Proteínas de Unión a Telómeros , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
Graphene-based one-dimensional macroscopic assemblies (GBOMAs) have attracted great attention and extensive efforts have been devoted to enabling great progress. However, their applications are still restricted to less functionalized electronics, and the superior potentials remain scarce. Herein, inspired by natural scallion structure, a novel strategy was introduced to effectively improve battery performances through the mesoscale scallion-like wrapping of graphene. The obtained RGO/Ag-Li anodes demonstrated an ultralow overpotential of â¼11.3 mV for 1800 h at 1 mA cm-2 in carbonate electrolytes, which is superior to those of the most previous reports. Besides, this strategy can also be further expanded to the high mass loading of various cathode nanomaterials, and the resulting RGO/LiFePO4 cathodes exhibited remarkable rate performance and cycle stability. This work opens a new avenue to explore and broaden the applications of GBOMAs as scaffolds in fabricating full lithium batteries via maximizing their advantages derived from the unique structure and properties.