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Proteínas de Ligação a DNA , Leiomiossarcoma , Neoplasias Uterinas , Humanos , Leiomiossarcoma/patologia , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/genética , Feminino , Neoplasias Uterinas/patologia , Neoplasias Uterinas/genética , Neoplasias Uterinas/diagnóstico , Proteínas de Ligação a DNA/genética , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genéticaRESUMO
Changes in soil nitrogen components in tea gardens affect the soil nitrogen supply capacity and nitrogen cycle. In this study, soil samples were collected from forest land, cultivated land, and tea gardens with different plantation ages (30, 50, and 70 years) to explore the changes in soil nitrogen components and their relationship with physicochemical properties and enzyme activities. The results showed that:â with the increase in tea plantation age, the silt, total phosphorus, and urease and catalase activities gradually increased, whereas the sand, clay, pH, electrical conductivity, soil organic carbon, and the activities of invertase gradually decreased. The alkaline phosphatase activity increased first and then decreased with the increase in tea plantation age, and no significant differences were observed in soil water content and acid phosphatase activity. â¡ With the increase in tea plantation age, the contents of acid ammonia nitrogen, amino acid nitrogen, and nitrate nitrogen (NO3--N) increased significantly, and the contents of total nitrogen, acid ammonia nitrogen, hydrolyzable unknown nitrogen, and non-hydrolyzable nitrogen in tea gardens were significantly higher than those in forest land. ⢠The total phosphorus, alkaline phosphatase, and urease were the main factors affecting soil nitrogen components. Among them, organic nitrogen components were significantly correlated with total phosphorus and alkaline phosphatase, and inorganic nitrogen components were significantly correlated with alkaline phosphatase, whereas total nitrogen had significant correlations with sand, silt, total phosphorus, urease, and alkaline phosphatase.
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Fosfatase Alcalina , Solo , Solo/química , Areia , Nitrogênio/análise , Carbono , Urease , Amônia , Fósforo/análise , Chá , Microbiologia do Solo , ChinaRESUMO
OBJECTIVE: To investigate the efficacy and prognosis of chemotherapy regimen containing Bruton's tyrosine kinase (BTK) inhibitor in the treatment of relapsed/refractory mantle cell lymphoma (R/R MCL). METHODS: The clinical data of 134 patients with R/R MCL were collected and analyzed retrospectively. The clinical characteristics of patients and effect of chemotherapy regimen on efficacy, overall survival (OS) and progression-free survival (PFS) were observed. RESULTS: The median age of the patients was 58(56-61) years old, and male to female ratio was about 2.9â¶1. Patients with Ann Arbor stage III-IV accounted for 77.6%, extranodal involvement > 2 for 43.3%, bone marrow involvement for 60.4%, gastrointestinal involvement for 24.6%, and hepatosplenomegaly for 38.1%. The median follow-up time was 30 (2-103) months, overall response rate (ORR) was 41.8%, 3-year PFS was not reached, and 3-year and 5-year OS rate was 62.7% and 53.8%, respectively. The ORR of BTK inhibitor group was 56.9%, which was higher than 32.5% of non-BTK inhibitor group (P =0.006). The difference was statistically significant in PFS between the two groups (P =0.002), but was not in OS (P>0.05). The difference was statistically significant in OS between classical and special morphology (P < 0.001), but was not in PFS (P >0.05). Ki-67 was an influencing factor for OS and PFS. Multivariate analysis showed that Ki-67, B symptoms, MIPI score, and Ann Arbor stage were independent prognostic factors affecting patients' OS. The second-line treatment regimen was an independent prognostic factor affecting patients' PFS. CONCLUSIONS: The chemotherapy regimen containing BTK inhibitors can effectively improve the efficacy and prolong the PFS of R/R MCL patients. Ki-67, B symptoms, MIPI score, and Ann Arbor stage are independent prognostic factors for R/R MCL patients.
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Linfoma de Célula do Manto , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Antígeno Ki-67 , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , PrognósticoRESUMO
BACKGROUND: In pesticide research, bleaching herbicides have always been a hot topic. Our previous research showed that N-(4-fluorobenzyl)-2-methoxybenzamide is an innovative lead compound for bleaching herbicides. RESULTS: A total of 40 derivatives of picolinamides were prepared and evaluated for their herbicidal activity by Petri dish tests and postemergence trials. The structure-activity relationship (SAR) revealed that introducing electron-withdrawing groups at the 3- or 4-positions of the benzyl significantly enhances herbicidal activity. Furthermore, ZI-04 induced similar symptoms such as bleaching effect in treated weeds and accumulation of biosynthetic precursors for carotenoids as observed with diflufenican. ZI-04 also exhibited significant cross-resistance to diflufenican and had a lower resistance risk than diflufenican. CONCLUSION: N-benzyl-6-methylpicolinamides were discovered as a novel scaffold for bleaching herbicides. The accumulation of phytoene, phytofluene and ζ-Carotene in radish cotyledons, and cross-resistance observed with diflufenican, showed that title compounds can interfere with carotenoid biosynthesis. © 2024 Society of Chemical Industry.
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Herbicidas , Ácidos Picolínicos , Herbicidas/farmacologia , Herbicidas/química , Ácidos Picolínicos/química , Ácidos Picolínicos/farmacologia , Relação Estrutura-Atividade , Plantas Daninhas/efeitos dos fármacos , Amidas/química , Amidas/farmacologiaRESUMO
BACKGROUND: Whole-process management is a novel approach widely applied in industry and commerce; however, it is not widely used in the management of medical records in hospitals. OBJECTIVE: The purpose of this study is to investigate the application of whole-process control in the administration of a hospital's medical records department to achieve refined management of medical records. METHODS: Whole-process control is a management measure that begins with process conception and implementation and includes control over all processes. The control group included medical records that were created prior to the implementation of whole-process control, i.e., those created between June 1 and December 31, 2020. The observation group included medical records that were created after the implementation of whole-process control. The behavior of the medical records staff (in terms of medical record collection, sorting, entry, inquiry, and supply) and the final quality of the medical records (the number of grade-A medical records and their front-page quality) were compared between the two groups, and subjective judgments related to staff satisfaction were reviewed. RESULTS: The implementation of whole-process control improved the behavior of the medical records staff. The final quality of the medical records was also improved, as was the job satisfaction of the medical records staff. CONCLUSION: Implementing whole-process control improved the management of medical records and quality of medical records.
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Hospitais , Prontuários Médicos , Humanos , Estudos Retrospectivos , Controle de Formulários e RegistrosRESUMO
The invasion of Spartina alterniflora poses a great threat to coastal wetland ecosystems. In this study, the stoichiometric characteristics of soil carbon, nitrogen, and phosphorus under a Spartina alterniflora invasion were explored using ANOVA in a coastal wetland in Hangzhou Bay, and the driving coupling relationship between soil environmental factors and soil C:N:P stoichiometric characteristics of the coastal wetland were further explored based on the redundancy analysis (RDA), boosted regression tree (BRT), and partial least squares-structural equation (PLS-SEM) model. The results showed that:â after the invasion of Spartina alterniflora, soil N:P and total nitrogen (TN) in the wetland increased significantly, and with the increase in invasion time, TN and N:P decreased significantly, whereas soil organic carbon (SOC), C:N, and C:P increased significantly. â¡ The RDA model revealed that the main factors affecting the stoichiometric characteristics of topsoil C:N:P were SOC>electrical conductivity (EC)>TN in winter and SOC>bulk density (BD)>TN in summer. ⢠The BRT model showed that under the invasion of Spartina alterniflora, TN was the key factor affecting soil C:N and N:P, and SOC was the key factor affecting C:P. ⣠The PLS-SEM model showed that clay and water content directly affected SOC, thus affecting C:N and C:P; the clay and EC directly affected total phosphorus (TP), thus affecting N:P and C:P; and the EC directly affected TN, thus affecting C:N and N:P. In conclusion, the invasion of Spartina alterniflora had a significant impact on soil C:N:P stoichiometric characteristics in the study area. Soil physical properties and nutrient content directly or indirectly affected soil C:N:P stoichiometric characteristics to varying degrees.
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Ecossistema , Áreas Alagadas , Solo/química , Baías , Argila , Carbono/análise , Espécies Introduzidas , Poaceae , Nitrogênio/análise , Fósforo/análise , ChinaRESUMO
Uniformly narrowed internal carotid artery (ICA) without proximal steno-occlusion or parietal anomalies is often subject to misdiagnosis due to lack of awareness. We combined our experiences of 4 cases with 29 previously published cases to form a retrospective series including 18 cases of ICA hypoplasia and 15 cases of ICA acquired narrowing. The ultrasonic manifestations of ICA acquired narrowing and ICA hypoplasia are extremely similar, but narrowed ICA without intracranial occlusion or bottle-neck-sign highly indicates ICA hypoplasia, whereas moyamoya vessels favor ICA acquired narrowing, thus promoting the understanding of and discriminability between the two on neurovascular ultrasound.
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Estenose das Carótidas , Doença de Moyamoya , Humanos , Artéria Carótida Interna/diagnóstico por imagem , Estudos Retrospectivos , UltrassonografiaRESUMO
Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.
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Neoplasias Colorretais , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Linhagem Celular Tumoral , Neovascularização Patológica/metabolismo , Miosinas , Autofagia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Colorretais/patologia , Miosina Tipo I/genéticaRESUMO
BACKGROUND: Plentiful evidence proves that lncRNAs play a crucial role in tumor development. However, the function and mechanism that were mediated by lncRNA HIF1A-AS2 in cervical cancer remain unclear. METHODS: The lncRNA HIF1A-AS2 was identified via high-throughput microarray analysis of three HPV 16-positive cervical squamous cell carcinoma (CSCC) samples and three HPV-negative normal controls. The expression of HIF1A-AS2 was detected by qRT-PCR in clinical tissues and cancer cells. In vitro and in vivo assays were performed through downregulation or upregulation of HIF1A-AS2. The possible mechanisms of HIF1A-AS2 in cervical cancer cells were explored by western blot, flow cytometric analysis and rescue assays. RESULTS: HIF1A-AS2 was significantly increased in cervical cancer tissue, and in the HPV- positive cervical cancer cells. Further investigation showed that the inhibition of HIF1A-AS2 suppressed cell proliferation, migration, invasion, and induced apoptosis, while up-regulation of HIF1A-AS2 revealed opposite results. In terms of mechanism, we found that HIF1A-AS2 was mediated by HPV16 E6 and regulated cell apoptosis via P53/caspase 9/caspase 3 axis. CONCLUSION: Our findings demonstrate that HIF1A-AS2 functions as a carcinogenic lncRNA that promotes tumor development, and serves as a candidate prognostic factor, which may contribute to the treatment of cervical cancer.
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Apoptose , Infecções por Papillomavirus , RNA Longo não Codificante , Neoplasias do Colo do Útero , Apoptose/genética , Caspase 3/metabolismo , Caspase 9 , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Oncogênicas Virais , Infecções por Papillomavirus/genética , RNA Longo não Codificante/genética , Proteínas Repressoras , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias do Colo do Útero/genéticaRESUMO
Acute ischemic stroke is a severe condition that a vessel supplying blood to the brain is abruptly blocked mostly due to cerebral thrombosis and embolism. There is a dearth of the effective prevention and early intervention strategies. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation plays a crucial role in the pathophysiology of ischemic stroke. Hirudin is a secretion from the salivary glands of the leech Hirudo medicinalis and has a role in regulating inflammation. In this study, hirudin with a dose of 10-40 mg/kg was given to middle cerebral artery occlusion/reperfusion mice. Hirudin markedly constrained cerebral infarct area in a dose-dependent manner, and significantly improved locomotor disability at 40 mg/kg dose. Similar to MCC950, a selective NLRP3 inflammasome inhibitor, hirudin inhibited M1 polarization and promoted M2 polarization. It also strikingly suppressed the ischemia-induced overexpression of NLRP3 and its downstream components, caspase-1, apoptosis-associated speck-like protein (ASC), and interleukin-1ß (IL-1ß). Hirudin and MCC950 equivalently protected viability and death of BV-2 microglia cells against oxygen-glucose deprivation/reperfusion (OGD/R), an in vitro cell model of brain ischemia. Both agents had similar effects in normalizing the OGD/R-evoked aberrant microglial profiles and NLRP3 pathway dysregulation as observed in the mice. These results demonstrated anti-ischemic effects of hirudin and its association with the inhibition of microglial NLRP3 inflammasome-mediated neuroinflammation. Hirudin is a promising agent for the early intervention of acute ischemic stroke.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Hirudinas , Inflamassomos/metabolismo , AVC Isquêmico/tratamento farmacológico , Camundongos , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismoRESUMO
[This corrects the article DOI: 10.3389/fphar.2020.577108.].
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Mitochondrial dysfunction with oxidative damage plays the fundamental roles in the pathogenesis of Alzheimer's disease. In traditional Chinese medicine (TCM) practice, animal tissue-derived gelatins are often used as nootropic agents to treat cognitive deterioration and senile dementia. Tortoise plastron gelatin (TPG) and deer antler gelatin (DAG) are the two most commonly used gelatins for this purpose. This study sought to examine the effects of the two gelatins in preventing neuronal mitochondria from oxidative damage. PC12 cells, a cell line derived from rat pheochromocytoma, exposed to the neurotoxin Aß25-35 served as an in vitro model of Alzheimer's disease. The cells were separately pre-treated with TPG and DAG at various concentrations ranging from 6.26 µg/ml-200 µg/ml, followed by co-incubation with 20 µM Aß25-35 for different duration. Cell viability, mitochondrial membrane potential (MMP) and ultrastructure, intracellular ATP, reactive oxygen species (ROS) and calcium (Ca2+) level, the expression of mitochondrial dynamic proteins and biomarkers of apoptosis were measured. Pretreatment with TPG and DAG reversed the Aß-induced reduction of cell viability in a dose-dependent manner. Both TPG and DAG significantly increased MMP and ATP, alleviated the accumulation of damaged mitochondrial fragments, and normalized the aberrant expression of multiple mitochondrial dynamic proteins of the Aß-exposed cells. Both gelatins also suppressed intracellular ROS overproduction and Ca2+ overload, overexpression of cytochrome c and pro-apoptosis biomarkers induced by the Aß exposure. These results suggest that TPG and DAG may have the anti-dementia potential by preventing neuronal mitochondria from oxidative damage.
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High-mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma (HCC) cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism through which HMGA2 is transcriptionally regulated in HCC cells remains largely unclear. Here, we showed that the expression HMGA2 was upregulated in HCC, and that elevated HMGA2 could promote tumor metastasis. Incubation of HCC cells with epidermal growth factor (EGF) could promote the expression of HMGA2 mRNA and protein. Mechanistic studies suggested that EGF can phosphorylate p300 at Ser1834 residue through the PI3K/Akt signaling pathway in HCC cells. Knockdown of p300 can reverse EGF-induced HMGA2 expression and histone H3-K9 acetylation, whereas a phosphorylation-mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3-K9 acetylation in HCC cells. Furthermore, we identified that p300-mediated H3-K9 acetylation participates in EGF-induced HMGA2 expression in HCC. In addition, the levels of H3-K9 acetylation positively correlated with the expression levels of HMGA2 in a chemically induced HCC model in rats and human HCC specimens.
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Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteína HMGA2/biossíntese , Histonas/metabolismo , Neoplasias Hepáticas/patologia , Acetilação , Animais , Carcinoma Hepatocelular/metabolismo , Receptores ErbB/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ratos , Ratos Sprague-Dawley , Transcrição Gênica , Fatores de Transcrição de p300-CBP/metabolismoRESUMO
BACKGROUND: Delayed gastric emptying (DGE) is the main complication after pancreaticoduodenectomy (PD), but the mechanism is still unclear. The aim of this study was to elucidate the role of complete resection of the gastric antrum in decreasing incidence and severity of DGE after PD. METHODS: Sprague-Dawley rats were divided into three groups: expanded resection (ER group), complete resection (CR group), and incomplete resection (IR group) of the gastric antrum. The tension (g) of remnant stomach contraction was observed. We analyzed the histological morphology of the gastric wall by different excisional methods after distal gastrectomy. Moreover, patients underwent PD at our department between January 2012 and May 2016 were included in the study. These cases were divided into IR group and CR group of the gastric antrum, and the clinical data were retrospectively analyzed. RESULTS: The ex vivo remnant stomachs of CR group exhibited much greater contraction tension than others (P < 0.05). The contraction tension of the remnant stomach increased with increasing acetylcholine concentration, while remained stable at the concentration of 10 × 10-5 mol/L. Furthermore, 174 consecutive patients were included and retrospectively analyzed in the study. The incidence of DGE was significantly lower (3.5% vs. 21.3%, P < 0.01) in CR group than in IR group. In addition, hematoxylin-eosin staining analyses of the gastric wall confirmed that the number of transected circular smooth muscle bundles were higher in IR group than in CR group (8.24 ± 0.65 vs. 3.76 ± 0.70, P < 0.05). CONCLUSIONS: The complete resection of the gastric antrum is associated with decreased incidence and severity of DGE after PD. Gastric electrophysiological and physiopathological disorders caused by damage to gastric smooth muscles might be the mechanism underlying DGE.
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Gastroparesia , Pancreaticoduodenectomia , Animais , Esvaziamento Gástrico , Gastroparesia/epidemiologia , Gastroparesia/etiologia , Gastroparesia/prevenção & controle , Humanos , Incidência , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Antro Pilórico/diagnóstico por imagem , Antro Pilórico/cirurgia , Ratos , Ratos Sprague-Dawley , Estudos RetrospectivosRESUMO
High expression of programmed death-ligand-1 (PD-L1) in hepatocellular carcinoma (HCC) cells usually inhibits the proliferation and functions of T cells, leading to immune suppression in tumor microenvironment. However, very little has been described regarding the mechanism of PD-L1 overexpression in HCC cells. In the present study, we found epidermal growth factor (EGF) stimulation promoted the expression of PD-L1 mRNA and protein in HCC cells. Inhibition of epidermal growth factor receptor (EGFR) could reverse EGF-induced the expression of PD-L1 mRNA and protein. Subsequently, we also observed that the phosphorylation level of Pyruvate kinase isoform M2 (PKM2) at Ser37 site was also increased in response to EGF stimulation. Expression of a phosphorylation-mimic PKM2 S37D mutant stimulated PD-L1 expression as well as H3-Thr11 phosphorylation in HCC cells, while inhibition of PKM2 significantly blocked EGF-induced PD-L1 expression and H3-Thr11 phosphorylation. Furthermore, mutation of Thr11 of histone H3 into alanine abrogated EGF-induced mRNA and protein expression of PD-L1, Chromatin immunoprecipitation (ChIP) assay also suggested that EGF treatment resulted in enhanced H3-Thr11 phosphorylation at the PD-L1 promoter. In a diethylnitrosamine (DEN)-induced rat model of HCC, we found that the expression of phosphorylated EGFR, PKM2 nuclear expression, H3-Thr11 phosphorylation as well as PD-L1 mRNA and protein was higher in the livers than that in normal rat livers. Taken together, our study suggested that PKM2-dependent histone H3-Thr11 phosphorylation was crucial for EGF-induced PD-L1 expression at transcriptional level in HCC. These findings may provide an alternative target for the treatment of hepatocellular carcinoma.
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The protein Dickkopf-1 (DKK1) is frequently overexpressed at the transcript level in hepatocellular carcinoma (HCC) and promotes metastatic progression through the induction of ß-catenin, a Wnt signaling effector. We investigated how DKK1 expression is induced in HCC and found that activation of the epidermal growth factor receptor (EGFR) promoted parallel MEK-ERK and PI3K-Akt pathway signaling that converged to epigenetically stimulate DKK1 transcription. In HCC cell lines stimulated with EGF, EGFR-activated ERK phosphorylated the kinase PKM2 at Ser37, which promoted its nuclear translocation. Also in these cells, EGFR-activated Akt phosphorylated the acetyltransferase p300 at Ser1834 Subsequently, PKM2 and p300 mediated the phosphorylation and acetylation, respectively, of histone H3 at the DKK1 promoter, which synergistically enhanced DKK1 transcription. The mechanism was supported with mutational analyses in cells and in a chemically induced HCC model in rats. The findings suggest that dual inhibition of the MEK and PI3K pathways might suppress the expression of DKK1 and, consequently, tumor metastasis in patients with HCC.
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Carcinoma Hepatocelular/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Histonas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas de Neoplasias/metabolismo , Transcrição Gênica , Acetilação , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular , Fator de Crescimento Epidérmico/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/genética , Fosforilação , Ratos , Ratos Sprague-DawleyRESUMO
Redox balance, an essential feature of healthy physiological steady states, is regulated by circadian clocks, but whether or how endogenous redox signalling conversely regulates clockworks in mammals remains unknown. Here, we report circadian rhythms in the levels of endogenous H2O2 in mammalian cells and mouse livers. Using an unbiased method to screen for H2O2-sensitive transcription factors, we discovered that rhythmic redox control of CLOCK directly by endogenous H2O2 oscillations is required for proper intracellular clock function. Importantly, perturbations in the rhythm of H2O2 levels induced by the loss of p66Shc, which oscillates rhythmically in the liver and suprachiasmatic nucleus (SCN) of mice, disturb the rhythmic redox control of CLOCK function, reprogram hepatic transcriptome oscillations, lengthen the circadian period in mice and modulate light-induced clock resetting. Our findings suggest that redox signalling rhythms are intrinsically coupled to the circadian system through reversible oxidative modification of CLOCK and constitute essential mechanistic timekeeping components in mammals.
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Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Peróxido de Hidrogênio/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Animais , Feminino , Fígado/metabolismo , Fígado/fisiologia , Masculino , Mamíferos/metabolismo , Mamíferos/fisiologia , Camundongos , Camundongos Knockout , Oxirredução , Proteínas Circadianas Period/metabolismo , Transdução de Sinais/fisiologia , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/fisiologiaRESUMO
Dendritic spines on the dendrites of pyramidal neurons are one of the most important components for excitatory synapses, where excitatory information exchanges and integrates. The defects of dendritic spine development have been closely connected with many nervous system diseases including autism, intellectual disability and so forth. Based on our previous studies, we here report a new functional signaling link between phospholipase D1 (PLD1) and protein kinase D1 (PKD1) in dendritic spine morphogenesis. Coimmunoprecipitation assays showed that PLD1 associates with PKD1. A series of knocking down and rescuing experiments demonstrated that PLD1 acts upstream of PKD1 in positively regulating dendritic spine morphogenesis. Using PLD1 inhibitor, we found that PLD1 activates PKD1 to promote dendritic spine morphogenesis. Thus, we further reveal the roles of the two different enzymes in neuronal development.
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Espinhas Dendríticas/metabolismo , Neurogênese , Fosfolipase D/metabolismo , Canais de Cátion TRPP/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Espinhas Dendríticas/fisiologia , Camundongos , Fosfolipase D/antagonistas & inibidores , Ligação Proteica , Ratos , Ratos Sprague-DawleyRESUMO
A new flexible 2-ethylthiophene pendant-armed dialdehyde (H2tdd) was reacted with 1,3-propanediamine, [( S, S),( R, R),(±)]-1,2-diaminocyclohexane, and 1,2-bis(2-aminoethoxy)ethane, giving birth to 36-membered [2 + 2] Schiff-base macrocyclic trinuclear ZnII complex 1, 18-membered [1 + 1] mononuclear ZnII macrocycles 2-4, chiral/racemic 34-membered [2 + 2] dinuclear ZnII complexes 5-9, and 46-membered [2 + 2] dinuclear ZnII macrocycles 10-12 via ZnII ion template-assisted Schiff-base condensation. It is worth mentioning that the secondary template effects for nitrate and halide counterions have been observed in the 1,3-propanediamine involved imine condensation. In all [2 + 2] ZnII macrocycles, dinuclear complexes 5-9 display a full-folded molecular conformation, while trinuclear complex 1 and dinuclear complexes 10-12 exhibit distinct half-folded structures in the presence or absence of intramolecular π-π stacking interactions between two phenolic rings of the dialdehyde component. Interestingly, a solvent-induced single-crystal-to-single-crystal transformation was first achieved for two types of solvated mononuclear macrocycles 3a and 3b (H2O vs CH3CN) with folded and unfolded ligand conformations. In addition, the photoluminescent properties were studied for this family of Schiff-base macrocyclic ZnII complexes as well as the dialdehyde precursor H2tdd.