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AIMS: To investigate the diagnostic and predictive role of 18F-FDG PET/CT in patients with autoimmune encephalitis (AE) as a whole group. METHODS: Thrty-five patients (20 females and 15 males) with AE were recruited. A voxel-to-voxel semi-quantitative analysis based on SPM12 was used to analyze 18F-FDG PET/CT imaging data compared to healthy controls. Further comparison was made in different prognostic groups categorized by modified Rankin Scale (mRS). RESULTS: In total, 24 patients (68.6%) were tested positive neuronal antibodies in serum and/or CSF. Psychiatric symptoms and seizure attacks were major clinical symptoms. In the acute stage, 13 patients (37.1%) demonstrated abnormal brain MRI results, while 33 (94.3%) presented abnormal metabolism patterns. 18F-FDG PET/CT was more sensitive than MRI (p < 0.05). Patients with AE mainly presented mixed metabolism patterns compared to the matched controls, demonstrating hypermetabolism mainly in the cerebellum, BG, MTL, brainstem, insula, middle frontal gyrus, and relatively hypometabolism in the frontal cortex, occipital cortex, temporal gyrus, right parietal gyrus, left cingulate gyrus (p < 0.05, FWE corrected). After a median follow-up of 26 months, the multivariable analysis identified a decreased level of consciousness as an independent risk factor associated with poor outcome of AE (HR = 3.591, p = 0.016). Meanwhile, decreased metabolism of right superior frontal gyrus along with increased metabolism of the middle and upper brainstem was more evident in patients with poor outcome (p < 0.001, uncorrected). CONCLUSION: 18F-FDG PET/CT was more sensitive than MRI to detect neuroimaging abnormalities of AE. A mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism was a general metabolic pattern. Decreased metabolism of right superior frontal gyrus with increased metabolism of the middle and upper brainstem may predict poor long-term prognosis of AE.
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Encefalite , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Pessoa de Meia-Idade , Encefalite/diagnóstico por imagem , Encefalite/metabolismo , Adulto Jovem , Estudos de Coortes , Valor Preditivo dos Testes , Doença de Hashimoto/diagnóstico por imagem , Doença de Hashimoto/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Adolescente , China , Compostos Radiofarmacêuticos , Idoso , Imageamento por Ressonância Magnética , População do Leste AsiáticoRESUMO
Aims: This study aimed to comprehensively explore the cerebellar structural and functional changes in temporal lobe epilepsy (TLE) and its association with clinical information. Methods: The SUIT toolbox was utilized to perform cerebellar volume and diffusion analysis. In addition, we extracted the average diffusion values of cerebellar peduncle tracts to investigate microstructure alterations. Seed-based whole-brain analysis was used to investigate cerebellar-cerebral functional connectivity (FC). Subgroup analyses were performed to identify the cerebellar participation in TLE with/without hippocampal sclerosis (HS)/focal-to-bilateral tonic-clonic seizure (FBTCS) and TLE with different lateralization. Results: TLE showed widespread gray matter atrophy in bilateral crusII, VIIb, VIIIb, left crusI, and left VIIIa. Both voxel and tract analysis observed diffusion abnormalities in cerebellar afferent peduncles. Reduced FC between the right crus II and the left parahippocampal cortex was found in TLE. Additionally, TLE showed increased FCs between left lobules VI-VIII and cortical nodes of the dorsal attention and visual networks. Across all patients, decreased FC was associated with poorer cognitive function, while increased FCs appeared to reflect compensatory effects. The cerebellar structural changes were mainly observed in HS and FBTCS subgroups and were regardless of seizure lateralization, while cerebellar-cerebral FC alterations were similar in all subgroups. Conclusion: TLE exhibited microstructural changes in the cerebellum, mainly related to HS and FBTCS. In addition, altered cerebellar-cerebral functional connectivity is associated with common cognitive alterations in TLE.
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Cyhexatin (CYT), an organotin acaricide, is extensively utilized in developing countries to mitigate plant diseases caused by mites and minimize agricultural crop losses. However, the comprehensive mechanisms underlying the developmental stage of non-target organisms remain largely unexplored. In this study, zebrafish embryos were firstly exposed to CYT (0.06, 0.12, and 0.20 ng/mL, referred to as CYTL, CYTM, and CYTH, respectively) from 2 hpf (hours post fertilization) to 30 dpf (days post fertilization). No developmental toxicity was observed in the CYTL and CYTM groups, except for induced deformed phenotypes in the CYTM group at 120 hpf. However, exposure to CYTH resulted in significant reductions in spontaneous movement (24 hpf), heart rate (48 hpf), hatching rate (48 and 72 hpf), body weight (30 dpf), whole body length (30 dpf), and locomotion (30 dpf). Additionally, CYTH exposure induced morphological malformations, including spinal curvature, pericardial edema, and tail curvature in zebrafish larvae. Moreover, CYTH treatment induced apoptosis, increased reactive oxygen species (ROS) production, and resulted in significant reductions in free T3, cholesterol, estradiol, and testosterone levels in zebrafish larvae, while free T4 levels were increased. RNA-Seq analysis indicated that CYTH exposure led to significant alterations in the genome-wide gene expression profiles of zebrafish, particularly in the thyroid hormone and steroid biosynthesis signaling pathways, indicating endocrine disruption. Furthermore, CYTH exposure induced global DNA hypomethylation, reduced S-adenosylmethionine (SAM) levels and the SAM/S-adenosylhomocysteine (SAH) ratio, elevated SAH levels, and suppressed the mRNA expression of DNA methyltransferases (DNMTs) while also downregulating DNMT1 at both the gene and protein levels in zebrafish larvae. Overall, this study partially elucidated the developmental toxicity and endocrine disruption caused by CYT in zebrafish, providing evidence of the environmental hazards associated with this acaricide.
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Acaricidas , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Larva , Embrião não Mamífero , Glândula Tireoide , DNA/metabolismoRESUMO
Background: Cerebellar functional alterations are common in patients with mesial temporal lobe epilepsy (MTLE), which contribute to cognitive decline. This study aimed to deepen our knowledge of cerebellar functional alterations in patients with MTLE. Methods: In this study, participants were recruited from an ongoing prospective cohort of 13 patients with left TLE (LTLE), 17 patients with right TLE (RTLE), and 30 healthy controls (HCs). Functional magnetic resonance imaging data were collected during a Chinese verbal fluency task. Group independent component (IC) analysis (group ICA) was applied to segment the cerebellum into six functionally separated networks. Functional connectivity was compared among cerebellar networks, cerebellar activation maps, and the centrality parameters of cerebellar regions. For cerebellar functional profiles with significant differences, we calculated their correlation with clinical features and neuropsychological scores. Result: Compared to HCs and patients with LTLE, patients with RTLE had higher cerebellar functional connectivity between the default mode network (DMN) and the oculomotor network and lower cerebellar functional connectivity from the frontoparietal network (FPN) to the dorsal attention network (DAN) (p < 0.05, false discovery rate- (FDR-) corrected). Cerebellar degree centrality (DC) of the right lobule III was significantly higher in patients with LTLE compared to HC and patients with RTLE (p < 0.05, FDR-corrected). Higher cerebellar functional connectivity between the DMN and the oculomotor network, as well as lower cerebellar degree centrality of the right lobule III, was correlated with worse information test performance. Conclusion: Cerebellar functional profiles were altered in MTLE and correlated with long-term memory in patients.
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To facilitate better implementation of flood control and risk mitigation strategies, a model for evaluating the flood defense capability of China is proposed in this study. First, nine indicators such as slope and precipitation intensity are extracted from four aspects: objective inclusiveness, subjective prevention, etc. Secondly, the entropy weight method in the multi-attribute decision making (MADM) model and the improved three-dimensional technique for order preference by similarity to ideal solution (3D-TOPSIS) method were combined to construct a flood defense capacity index evaluation system. Finally, the receiver operating characteristic (ROC) curve and the Taylor plot method were innovatively used to test the model and indicators. The results show that nationwide, there is fine flood defense performance in Shandong, Jiangsu and room for improvement in Guangxi, Chongqing, Tibet and Qinghai. The good representativity of nine indicators selected by the model was verified by the Taylor plot. Simultaneously, the ROC calculated area under the curve (AUC) was 70%, which proved the good problem-solving ability of the MADM-GIS model. An accurate assessment of the sensitivity of flood control capacity in China was achieved, and it is suitable for situations where data is scarce or discontinuous. It provided scientific reference value for the planning and implementation of China's flood defense and disaster reduction projects and emergency safety strategies.
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Macrophages are among the most abundant immune cells in colorectal cancer (CRC). Re-educating tumor-associated macrophages (TAMs) to switch from protumoral to anti-tumoral activity is an attractive treatment strategy that warrants further investigation. However, little is known about the key pathway that is activated in TAMs. In this study, infitrating CD206+ TAMs in CRC were sorted and subjected to RNA-seq analysis. Differentially expressed genes were found to be enriched in unfolded protein response/endoplasmic reticulum stress response processes, and XBP1 splicing/activation was specifically observed in TAMs. XBP1 activation in TAMs promoted the growth and metastasis of CRC. Ablation of XBP1 inhibited the expression of the pro-tumor cytokine signature of TAMs, including IL-6, VEGFA, and IL-4. Simultaneously, XBP1 depletion could directly inhibit the expression of SIRPα and THBS1, thereby blocking "don't eat me" recognition signals and enhancing phagocytosis. Therapeutic XBP1 gene editing using AAV2-sgXBP1 enhanced the anti-tumor activity. Together, XBP1 activation in TAMs drives CRC progression by elevating pro-tumor cytokine expression and secretion, as well as inhibiting macrophage phagocytosis. Targeting XBP1 signaling in TAMs may be a potential strategy for CRC therapy.
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Antígenos de Diferenciação/genética , Neoplasias Colorretais/genética , Receptores Imunológicos/genética , Trombospondinas/genética , Macrófagos Associados a Tumor/transplante , Proteína 1 de Ligação a X-Box/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Estresse do Retículo Endoplasmático/genética , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Células HCT116 , Xenoenxertos , Humanos , Interleucina-4 , Interleucina-6/genética , Masculino , Receptor de Manose/imunologia , Camundongos , Pessoa de Meia-Idade , Fagocitose , RNA-Seq , Macrófagos Associados a Tumor/imunologia , Resposta a Proteínas não Dobradas/genética , Fator A de Crescimento do Endotélio Vascular/genética , Proteína 1 de Ligação a X-Box/antagonistas & inibidores , Proteína 1 de Ligação a X-Box/imunologiaRESUMO
Epidemiological and experimental evidence indicate that selenium is associated with a reduced risk of some cancers, including esophageal cancer. However, the exact mechanism is still unclear. In the present study, we used esophageal squamous cell carcinoma (ESCC) cell lines and animal models to explore the anti-cancer mechanism of methylseleninic acid (MSA). Firstly, MSA treatment dramatically attenuated Epidermal Growth Factor Receptor (EGFR) protein expression but did not alter mRNA levels in ESCC cells. On the contrary, EGFR overexpression partly abolished the inhibitory effect of MSA. With a microRNA-array, we found MSA up-regulated miR-146a which directly targeted EGFR, whereas miR-146a inhibitor antagonized MSA-induced decrease of EGFR protein. We further used 4-nitroquinoline-1-oxide (4NQO)-induced esophageal tumor mice model to evaluate the inhibitory effect of MSA in vivo. MSA treatment significantly decreased the tumor burden and EGFR protein expression in tumor specimens. Furthermore, MSA treatment inhibited EGFR pathway and subsequntly reduced Interleukin-6 (IL-6) secretion in the supernatant of cancer cell lines. MSA-induced IL-6 suppression was EGFR-dependent. To further evaluate the association of IL-6 and the anti-tumor effect of MSA on esophageal cancer, we established the 4NQO-induced esophageal tumor model in IL-6 knock-out (IL-6 KO) mice. The results showed that IL-6 deficiency did not affect esophageal tumorigenesis in mice, but the inhibitory effect of MSA was abolished in IL-6 KO mice. In conclusion, our study demonstrated that MSA upregulated miR-146a which directly targeted EGFR, and inhibited EGFR protein expression and pathway activity, subsequently decreased IL-6 secretion. The inhibitory effect of MSA on esophageal cancer was IL-6 dependent. These results suggested that MSA may serve as a potential drug treating esophageal cancer.
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AIMS: Cetuximab improves the survival of patients with advanced colorectal cancer (CRC). However, how cetuximab affects the tumor microenvironment has not been sufficiently understood. This study was to investigate whether cetuximab could inhibit the pro-tumor function of tumor-associated macrophages (TAMs) by suppressing the EGFR/IL-6 pathway. MAIN METHODS: The azoxymethane/dextran sodium sulfate (AOM/DSS) and tumor xenograft mouse models were used to assess the effect of cetuximab on TAMs. Flow cytometry, Western blotting, RT-qPCR, and ELISA were used to assess the prevalence of M2 and M1 phenotypes. Publicly available datasets of CRC patients were used to assess the relevance of EGFR and IL-6 expression as prognostic indicators. KEY FINDINGS: The two mouse models showed that cetuximab could attenuate the pro-tumor function of TAMs and decrease tumor burden. Cetuximab repolarized TAMs from M2-like to M1-like phenotypes, mainly by suppressing the IL-6 expression through NFκB and STAT3 pathways. Analysis of public scRNA-seq data indicated EGFR was mainly expressed on the surface of macrophage infiltration into tumor microenvironment. The public transcriptomics datasets showed that the expression level of IL-6 was positively correlated with EGFR in CRC patients, and PROGgeneV2 analysis indicated that IL-6 and CD206 both predicted poor recurrence-free and overall survival of CRC patients. Furthermore, the inhibition efficacy of cetuximab was significantly attenuated in IL-6 knockout CRC mice model. SIGNIFICANCE: These results indicate a new macrophage-based molecular mechanism explaining the effect of cetuximab in treatment of colorectal cancer.
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Cetuximab/farmacologia , Interleucina-6/metabolismo , Macrófagos Associados a Tumor/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Cetuximab/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Receptores ErbB/efeitos dos fármacos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Prognóstico , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Macrófagos Associados a Tumor/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Targeting EGFR combined with chemotherapy is one of the most valuable therapeutic strategies in colorectal cancer. However, resistance remains a major obstacle to improve efficacy. IRE1α-XBP1s signaling pathway is activated in many malignant tumors, and plays important roles in chemoresistance. Therefore, IRE1α-XBP1s might be a potential target to overcome the chemoresistance in colorectal cancer. In this study, we detected the activation of IRE1α-XBP1s signaling in patient cancer tissues and colorectal cancer cell lines. The phosphorylation level of IRE1α and the spliced XBP1s were aberrantly elevated in colorectal cancer, and IRE1α-XBP1s signaling activation was correlated with high EGFR expression. By overexpression of EGFR protein or activation by EGF treatment, we found that EGFR activation could enhance the phosphorylation of IRE1α and spliced XBP1s expression. On the contrary, inhibition of EGFR decreased the IRE1α-XBP1s signaling. Further, we examined the downstream signaling pathways regulated by EGFR. Inhibition of ERK activity could reverse the EGFR induced IRE1α-XBP1s activation. Co-IP confirmed the physical interaction of ERK and IRE1α. Cell growth and colony formation assay showed that the inhibition of IRE1α activity could suppress EGFR driven colorectal cancer cell proliferation. Furthermore, we found that oxaliplatin could activate IRE1α-XBP1s signaling, and combination with cetuximab partially reversed the activation. Inhibition of EGFR signaling could enhance the efficacy of oxaliplatin in vitro and in vivo. Our results showed that IRE1α RNase activity is aberrantly elevated in colorectal cancer, and EGFR signaling could activate IRE1α/XBP1s possibly through EGFR-MEK-ERK pathway. IRE1α-XBP1s pathway might involve in EGFR driven tumor cell proliferation. Cetuximab could partially recover oxaliplatin-induced IRE1α-XBP1s activation, and therefore enhance the anti-tumor efficacy of oxaliplatin. Our findings declare a new mechanism that targeting EGFR could inhibit chemotherapy-induced IRE1α-XBP1s activation and therefore enhance the efficacy.
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Due to the increasing incidence and mortality, the early diagnosis, specific targeted therapies, and prognosis for colorectal cancer (CRC) attract more and more attention. Wild-type p53-induced phosphatase 1 (Wip1) and karyopherin α2 (KPNA2) have been regarded as oncogenes in many cancers, including CRC. Wip1 dephosphorylates p53 to inactivate it. TP53 activator and Wip1 inhibitor downregulate KPNA2 expression. Therefore, we speculate that Wip1 may co-operate with KPNA2 to modulate CRC progression in a p53-dependent manner. Here, Wip1 and KPNA2 messenger RNA expression and protein levels are significantly increased in CRC tissues and cell lines and are positively correlated with each other. Wip1 silence increases p53 phosphorylation while decreases KPNA2 protein. Wip1 knockdown remarkably suppresses CRC cell proliferation and migration while KPNA2 overexpression exerts an opposing effect. KPNA2 overexpression could partially rescue Wip1 silence-inhibited CRC cell proliferation and migration. Finally, Wip1 interacts with KPNA2 to modulate the activation of AKT/GSK-3ß signaling and metastasis-related factors. In summary, Wip1 could co-operate with KPNA2 to modulate CRC cell proliferation and migration, possibly via a p53-dependent manner, through downstream AKT/GSK-3ß pathway. We provided a novel mechanism of Wip1 interacting with KPNA2, therefore modulating CRC cell proliferation and migration.
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Neoplasias Colorretais/metabolismo , Proteína Fosfatase 2C/metabolismo , Proteína Supressora de Tumor p53/metabolismo , alfa Carioferinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Fosforilação , Prognóstico , Proteína Fosfatase 2C/genética , Regulação para Cima , alfa Carioferinas/genéticaRESUMO
PURPOSE: Strategies to increase radiosensitivity are urgently needed. Combining radiosensitizing reagents with radiotherapy could improve the outcome of cancer treatment. Some preclinical studies showed that sepantronium bromide (YM155) could sensitize cancer cells to radiation by inhibiting the survivin protein. In this study, we try to investigate the function of YM155 on radiosensitivity of esophageal squamous cell carcinoma (ESCC) cells. MATERIALS AND METHODS: ESCC cell lines were treated with radiation and YM155, and the radiation efficacy was evaluated by cell counting kit-8 assay and clonogenic survival assay. Cell senescence was measured by senescence-associated ß-galactosidase staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, fluorescein isothiocyanate-labeled Annexin V/propidium iodide assay, and poly ADP-ribose polymerase cleavage were used to detect apoptosis. KYSE150 xenografts model was used to test the efficacy of radiation combined with YM155. RESULTS: YM155 could inhibit the upregulation of survivin induced by radiation in all ESCC cell lines, but the efficacy of radiosensitization varied in different cell lines. Radiation-induced senescence in KYSE150 and KYSE410 cells, and the combination with YM155 inhibited senescence and promoted apoptosis of ESCC cells, thereby enhancing radiosensitivity. Combination with YM155 and radiation delayed the growth of KYSE150 xenografts in nude mice by switching radiation-induced senescence to apoptosis. When p21 was inhibited in KYSE150 cells, radiation did not induce senescence, and the radiosensitization of YM155 was also attenuated. In KYSE510 and KYSE180 cells, radiation did not induce senescence, and YM155 could not enhance the radiosensitivity. CONCLUSION: Our results suggest a new mechanism that YM155 might sensitize ESCC cells to radiation by switching radiation-induced senescence to apoptosis. The major determinant of radiosensitization by YM155 might be the induction of senescence by radiation.
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Epidermal growth factor receptor (EGFR) is a target of colon cancer therapy, but the effects of this therapy on the tumor microenvironment remain poorly understood. Our in vivo studies showed that cetuximab, an anti-EGFR monoclonal antibody, effectively inhibited AOM/DSS-induced, colitis-associated tumorigenesis, downregulated M2-related markers, and decreased F4/80+/CD206+ macrophage populations. Treatment with conditioned medium of colon cancer cells increased macrophage expression of the M2-related markers arginase-1 (Arg1), CCL17, CCL22, IL-10 and IL-4. By contrast, conditioned medium of EGFR knockout colon cancer cells inhibited expression of these M2-related markers and induced macrophage expression of the M1-related markers inducible nitric oxide synthase (iNOS), IL-12, TNF-α and CCR7. EGFR knockout in colon cancer cells inhibited macrophage-induced promotion of xenograft tumor growth. Moreover, colon cancer-derived insulin-like growth factor-1 (IGF-1) increased Arg1 expression, and treatment with the IGF1R inhibitor AG1024 inhibited that increase. These results suggest that inhibition of EGFR signaling in colon cancer cells modulates cytokine secretion (e.g. IGF-1) and prevents M1-to-M2 macrophage polarization, thereby inhibiting cancer cell growth.
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Neoplasias do Colo/etiologia , Neoplasias do Colo/metabolismo , Receptores ErbB/metabolismo , Macrófagos/metabolismo , Transdução de Sinais , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Cetuximab/farmacologia , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Receptores ErbB/genética , Feminino , Técnicas de Inativação de Genes , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Krüppel-like factor 4 (KLF4) is a transcription factor and functions as a tumor suppressor or tumor promoter in different cancer types. KLF4 regulates many gene expression, thus affects the process of cell proliferation, differentiation, and apoptosis. Recently, KLF4 was reported to induce senescence during the generation of induced pluripotent stem (iPS) cells, but the exact mechanism is still unclear. In this study, we constructed two doxycycline-inducing KLF4 cell models, and demonstrated overexpression of KLF4 could promote cell senescence, detected by senescence-associated ß-galactosidase activity assay. Then we confirmed that p21, a key effector of senescence, was directly induced by KLF4. KLF4 could also inhibit survivin, which could indirectly induce p21. By miRNA microarray, we found a series of miRNAs regulated by KLF4 and involved in senescence. We demonstrated that KLF4 could upregulate miR-203, and miR-203 contributed to senescence through miR-203-survivin-p21 pathway. Our results suggest that KLF4 could promote cell senescence through a complex network: miR-203, survivin, and p21, which were all regulated by overexpression of KLF4 and contributed to cell senescence.
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Senescência Celular/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Proteínas Inibidoras de Apoptose/genética , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , Sequência de Bases , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Células HEK293 , Células HeLa , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Estimativa de Kaplan-Meier , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/metabolismo , Prognóstico , Transdução de Sinais/genética , SurvivinaRESUMO
The effect of dietary amylose/amylopectin (AM/AP) ratio on growth, feed utilization, digestive enzyme activities, plasma parameters, and postprandial blood glucose responses was evaluated in juvenile obscure puffer, Takifugu obscurus. Five isonitrogenous (430 g kg(-1) crude protein) and isolipidic (90 g kg(-1) crude lipid) diets containing an equal starch level (250 g kg(-1) starch) with different AM/AP ratio diets of 0/25, 3/22, 6/19, 9/16 and 12/13 were formulated. Each experimental diet was fed to triplicate groups (25 fish per tank), twice daily during a period of 60 days. After the growth trial, a postprandial blood response test was carried out. Fish fed diet 6/19 showed best growth, feed efficiency and protein efficiency ratio. Hepatosomatic index, plasma total cholesterol concentration, liver glycogen and lipid content, and gluconokinase, pyruvate kinase and fructose-1,6-bisphosphatase activities were lower in fish fed highest AM/AP diet (12/13) than in fish fed the low-amylose diets. Activities of liver and intestinal trypsin in fish fed diet 3/22 and diet 6/19 were higher than in fish fed diet 9/16 and diet 12/13. Activities of liver and intestinal amylase and intestinal lipase, and starch digestibility were negatively correlated with dietary AM/AP ratio. Fish fed diet 3/22 and diet 6/19 showed higher plasma total amino acid concentration than fish fed the other diets, while plasma urea nitrogen concentration and activities of alanine aminotransferase and aspartate aminotransferase showed the opposite trend. Equal values were found for viscerosomatic index and condition factor, whole body and muscle composition, plasma high-density and low-density lipoprotein cholesterol concentrations, and activities of lipase and hexokinase and glucose-6-phosphatase in liver. Postprandial plasma glucose and triglyceride peak value of fish fed diet 12/13 were lower than in fish fed the low-amylose diets, and the peak time of plasma glucose was later than in fish fed the other diets. Plasma glucose and triglyceride concentrations showed a significant difference at 2 and 4 h after a meal and varied between dietary treatments. According to regression analysis of weight gain against dietary AM/AP ratio, the optimum dietary AM/AP ratio for maximum growth of obscure puffer was 0.25. The present result indicates that dietary AM/AP ratio could affect growth performance and feed utilization, some plasma parameters, digestive enzyme as well as hepatic glucose metabolic enzyme activities in juvenile obscure puffer.
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Amilopectina/farmacologia , Amilose/farmacologia , Digestão/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Período Pós-Prandial/efeitos dos fármacos , Takifugu/crescimento & desenvolvimento , Alanina Transaminase/sangue , Aminoácidos/metabolismo , Amilopectina/administração & dosagem , Amilose/administração & dosagem , Análise de Variância , Animais , Aspartato Aminotransferases/sangue , Glicemia , Nitrogênio da Ureia Sanguínea , Colesterol/sangue , Colorimetria/veterinária , Digestão/fisiologia , Alimentos Formulados , Frutose-Bifosfatase/metabolismo , Glicogênio/metabolismo , Fígado/metabolismo , Espectrometria de Massas/veterinária , Redes e Vias Metabólicas/fisiologia , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Período Pós-Prandial/fisiologia , Piruvato Quinase/metabolismo , Takifugu/metabolismo , Triglicerídeos/metabolismoRESUMO
Hereditary retinal dystrophy usually leads to blindness. Using Royal College of Surgeons (RCS) rats as a hereditary retinal dystrophy model, we investigated the possible neuroprotective effects of the aqueous extract of dried Lycium barbarum (LBA). Sixty postnatal RCS rats were selected and randomly divided into a control group (CG, thirty rats) and an experimental group (EG). Ten days after birth, EG rats were treated by 1 mg/kg of LBA per day, and CG rats were normally fed. These rats were killed at postnatal day (P) 25, P35 and P50, and retinal tissue was prepared for analysis. Photoreceptor cells were assessed by hematoxylin and eosin (HE) staining, TUNEL detection and Caspase-2 protein expression. We found that in rats at P25, the outer nuclear layer (ONL) of EG was thicker and more photoreceptor cells survived. Meanwhile, the TUNEL expression in EG was obviously reduced compared with CG. The Caspase-2 positive cells were found in the ganglion cell layer and inner nuclear layer in both CG and EG at 25-50 postnatal days, but the expression in EG rats was significantly lower than in CG at P25. The results demonstrated that LBA might have a neuroprotective role on the retinal tissue of RCS rats at the early stage by protecting photoreceptors and inhibiting apoptosis involving Caspase-2 protein.