RESUMO
Background: Globally, the subsequent complications that accompany sepsis result in remarkable morbidity and mortality rates. The lung is among the vulnerable organs that incur the sepsis-linked inflammatory storm and frequently culminates into ARDS/ALI. The metformin-prescribed anti-diabetic drug has been revealed with anti-inflammatory effects in sepsis, but the underlying mechanisms remain unclear. This study aimed to ascertain metformin's effects and functions in a young mouse model of sepsis-induced ALI. Methods: Mice were randomly divided into 4 groups: sham, sham+ Met, CLP, and CLP+ Met. CLP was established as the sepsis-induced ALI model accompanied by intraperitoneal metformin treatment. At day 7, the survival state of mice was noted, including survival rate, weight, and M-CASS. Lung histological pathology and injury scores were determined by hematoxylin-eosin staining. The pulmonary coefficient was used to evaluate pulmonary edema. Furthermore, IL-1ß, CCL3, CXCL11, S100A8, S100A9 and NLRP3 expression in tissues collected from lungs were determined by qPCR, IL-1ß, IL-18, TNF-α by ELISA, caspase-1, ASC, NLRP3, P65, p-P65, GSDMD-F, GSDMD-N, IL-1ß and S100A8/A9 by Western blot. Results: The data affirmed that metformin enhanced the survival rate, lessened lung tissue injury, and diminished the expression of inflammatory factors in young mice with sepsis induced by CLP. In contrast to sham mice, the CLP mice were affirmed to manifest ALI-linked pathologies following CLP-induced sepsis. The expressions of pro-inflammatory factors, for instance, IL-1ß, IL-18, TNF-α, CXCL11, S100A8, and S100A9 are markedly enhanced by CLP, while metformin abolished this adverse effect. Western blot analyses indicated that metformin inhibited the sepsis-induced activation of GSDMD and the upregulation of S100A8/A9, NLRP3, and ASC. Conclusion: Metformin could improve the survival rate, lessen lung tissue injury, and minimize the expression of inflammatory factors in young mice with sepsis induced by CLP. Metformin reduced sepsis-induced ALI via inhibiting the NF-κB signaling pathway and inhibiting pyroptosis by the S100A8/A9-NLRP3-IL-1ß pathway.
RESUMO
In dermatology, a keloid is one of the most common skin morphological abnormalities caused by excessive proliferation of fibroblasts. Keloids that are large or occur near important joint sites often cause varying degrees of physiological dysfunction in patients, therefore requiring medical treatment. A boy with congenital syndactyly developed huge keloids at the surgical site after undergoing surgical correction treatment. After treatment using trepanation combined with superficial radiotherapy (SRT-100) in our hospital, most of the boy's keloids shrank and flattened. The affected foot returned to its normal appearance, and the boy could wear shoes normally. The boy did not complain of pain, numbness, or any other distinctive discomfort after completing the treatment. This suggested that the combination of trepanation and SRT-100 may be one of the options for treating hypertrophic keloids that cannot be treated by surgical excision.
RESUMO
The developmental toxicity of fenvalerate, a representative pyrethroid insecticide, is well documented. The present study aimed to explore whether prenatal exposure to fenvalerate causes depression-like behavior in adulthood. Pregnant mice were orally administrated with either corn oil or fenvalerate (2 or 20 mg/kg) during pregnancy. Depressive-like behaviors were assessed by tail suspension test (TST), forced swim test (FST) and sucrose preference test (SPT). Immobility times in TST and FST were increased in offspring whose mothers were exposed to fenvalerate throughout pregnancy. By contrast, sugar preference index, as determined by SPT, was decreased in fenvalerate-exposed offspring. Prefrontal PSD95, a postsynaptic membrane marker, was downregulated in fenvalerate-exposed adulthood offspring. Fenvalerate-induced reduction of prefrontal PSD95 began at GD18 fetal period. Accordingly, prefrontal 5-HT, a neurotransmitter for synaptogenesis, was also reduced in fenvalerate-exposed GD18 fetuses. Tryptophan hydroxylase 2 (TPH2), a key enzyme for 5-HT synthesis, was downregulated in the midbrain of fenvalerate-exposed GD18 fetuses. Additional experiment showed that GRP78 and p-eIF2α, two endoplasmic reticulum stress-related proteins, were increased in the midbrain of fenvalerate-exposed fetal mice. The present results suggest that prenatal exposure to fenvalerate causes depressive-like behavior in adulthood, partially by inhibiting brain-derived 5-HT synthesis.
Assuntos
Depressão , Inseticidas , Nitrilas , Efeitos Tardios da Exposição Pré-Natal , Piretrinas , Serotonina , Animais , Piretrinas/toxicidade , Feminino , Gravidez , Camundongos , Nitrilas/toxicidade , Depressão/metabolismo , Serotonina/metabolismo , Inseticidas/toxicidade , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Comportamento Animal/efeitos dos fármacos , Masculino , Exposição MaternaRESUMO
Objective: In patients with post-stroke oropharyngeal dysphagia (PSOD), classical dysphagia therapy (CDT) continues to provide unsatisfactory outcomes and makes it challenging for them to remove the nasal feeding tube. Increasing bolus viscosity helps prevent aspiration in PSOD. However, conventional starch thickeners enhance post-digestion residue. This study aims to evaluate the efficacy of swallow training with xanthan gum-based thickener (XGT) (Softia G, NUTRI Co., Ltd., Yokkaichi, Japan) additional to CDT in Chinese PSOD patients with a nasogastric tube when compared to CDT alone. Methods: Patients with PSOD who had a nasogastric tube were randomly assigned to either the experimental group (E-group) or the control group (C-group) in this randomized controlled, single-blind, parallel-group study. Both groups received CDT for 4 weeks. The E-group cases received additional swallow training with a Softia G-prepared hydrogel training material. The Functional Oral Intake Scale (FOIS) and modified volume-viscosity swallow test (M-VVST) for swallowing safety and efficacy according to adjusted Chinese dietary habits were administered before and after treatment. Post-training, both groups' nasogastric tube removal rates were calculated. Results: One hundred sixty-seven participants (E-group: 82 and C-group: 85) completed the study. The E-group's median score of FOIS improved significantly than the C-group after training (median = 5 vs. 3, P < 0.001). The incidence of coughing, voice changes, oxygen desaturation of 3% or more, pharyngeal residue and piecemeal deglutition in the E-group was significantly lower than that in the C-group (P < 0.05). The E-group had 100% nasogastric tube removal, while the C-group had 28.24% (P < 0.001). Conclusion: Swallow training with XGT Softia G in addition to CDT can promote swallowing safety and efficacy in Chinese patients with PSOD more effectively than CDT alone.
RESUMO
The investigation of the properties of aggregate materials is highly interesting because the process of aggregation can result in the disappearance of original properties and the emergence of new ones. Here, a novel fluorescent material (TPEIP), which synergistically combines aggregation-induced emission (AIE) and aggregation caused quenching (ACQ) moieties, was first synthesized by the cyclization reaction of 2,3-diamino-phenazine with 4-tetraphenylenthenealdehyde. We controlled the degree of aggregation of TPEIP to shed light on the impact of the aggregation on the excited state dynamics. TPEIP aggregation realized control over the Intersystem Crossing (ISC) rates and, in turn, the suppression of triplet excited states in MeOH, EtOH or via the simple addition of water to TPEIP solutions in DMSO. From global target analysis, the time scale was 966.2 ps for ISC for TPEIP in DMSO, but it was 860 ps in the case of TPEIP solutions featuring 5% water. The dynamics of TPEIP excited states undergo significant changes as the degree of aggregation increases. Notably, the lifetime of singlet excited states decreases, and there was a gradual diminishment in triplet states.
RESUMO
The precise aromatization of the C-ring of podophyllotoxone to access value-added dehydropodophyllotoxin derivatives conventionally requires the use of equivalent amounts of unsustainable oxidants and suffers from inefficiencies. Taking advantage of the hydridic character of the C8 and C8' of podophyllotoxone, we have developed an I2-DMSO catalytic manifold that enables a green and selective dehydrogenative aromatization to overcome these synthetic challenges. An unprecedented dehydrogenative amination of podophyllotoxone derivatives was also realized using aniline as the reaction partner.
RESUMO
BACKGROUND: Microvascular invasion (MVI) adversely affects long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to examine the association between preoperative type 2 diabetes mellitus (T2DM) with incidences of MVI and prognosis in HBV-related HCC after liver resection (LR). MATERIAL AND METHODS: Data of HBV-related HCC patients who underwent LR as an initial therapy from four hospitals in China were retrospectively collected. Clinicopathological factors associated with the incidence of MVI were identified using univariate and multivariate logistic regression analysis. The recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Of 1473 patients who were included, 219 (14.9%) patients had T2DM. Preoperative T2DM, HBV DNA load, antiviral treatment, AFP level, varices, and tumor encapsulation were identified to be independent predictors of the incidence of MVI. Patients with HBV-related HCC and T2DM had a higher incidence of MVI (65.8%) than those without T2DM (55.4%) (P = 0.004). The RFS and OS were significantly worse in patients with T2DM than those without T2DM (median RFS: 11.1 vs 16.7 months; OS: 26.4 vs 42.6 months, both P < 0.001). Equivalent results were obtained in HCC patients with MVI who had or did not have T2DM (median RFS: 10.0 vs 15.9 months; OS: 24.5 vs 37.9 months, both P < 0.001). CONCLUSIONS: Preoperative T2DM was an independent risk factor of incidence of MVI. Patients with HBV-related HCC and T2DM had worse prognosis than those without T2DM after LR.
Assuntos
Carcinoma Hepatocelular/patologia , Diabetes Mellitus Tipo 2/epidemiologia , Hepatite B Crônica/complicações , Neoplasias Hepáticas/patologia , Microvasos/patologia , Adulto , Idoso , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/cirurgia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The impairments of maternal fenvalerate exposure have been well documented in previous study, but little was known about the effects of paternal fenvalerate exposure. The current study aimed to assess the effects of paternal fenvalerate exposure on spatial cognition and hippocampus across generations. Adult male mice (F0) were orally administered with fenvalerate (0, 2 or 20 mg/kg) for 5 weeks. F0 males were mated with untreated-females to generate F1 generation. F1 males were mated with F1 control females to generate F2 generation. For F1 and F2 adult offspring, spatial learning and memory were detected by Morris water maze. Results showed that spatial learning and memory were impaired in F1 females but not F1 males derived from F0 males exposed to 20 mg/kg FEN. Furthermore, significant impairment of spatial learning and memory were found in F2 females but not F2 males derived from F0 males exposed to 20 mg/kg FEN. As expected, histopathology showed that neural density in hippocampal CA3 region was reduced in F1 and F2 females but not F1 and F2 males derived from F0 males exposed to 20 mg/kg FEN. Mechanistically, hippocampal thyroid hormone receptor alpha1 (TRα1) was down-regulated in F1 and F2 females derived from F0 males exposed to 20 mg/kg FEN. Correspondingly, hippocampal brain-derived neurotrophic factor, tropomyosin receptor kinase B and p75 neurotrophin receptor, three downstream genes of TR signaling, were down-regulated in F1 and F2 females. Taken together, the present study firstly found that paternal fenvalerate exposure transgenerationally impaired spatial cognition in a gender-dependent manner. Hippocampal TR signaling may, at least partially, contribute to the process of cognitive impairment induced by paternal fenvalerate exposure. Further exploration in the mode of action of fenvalerate is critically important to promote human health and environmental safety.
Assuntos
Piretrinas , Animais , Cognição , Feminino , Hipocampo , Masculino , Camundongos , Nitrilas/toxicidade , Piretrinas/toxicidadeRESUMO
Septic cardiomyopathy is characterized by impaired contractive function with mitochondrial dysregulation. Songorine is a typical active C20-diterpene alkaloid from the lateral root of Aconitum carmichaelii, which has been used for the treatment of heart failure. This study investigated the protective role of songorine in septic heart injury from the aspect of mitochondrial biogenesis. Songorine (10, 50 mg/kg) protected cardiac contractive function against endotoxin insult in mice with Nrf2 induction. In cardiomyocytes, lipopolysaccharide (LPS) evoked mitochondrial reactive oxygen species (ROS) production and redistributed STIM1 to interact with Orai1 for the formation of calcium release-activated calcium (CRAC) channels, mediating calcium influx, which were prevented by songorine, likely due to ROS suppression. Songorine activated Nrf2 by promoting Keap1 degradation, having a contribution to enhancing antioxidant defenses. When LPS shifted metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) in cardiomyocytes, songorine upregulated mitochondrial genes involved in fatty acid ß-oxidation, tricarboxylic acid (TCA) cycle and electron transport chain in a manner dependent on Nrf2, resultantly protecting the capability of OXPHOS. Songorine increased luciferase report gene activities of nuclear respiratory factor-1 (Nrf1) and mitochondrial transcription factor A (Tfam) dependently on Nrf2, indicative of the regulation of Nrf2/ARE and NRF1 signaling cascades. Songorine promoted PGC-1α binding to Nrf2, and the cooperation was required for songorine to activate Nrf2/ARE and NRF1 for the control of mitochondrial quality and quantity. In support, the beneficial effects of songorine on cardioprotection and mitochondrial biogenesis were diminished by cardiac Nrf2 deficiency in mice subjected to LPS challenge. Taken together, these results showed that Nrf2 transcriptionally promoted mitochondrial biogenesis in cooperation with PGC-1α. Songorine activated Nrf2/ARE and NRF1 signaling cascades to rescue cardiomyocytes from endotoxin insult, suggesting that protection of mitochondrial biogenesis was a way for pharmacological intervention to prevent septic heart injury.
Assuntos
Fator 2 Relacionado a NF-E2 , Sepse , Alcaloides , Animais , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Sepse/tratamento farmacológico , Sepse/genéticaRESUMO
OBJECTIVE: To systematically evaluate the clinical efficacy of high-quality direct anterior approach (DAA) and other approaches for the treatment of elderly patients with femoral neck fracture. METHODS: Literatures published in English or Chinese about the direct anterior approach and other approaches for hemiarthroplasty in femoral neck fracture were searched on Cochrane Library, PubMed, EMBASE, Web of science, Wanfang, CNKI databases from their establishment to May 2019. According to the inclusion and exclusion criteria, two researchers independently screened the literatures, and extracted the data. The quality of RCT were evaluated by Cochrane Risk of Bias Assessment Tool, and non-RCT were evaluated by the NOS scale. Meta-analysis was performed using the RevMan 5.3 software. RESULTS: A total of 9 articles were included with 901 cases, in which 429 cases used DAA, and 472 used other approaches. DAA had a significantly lower dislocation rate compared to subgroup of posterior and posterolateral approach [OR=0.19, 95%CI (0.06, 0.61), P=0.005]. No significant differences were found between DAA group and subgroup of direct lateral and anterolateral approach[OR=1.08, 95%CI(0.20, 5.76), P=0.93]. Also there were no relevant differences between the DAA group and control in infection rate[OR=1.07, 95%CI(0.47, 2.43), P=0.88], perioperative fracture rate[OR=0.95, 95%CI(0.36, 2.50), P=0.92], re operation rate[OR=0.76, 95%CI(0.30, 1.89), P=0.55], overall complication rate [OR=0.88, 95%CI (0.63, 1.22), P=0.44], mortality [OR=1.33, 95%CI (0.84, 2.11), P=0.23], operative time[MD=1.43, 95%CI(-5.85, 8.71), P=0.70]. CONCLUSION: The current evidenceindicates that the DAA was associated with a significantly lower dislocation rate compared to posterior capsular approaches for hemiarthroplasty. There was no significant difference in dislocation rate with the lateral and anterolateral approach.
Assuntos
Antivirais , Artroplastia de Quadril , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia , Hepatite C Crônica , Idoso , Humanos , Reoperação , Resultado do TratamentoRESUMO
The dried roots of Berberis heteropoda Schrenk have traditionally been used to treat acute gastroenteritis and dysentery. The aim of this study was to confirm the antibacterial activity of an extract of Berberis heteropoda Schrenk rootin vitro and its therapeutic effects on rats with diarrhea-predominant irritable bowel syndrome (D-IBS) in vivo, as well as to identify the related signaling pathways. A water extract of Berberis heteropoda Schrenk root (BHS) inhibited the growth of S. aureus, E. coli, P. aeruginosa and S. faecalis. BHS potentially damaged the structure of the bacterial cell membrane and decreased the activity of some membranous enzymes, eventually killing the S. aureus, E. coli, P. aeruginosa and S. faecalis bacteria. Oral administration of BHS (low, middle and high dose group, L, M and H) significantly alleviated the abdominal pain, diarrhea, and depression-like symptoms of D-IBS rats, and the efficacy index ranged from 30% to 60%, indicating that the BHS treatment was effective. BHS (L, M and H) alleviated the abnormal pathological changes in the brain, as evidenced by HE staining. The expression of CHAT, 5-HT, C-FOS and CGRP was reduced by the BHS treatment (L, M and H). Our findings provide novel insights into the use of the natural product BHS to inhibit pathogenic bacteria by destroying the bacterial structure, indicating that BHS possesses certain biological activities. Furthermore, BHS has the potential to alleviate diarrhea, abdominal pain and depression-like behaviors in D-IBS rats by regulating the brain-gut peptide levels.
Assuntos
Antibacterianos/administração & dosagem , Berberis/química , Medicamentos de Ervas Chinesas/administração & dosagem , Síndrome do Intestino Irritável/tratamento farmacológico , Animais , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Feminino , Humanos , Síndrome do Intestino Irritável/microbiologia , Masculino , Raízes de Plantas/química , Ratos , Ratos WistarRESUMO
BACKGROUND: Species of the Anopheles hyrcanus group are widely distributed in Palearctic and Oriental regions and some of them are important malaria vectors. The cryptic species of An. hyrcanus group was almost impossible to identify based only on their morphology. The phylogenetic relationship of An. hyrcanus group was also not clear. METHODS: Five members of An. hyrcanus group were identified by rDNA ITS2 sequencing as An. yatsushiroensis, An. belenrae, An. kleini, An. lesteri and An. sineroides. The mitochondrial genome fragments were sequenced and annotated using the mitochondrial genome of An. sinensis as reference. Based on the four segments and Joint Data sequences of these species, and other four anopheline species downloaded from GenBank, intraspecific as well as interspecific genetic distances were calculated and the phylogenetic trees were reconstructed by the methods of neighbor joining, maximum parsimony, minimum evolution and maximum likelihood. FINDINGS: Four parts of mitochondrial genomes, which were partial fragments COI + tRNA + COII (F5), ATP6 + COIII(F7 + F8), ND1(F19) and lrRNA (F21), were obtained. All fragments were connected as one sequence (referred as Joint Data), which had a total length of 3393 bp. All fragment sequences were highly conservative within species, with the maximum p distance (0.026) calculated by F19 of An. belenrae. The pairwise interspecific p distance calculated by each fragment showed minor or even no difference among An. sinensis, An. kleini and An. belenrae. However, interspecific p distances calculated by the Joint Data sequence ranged from 0.004 (An. belenrae vs An. kleini) to 0.089 (An. sineroides vs An. minimus), and the p distances of the six members of An. hyrcanus group were all less than 0.029. The phylogenetic tree showed two major clades: all subgenus Anopheles species (including six members of An. hyrcanus group, An. atroparvus and An. quadrimaculatus A) and subgenus Cellia (including An. dirus and An. minimus). The An. hyrcanus group was divided into two clusters as ((An. lesteri, An. sineroides) An. yatsushiroensis) and ((An. belenrae, An. sinensis) An. kleini)). CONCLUSIONS: The An. hyrcanus group in this study could be divided into two clusters, in one of which An. belenrae, An. sinensis and An. kleini were most closely related. More molecular markers would make greater contribution to phylogenetic analysis.
Assuntos
Anopheles/classificação , Genoma Mitocondrial , Mosquitos Vetores/classificação , Filogenia , Animais , Anopheles/genética , China , Mosquitos Vetores/genéticaRESUMO
BACKGROUND: The aim of the present study was to investigate the antidiarrheal effect of Berberis heteropoda Schrenk roots (BHS), which are used by Chinese minorities to treat diarrhea, through regulation of intestinal flora and related signaling pathways. METHODS: Wistar rats were randomly divided into 6 groups: Control group (Con), Model group (Mod), three BHS groups (BHS-L (0.65â¯g/kg), BHS-M (1.955â¯g/kg), BHS-H (5.86â¯g/kg) and Bifidobacterium group (Bif). The model of diarrhea-based irritable bowel syndrome (D-IBS) was induced by intragastric administration combined with restraint stress. The CRD method was used to determine the AWR score and the Bristol fecal score. Quantification of the intestinal bacteria groups in feces was performed using colony counting on plates. The mRNA expression levels of Gpr41, Gpr43, TLR2, TLR4, and nuclear protein κB were determined by qRT-PCR, and the relative abundances of intestinal flora in the intestinal contents were determined by high-throughput gene sequencing ratios. RESULTS: Oral administration of BHS (L, M and H) significantly reduced the AWR score and the Bristol fecal score, significantly relieved diarrhea in D-IBS rats, reduced the number of Enterococci and Enterobacteria in feces, increased the number of Bifidobacteria and Lactobacilli, and upregulated the expression of SCFA in plasma. qRT-PCR analysis showed that the expression of TLR2, TLR4, Gpr41, Gpr43 and NF-κB in the BHS groups was downregulated. D-IBS rats reduced the abundance and diversity of intestinal flora and BHS (L, M and H) regulated the abundance and diversity of their intestinal flora. CONCLUSION: The above data suggest that BHS potentially alleviates diarrhea, intestinal flora disorder and intestinal inflammation in D-IBS rats by regulating the immunological pathways. BHS is a promising agent in the treatment of D-IBS.
Assuntos
Antidiarreicos/uso terapêutico , Berberis , Diarreia/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Antidiarreicos/farmacologia , Bactérias/isolamento & purificação , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Diarreia/genética , Diarreia/microbiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/microbiologia , Masculino , Fitoterapia , Extratos Vegetais/farmacologia , Raízes de Plantas , Ratos WistarRESUMO
Induced pluripotent stem cells (iPSCs) are reprogrammed somatic cells that gained self-renewal and differentiation capacity similar to embryonic stem cells. Taking the precious opportunity of the TianZhou-1 spacecraft mission, we studied the effect of space microgravity (µg) on the self-renewal capacity of iPSCs. Murine iPSCs carrying pluripotency reporter Oct4-GFP were used. The Oct4-EGFP-iPSCs clones were loaded into the bioreactor and exposed to µg in outer space for 14 days. The control experiment was performed in identical device but on the ground in earth gravity (1 g). iPSCs clones were compact and highly expressed Oct4 before launch. In µg condition, cells in iPSC clones spread out more rapidly than those in ground 1 g condition during the first 3 days after launch. However, in 1 g condition, as the cell density increases, the Oct4-GFP signal dropped significantly during the following 3 days. Interestingly, in µg condition, iPSCs originated from the spread-out clones during the first 3 days appeared to cluster together and reform colonies that activated strong Oct4 expression. On the other hand, iPSC clones in 1 g condition were not able to recover Oct4 expression after overgrown. Our study for the first time performed real-time imaging on the proliferation process of iPSCs in space and found that in µg condition, cell behaviour appeared to be more dynamic than on the ground.
Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Voo Espacial , Ausência de Peso , Animais , Reatores Biológicos , Proliferação de Células , Autorrenovação Celular , Células Clonais , Sistemas Computacionais , Camundongos , Camundongos Transgênicos , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , RegeneraçãoRESUMO
Exposure to ambient particulate matter (PM) has been linked to the increasing incidence and mortality of lung cancer, but the principal toxic components and molecular mechanism remain to be further elucidated. In this study, human lung adenocarcinoma A549 cells were treated with serial concentrations of water-extracted PM10 (WE-PM10) collected from Beijing, China. Our results showed that exposure to 25 and 50 µg/ml of WE-PM10 for 48 h significantly suppressed miR-26a to upregulate lin-28 homolog B (LIN28B), and in turn activated interleukin 6 (IL6) and signal transducer and activator of transcription 3 (STAT3) in A549 cells, subsequently contributing to enhanced epithelial-mesenchymal transition and accelerated migration and invasion. In vivo pulmonary colonization assay further indicated that WE-PM10 enhanced the metastatic ability of A549 cells. In addition, luciferase reporter assay demonstrated that 3' untranslated region of LIN28B was a direct target of miR-26a. Last but not the least, the key toxic contribution of metals in WE-PM10 was confirmed by the finding that removal of metals through chelation significantly rescued WE-PM10-mediated inflammatory, carcinogenic and metastatic responses. Taken together, miR-26a could act as the tumor suppressor in PM10-related lung cancer, and PM10-bound metals promoted lung cancer cell metastasis through downregulation of miR-26a that directly mediated LIN28B expression.
Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Material Particulado/toxicidade , Proteínas de Ligação a RNA/genética , Células A549 , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Metais/análise , Metais/toxicidade , Camundongos Endogâmicos BALB C , Material Particulado/química , Proteínas de Ligação a RNA/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The study was designed to explore the effects of HS060098 on activation of peroxisome proliferator-activated receptors (PPARα, γ and δ) and in the down-regulation of hyperlipidemia in golden hamster. Luciferase gene reporters of PPARα, PPARγ and PPARδ were constructed in HepG2 cells and the green fluorescent protein (GFP) was used as an internal reference. Transfected cells were then cultured with various concentrations of HS060098 for 24 h. The peroxisome proliferator-response element luciferase activity was determined by the dual-luciferase reporter gene assay system. To investigate the lipid-lowering effect of HS060098, hyperlipidemic golden hamsters fed by high-diet were administered orally with HS060098 through prophylactic and therapeutic approaches respectively. The levels of blood lipids such as total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and fat index in hamsters were evaluated. The results showed that HS060098 was a potent activator of PPARδ with a good selectivity and the median effective concentration (EC(50)) is 0.01 µmol·L(-1), while no obvious PPARα and PPARγ activation was observed. In the golden hamster, oral administration of HS060098 (5, 10, 20 mg·kg(-1)·d(-1)) for 2 weeks, led to a significant decrease the concentrations of plasma TC, TG, LDL-C and fat index (P < 0.05 or P < 0.01), whereas the contents of plasma HDL-C were increased significantly (P < 0.05 or P < 0.01). The data suggest that HS060098 is a novel PPARδ agonist with a significant activity in the prevention and therapy of hyperlipemia in golden hamster.
Assuntos
Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , PPAR delta/agonistas , Animais , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cricetinae , Células Hep G2 , Humanos , Mesocricetus , PPAR alfa , PPAR gama , Transfecção , Triglicerídeos/sangueRESUMO
OBJECTIVE: To observe the effects of comprehensive therapy (CT) with electroacupuncture (EA) in combination with psycho-intervention (PI) on the cognitive function and event-related potentials (ERP), P300 and mismatch negativity (MMN), in patients with internet addiction (IA) for a preliminary exploration of the possible mechanism of the therapy. METHODS: One hundred and twenty patients with IA were randomly divided into three groups, and a total of 112 subjects reached the final analysis of the trial, the EA group (39 patients), the PI group (36 patients) and the CT group (37 patients). EA was applied at acupoints Baihui (GV20), Sishencong (EX-HN1), Hegu (LI4), Neiguan (PC6), Taichong (LR3) and Sanyinjiao (SP6), once every other day; PI with the cognitionbehavior mode was implemented every 4 days; both EA and PI were used in the CT group. The treatment course for all patients was 40 days. Changes before and after treatment in terms of scoring by the IA self-rating scale, short-term memory capacity, short-term memory span, and the latency and amplitude of P300 and MMN in patients were observed. RESULTS: After treatment, in all groups, the IA score was lowered significantly (P <0.05) and scores of short-term memory capacity and short-term memory span increased significantly (P <0.05), while the decreased IA score in the CT group was more significant than that in the other two groups (P <0.05). ERP measurements showed that P300 latency was depressed and its amplitude raised in the EA group; MMN amplitude increased in the CT group (all P<0.05). CONCLUSION: The EA in combination with PI could improve the cognitive function of IA patients, and its mechanism might be related to the speedup of cerebral discrimination on external stimulus and the enhancement of effective resource mobilization during information processing of the brain.
Assuntos
Comportamento Aditivo/psicologia , Comportamento Aditivo/terapia , Cognição/fisiologia , Eletroacupuntura/métodos , Potenciais Evocados P300/fisiologia , Internet , Comportamento Aditivo/fisiopatologia , Terapia Combinada , Feminino , Humanos , Período de Latência Psicossexual , Masculino , Memória de Curto Prazo/fisiologia , Pacientes Desistentes do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To analyze the clinical features of lateral orbital wall blow-in fracture and summarize the points of treatment. METHODS: A retrospective analysis of 12 patients with lateral orbital wall blow-in fracture treated in the Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine from January 2007 to January 2010 was investigated. Clinical records and results of follow-up were analyzed. RESULTS: Twelve cases of the lateral orbital wall blow-in fracture with the frontal process of the zygoma impacted into the orbit were confirmed. Globe rupture occurred in 1 case, 4 cases had traumatic optic neuropathy. 1 case suffered exophthalmos, 8 cases had enophthalmos. Diplopia was found in 5 cases and eyeball movement disturbance in 5 cases.3 cases had upper eyelid deformity, 1 case had ptosis, 3 cases had telecanthus accompanied with lacrimal ducts obstruction. 11 cases suffered orbital floor fracture, 9 cases had zygomatic arc fracture, 6 cases had orbital medial wall fracture, and 3 cases had naso-orbito-ethmoid fracture. Surgical treatment was performed by different combination of approaches according to the extents of injury; Osteotomy was performed in patients whose blow-in fracture was malformation. Orbital reconstructive surgery was performed in 11 patients and fractures were completely restored. CONCLUSIONS: The lateral orbital wall blow-in fracture could cause serious impairment to the ocular components, better outcomes could be achieved by timely and proper treatment with improving recognition of this type of fracture.
Assuntos
Procedimentos Cirúrgicos Oftalmológicos , Fraturas Orbitárias/diagnóstico , Fraturas Orbitárias/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Fraturas Orbitárias/etiologia , Estudos Retrospectivos , Adulto JovemRESUMO
A novel method for the simultaneous determination of norfloxacin (NFLX) and lomefloxacin (LFLX) in milk samples was developed by using first derivative synchronous fluorimetry. The synchronous fluorescence (Δλ=160 nm) spectra and first derivative synchronous fluorescence spectra of NFLX, LFLX and their mixture were studied. The zero-crossing method was utilized to measure the first derivative value of the derivative spectrum. The zero-crossing points were located at 275.0 nm for NFLX and at 283.8 nm for LFLX, in first derivative synchronous fluorescence spectra. Therefore, 283.8 nm and 275.0 nm were selected for the determination of NFLX and LFLX. The first derivative values varied linearly with the concentrations in the range of 1.68×10(-8)-5.64×10(-6) mol L(-1) for NFLX and 1.89×10(-8)-6.19×10(-6) mol L(-1) for LFLX. The detection limits were 5.03×10(-9) mol L(-1) for NFLX and 7.58×10(-9) mol L(-1) for LFLX. The proposed method is reliable, selective and sensitive, and has been used successfully in the simultaneous determination of NFLX and LFLX in milk samples, whose results were in good agreement with those obtained by HPLC.
Assuntos
Compostos de Alumínio/análise , Fluoroquinolonas/análise , Leite/química , Norfloxacino/análise , Compostos de Alumínio/química , Animais , Fluoroquinolonas/química , Norfloxacino/química , Espectrometria de Fluorescência/métodosRESUMO
OBJECTIVE: To observe the preventive effect of Radix Paeoniae Rubra (RPR) to restenosis after carotid balloon injury in rabbits. METHODS: The rabbit model of carotid balloon injury was established adopting Clowes method, and treated with extract of RPR. Component of new genesic intima and expression of proliferating cell nuclear antigen (PCNA) and macrophage was determined by immunochemical stain. The collagen of type I was detected by special staining for blood vessels and the area of new genesic intima was measured by image assay system. RESULTS: RPR could remarkably decreased the PCNA positive expression and inhibit the proliferation of collagen type I and reduce the generating of new intima. CONCLUSION: RPR has significant preventive effect on the restenosis after carotid ballon injury in high fat-diet induced atherosclerotic rabbits.