RESUMEN
The clinical application of doxorubicin (DOX) was limited by the serious cardiotoxicity. The traditional Chinese medicine Andrographis paniculata and its principal active component (Dehydroandrographolide, DA) have been well known for their diverse cardiovascular protective effects. However, the effects of DA on DOX-induced cardiotoxicity (DIC) were still unknown. In this study, we evaluated the effects and revealed the potential mechanisms of DA on DIC both in vivo and in vitro. The effects of DA on DIC were systematically assessed by echocardiography and histological assays. Western blot and flow cytometry were used to measure apoptosis of cardiomyocytes. Transmission electron microscopy and StubRFP-SensGFP-LC3 lentivirus were further used to assay autophagic flux. Our results showed that DA administration significantly improved cardiac function and attenuated DOX-induced cardiomyocyte apoptosis. Mechanically, DA restored autophagic flux and lysosome functions via inhibiting DOX-induced mTOR signal pathway activation and increasing the translocation of TFEB to the nucleus. However, activation of mTOR or knockdown of TFEB significantly inhibited the protective effects of DA against DIC by impacting lysosomal functions and autophagic flux. In conclusion, our results revealed that DA might be a potential cardioprotective agent against DIC.
Asunto(s)
Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Cardiotoxicidad , Diterpenos , Doxorrubicina , Miocitos Cardíacos , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Doxorrubicina/toxicidad , Autofagia/efectos de los fármacos , Diterpenos/farmacología , Diterpenos/química , Serina-Treonina Quinasas TOR/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Transducción de Señal/efectos de los fármacos , Cardiotoxicidad/prevención & control , Apoptosis/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND OBJECTIVES: 25-hydroxyvitamin D [25(OH)D] deficiency is prevalent in patients with chronic kidney disease (CKD), the associations between serum 25(OH)D levels and mortality in patients with CKD remain unclear, and this study aimed to explore these associations further. METHODS: 4989 participants with CKD were enrolled in the study, and the Cox regression model was used to assess the effects of serum 25(OH)D concentrations on mortality risk. A restricted cubic spline model was used to explore the dose-response relationships, and threshold effect analysis was performed based on inflection points identified by a two-piecewise linear regression model. In addition, subgroup and sensitivity analyses were employed. RESULTS: 1255 participants died during a mean follow-up period of 70 months. Compared with the 25(OH)D-deficient group, the fully adjusted hazard ratios and 95% confidence intervals for the 25(OH)D-adequate group were 0.631 (0.545, 0.730) for all-cause mortality, 0.569 (0.435, 0.743) for cardiovascular mortality, 0.637 (0.461, 0.878) for hypertension mortality, and cancer mortality was 0.596 (0.426, 0.834). The inflection points of serum 25(OH)D concentration affecting all-cause and cardiovascular mortality were 89 nmol/L, and 107 nmol/L, respectively. Subgroup analyses and interaction tests suggested that the effects varied across populations. The results of sensitivity analyses indicated a reliable correlation. CONCLUSION: We found an association between serum 25(OH)D concentrations and the prognosis of patients with CKD as a reliable predictor of early intervention and intensive care.
RESUMEN
BACKGROUND: Smilax china L. (SCL) is a traditional herbal medicine for the potential treatment of intrauterine adhesion (IUA). However, the mechanisms of action have not yet been determined. In this study, we explored the effects and mechanisms of SCL in IUA by network pharmacology, molecular docking and molecular biology experiments. METHODS: Active ingredients and targets of SCL were acquired from TCMSP and SwissTargetPrediction. IUA-related targets were collected from the GeneCards, DisGeNET, OMIM and TTD databases. A proteinâprotein interaction (PPI) network was constructed by Cytoscape 3.9.1 and analysed with CytoHubba and CytoNCA to identify the core targets. The DAVID tool was used for GO and KEGG enrichment analyses. Furthermore, molecular docking was employed to assess the interaction between the compounds and key targets. Finally, the mechanisms and targets of SCL in IUA were verified by cellular experiments and western blot. RESULTS: A total of 196 targets of SCL were identified, among which 93 were related to IUA. Topological and KEGG analyses results identified 15 core targets that were involved in multiple pathways, such as inflammation, apoptosis, and PI3K/AKT signalling pathways. Molecular docking results showed that the active compounds had good binding to the core targets. In vitro experiments showed that astilbin (AST), a major component of SCL, significantly reduced TGF-ß-induced overexpression of fibronectin (FN), activation of the PI3K/AKT signalling pathway and the expression of downstream factors (NF-κB and BCL2) in human endometrial stromal cells, suggesting that AST ameliorates IUA by mediating the PI3K/AKT/NF-κB and BCL2 proteins. CONCLUSIONS: AST, a major component of SCL, may be a potential therapeutic agent for IUA. Moreover, its mechanism is strongly associated with regulation of the PI3K/AKT signalling pathway and the downstream NF-κB and BCL2 proteins. This study will provide new strategies that utilize AST for the treatment of IUA.
Asunto(s)
FN-kappa B , Smilax , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Proteínas Proto-Oncogénicas c-bcl-2 , ChinaRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is linked to immunity and inflammation. Systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are novel measures for gauging an individual's systemic inflammatory activity. We aim to investigate the potential associations between them. METHODS: This study encompassed a cohort of 40,937 adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. SII and SIRI were log2-transformed before conducting regression analysis, considering that these inflammatory markers were right skewed distributed. Weighted logistic regression models assessed the association of log2-SII and log2-SIRI levels with CKD prevalence. Weighted Cox regression models were utilized to estimate the risk of death. Subgroup analyses were performed to further clarify the effects of other covariates on the associations. Sensitivity analyses were performed to assess the robustness of our results. RESULTS: 6986 participants with CKD were recorded, and 2818 patients died during a mean follow-up time of 100 months. After adjusting for all covariates, the highest level of log2-SII increased the CKD incidence (odds ratio [OR]: 1.47, 95% confidence intervals [CI]: 1.32-1.65, P < 0.001), as well as log2-SIRI (OR: 1.79, 95% CI 1.60-2.01, P < 0.001) when compared with the lowest level reference group. The highest level of log2-SII significantly increased all-cause mortality (hazard risk [HR]: 1.29; 95% CI 1.13-1.48, P < 0.001), cardiovascular mortality (HR: 1.61, 95% CI 1.25-2.09, P < 0.001), and hypertension mortality (HR: 1.73, 95% CI 1.23-2.42, P = 0.001) in CKD patients. Additionally, the positive associations were also found between log2-SIRI and all cause (HR: 1.54, 95% CI 1.35-1.76, P < 0.001), cardiovascular (HR: 1.90, 95% CI 1.38-2.60, P < 0.001), and hypertension mortality (HR: 2.15, 95% CI 1.56-2.94, P < 0.001). Subgroup analyses unveiled variations in these effects among different populations. CONCLUSION: There existed a substantial association of SII and SIRI levels with CKD prevalence, as well as mortality in patients with CKD in the U.S.
Asunto(s)
Hipertensión , Insuficiencia Renal Crónica , Adulto , Humanos , Encuestas Nutricionales , Inflamación/epidemiología , Oportunidad RelativaRESUMEN
Eosinophils are a group of granulocytes well known for their capacity to protect the host from parasites and regulate immune function. Diverse biological roles for eosinophils have been increasingly identified, but the developmental pattern and regulation of the eosinophil lineage remain largely unknown. Herein, we utilize the zebrafish model to analyze eosinophilic cell differentiation, distribution, and regulation. By identifying eslec as an eosinophil lineage-specific marker, we establish a Tg(eslec:eGFP) reporter line, which specifically labeled cells of the eosinophil lineage from early life through adulthood. Spatial-temporal analysis of eslec+ cells demonstrates their organ distribution from larval stage to adulthood. By single-cell RNA-Seq analysis, we decipher the eosinophil lineage cells from lineage-committed progenitors to mature eosinophils. Through further genetic analysis, we demonstrate the role of Cebp1 in balancing neutrophil and eosinophil lineages, and a Cebp1-Cebpß transcriptional axis that regulates the commitment and differentiation of the eosinophil lineage. Cross-species functional comparisons reveals that zebrafish Cebp1 is the functional orthologue of human C/EBPεP27 in suppressing eosinophilopoiesis. Our study characterizes eosinophil development in multiple dimensions including spatial-temporal patterns, expression profiles, and genetic regulators, providing for a better understanding of eosinophilopoiesis.
Asunto(s)
Proteínas Potenciadoras de Unión a CCAAT , Eosinófilos , Pez Cebra , Animales , Humanos , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Diferenciación Celular/genética , Eosinófilos/metabolismo , Neutrófilos/metabolismo , Pez Cebra/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismoRESUMEN
Graphitic carbon nitride (g-C3N4), as a kind of nonmetallic low-cost photocatalyst, has great potential in photocatalytic hydrogen (H2) evolution, but its poor hydrophilicity and nonwetting extremely limit its H2 evolution efficiency. Herein, highly hydrophilic and defective g-C3N4 photocatalysts (NH3-CN-P as a representative example) have been fabricated on the basis of the strategy of joint phosphorus doping and ammonia stripping. The dopant of phosphorus prefers to occupy the C atoms bonded to -NH2 groups in the g-C3N4 skeleton, which is conducive to the formation of N defects caused by the effects of electronegativity and charge balance. Moreover, ammonia stripping plays a dual role in exposing plentiful two-dimensional defective planar structure and implanting the hydrophilic groups on the surface. As expected, the photocatalytic H2 evolution property of NH3-CN-P reaches 11.31 mmol g-1 h-1, with an apparent quantum yield of 17.9% at 420 nm, outperforming the majority of the reported g-C3N4-based photocatalysts.
RESUMEN
Microglia activation and associated inflammation are implicated in the periventricular white matter damage (PWMD) in septic postnatal rats. This study investigated whether melatonin would mitigate inflammation and alleviate the axonal hypomyelination in the corpus callosum in septic postnatal rats. We further explored if this might be related to the modulation of microglial polarization from M1 phenotype to M2 through the JAK2/STAT3/telomerase pathway. We reported here that indeed melatonin not only can it reduce the neurobehavioral disturbances in LPS-injected rats, but it can also dampen microglia-mediated inflammation. Thus, in LPS + melatonin group, the expression of proinflammatory mediators in M1 phenotype microglia was downregulated. As opposed to this, M2 microglia were increased which was accompanied by upregulated expression of anti-inflammatory mediators along with telomerase reverse transcriptase or melatonin receptor 1(MT1). In parallel to this was decreased NG2 expression but increased expression of myelin and neurofilament proteins. Melatonin can improve hypomyelination which was confirmed by electron microscopy. In vitro in primary microglia stimulated by LPS, melatonin decreased the expression of proinflammatory mediators significantly; but it increased the expression of anti-inflammatory mediators. Additionally, the expression levels of p-JAK2 and p-STAT3 were significantly elevated in microglia after melatonin treatment. Remarkably, the effect of melatonin on LPS-treated microglia was blocked by melatonin receptor, JAK2, STAT3 and telomerase reverse transcriptase inhibitors, respectively. Taken together, it is concluded that melatonin can attenuate PWMD through shifting M1 microglia towards M2 via MT1/JAK2/STAT3/telomerase pathway. The results suggest a new therapeutic strategy whereby melatonin may be adopted to convert microglial polarization from M1 to M2 phenotype that would ultimately contribute to the attenuation of PWMD.
Asunto(s)
Axones/efectos de los fármacos , Melatonina/farmacología , Microglía/efectos de los fármacos , Vaina de Mielina/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Axones/metabolismo , Polaridad Celular/efectos de los fármacos , Janus Quinasa 2/metabolismo , Lipopolisacáridos/farmacología , Melatonina/uso terapéutico , Microglía/metabolismo , Vaina de Mielina/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Ratas , Factor de Transcripción STAT3/metabolismo , Telomerasa/metabolismo , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/metabolismoRESUMEN
Neonatal sepsis is associated with cognitive deficit in the later life. Axonal myelination plays a pivotal role in neurotransmission and formation of learning and memory. This study aimed to explore if systemic lipopolysaccharide (LPS) injection would induce hypomyelination in the prefrontal cortex and hippocampus in developing septic neonatal rats. Sprague-Dawley rats (1-day old) were injected with LPS (1 mg/kg) intraperitoneally. By electron microscopy, axonal hypomyelination was evident in the subcortical white matter and hippocampus. The expression of myelin proteins including CNPase, MBP, PLP and MAG was downregulated in both areas of the brain at 7, 14 and 28 days after LPS injection. The frequency of MBP and PLP-positive oligodendrocyte was significantly reduced using in situ hybridization in the cerebral cortex and hippocampus at the corresponding time points after LPS injection, whereas the expression of NG2 and PDGFRα was noticeably increased. In tandem with this was reduction of Olig1 and Olig2 expressions which are involved in differentiation/maturation of OPCs. Expression of NFL, NFM, and NFH was significantly downregulated, indicating that axon development was disrupted after LPS injection. Morris Water Maze behavioral test, Open field test, Rotarod test, and Pole test were used to evaluate neurological behaviors of 28 days rats. The rats in the LPS group showed the impairment of motor coordination, balance, memory, and learning ability and represented bradykinesia and anxiety-like behavior. The present results suggest that following systemic LPS injection, differentiation/maturation of OPCs was affected which may be attributed to the inhibition of transcription factors Olig1 and Olig2 expression resulting in impairment to axonal development. It is suggested that this would ultimately lead to axonal hypomyelination in the prefrontal cortex and hippocampus, which may be associated with neurological deficits in later life.
Asunto(s)
Hipocampo/patología , Proteínas de la Mielina/deficiencia , Trastornos del Neurodesarrollo/etiología , Corteza Prefrontal/patología , Sepsis/patología , Sustancia Blanca/patología , Animales , Animales Recién Nacidos , Ansiedad/etiología , Axones/patología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/biosíntesis , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Diferenciación Celular , Lóbulo Frontal/metabolismo , Lóbulo Frontal/patología , Hipocampo/metabolismo , Hipocinesia/etiología , Lipopolisacáridos/toxicidad , Masculino , Trastornos de la Memoria/etiología , Microscopía Electrónica , Prueba del Laberinto Acuático de Morris , Proteínas de la Mielina/biosíntesis , Proteínas de la Mielina/genética , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Células Precursoras de Oligodendrocitos/metabolismo , Células Precursoras de Oligodendrocitos/patología , Factor de Transcripción 2 de los Oligodendrocitos/biosíntesis , Factor de Transcripción 2 de los Oligodendrocitos/genética , Oligodendroglía/patología , Prueba de Campo Abierto , Corteza Prefrontal/metabolismo , Ratas , Ratas Sprague-Dawley , Prueba de Desempeño de Rotación con Aceleración Constante , Sepsis/complicaciones , Sepsis/metabolismoRESUMEN
Neuroinflammation is thought to play a pivotal role in the pathogenesis of periventricular white matter (PWM) damage (PWMD) induced by neonatal sepsis. Because the complement cascade is implicated in inflammatory response, this study was carried out to determine whether C3a is involved in PWMD, and, if so, whether it would induce axonal hypomyelination. Furthermore, we explored if C3a would act through its C3a receptor (C3aR) and thence inhibit maturation of oligodendrocyte precursor cells (OPCs) via the WNT/ß-catenin signal pathway. Sprague Dawley (SD) rats aged 1 day were intraperitoneally injected with lipopolysaccharide (LPS) (1 mg/kg). C3a was upregulated in activated microglia and astrocytes in the PWM up to 7 days after LPS injection. Concomitantly, enhanced C3aR expression was observed in NG2+ oligodendrocytes (OLs). Myelin proteins including CNPase, PLP, MBP and MAG were significantly reduced in the PWM of 28-day septic rats. The number of PLP+ and MBP+ cells was markedly decreased. By electron microscopy, myelin sheath thickness was thinner and the average g-ratios were higher. This was coupled with an increase in number of NG2+ cells and decreased number of CC1+ cells. Olig1, Olig2 and SOX10 protein expression was significantly reduced in the PWM after LPS injection. Very strikingly, C3aRa administration for the first 7 days could reverse the above-mentioned pathological alterations in the PWM of septic rats. When incubated with C3a, expression of MBP, CNPase, PLP, MAG, Olig1, Olig2, SOX10 and CC1 in primary cultured OPCs was significantly downregulated as opposed to increased NG2. Moreover, WNT/ß-catenin signaling pathway was found to be implicated in inhibition of OPCs maturation and differentiation induced by C3a in vitro. As a corollary, it is speculated that C3a in the PWM of septic rats is closely associated with the disorder of OPCs differentiation and maturation through WNT/ß-catenin signaling pathway, which would contribute ultimately to axonal hypomyelination.
Asunto(s)
Complemento C3a/metabolismo , Enfermedades Desmielinizantes/etiología , Vaina de Mielina/patología , Sepsis Neonatal/complicaciones , Sustancia Blanca/patología , Vía de Señalización Wnt/fisiología , Animales , Animales Recién Nacidos , Diferenciación Celular/fisiología , Células Cultivadas , Enfermedades Desmielinizantes/metabolismo , Enfermedades Desmielinizantes/patología , Lipopolisacáridos , Vaina de Mielina/metabolismo , Sepsis Neonatal/inducido químicamente , Sepsis Neonatal/metabolismo , Sepsis Neonatal/patología , Células Precursoras de Oligodendrocitos/metabolismo , Células Precursoras de Oligodendrocitos/patología , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba , Sustancia Blanca/metabolismoRESUMEN
Synaptic structure integrity plays a key role in learning and memory. Previous studies have shown that there is cognitive dysfunction in septic neonates in later life. In this study, intraperitoneal injection of lipopolysaccharide (LPS) in the developing rats was used as a sepsis model to determine whether hippocampal synapses would be affected. Expression of synaptophysin (Syn), synaptosomal associated protein of 25â¯kD (SNAP-25), and N-methyl d-aspartate receptor (NMDAR) in the hippocampus in septic brain were significantly reduced. Consistent with this, the number of dendritic spines associated with the pyramidal neurons in the CA1 region of hippocampus at 28d after LPS administration was decreased. Additionally, the number of synapse and synaptic vesicles were reduced and appeared swollen. The number of neurons in the CA1 and CA3 of hippocampus at 14, and 28d after LPS injection remained unchanged. Coupled with the above was upregulated expression of interleukin-1ß (IL-1ß), IL-1 receptor 1 (IL-R1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) at 1-3d after LPS injection. IL-1ß expression was specifically detected in activated microglia. The plasma corticosterone (CORT) concentration in the LPS treatment rats was increased; but the glucocorticoid receptor (GR) expression in the hippocampus was decreased. We conclude that LPS injection in neonatal rats can cause synaptic disruption in the hippocampus which may be attributed to inflammatory response due to excess production of proinflammatory cytokines e.g., IL-1ß derived from activated microglia. The significance of increased plasma CORT concentration and decreased GR expression in the hippocampus is discussed.
Asunto(s)
Hipocampo/metabolismo , Hipocampo/patología , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/toxicidad , Sinapsis/metabolismo , Sinapsis/patología , Animales , Animales Recién Nacidos , Femenino , Hipocampo/efectos de los fármacos , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Sinapsis/efectos de los fármacosRESUMEN
Infectious exposure during the perinatal period may predispose to permanent neurological disorders in later life. Here we investigated whether changes in interleukin-1ß (IL-1ß) are associated with cognitive dysfunction in later life of septic neonatal rats through suppression of neurogenesis in the hippocampus. Sprague-Dawley rats (1-day old) administered lipopolysaccharide (LPS) showed upregulated expression of IL-1ß and IL-1 receptors in the hippocampus. At 28 days of age, rats showed longer escape latencies and decreased numbers of crossings after LPS administration. This was coupled with increased numbers of glial fibrillary acidic protein positive (GFAP+) astrocytes and decreased numbers of neuronal nuclei positive (NeuN+) cells. The numbers of sex-determining region Y-box 2 positive (SOX2+) and doublecortin positive (DCX+) cells were decreased at 1 and 3 days but was increased at 7 and 14 days. The proliferation of SOX2+ cells was inhibited at 1 and 3 days but increased at 7 and 14 days. In vitro IL-1ß administration suppressed the proliferation of neural progenitor cells (NPCs) in neurospheres derived from the hippocampus. GFAP expression was upregulated in differentiated NPCs treated with IL-1ß for 4 days, but expression of DCX and microtubule associated protein-2 (MAP2) was decreased. Remarkably, the Notch signaling pathway involved in antineurogenic and progliogenic differentiation of NPCs was activated after IL-1ß administration. The results show that following LPS injection in neonatal rats, microglia were activated and generated excess amounts of IL-1ß in the hippocampus. It is suggested that this might have contributed to inhibiting neurogenesis but promoting gliogenesis of NPCs via activation of the Notch signaling pathway and maybe one of the causes for cognitive dysfunction in septic neonatal rats in later life.
Asunto(s)
Hipocampo/fisiología , Interleucina-1beta/farmacología , Lipopolisacáridos/farmacología , Células-Madre Neurales/fisiología , Receptores Notch/fisiología , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Proteína Doblecortina , Femenino , Masculino , Ratas Sprague-Dawley , Transducción de Señal/fisiologíaRESUMEN
INTRODUCTION: The aim of this study is to compare the efficacy and safety of novelBL/BLIs with alternative antibiotics for the treatment of cIAI and cUTI. Area covered: We performed a systematic review and meta-analysis of all randomized controlled trials comparing novel BL/BLIs with other antibiotics for the treatment of cIAI and cUTI. The primary outcome included clinical and microbiological treatment success. Expert commentary: We found that novel BL/BLIs obtained a similar clinical outcome with other antibiotics in CE population (OR = 1.07, 95%CI = (0.80, 1.44), P = 0.64). However, novel BL/BLIs had better clinical treatment success in the cUTI subgroup (OR = 2.14, 95%CI = (1.06, 4.31), P = 0.03). Furthermore, novel BL/BLIs achieved significant microbiological treatment success in patie nts with cUTI (OR = 1.70, 95%CI = (1.29, 2.25), P = 0.0002) and had higher eradication rates for Gram-negative pathogens (OR = 1.82, 95%CI = (1.26, 2.64), P = 0.001) including E.coli and K.pneumoniae. No difference was observed concerning the incidence of mortality and adverse events between the two groups. Therefore, we concluded that novel BL/BLIs are not inferior to other available antibiotics for the treatment of cIAI, and they have advantages in patients with cUTI. Simultaneously, they are sensitive to Gram-negative pathogens, especially for E.coli and K.pneumoniae.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Intraabdominales/tratamiento farmacológico , Infecciones Urinarias/tratamiento farmacológico , Antibacterianos/farmacología , Humanos , Infecciones Intraabdominales/microbiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones Urinarias/microbiología , Inhibidores de beta-Lactamasas/farmacología , Inhibidores de beta-Lactamasas/uso terapéutico , beta-Lactamas/farmacología , beta-Lactamas/uso terapéuticoRESUMEN
BACKGROUND: Long noncoding RNAs (LncRNAs) are involved in the development and progression of various cancers. Accumulating evidences indicated that expression of lncRNAs was related to the prognosis of tumors. METHODS: Here, 3 well-known lncRNAs associated with cancer were gathered to prove the potential role of lncRNAs as novel predictors of survival in human cancer. This meta-analysis collected all eligible studies about TUG1, SPRY4-IT1, and HULC and explored the relationship between lncRNAs expression and lymph node metastasis (LNM) or overall survival (OS). A comprehensive, computerized literature search was undertaken by using PubMed, EMBASE, Cochrane Library, and Web of Science (up to October 10, 2017). Strength of association between 3 lncRNAs and cancer prognosis was assessed by computing the hazard ratios (HR) with its corresponding 95% confidence interval (CI). According to the inclusion and exclusion criteria, respectively, 10, 9, and 7 studies of 3 lncRNAs were included in this meta-analysis. RESULTS: In the current meta-analysis, it could be concluded that the expression of these 3 lncRNAs in tumor tissues is not a direct evidence of LNM. In general, there was a significant negative correlation between TUG1 levels and OS time (pooled HR 1.54, 95% CI 1.06-2.24), SPRY4-IT1 levels and OS time (pooled HR 2.12, 95% CI 1.58-2.86) and HULC levels and OS time (pooled HR 2.10, 95% CI 1.18-3.73). It could be revealed from the result that high level expression of these 3 lncRNAs might be correlated with a bad prognosis. CONCLUSIONS: In conclusion, the current meta-analysis demonstrated that TUG1, SPRY4-IT1, and HULC might serve as a moderate predictor of survival in human cancer.
Asunto(s)
Neoplasias/mortalidad , ARN Largo no Codificante/metabolismo , Biomarcadores de Tumor/metabolismo , Humanos , Neoplasias/diagnóstico , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND: Axon development plays a pivotal role in the formation of synapse, nodes of Ranvier, and myelin sheath. Interleukin-1ß (IL-1ß) produced by microglia may cause myelination disturbances through suppression of oligodendrocyte progenitor cell maturation in the septic neonatal rats. Here, we explored if a microglia-derived IL-1ß would disturb axon development in the corpus callosum (CC) following lipopolysaccharide (LPS) administration, and if so, whether it is associated with disorder of synapse formation in the cerebral cortex and node of Ranvier. METHODS: Sprague-Dawley rats (1-day old) in the septic model group were intraperitoneally administrated with lipopolysaccharide (1 mg/kg) and then sacrificed for detection of IL-1ß, interleukin-1 receptor (IL-1R1), neurofilament-68, neurofilament-160, and neurofilament-200, proteolipid, synaptophysin, and postsynaptic density 95 (PSD95) expression by western blotting and immunofluorescence. Electron microscopy was conducted to observe alterations of axonal myelin sheath and synapses in the cortex, and proteolipid expression was assessed using in situ hybridization. The effect of IL-1ß on neurofilament and synaptophysin expression in primary neuron cultures was determined by western blotting and immunofluorescence. P38-MAPK signaling pathway was investigated to determine whether it was involved in the inhibition of IL-1ß on neurofilament and synaptophysin expression. RESULTS: In 1-day old septic rats, IL-1ß expression was increased in microglia coupled with upregulated expression of IL-1R1 on the axons. The expression of neurofilament-68, neurofilament-160, and neurofilament-200 (NFL, NFM, NFH) and proteolipid (PLP) was markedly reduced in the CC at 7, 14, and 28 days after LPS administration. Simultaneously, cortical synapses and mature oligodendrocytes were significantly reduced. By electron microscopy, some axons showed smaller diameter and thinner myelin sheath with damaged ultrastructure of node of Ranvier compared with the control rats. In the cerebral cortex of LPS-injected rats, some axo-dendritic synapses appeared abnormal looking as manifested by the presence of swollen and clumping of synaptic vesicles near the presynaptic membrane. In primary cultured neurons incubated with IL-1ß, expression of NFL, NFM, and synaptophysin was significantly downregulated. Furthermore, p38-MAPK signaling pathway was implicated in disorder of axon development and synaptic deficit caused by IL-1ß treatment. CONCLUSIONS: The present results suggest that microglia-derived IL-1ß might suppress axon development through activation of p38-MAPK signaling pathway that would contribute to formation disorder of cortical synapses and node of Ranvier following LPS exposure.
Asunto(s)
Microglía/metabolismo , Sepsis Neonatal/complicaciones , Sepsis Neonatal/patología , Transducción de Señal/fisiología , Sinapsis/patología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Factores de Edad , Animales , Animales Recién Nacidos , Células Cultivadas , Corteza Cerebral/citología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-1beta/metabolismo , Lipopolisacáridos/toxicidad , Microglía/efectos de los fármacos , Sepsis Neonatal/inducido químicamente , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Neuronas/patología , Neuronas/ultraestructura , Ratas , Ratas Sprague-Dawley , Sincalida/metabolismo , Sinapsis/metabolismo , Sinapsis/ultraestructura , Sinaptofisina/metabolismoRESUMEN
BACKGROUND: Water immersion during the first stage of labor can reduce the length of the first stage and epidural/spinal analgesia use; however, there is limited information regarding other outcomes. Our purpose was to compare maternal and neonatal outcomes of women who underwent water immersion during the first stage of labor with those who underwent conventional labor and delivery. METHODS: Healthy primipara with singleton pregnancies and cephalic presentation were included in the study. Patients were allowed to choose water immersion during labor or conventional labor and delivery. For water immersion, the water temperature was maintained at 35-38°C and subjects left the tub on complete cervical dilatation. A visual analogue scale (VAS) was used to assess pain during labor. Other outcome measures included duration of labor, type of delivery, blood loss, pelvic floor dysfunction and symptoms of stress urinary incontinence (SUI) at 42 days after delivery, infant Apgar scores, and need for transfer of the infant to the neonatal intensive care unit. RESULTS: Thirty eight subjects (mean age, 28.66 ± 3.08 y) received water immersion and 70 (mean age, 27.89 ± 2.99 y) underwent conventional labor and delivery. There were no differences in maternal height, weight, age, gestational age, gravidity, and newborn weight between the groups (all, p>0.05). VAS pain scores were significantly greater in the conventional labor group at 30 min and 60 min after a cervical dilatation of 3 cm (30 min: 10 [9, 10] vs. 6 [5, 8]; 60 min: 10 [10, 10] vs. 7 [6, 8], respectively, both, p<0.001). The duration of labor and postpartum bleeding were similar between the groups (all, p>0.05). The cesarean section rate was higher in the conventional labor group (32.9% vs. 13.2%, p=0.026). The 1-minute and 5-minute Apgar scores were similar between the groups. Maternal and neonatal culture results were similar between the groups. SUI symptoms at 42 days after delivery was significantly higher in the conventional labor group (25.5% vs. 6.1%, respectively, p=0.035). CONCLUSIONS: Water immersion can reduce labor pain, and is associated with a lower rate of cesarean delivery and SUI symptoms at 42 days.