RESUMEN
The present study aimed to investigate the protective effect of S-propargyl-cysteine (SPRC) on atherosclerosis progression in mice. A mouse model of vulnerable atherosclerotic plaque was created in ApoE-/- mice by carotid artery tandem stenosis (TS) combined with a Western diet. Macrophotography, lipid profiles, and inflammatory markers were measured to evaluate the antiatherosclerotic effects of SPRC compared to atorvastatin as a control. Histopathological analysis was performed to assess the plaque stability. To explore the protective mechanism of SPRC, human umbilical vein endothelial cells (HUVECs) were cultured in vitro and challenged with oxidized low-density lipoprotein (ox-LDL). Cell viability was determined with a Cell Counting Kit-8 (CCK-8). Endothelial nitric oxide synthase (eNOS) phosphorylation and mRNA expression were detected by Western blot and RT-qPCR respectively. The results showed that the lesion area quantified by en face photographs of the aortic arch and carotid artery was significantly less, plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced, plaque collagen content was increased and matrix metalloproteinase-9 (MMP-9) was decreased in 80 mg/kg per day SPRC-treated mice compared with model mice. These findings support the role of SPRC in plaque stabilization. In vitro studies revealed that 100 µmol/L SPRC increased the cell viability and the phosphorylation level of eNOS after ox-LDL challenge. These results suggest that SPRC delays the progression of atherosclerosis and enhances plaque stability. The protective effect may be at least partially related to the increased phosphorylation of eNOS in endothelial cells.
Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Animales , Humanos , Ratones , Colesterol/metabolismo , Cisteína/farmacología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Lipoproteínas LDL/farmacología , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosforilación , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologíaRESUMEN
Skin wound healing tends to slow down with aging, which is detrimental to both minor wound recovery in daily life and the recovery after surgery. The aim of current study was to explore the effect of histone deacetylase 6 (HDAC6) on wound healing during aging. Cultured human dermal fibroblasts (HDFs) and mouse full-thickness skin wound model were used to explore the functional changes of replicative senescent dermal fibroblasts and the effect of aging on skin wound healing. Scratch wound healing assay revealed significantly decreased migration speed of senescent HDFs, and BrdU incorporation assay indicated their considerably retardant proliferation. The protein expression levels of collagen and HDAC6 were significantly decreased in both senescent HDFs and skin tissues from aged mice. HDAC6 activity inhibition with highly selective inhibitor tubastatin A (TsA) or HDAC6 knockdown with siRNA decreased the migration speed of HDFs and considerably suppressed fibroblast differentiation induced by transforming growth factor-ß1 (TGF-ß1), which suggests the involvement of HDAC6 in regulating fundamental physiological activities of dermal fibroblasts. In vivo full-thickness skin wound healing was significantly delayed in young HDAC6 knockout mice when compared with young wild type mice. In addition, the wound healing was significantly slower in aged wild type mice than that in young wild type mice, and became even worse in aged HDAC6 knockout aged mice. Compared to the aged wild type mice, aged HDAC6 knockout mice exhibited delayed angiogenesis, reduced collagen synthesis, and decreased collagen deposition in skin wounds. Together, these results suggest that delayed skin wound healing in aged mice is associated with impaired fibroblast function. Adequate expression and activity of HDAC6 are required for fibroblasts migration and differentiation.
Asunto(s)
Piel , Cicatrización de Heridas , Humanos , Animales , Ratones , Anciano , Histona Desacetilasa 6 , Movimiento Celular , Colágeno/metabolismo , Colágeno/farmacología , Fibroblastos , Ratones Noqueados , Células CultivadasRESUMEN
OBJECTIVES: To study the effect of improvement in antibiotic use strategy on the short-term clinical outcome of preterm infants with a gestational age of <35 weeks. METHODS: The medical data were retrospectively collected from 865 preterm infants with a gestational age of <35 weeks who were admitted to the Neonatal Intensive Care Unit of Xiangya Hospital of Central South University from January 1, 2014 to December 31, 2016. The improved antibiotic use strategy was implemented since January 1, 2015. According to the time of implementation, the infants were divided into three groups: pre-adjustment (January 1, 2014 to December 31, 2014; n=303), post-adjustment â (January 1, 2015 to December 31, 2015; n=293), and post-adjustment â ¡ (January 1, 2016 to December 31, 2016; n=269). The medical data of the three groups were compared. RESULTS: There were no significant differences among the three groups in gestational age, proportion of small-for-gestational-age infants, sex, and method of birth (P>0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment â ¡ groups had a significant reduction in the rate of use of antibiotics and the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days or 4-7 days and a significant reduction in the proportion of infants with a duration of antibiotic use of >7 days in the early postnatal period (P<0.05). Compared with the post-adjustment â group, the post-adjustment â ¡ group had a significant reduction in the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days and a significant reduction in the proportion of infants with a duration of antibiotic use of 4-7 days or >7 days (P<0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment â ¡ groups had significantly shorter duration of parenteral nutrition and length of hospital stay (P<0.05). There were gradual reductions in the incidence rates of grade ≥â ¢ intraventricular hemorrhage (IVH) and late-onset sepsis (LOS) after the adjustment of antibiotic use strategy. The multivariate logistic regression analysis showed that the adjustment of antibiotic use strategy had no effect on short-term adverse clinical outcomes, and antibiotic use for >7 days significantly increased the risk of adverse clinical outcomes (P<0.05). CONCLUSIONS: It is feasible to reduce unnecessary antibiotic use by the improvement in antibiotic use strategy in preterm infants with a gestational age of <35 weeks, which can also shorten the duration of parenteral nutrition and the length of hospital stay and reduce the incidence rates of grade ≥â ¢ IVH and LOS.
Asunto(s)
Enfermedades del Recién Nacido , Sepsis , Antibacterianos/uso terapéutico , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Estudios Retrospectivos , Sepsis/epidemiologíaRESUMEN
Atherosclerosis is a chronic inflammatory disease. Cytokine-related research provides an important direction for the prevention and treatment of atherosclerosis. Cytokines, produced by different types of cells and acting on a range of targets, play a key role in the pathogenesis and progression of atherosclerosis. This review summarizes the main pro-inflammatory and anti-inflammatory cytokines related to atherosclerosis and their underlying mechanism. We also outline current anti-atherosclerosis treatments targeting cytokines. The research and treatment prospects of cytokines in the prevention and treatment of atherosclerosis are discussed briefly as well.
Asunto(s)
Aterosclerosis , Citocinas , Antiinflamatorios/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Humanos , Inflamación/tratamiento farmacológicoRESUMEN
A 15-day-old boy was admitted to the hospital due to repeated convulsions for 14 days. The main clinical manifestations were uncontrolled seizures, hypoergia, feeding difficulties, limb hypotonia, and bilateral hearing impairment. Clinical neurophysiology showed reduced brainstem auditory evoked potential on both sides and burst-suppression pattern on electroencephalogram. Measurement of very-long-chain fatty acids in serum showed that C26:0 was significantly increased. Genetic testing showed a pathogenic compound heterozygous mutation, c.101C>T(p.Ala34Val) and c.1448_1460del(p.Ala483Aspfs*37), in the HSD17B4 gene. This article reports a case of D-bifunctional protein deficiency caused by HSD17B4 gene mutation and summarizes the epidemiological and clinical features, diagnosis, and treatment of this disease, with a focus on the differential diagnosis of this disease from Ohtahara syndrome.
Asunto(s)
Hipotonía Muscular , Deficiencia de Proteína , Pruebas Genéticas , Humanos , Recién Nacido , Masculino , Mutación , Proteína-2 Multifuncional Peroxisomal/genética , Deficiencia de Proteína/genéticaRESUMEN
Endogenous hydrogen sulfide (H2S) affects cholesterol homeostasis and liver X receptor α (LXRα) expression. However, whether low-density lipoprotein (LDL) receptor (LDLR), a key player in cholesterol homeostasis, is regulated by exogenous H2S through LXRα signaling has not been determined. We investigated the effects of sodium hydrosulfide (NaHS, H2S donor) on LDLR expression in the presence or absence of LXR agonists, T0901317 or GW3965 in HepG2 cells. We found that H2S strongly accumulated LDLR precursor in the presence of T0901317. Hence, LDLR transcription and the genes involved in LDLR precursor maturation and degradation were studied. T0901317 increased the LDLR mRNA level, whereas H2S did not affect LDLR transcription. H2S had no significant effect on the expression of LXRα and inducible degrader of LDLR (IDOL). H2S and T0901317 altered mRNA levels of several enzymes for N- and O-glycosylation and endoplasmic reticulum (ER) chaperones assisting LDLR maturation, but did not affect their protein levels. H2S decreased proprotein convertase subtilisin/kexin type 9 (PCSK9) protein levels and its mRNA level elevated by T0901317. T0901317 with PCSK9 siRNA also accumulated LDLR precursor as did T0901317 with H2S. High glucose increased PCSK9 protein levels and attenuated LDLR precursor accumulation induced by T0901317 with H2S. Taken together, H2S accumulates LDLR precursor by downregulating PCSK9 expression but not through the LXRα-IDOL pathway, LDLR transcriptional activation, or dysfunction of glycosylation enzymes and ER chaperones. These results also indicate that PCSK9 plays an important role in LDLR maturation in addition to its well-known effect on the degradation of LDLR mature form.
Asunto(s)
Sulfuro de Hidrógeno/metabolismo , Receptores X del Hígado/metabolismo , Proproteína Convertasa 9/metabolismo , Receptores de LDL/metabolismo , Benzoatos/farmacología , Bencilaminas/farmacología , Línea Celular Tumoral , Colesterol/metabolismo , Retículo Endoplásmico/fisiología , Glicosilación/efectos de los fármacos , Células Hep G2 , Homeostasis/fisiología , Humanos , Hidrocarburos Fluorados/farmacología , Receptores X del Hígado/agonistas , Proproteína Convertasa 9/genética , Interferencia de ARN , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Sulfuros/farmacología , Sulfonamidas/farmacología , Transcripción Genética/efectos de los fármacos , Activación Transcripcional/genéticaRESUMEN
Diabetes (especially Type II) is one of the primary threats to cardiovascular health. Wound healing defects and vascular dysfunction are common in diabetic patients, and the primary cause of deterioration is sustained high plasma glucose. microRNA, a noncoding RNA, has regulatory functions that are critical to maintaining homeostasis. MicroRNA (miR)-126-3p is a potential diabetes biomarker and a proangiogenic factor, and its plasma level decreases in diabetic patients. Previous studies have revealed the proangiogenic character of the gasotransmitter hydrogen sulfide (H2S). However, little is known about the relationship between H2S and miR-126-3p when the extracellular glucose level is high, let alone their influences on deteriorated endothelial cell migration, a key component of angiogenesis, which is crucial for wound healing. Human umbilical vein endothelial cells (HUVECs) were treated with high glucose (33.3 mmol/L) or normal glucose (5.5 mmol/L) for 48 h. Affymetrix miRNA profiling and real-time PCR were used to validate the miRNA expression. An H2S probe (HSip-1) was used to detect endogenous H2S. Scratch wound-healing assays were used to evaluate HUVEC migration. The protein levels were quantified by Western blot. Both exogenous and endogenous H2S could upregulate the miR-126-3p levels in HUVECs or muscle tissue. High glucose decreased the H2S level and the protein expression of the H2S-producing enzyme cystathionine γ-lyase (CSE) in HUVECs; however, the DNA methyltransferase 1 (DNMT1) protein level was upregulated. CSE overexpression not only increased the miR-126-3p level by decreasing the DNMT1 protein level but also rescued the deteriorated cell migration in HUVECs treated with high glucose. DNMT1 overexpression decreased the miR-126-3p level and inhibited the migration of HUVECs, whereas silencing DNMT1 improved cell migration. High glucose decreased the endogenous H2S and miR-126-3p levels and increased the DNMT1 expression, thus inducing the migration dysfunction of HUVECs. Treatment with exogenous H2S or the overexpression of the endogenously produced enzyme CSE would rescue this migration dysfunction through H2S-DNMT1-miR-126-3p.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Sulfuro de Hidrógeno/farmacología , MicroARNs/genética , Neovascularización Fisiológica/efectos de los fármacos , Animales , Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/crecimiento & desarrollo , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Movimiento Celular/efectos de los fármacos , Cistationina gamma-Liasa/genética , ADN (Citosina-5-)-Metiltransferasa 1/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Glucosa/toxicidad , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Sulfuro de Hidrógeno/metabolismo , Ratones , Neovascularización Fisiológica/genética , Transducción de Señal/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Next-generation sequencing of cell-free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer-related genes. As results, log2-based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future.
Asunto(s)
Ácidos Nucleicos Libres de Células/genética , Neoplasias Pulmonares/genética , Linfangioleiomiomatosis/genética , Mutación/genética , Adulto , Proteína BRCA2/genética , ADN Tumoral Circulante/genética , ADN de Neoplasias/genética , Proteínas de Unión al ADN/genética , Femenino , Frecuencia de los Genes/genética , Genoma/genética , Genómica/métodos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Hepatitis B virus (HBV) RNA may independently predict virological and serological response. This study aimed to compare dynamic changes in serum HBV RNA levels and HBV quasispecies evolution patterns between entecavir and pegylated-interferon mono-treatment in chronic hepatitis B patients and to determine the clinical significance during treatment. TaqMan real-time PCR was used for quantitative analysis. HBV RNA levels were retrospectively determined in serial serum samples from 178 chronic hepatitis B patients who received either entecavir or pegylated-interferon treatment. Both serum HBV DNA and RNA quasispecies were analyzed via next-generation sequencing. Receiver operating characteristics (ROC) analysis was performed to evaluate the prediction value of individual biomarkers for hepatitis B e antigen (HBeAg) seroconversion. Patients who received pegylated-interferon treatment showed stronger declines in HBV RNA levels than did those who received entecavir treatment. Serum HBV RNA levels were lower in patients with subsequent HBeAg seroconversion. At baseline, the level of HBV RNA was better than other indicators in predicting HBeAg seroconversion. Moreover, the predictive value of serum HBV RNA levels was better in the entecavir group. Baseline HBV RNA exhibited a significantly higher genetic diversity than HBV DNA and had a significant decline after 4 weeks of entecavir treatment. Higher baseline genetic diversity may result in a better outcome in pegylated-interferon-treated patients. Serum HBV RNA levels showed different decline kinetics, and HBV RNA quasispecies showed different evolution patterns in entecavir and pegylated-interferon mono-treatment. Taken together, serum HBV RNA may serve as a promising biomarker of HBeAg seroconversion in patients during antiviral treatment.
Asunto(s)
Virus de la Hepatitis B , Hepatitis B Crónica , Antivirales/uso terapéutico , ADN Viral/genética , Guanina/análogos & derivados , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Polietilenglicoles/uso terapéutico , Cuasiespecies , ARN , Proteínas Recombinantes , Estudios Retrospectivos , Resultado del Tratamiento , Carga ViralRESUMEN
Leonurine (LEO) is a bioactive small molecular compound that has protective effects on the cardiovascular system and prevents the early progression of atherosclerosis; however, it is not clear whether LEO is effective for plaque stability. A novel mouse atherosclerosis model involving tandem stenosis (TS) of the right carotid artery combined with western diet (WD) feeding was used. Apolipoprotein E gene-deficient mice were fed with a WD and received LEO administration daily for 13 weeks. TS was introduced 6 weeks after the onset of experiments. We found that LEO enhanced plaque stability by increasing fibrous cap thickness and collagen content while decreasing the population of CD68-positive cells. Enhanced plaque stability by LEO was associated with the nitric oxide synthase (NOS)-nitric oxide (NO) system. LEO restored the balance between endothelial NOS(E)- and inducible NOS(iNOS)-derived NO production; suppressed the NF-κB signaling pathway; reduced the level of the inflammatory infiltration in plaque, including cytokine interleukin 6; and downregulated the expression of adhesion molecules. These findings support the distinct role of LEO in plaque stabilization. In vitro studies with oxidized low-density lipoprotein-challenged human umbilical vein endothelial cells revealed that LEO balanced NO production and inhibited NF-κB/P65 nuclear translocation, thus mitigating inflammation. In conclusion, the restored balance of the NOS-NO system and mitigated inflammation contribute to the plaque-stabilizing effect of LEO. SIGNIFICANCE STATEMENT: LEO restored the balance between endothelial NOS and inducible NOS in NO production and inhibited excessive inflammation in atherosclerotic "unstable" and rupture-prone plaques in apolipoprotein E gene-deficient mice. The protective effect of LEO for stabilizing atherosclerotic plaques was due to improved collagen content, increased fibrous cap thickness, and decreased accumulation of macrophages/foam cells. So far, LEO has passed the safety and feasibility test of phase I clinical trial.
Asunto(s)
Aterosclerosis/tratamiento farmacológico , Ácido Gálico/análogos & derivados , Inflamación/tratamiento farmacológico , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxido Nítrico/metabolismo , Placa Aterosclerótica/tratamiento farmacológico , Animales , Aterosclerosis/metabolismo , Línea Celular , Ácido Gálico/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Placa Aterosclerótica/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Neonatal chylothorax is a common cause of neonatal congenital pleural effusion and is often caused by the accumulation of chylous fluid in the thoracic cavity due to the rupture of the thoracic duct and its branched lymphatic vessels for a variety of reasons. Neonatal chylothorax caused by malignant tumors is extremely rare, and this is the first case of neonatal mediastinal neuroblastoma with chylothorax in China. The boy was found to have pleural effusion in the left thoracic cavity in the uterus, and experienced apnea at birth, as well as dyspnea and cyanosis as the main manifestations after birth. He was diagnosed with left chylothorax based on conventional biochemical analysis of pleural effusion. After the treatment including persistent chest drainage and symptomatic and supportive treatment, the drainage of the left thoracic cavity reached a volume of 90-180 mL per day. Neonatal refractory chylothorax was considered. Chest radiograph on day 13 after birth showed lesions in the upper left lung field, and contrast-enhanced plain CT scan of the chest suggested the possibility of posterior mediastinal neuroblastoma. The autopsy confirmed giant posterior mediastinal neuroblastoma (poorly differentiated), which involved the C7-T6 spinal canal and the nearby erector spinae, with a small amount of tumor tissue in the liver and both adrenal glands. Mediastinal tumor is considered the underlying cause of chylothorax in this case.
Asunto(s)
Derrame Pleural , China , Quilotórax , Disnea , Femenino , Humanos , Recién Nacido , Masculino , ÚteroRESUMEN
Since December 2019, an epidemic of novel coronavirus pneumonia (NCP) has occurred in China. How to effectively prevent and control NCP among children with limited resources is an urgent issue to be explored. Under the unified arrangement of the Xiangya Hospital of Central South University, the Department of Pediatrics has formulated an action plan with Xiangya unique model to prevent and control NCP among children according to the current epidemic situation and diagnostic and therapeutic program in China.
Asunto(s)
Coronavirus , Neumonía , Niño , China , Infecciones por Coronavirus , Humanos , UniversidadesRESUMEN
OBJECTIVE: To compare the efficacy of domestic and imported caffeine citrate in the treatment of apnea in preterm infants. METHODS: A total of 98 preterm infants with a gestational age of 28 - <34 weeks between April 2018 and December 2019 were enrolled. They were randomly administered with domestic (n=48) or imported caffeine citrate (n=50) within 6 hours after birth. The therapeutic effects, complications, adverse effects and clinical outcomes were compared between the two groups. RESULTS: There were no significant differences in the incidence of apnea within 7 days after birth, daily frequency of apnea, the time of apnea disappearance, the failure rate of intubation-surfactant-extubation strategy, the time of non-invasive assisted ventilation, the duration of oxygen therapy, the duration of caffeine citrate therapy, the length of hospital stay, blood gas analysis results, liver and kidney function testing results between the two groups (P>0.05). There were no significant differences in the incidence of complications and the mortality rate between the two groups (P>0.05). There was no significant difference in the incidence of adverse effects between the two groups (P>0.05). CONCLUSIONS: The efficacy and safety of domestic caffeine citrate in the treatment of apnea are similar to those of imported caffeine citrate in preterm infants.
Asunto(s)
Apnea , Cafeína/uso terapéutico , Citratos/uso terapéutico , Enfermedades del Prematuro , Apnea/tratamiento farmacológico , Método Doble Ciego , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Estudios ProspectivosRESUMEN
OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1â442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (rs=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (rs=0.196, P<0.01). CONCLUSIONS: Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Asunto(s)
Recien Nacido con Peso al Nacer Extremadamente Bajo , Antibacterianos , Peso al Nacer , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Encuestas y CuestionariosRESUMEN
BACKGROUND Bone neoplasms are common in humans and have high lethality. Recently, great progress has been made in understanding the pathophysiological mechanisms, but little is known about the molecular and genetic networks involved. MATERIAL AND METHODS qRT-PCR assays were conducted to detect the expression levels of lncRNA HULC in various cell lines. MTT assay, Transwell assay, and wound-healing assay were performed to investigate the proliferation speed, invasion ability, and migration ability of each cell line, respectively. Western blot analysis was also done to assess the expression level of EMT-related factors. Statistical analysis was performed using the t test, Kaplan-Meier method, and log-rank test. RESULTS Compared to the human normal bone cell line, we found lncRNA HULC was over-expressed in all 6 bone neoplasm cell lines, and we finally chose HT1080 and Saos-2 cell lines, which possessed the highest lncRNA HULC expression level, for the subsequent studies. We then observed that the expression level of lncRNA HULC was negatively correlated with overall survival rate of bone neoplasm patients, which means that lncRNA HULC has prognostic value in patients with bone neoplasms. Thus, we assessed the influence of lncRNA HULC down-regulation on proliferation, invasion, and migration abilities of bone neoplasm cells, and found a significant decrease in these abilities. Finally, we found that down-regulating lncRNA HULC led to decreased expression of EMT-related factors in bone neoplasm cells. CONCLUSIONS LncRNA HULC can promote the tumorigenesis of bone neoplasms through increasing the proliferation, invasion, and migration abilities and the expression level of EMT-related factors.
Asunto(s)
Neoplasias Óseas/genética , Neoplasias Óseas/patología , Progresión de la Enfermedad , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación hacia Abajo/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Invasividad Neoplásica , ARN Largo no Codificante/genéticaRESUMEN
We previously found hydrogen sulfide (H2S) to be a new proangiogenic factor. However, the mechanisms underlying the cardiovascular effect of this small gas molecule remain largely unknown. The aim of the present study was to identify the essential microRNAs (miRNAs) involved in the transduction of H2S signals in vascular endothelial cells (ECs). The expression of miR-640 and its signaling elements, vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia inducible factor 1-α (HIF1A), and mammalian target of rapamycin (mTOR), was measured using quantitative PCR and Western blotting. Overexpression and inhibition of miR-640 were performed to clarify their roles in mediating the effect of H2S. In addition, knockdown of VEGFR2, HIF1A, and mTOR was performed using siRNAs, dominant negative mutants, or inhibitors to examine their roles in the transduction of the H2S signals. miR-640 levels decreased in vascular ECs that were treated with H2S, whereas overexpression of miR-640 blunted the proangiogenic effect of H2S. Knockdown of either VEGFR2 or mTOR blunted the downregulation of miR-640 and the proangiogenic effect induced by H2S. In addition, miR-640 bound to the 3'-UTR of HIF1A mRNA and then inhibited the expression of HIF1A. The inhibition could be recovered by treating cells with H2S. Thus we concluded that miR-640 plays a pivotal role in mediating the proangiogenic effect of H2S; H2S acts through downregulation of the expression of miR-640 and increasing the levels of HIF1A through the VEGFR2-mTOR pathway.
Asunto(s)
Inductores de la Angiogénesis/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Sulfuro de Hidrógeno/farmacología , MicroARNs/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Regiones no Traducidas 3' , Sitios de Unión , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Regulación hacia Abajo , Células Endoteliales de la Vena Umbilical Humana/enzimología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , MicroARNs/genética , Mutación , Interferencia de ARN , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/genética , Transfección , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genéticaRESUMEN
Hepatitis B virus (HBV) infection results in different clinical presentation due to different levels of immune response. Our study aimed to characterize HBV full-length genome quasispecies (QS) in patients with different phases of infection to better understand its pathogenesis. Forty treatment-naive HBV-infected patients were enrolled, including 10 cases of acute hepatitis B (AHB), 9 cases of immunotolerant (IT) HBV carriers, 11 cases of chronic hepatitis B (CHB), and 10 cases of acute-on-chronic liver failure (ACLF). The present study was conducted by clone-based sequencing. QS heterogeneity within each open reading frame was calculated. The mutation frequency index (MFI) and amino acid variations within the large HBsAg, HBcAg, and HBxAg regions were analyzed based on the different infection phases. In total, 606 HBV full-length sequences were obtained. HBV QS had higher heterogeneity in ACLF and CHB than that in IT among chronically infected individuals. AHB patients had the lower QS heterogeneity at onset than those with chronic infection. ACLF patients had the highest frequency of mutations in the core promoter and precore region. A triple mutation (A1762T/G1764A/G1896A) was observed more frequently in genotype C than in genotype B. The MFI indicated that specific peptides of the studied regions had more frequent mutations in ACLF. Furthermore, several amino acid variations, known as T- and B-cell epitopes, were potentially associated with the immunoactive phase of infection. More HBV genome mutations and deletions were observed in patients with more severe diseases, particularly in specific regions of the core and preS regions, the clinical significance and mechanism of which need to be further investigated.
Asunto(s)
Variación Genética , Genoma Viral , Genotipo , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Hepatitis B/virología , Epítopos/genética , Hepatitis B/patología , Antígenos de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Tasa de Mutación , Mutación Missense , Eliminación de SecuenciaRESUMEN
INTRODUCTION: Hydrogen sulfide (H2S) has been reported to inhibit myocardial hypertrophy in a cell model of cardiomyocyte hypertrophy. Our previous study also shows an H2S-induced increase in glucose metabolism in insulin-targeting cells. The present study aims to examine the hypothesis that H2S attenuates myocardial hypertrophy and promotes glucose utilization in cardiomyocytes. METHODS: The cell model of cardiomyocyte hypertrophy was induced by application of phenylephrine and cardiomyocyte hypertrophy was examined using leucine incorporation assay. Protein levels were measured using Western blot analysis. The activity of related enzymes was measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: NaHS (an H2S donor) treatment increased the activity of cultured cardiomyocytes and reduced hypertrophy in cultured cardiomyocytes at concentrations ranging from 25 to 200 µmol/L. NaHS treatment increased glucose uptake and the efficiency of glycolysis and the citric acid cycle. The key enzymes in these reactions, including lactate dehydrogenase and pyruvate kinase and succinate dehydrogenase, were activated by NaHS treatment (100 µmol/L). Some intermediates of glycolysis and the citric acid cycle, including lactic acid, cyclohexylammonium, oxaloacetic acid, succinate, L-dimalate, sodium citrate, cis-aconitic acid, ketoglutarate and DL-isocitric acid trisodium also showed anti-hypertrophic effects in cardiomyocytes. CONCLUSIONS: H2S improves glucose utilization and inhibits cardiomyocyte hypertrophy.
Asunto(s)
Glucosa/metabolismo , Sulfuro de Hidrógeno/farmacología , Miocitos Cardíacos/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Animales , Aumento de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ciclo del Ácido Cítrico/efectos de los fármacos , Ventrículos Cardíacos/citología , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Fenilefrina , RatasRESUMEN
[This retracts the article DOI: 10.3892/etm.2019.8036.].
RESUMEN
The present study examines whether there is a mechanism beyond the current concept of post-translational modifications to regulate the function of a protein. A small gas molecule, hydrogen sulfide (H2S), was found to bind at active-site copper of Cu/Zn-SOD using a series of methods including radiolabeled binding assay, X-ray absorption near-edge structure (XANES), and crystallography. Such an H2S binding enhanced the electrostatic forces to guide the negatively charged substrate superoxide radicals to the catalytic copper ion, changed the geometry and energy of the frontier molecular orbitals of the active site, and subsequently facilitated the transfer of an electron from the superoxide radical to the catalytic copper ion and the breakage of the copper-His61 bridge. The physiological relevance of such an H2S effect was also examined in both in vitro and in vivo models where the cardioprotective effects of H2S were dependent on Cu/Zn-SOD.