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BACKGROUND: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1, has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis. METHODS: We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice (Apoe-/-PSMB8-AS1KI) and global Apoe and proteasome subunit-ß type-9 (Psmb9) double knockout mice (Apoe-/-Psmb9-/-). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks. RESULTS: Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe-/-PSMB8-AS1KI mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe-/- mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe-/-PSMB8-AS1KI mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that PSMB8-AS1 induced PSMB9 transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the PSMB9 promoter. PSMB9 (proteasome subunit-ß type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1). Psmb9 deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in Apoe-/- mice in vivo. Importantly, endothelial overexpression of PSMB8-AS1-increased atherosclerosis and vascular inflammation were attenuated by Psmb9 knockout. CONCLUSIONS: PSMB8-AS1 promotes vascular inflammation and atherosclerosis via the NONO/PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA-based strategies to counteract atherosclerotic cardiovascular disease.
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Aterosclerose , Placa Aterosclerótica , RNA Longo não Codificante , Animais , Humanos , Camundongos , Apolipoproteínas E/genética , Aterosclerose/metabolismo , Células Endoteliais/metabolismo , Inflamação/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placa Aterosclerótica/patologia , Complexo de Endopeptidases do Proteassoma/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
PURPOSE: There is currently a lack of understanding of children's experience in the pediatric intensive care unit (PICU) environment. Additionally, pediatric patients may experience post-PICU syndrome following discharge. Thus, we aimed to adapt and evaluate the psychometric properties of a tool specifically for use with children in the PICU. DESIGN AND METHODS: According to Brislin's Model, the Intensive Care Unit Environment Stress Scale (ICUESS) was translated both forward and backward and adapted cross-culturally. A total of 210 PICU patients were selected from four hospitals in XXX to analyze the final translated version of the questionnaire, the Pediatric Intensive Care Unit Environmental Stress Scale (PICUESS). Content validity, exploratory factor analysis (EFA) and Confirmatory Factor Analysis (CFA) were used to assess the validity, while reliability was assessed using Cronbach's alpha and split-half reliability analysis. RESULTS: For PICUESS, seven of 42 items were modified. Content validity was high (overall = 0.96, item validity = 0.8 to 1.0). Exploratory factor analysis revealed eight common factors (Kaiser-Meyer-Olkin = 0.857, significant Bartlett's test). The results of the CFA indicate that the scale model fits well across the 8 factors. The entire scale demonstrated excellent internal consistency (Cronbach's alpha = 0.934). The overall split-half reliability was 0.935. CONCLUSIONS: The Chinese version of PICUESS demonstrates good reliability and validity, making it suitable for assessing pediatric patients' perceptions of the PICU environment. PRACTICE IMPLICATIONS: The PICUESS can assist healthcare professionals in providing personalized environment care for PICU patients. It has the potential to serve as a tool for further testing and international comparisons of pediatric patients' perceptions of the PICU environment.
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Unidades de Terapia Intensiva Pediátrica , Psicometria , Estresse Psicológico , Traduções , Humanos , Masculino , Feminino , Reprodutibilidade dos Testes , Criança , Inquéritos e Questionários/normas , China , Pré-Escolar , Comparação Transcultural , Análise FatorialRESUMO
Atherosclerosis is a chronic inflammatory disease of arterial wall, and circulating monocyte adhesion to endothelial cells is a crucial step in the pathogenesis of atherosclerosis. Epithelial-stromal interaction 1 (EPSTI1) is a novel gene, which is dramatically induced by epithelial-stromal interaction in human breast cancer. EPSTI1 expression is not only restricted to the breast but also in other normal tissues. In this study we investigated the role of EPSTI1 in monocyte-endothelial cell adhesion and its expression pattern in atherosclerotic plaques. We showed that EPSTI1 was dramatically upregulated in human and mouse atherosclerotic plaques when compared with normal arteries. In addition, the expression of EPSTI1 in endothelial cells of human and mouse atherosclerotic plaques is significantly higher than that of the normal arteries. Furthermore, we demonstrated that EPSTI1 promoted human monocytic THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs) via upregulating VCAM-1 and ICAM-1 expression in HUVECs. Treatment with LPS (100, 500, 1000 ng/mL) induced EPSTI1 expression in HUVECs at both mRNA and protein levels in a dose- and time-dependent manner. Knockdown of EPSTI1 significantly inhibited LPS-induced monocyte-endothelial cell adhesion via downregulation of VCAM-1 and ICAM-1. Moreover, we revealed that LPS induced EPSTI1 expression through p65 nuclear translocation. Thus, we conclude that EPSTI1 promotes THP-1 cell adhesion to endothelial cells by upregulating VCAM-1 and ICAM-1 expression, implying its potential role in the development of atherosclerosis.
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Aterosclerose , Placa Aterosclerótica , Animais , Humanos , Camundongos , Aterosclerose/metabolismo , Adesão Celular , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos , Monócitos/metabolismo , Proteínas de Neoplasias/metabolismo , Placa Aterosclerótica/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Chinese medicinal resources are the material basis for the survival and development of traditional Chinese medicine(TCM)and the sustainable development of Chinese medicinal resources is also an important project for the modernization of TCM in China. With the increasing demand for Chinese medicinal resources in China, over-exploitation has destroyed Chinese medicinal resources, resulting in a shortage of many natural medicinal resources in China and making the sustainable development of TCM in trouble. The introduced new foreign medicinal resources have become effective supplement and replacement for Chinese medicinal resources to some extent. However, the development and utilization of new foreign medicinal resources in China are different. To fully understand the development of new foreign medicinal resources in China, this paper, taking 43 new foreign medicinal resources such as Acacia nilotica as objects, sorted out the introduction forms and policies of new foreign medicinal resources, overviewed its current development status in China, summarized the application experience of new foreign medicinal resources in the place of origin, as well as the research progress and problems of new foreign medicinal resources in China and abroad, and analyzed the research situation, which can enrich Chinese medicinal resources and other uses, promote the sustainable development of Chinese medicinal resources, and provide ideas for further development and research of new foreign medicinal resources.
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Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Conservação dos Recursos Naturais , Desenvolvimento Sustentável , Internacionalidade , ChinaRESUMO
Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.
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Medicina Tradicional Chinesa , Neoplasias Ovarianas , Humanos , Feminino , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Endoteliais/metabolismo , Angiogênese , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genéticaRESUMO
Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.
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Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Rim/metabolismo , Camundongos , Camundongos Transgênicos , Presenilina-1/metabolismoRESUMO
OBJECTIVES: To study the value of metagenomic next-generation sequencing (mNGS) in detecting intracranial Epstein-Barr virus (EBV) infection in children with hemophagocytic syndrome (HPS) with central nervous system involvement. METHODS: A retrospective analysis was performed for the cerebrospinal fluid mNGS results of 30 HPS children with central nervous system involvement, which were compared with the results of cerebrospinal fluid EBV-DNA detection and serum EBV antibody profile. The change in serum EBV-DNA copy number after treatment was used to evaluate the efficacy of targeted therapy. RESULTS: The positive rate of EBV in cerebrospinal fluid determined by mNGS was significantly higher than that of EBV-DNA in cerebrospinal fluid (100% vs 10%, P<0.001) and had no significant difference from the positive rate of serum EBV antibody profile (100% vs 93%, P>0.05). The median number of sequences determined by mNGS was 2 400, and serum EBV-DNA copy number before treatment was moderately positively correlated with the number of EBV sequences (rs=0.693, P<0.001). The multiple linear regression analysis showed that the number of sequences determined by mNGS in cerebrospinal fluid increased with the increase in serum EBV-DNA copy number before treatment (P<0.05). CONCLUSIONS: EBV-associated HPS often results in EBV-infected viral encephalitis, and mNGS can significantly increase the detection rate of EBV in cerebrospinal fluid, which may help with clinical diagnosis.
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Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Criança , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Estudos Retrospectivos , Sequenciamento de Nucleotídeos em Larga Escala , Sistema Nervoso CentralRESUMO
BACKGROUND: The quantification of mitochondrial DNA heteroplasmy for the diagnosis of mitochondrial disease or after mitochondrial donation, is performed mainly using next-generation sequencing strategies (NGS). Digital PCR (dPCR) has the potential to offer an accurate alternative for mutation load quantification. METHODS: We assessed the mutation load of 23 low-input human samples at the m.11778 locus, which is associated with Leber's hereditary optic neuropathy (LHON) using 2 droplet digital PCR platforms (Stilla Naica and Bio-Rad QX200) and the standard NGS strategy. Assay validation was performed by analyzing a titration series with mutation loads ranging from 50% to 0.01%. RESULTS: A good concordance in mutation rates was observed between both dPCR techniques and NGS. dPCR established a distinctly lower level of background noise compared to NGS. Minor alleles with mutation loads lower than 1% could still be detected, with standard deviations of the technical replicates varying between 0.07% and 0.44% mutation load. Although no significant systematic bias was observed when comparing dPCR and NGS, a minor proportional bias was detected. A slight overestimation of the minor allele was observed for the NGS data, most probably due to amplification and sequencing errors in the NGS workflow. CONCLUSION: dPCR has proven to be an accurate tool for the quantification of mitochondrial heteroplasmy, even for samples harboring a low mutation load (<1%). In addition, this alternative technique holds multiple benefits compared to NGS (e.g., less hands-on time, more straightforward data-analysis, and a lower up-front capital investment).
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DNA Mitocondrial , Sequenciamento de Nucleotídeos em Larga Escala , DNA Mitocondrial/genética , Fertilização in vitro , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação , Reação em Cadeia da Polimerase/métodosRESUMO
Priming plays important roles in terrestrial carbon cycling, but the patterns and drivers of priming and its responses to nutrient addition in tropical forests remain unclear. By collecting soils along a tropical forest elevation gradient, we conducted an incubation experiment with 13 C-labeled glucose and nutrient (N and/or P) additions. Results showed that priming effects increased soil organic matter decomposition by 44 ± 12% across elevations, and priming intensity decreased significantly with elevation. Among soil and microbial properties, soil organic carbon (SOC) content and pH were two key factors negatively and positively regulating priming, respectively. Across elevations, the additions of N, P, or both of them (NP) did not significantly change priming. However, the variations in the effects of nutrient (N and/or P) addition on priming significantly correlated with initial soil nutrient (N or P) availability. The intensity for the effects of N addition on priming decreased significantly with initial soil N availability, and that for the effects of P and NP addition on priming decreased with initial soil P availability. Based on these relationships, we proposed a conceptual framework linking stoichiometric decomposition and nutrient mining hypotheses, in which the former dominates in low-nutrient availability soils and the latter dominates in high-nutrient availability soils. This conceptual framework can help to explain the contrasting effects of nutrient addition on priming. Collectively, our findings highlight the roles of SOC content and soil pH in regulating priming intensity, and the role of initial soil nutrient availability in regulating the effects of nutrient addition on priming.
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Carbono , Solo , Florestas , Nitrogênio/análise , Nutrientes , Microbiologia do SoloRESUMO
When a femtosecond laser pulse propagates through water clouds, optical breakdown can occur once the laser intensity exceeds a certain threshold. This photoionization process, along with the resultant laser-induced plasma, can strongly influence laser communications and laser-induced precipitation. However, the calculation model for the initial evolution of the laser field and its self-generated plasma remain insufficient. Here, we provide a theoretical transient coupling model to investigate the evolution of the laser-induced plasma in the water-cloud droplets, along with the nonlinear absorption occurring during optical breakdown. Agreement is achieved between the experimentally determined breakdown threshold and our calculated prediction. The calculation results indicate that the optical breakdown occurring in a water cloud has a considerable influence on the laser field. It is recommended that the laser intensity does not exceed the breakdown threshold for laser communications. We expect that our findings will also be helpful for weather control.
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PURPOSE: To provide the anatomical basis of blood supply of brachial plexus for the clinical microsurgical treatment of brachial plexus injury. METHODS: Thirteen adult anticorrosive cadaveric specimens (8 males, 5 females) were dissected in this study. 3 fresh cases (2 males, 1 female) were used to observe the zonal pattern of arteries supplying brachial plexus, and 10 cases (6 males, 4 females) were used to observe the source and distribution of the brachial plexus arteries under microscope. RESULTS: The brachial plexus is supplied by branches of the subclavian-axillary axis (SAA), and these branches anastomose each other. According to distribution feature, blood supply of the brachial plexus could be divided into three zones. The first zone was from the nerve roots of intervertebral foramina to its proximal trunks, which was supplied by the vertebral artery and the deep cervical artery. The second zone was from the distal nerve trunks of the brachial plexus, encompassing the divisions to its proximal cords, which was supplied by direct branches of the subclavian artery or by branches originating from the dorsal scapular artery. The third zone was from the distal portion of the cords to terminal branches of the brachial plexus, which was supplied by direct branches of the axillary artery. CONCLUSIONS: The zonal pattern of arterial supply to the brachial plexus is a systematic and comprehensive modality to improve anatomical basis for the clinical microsurgical treatment for brachial plexus injury.
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Artéria Axilar/anatomia & histologia , Plexo Braquial/irrigação sanguínea , Artéria Subclávia/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos , Angiografia , Cadáver , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To investigate the effects of trimetazidine (TMZ) on the oxidative stress injury in adipose-derived mesenchymal stem cells (ADSCs). METHODS: ADSCs derived from adipose tissue of SD rats were characterized by flow cytometry and multiline age differentiation. ADSCs apoptosis was induced by H2O2 in vitro , Dirrerent concentration of TMZ (250 µmol/L, 500 µmol/L) was used to protect ADSCs from apoptosis. The morphological features of apoptotic ADSCs were analyzed by Hoechst 33342, mitochondrial potential and structure was analyzed by JC-1 staining and electron microscope, respectively. The apoptotic proteins were detected by Western blot. The effect of TMZ on antioxidant capacity of ADSCs was evaluated by detecting reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA). RESULTS: The isolated ADSCs expressed high levels of CD29 and CD90, low levels of CD34 and CD45 and no expression of CD31. ADSCs could be induced to adipocyte and osteoplastic cells. After being treated by H2O2, ADSCs displayed apoptosis characteristics with increased number of apoptotic cells, decreased mitochondrial transmembrane potential and damaged mitochondria. The expressions of apoptotic proteins, including Bax, Bad, and Caspase3, were dramatically increased compared to the controls; however, the anti-apoptotic protein Bcl2 was decreased. At the meantime, the contents of ROS and MDA were elevated, but the concentrations of SOD and GSH were reduced. The treatment of TMZ could partly reverse above negative impacts to ADSCs. CONCLUSION: TMZ could improve the survival rate of ADSCs by enhancing anti-oxidant defense systems to remove excessive ROS and regulating the expression of protective protein.
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Tecido Adiposo/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Estresse Oxidativo , Trimetazidina/farmacologia , Animais , Antígenos CD/metabolismo , Células Cultivadas , Glutationa/metabolismo , Peróxido de Hidrogênio , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: This prospective study sought to compare the acute effects of haloperidol, amisulpride, and quetiapine on serum markers of bone formation and resorption in relatively young patients with minimal previous exposure to antipsychotic drugs. METHODS: Patients included in the study were randomly assigned to receive haloperidol, amisulpride, or quetiapine monotherapy in an open-label manner. Serum osteocalcin (OC, a marker of bone formation), C-terminal peptide of type I collagen (CTX, a marker of bone resorption), prolactin (PRL), estradiol, and testosterone were measured in 70 patients at baseline and after 4 weeks of antipsychotic treatment. RESULTS: A repeated-measures analysis of variance revealed a significant difference in CTX levels and in the OC to CTX ratio between treatment groups (F = 4.481, P < 0.05; F = 8.114, P < 0.01). After 4 weeks of treatment, only the amisulpride group had significantly increased CTX levels and decreased OC/CTX. In addition, an obvious increase in PRL level and a reduction of sex hormone secretion after amisulpride treatment were found. No significant changes in bone turnover were observed in the haloperidol or quetiapine groups. Notably, a positive correlation between the CTX change to the change in PRL after treatment (r = 0.255, P < 0.05) was observed. CONCLUSIONS: The PRL-raising antipsychotic drug amisulpride influenced bone turnover balance very early in the course of treatment, which may require long-term monitoring of bone metabolism. Bone resorption marker changes induced by acute antipsychotic drug treatment are likely related to increased PRL levels.
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Remodelação Óssea/efeitos dos fármacos , Haloperidol/efeitos adversos , Fumarato de Quetiapina/efeitos adversos , Sulpirida/análogos & derivados , Adulto , Amissulprida , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Biomarcadores/sangue , Reabsorção Óssea/induzido quimicamente , Feminino , Haloperidol/administração & dosagem , Haloperidol/uso terapêutico , Humanos , Masculino , Osteogênese/efeitos dos fármacos , Estudos Prospectivos , Fumarato de Quetiapina/administração & dosagem , Fumarato de Quetiapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Sulpirida/administração & dosagem , Sulpirida/efeitos adversos , Sulpirida/uso terapêutico , Adulto JovemRESUMO
Infant colic, excessive crying of unknown cause, is a major burden to families and effects about 10-30 % of infants. Despite decades of research, the exact cause and treatment of infant colic has remained elusive. The use of Lactobacillus reuteri (DSM 17938) in infant colic is somewhat controversial and hence, we designed this study to evaluate its efficacy in infantile colic. We recruited predominantly or exclusively breastfed infants, aged less than 4 months in a placebo controlled observational randomized study. Participants' were assigned to receive L. reuteri at a dose 10(8) colony forming units (n = 21) and placebo (n = 21). Placebo was an identical formulation without live micro-organisms. Treatment was given to subjects for 21 days and they were followed for 4 weeks. Treatment success (primary outcome), daily reduction in crying time, parent satisfaction and reduction in maternal depression (secondary outcomes) were assessed at the end of study period. Treatment success was observed in all infants (100 %) of the probiotic group while it was seen in 15.7 % of the placebo group. Mean daily crying time was more significantly reduced to 32.1 ± 8.3 min/day (P < 0.01) from 200.9 ± 6.3 min/day in the probiotic group as compared to the placebo group (120.6 ± 20.0 min/day). Moreover, throughout the study period, parent's satisfaction and improvement in maternal depression (Edinburgh postnatal depression scale) was also significantly higher in the probiotic group. In our study population, reduction in crying time was significant (P < 0.01) even during first week of initiation of therapy. We conclude that L. reuteri (DSM 17938) reduces daily crying time and maternal depression during infantile colic. We suggest L. reuteri may be a safe and efficacious option for reducing infant colic.
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Dor Abdominal/prevenção & controle , Dor Abdominal/psicologia , Cólica/prevenção & controle , Cólica/psicologia , Depressão/prevenção & controle , Limosilactobacillus reuteri , Probióticos/administração & dosagem , Humanos , Lactente , Recém-Nascido , Mães , Placebos/administração & dosagem , Distribuição Aleatória , Resultado do TratamentoRESUMO
Recent studies have shown that microRNAs, a class of small and noncoding RNA molecules, play crucial roles in the initiation and progression of pancreatic cancer. In the present study, the expression and roles of miR-191 were investigated. Through both gain-of function and loss-of function experiments, a pro-oncogenic function of miR-191 was demonstrated. At the molecular level, bioinformatic prediction, luciferase, and protein expression analysis suggested that miR-191 could inhibit protein levels of UPS10, which suppressed the proliferation and growth of cancer cells through stabilizing P53 protein. Collectively, these data suggest that miR-191 could promote pancreatic cancer progression through targeting USP10, implicating a novel mechanism for the tumorigenesis.
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MicroRNAs/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Interferência de RNA , Ubiquitina Tiolesterase/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Masculino , Camundongos , MicroRNAs/química , NF-kappa B/genética , NF-kappa B/metabolismo , Neoplasias Pancreáticas/metabolismo , Transdução de Sinais , Carga Tumoral , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina Tiolesterase/químicaRESUMO
Numerous studies have indicated that human metapneumovirus (hMPV) is an important viral pathogen in acute respiratory infections in children, presenting similar manifestations with respiratory syncytial virus (RSV). HMPV infection peaks in the winter-spring season and is more prevalent in younger ages, especially in children less than 1 year old. Host innate immune response has been implicated in recognition of pathogen-associated molecular patterns (PAMPs) of the virus. This recognition occurs through host pattern recognition receptors (PRRs). Toll like receptors (TLRs) are one of the largest class of PRRs which initiate and regulate adaptive immune responses. Some studies have indicated that TLR 3 and TLR 4 may play critical roles in hMPV infection. Construction of recombinant mutant viruses lacking one or two N-linked glycosylation sites in the F protein by using site-directed mutagenesis and reverse genetics may be helpful for developing attenuated live vaccines.
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Metapneumovirus/imunologia , Infecções por Paramyxoviridae/etiologia , Vacinas Virais/imunologia , Humanos , Infecções por Paramyxoviridae/prevenção & controle , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/imunologiaRESUMO
Using coconut shell and boric acid as raw materialsï¼ a new boron-doped coconut shell mesoporous carbon material ï¼B-CSCï¼ was prepared using a simple one-step pyrolysis method for efficient adsorption and removal of tetracycline pollutants in water. The effects of pyrolysis temperature and boron-carbon mass ratio on the adsorption performance under key preparation conditions were systematically studiedï¼ and their microstructure and physicochemical properties were characterized using a specific surface area and pore size analyzer ï¼BETï¼ï¼ field emission scanning electron microscopy ï¼SEMï¼ï¼ X-ray photon spectroscopy ï¼XPSï¼ï¼ Raman spectrometer ï¼Ramanï¼ï¼ and Zeta potentiometer ï¼Zetaï¼. The effects of initial pHï¼ different metal cationsï¼ and different background water quality conditions on the adsorption effect were systematically investigated. Combined with material characterization and correlation analysisï¼ the enhanced adsorption mechanism was discussed and analyzed in depth. The results showed that one-step pyrolysis could incorporate boron into the surface and crystal lattice of coconut shell charcoalï¼ resulting in a larger specific surface area and pore volumeï¼ and the main forms of boron introduced were H3BO3ï¼ B2O3ï¼ Bï¼ and B4C. The adsorption capacity of B-CSC to tetracycline reached 297.65 mg·g-1ï¼ which was 8.9 times that of the original coconut shell mesoporous carbon ï¼CSCï¼. At the same timeï¼ the adsorption capacity of B-CSC for rhodamine B ï¼RhBï¼ï¼ bisphenol Aï¼BPAï¼ï¼ and methylene blue ï¼MBï¼ï¼ common pollutants in aquatic environmentsï¼ was as high as 372.65ï¼ 255.24ï¼ and 147.82 mg·g-1ï¼ respectively. The adsorption process of B-CSC to tetracycline was dominated by physicochemical interactionï¼ mainly involving liquid film diffusionï¼ surface adsorptionï¼ mesoporous and microporous diffusionï¼ and active site adsorptionï¼ and H3BO3 was the main adsorption site. The adsorption strengthening mechanism mainly reduced the chemical inertness of the carbon network and enhanced its π-π interaction and hydrogen bonding with tetracycline molecules.
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Objective: This study sought to analyze the 18F-FDG PET/CT and contrast-enhanced computed tomography (CT) images of synchronous colorectal cancer (CRC) and renal clear cell carcinoma (ccRCC) and identify the shared genes between these two types of cancer through bioinformatic analysis. Methods: A retrospective analysis was conducted on a patient with synchronous CRC and ccRCC who underwent 18F-FDG PET/CT and contrast-enhanced CT before treatment. Databases were analyzed to identify differentially expressed genes between CRC and ccRCC, and co-expression genes were extracted for RCC and CRC. Results: 18F-FDG PET/CT revealed intense metabolic activity in the primary colorectal lesion (SUVmax 13.2), while a left renal mass (diameter = 35 mm) was observed with no significant uptake. Contrast-enhanced CT during the arterial phase showed heterogeneous intense enhancement of the renal lesion, and the lesion washed out earlier than in the renal cortex in the nephrographic and excretory phases, indicating ccRCC. The histopathological results confirmed synchronous double primary malignant tumors. Our bioinformatic analysis results showed that synchronous occurrence of CRC and ccRCC may correlate with simultaneous expression of Carbonic Anhydrase 9 (CA9), integrin-binding sialoprotein (IBSP), and Fibrinogen γ chain (FGG). Conclusion: 18F-FDG PET/CT combined with contrast-enhanced CT is an effective diagnostic tool in evaluating synchronous CRC and RCC. By analyzing this clinical case and conducting bioinformatic analysis, we improved our current understanding of the mechanisms underlying synchronous tumors.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/genética , Neoplasias Renais/patologiaRESUMO
OBJECTIVE: To establish a rapid and universal quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) method for measuring the exposure levels of five triazole antifungal drugs in human plasma, including voriconazole, fluconazole, posaconazole, itraconazole, and hydroxyitraconazole. METHODS: A triple quadrupole mass spectrometer operating in positive ionization mode was used to detect the analyte, and multiple reaction monitoring mode was employed to gather data. The mobile phase included 0.05â¯% formic acid in water (phase A) and acetonitrile (phase B). The analytes were separated on an Agilent EclipsePlusC18 RRHD column (30â¯×â¯50â¯mm, 1.8⯵m) using gradient elution. The flow rate was 0.3â¯mL/min with the column temperature set at 35⯰C. The acetonitrile was used to pretreat the plasma sample, and the itraconazole-D5 and hydroxyitraconazole-D5 were utilized as the internal standards. RESULTS: The calibration range was from 100 to 10,000â¯ng/mL for posaconazole, itraconazole, and hydroxyitraconazole, from 200 to 20,000â¯ng/mL for fluconazole and from 50 to 5000â¯ng/mL for voriconazole, with linear correlation coefficients more than 0.99 for all regression curves. The intra- and inter-day accuracy and precision of the method were within ±15â¯%. The mean extraction recovery of all the analytes ranged from 74.32â¯% to 117.83â¯%, and the matrix effect was from 72.54â¯% to 111.2â¯%. The results of stability fell into the scope of ±15â¯% deviation. CONCLUSION: This newly developed method is sensitive, simple, and robust, and successfully applied in determining triazole antifungal drugs in plasma from 66 IFI patients to provide reference for safe and effective drug administration in clinical practice.
RESUMO
Manipulation of the lactate metabolism is an efficient way for cancer treatment given its involvement in cancer development, metastasis, and immune escape. However, most of the inhibitors of lactate transport carriers suffer from poor specificity. Herein, we use the CRISPR/Cas9 system to precisely downregulate the monocarboxylate carrier 1 (MCT1) expression. To avoid the self-repairing during the gene editing process, a dual-Cas9 ribonucleoproteins (duRNPs) system is generated using the biological fermentation method and delivered into cells by the zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, enabling precise removal of a specific DNA fragment from the genome. For efficient cancer therapy, a specific glucose transporter 1 inhibitor (BAY-876) is co-delivered with the duRNPs, forming BAY/duRNPs@ZIF-8 nanoparticle. ZIF-8 nanoparticles can deliver the duRNPs into cells within 1 h, which efficiently downregulates the MCT1 expression, and prohibits lactate influx. Through simultaneous inhibition of the lactate and glucose influx, BAY/duRNPs@ZIF-8 prohibits ATP generation, arrests cell cycle, inhibits cell proliferation, and finally induces cellular apoptosis both in vitro and in vivo. Consequently, we demonstrate that the biologically produced duRNPs delivered into cells by the nonviral ZIF-8 carrier have expanded the CRISPR/Cas gene editing toolbox and elevated the gene editing efficiency, which will promote biological studies and clinical applications. STATEMENT OF SIGNIFICANCE: The CRISPR/Cas9 system, widely used as an efficient gene editing tool, faces a challenge due to cells' ability to self-repair. To address this issue, a strategy involving dual-cutting of the genome DNA has been designed and implemented. This strategy utilizes biologically produced dual-ribonucleoproteins delivered by a metal-organic framework. The effectiveness of this dual-cut CRISPR-Cas9 system has been demonstrated through a therapeutic approach targeting the simultaneous inhibition of lactate and glucose influx in cancer cells. The utilization of the dual-cut gene editing strategy has provided valuable insights into gene editing and expanded the toolbox of the CRISPR/Cas-based gene editing system. It has the potential to enable more efficient and precise manipulation of specific protein expression in the future.