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BACKGROUND: Stroke is one of the primary causes of disability in China and around the world, having an impact on the health and well-being of stroke patients. The importance of spiritual needs for stroke patients has always been a controversial topic internationally, partly because related research was mostly qualitative and may not directly reflect the degree of spiritual needs. In addition, most studies focus on the same cultural background, there is a lack of research that delves into the nuances of Chinese culture and background. The goal of this study is to evaluate the level of spiritual needs and influencing factors in Chinese stroke patients and to explore the mediating role and pathways of these variables on spiritual needs. METHODS: From August 2022 to January 2023, we conducted a cross-sectional questionnaire survey of 422 stroke patients in the affiliated hospitals of Hunan University of Chinese Medicine in Changsha Province by cluster sampling. We measured the patient's spiritual needs, quality of life, anxiety and depression levels, and family support using the Spiritual Needs Questionnaire (SPNQ), the MOS36 item Short Form Health Survey (SF-36), the Hospital Anxiety and Depression Scale (HADS), and the Family Support Self Rating Scale (PSS-Fa). We used the General Information Questionnaire to gain insight into the sociodemographic characteristics of the patients. Nonparametric tests and multiple linear regression models were used to analyze the independent relationship between spiritual needs and quality of life, anxiety, depression, and family support. The mediation model in AMOS 24.0 software was used to analyze the mediating role among the five variables. RESULTS: The score of spiritual needs of people with stroke included in this study was 37 points [IQR 33 to 40)]. The influencing factors of spiritual needs included primary economic sources for disease-related expenditures (p = 0.044), number of stroke occurrences (p = 0.001), duration of illness (p = 0.023), activities of daily living (p = 0.006), depression scores(p = 0.034), and family support scores(p = 0.008). Anxiety (ß = 0.347, p = 0.004), depression (ß = 0.368, p = 0.005), and family support (ß = 0.167, p = 0.023) had directly or indirectly affected the spiritual needs of people with stroke. Quality of life (ß=-0.202, p = 0.017) had a direct effect on spiritual needs. CONCLUSIONS: The spiritual needs of people with stroke were at an intermediate level. Our findings highlight that the SPNQ score is associated with anxiety, depression, quality of life, and family support. Therefore, nurses should identify the spiritual needs of patients and provide them with effective and comprehensive spiritual care by reducing negative emotions and enhancing social support, promoting the development and progress of spiritual care in China. This study offers a theoretical basis for the spiritual care of clinical people with stroke and constructing a stroke spiritual care model.
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OBJECTIVE: The aim of this study was to identify sex-specific biomarkers for ischemic stroke (IS) prophylaxis in elderly individuals. MATERIALS AND METHODS: The GSE22255 dataset for elderly individuals with IS was retrieved from the gene expression omnibus database. Thereafter, gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, as well as gene set enrichment analysis (GSEA). Furthermore, protein-protein interactions (PPIs) were explored using the STRING database, and to screen central genes from the Cytoscape PPI network, corresponding to peripheral blood samples from elderly individuals, we used the molecular complex detection plug-in and cytoHubba. Moreover, a Venn diagram was used to visualize the key genes common among elderly women and men with IS. Statistical analysis was also performed, and receiver operating characteristic (ROC) curves were constructed to evaluate the specificity and sensitivity of the prediction of IS in the elderly. RESULTS: Compared with the healthy controls, in elderly women with IS, 511 biological process (BP) terms, 16 molecular function (MF) terms, and 34 KEGG terms were significantly enriched, whereas in the elderly men with IS, 681 BP terms, 12 MF terms, and 44 KEGG terms were enriched. The GSEA revealed 99 and 140 significantly enriched gene sets in elderly women and men with IS, respectively. Furthermore, in the PPI network, 10 hub genes for each sex with high specificity and sensitivity were identified using ROC curves. CONCLUSIONS: Ten genes for each sex with significant differential expression were also identified in individuals with IS. The novel sex-specific gene targets may be promising diagnostic or prognostic markers and potential therapeutic targets for IS in the elderly.
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OBJECTIVE: The aim of the study was to evaluate the effect of a hot environment on several physiological variables of soccer players and suggest feasible solutions to it. SUBJECTS AND METHODS: The study is of prospective design, considering 66 participants comprising professional soccer players. All the participants completed the Physical Activity Readiness Questionnaire (PARQ). The participants were assigned to 3 different groups. Each group was assigned 22 participants. They were made to play in three different chambers, maintained at cool, moderate and hot temperatures. Players were made to play and various variables were determined to assess the effect of hot temperature on them. RESULTS: Several variables were determined including absolute and relative oxygen uptake, heart rate, minute ventilation, the blood concentration of lactate and time to get exhausted. All the variables of players who played in hot temperatures have revealed higher heart rate, ventilation and increased lactate concentration. Players in a hot environment ran out faster. CONCLUSIONS: The study was concluded due to the players' dehydration and physiological deteriorated factors in a hot environment, leading to poor performances and also affecting the players' health in the long run. Further, the study suggested improving the environment around the game venues.
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Futebol , Humanos , Temperatura Alta , Exercício Físico , Frequência Cardíaca , Ácido LácticoRESUMO
OBJECTIVE: The Tongmai Yangxin Pill (TMYX) is considered an effective treatment for coronary heart disease (CHD). However, its mechanism is unclear. This study aimed at exploring the molecular mechanisms and key genes of the TMYX in the treatment of CHD. MATERIALS AND METHODS: Differentially expressed genes (DEGs) in the GSE142008 dataset were screened with the R software, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Then, protein-protein interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes database. The correlation analysis between key genes was conducted, and gene expression was verified. RESULTS: A total of 1,614 DEGs were identified, including 1,591 upregulated and 23 downregulated genes. GO enrichment analysis revealed that 240 biological processes, 44 cellular components, and 23 molecular functions were significantly enriched for DEGs in elderly patients with CHD. Similarly, 36 KEGG terms were significantly enriched for DEGs. Ten key genes were screened, and after verification and analysis, seven key genes (RSL24D1, NMD3, DCAF13, WDR36, SDAD1, KRR1, and RPF1) were identified as significantly overexpressed. CONCLUSIONS: We identified seven key genes as candidate biomarkers for TMYX in the treatment of elderly patients with CHD; these results can serve as a theoretical basis for targeted therapy.
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Doença das Coronárias , Pacientes , Idoso , Humanos , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/genética , Ontologia Genética , Probabilidade , Ferramenta de Busca , Proteínas de Ligação a RNARESUMO
OBJECTIVE: The aim of the study was to find the significance of several factors with parameters of urine tests and blood tests. Finally, we aimed at evaluating the percentage of athletes from the study sample regarding their hydration level. SUBJECTS AND METHODS: The current study is the prospective type and was conducted on Chinese athletes between June 2021 to April 2022. The study was done in 2 parts for obtaining measurements in the summer season and the winter season and then they were correlated between them. Urine and blood samples were evaluated for determining the required parameters. The parameters of the physical environment like temperature, relative humidity, precipitation, etc. were obtained from the concerned weather station for each day. RESULTS: It was observed that 14.5%, 59% and 26.5% of the female participants were found to have hyper-hydrated, euhydrated and dehydrated, respectively. While 17.57%, 69.69% and 12.74% of the males were classified as hyper-hydrated, euhydrated and dehydrated, respectively. The participants with hyper-hydrated were found to have increased urine volume (p<0.001), reduced specific gravity (p<0.001) and reduced-sodium level (p<0.001). CONCLUSIONS: The study found that there is a significant difference in sodium levels between gender and seasons. The level of serum osmolality is also significantly different between the whole study populations concerning combined seasons. In this way, many other parameters are evaluated by correlation with seasons and gender. Hence, this study has brought forward various important findings and gives an overall evaluation of hydration status.
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Desidratação , Sódio , Masculino , Humanos , Feminino , Desidratação/urina , Estudos Prospectivos , Atletas , ChinaRESUMO
Despite the guidance of aseptic technology applied, bacterial meningitis seems to be an unavoidable obstacle in the process of neurosurgery, with high rates of disability and mortality. The diagnosis of post-neurosurgical bacterial meningitis (PNBM) mainly depends both on clinical symptoms and laboratory outcomes. Due to the excessive neuro-inflammatory reactions which are evoked by the primary brain disease or the craniotomy operation, the symptoms derived from the infection and aseptic may not be easily distinguished. On the other hand, the low positive rate and time-consuming character restrict the clinical practical values of bacterial culture. Therefore, it is always difficult to make a definite diagnosis of post-neurosurgical bacterial meningitis. Here, we reviewed the established literature about the diagnostic biomarkers for the PNBM and analyzed the potential obstacles in both clinical and scientific studies. Given the obstacle which has negative impacts on further investigation about the biology of PNBM, we only find relatively small numbers of study on PNBM. In this review, we summarize the established diagnostic methods and biomarkers for PNBM. Meanwhile, we also propose some potential investigation prospects. This review may help to better understand the character of PNBM in both clinical diagnosis and scientific investigations.
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Meningites Bacterianas , Neurocirurgia , Biomarcadores , Craniotomia/efeitos adversos , Humanos , Meningites Bacterianas/diagnóstico , Procedimentos Neurocirúrgicos/efeitos adversosRESUMO
OBJECTIVE: To explore the association between oxidative stress (OS) and Kashin-Beck disease (KBD). METHODS: Terms associated with "KBD" and "OS" were searched in the six different databases up to October 2021. Stata 14.0 was used to pool the means and standard deviations using random-effect or fixed-effect model. The differentially expressed genes in the articular chondrocytes of KBD were identified, the OS related genes were identified by blasting with the GeneCards. The KEGG pathway and gene ontology enrichment analysis was conducted using STRING. RESULTS: The pooled SMD and 95% CI showed hair selenium (-4.59; -6.99, -2.19), blood selenium (-1.65; -2.86, -0.44) and glutathione peroxidases (-4.15; -6.97, -1.33) levels were decreased in KBD, whereas the malondialdehyde (1.12; 0.60, 1.64), nitric oxide (2.29; 1.31, 3.27), nitric oxide synthase (1.07; 0.81, 1.33) and inducible nitric oxide synthase (1.69; 0.62, 2.77) were increased compared with external controls. Meanwhile, hair selenium (-2.71; -5.32, -0.10) and glutathione peroxidases (-1.00; -1.78, -0.22) in KBD were decreased, whereas the malondialdehyde (1.42; 1.04, 1.80), nitric oxide (3.08; 1.93, 4.22) and inducible nitric oxide synthase (0.81; 0.00, 1.61) were elevated compared with internal controls. Enrichment analysis revealed apoptosis was significantly correlated with KBD. The significant biological processes revealed OS induced the release of cytochrome c from mitochondria. The cellular component of OS located in the mitochondrial outer membrane. CONCLUSIONS: The OS levels in KBD were significantly increased because of selenium deficiency, OS mainly occurred in mitochondrial outer membrane, released of cytochrome c from mitochondria, and induced apoptotic signaling pathway.
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Doença de Kashin-Bek , Selênio , Humanos , Doença de Kashin-Bek/genética , Doença de Kashin-Bek/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Selênio/metabolismo , Biologia Computacional , Óxido Nítrico/metabolismo , Citocromos c/metabolismo , Citocromos c/farmacologia , Estresse Oxidativo , Malondialdeído/farmacologia , Glutationa/metabolismo , Glutationa/farmacologia , Peroxidases/metabolismo , Peroxidases/farmacologiaRESUMO
OBJECTIVE: Women have a higher lifetime risk of stroke than men and are more likely to die from it. Ferroptosis is a recently discovered form of programmed cell death implicated in many diseases. The role of ferroptosis-related genes in the diagnosis, prognosis, and treatment of elderly women with ischemic stroke (IS) requires additional clarification. This paper aimed to screen ferroptosis-related genes associated with IS in elderly women and to identify hub genes and candidate drugs. MATERIALS AND METHODS: Ferroptosis-related differentially expressed genes (DEGs) in elderly women with IS were identified by bioinformatics analysis of the GSE22255 and ferroptosis-related gene datasets. Subsequently, ferroptosis-related hub genes were used to predict targeted miRNA, construct the miRNA-mRNA network, and identify candidate drugs. RESULTS: Eleven ferroptosis-related DEGs were identified in elderly women with IS vs. controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that the 11 genes were mainly enriched in the IL-17, TNF, and NF-κB signaling pathways. Moreover, the hub genes suggested 10 ferroptosis-related biomarkers for IS, including SOCS1, IFNG, TNFAIP3, IL1B, IL-6, PTGS2, DDIT3, CXCL2, NFE2L2, and ATF3. Furthermore, our findings revealed the miRNA-mRNA network of the hub genes and identified candidate drugs. 10 potential therapeutic compounds, especially estradiol CTD 00005920, corresponded to the 10 key genes which could be targets for IS treatment in elderly women. CONCLUSIONS: Our results suggested ferroptosis-related DEGs (SOCS1, IFNG, TNFAIP3, IL1B, IL-6, PTGS2, DDIT3, CXCL2, NFE2L2, and ATF3) as potential biomarkers for IS diagnosis, prognosis, and treatment, providing additional evidence of the important role of ferroptosis in IS in elderly women.
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Ferroptose , AVC Isquêmico , MicroRNAs , Idoso , Biomarcadores , Biologia Computacional/métodos , Ciclo-Oxigenase 2 , Feminino , Ferroptose/genética , Perfilação da Expressão Gênica/métodos , Humanos , Interleucina-6/genética , Masculino , MicroRNAs/genética , RNA Mensageiro/genéticaRESUMO
OBJECTIVE: To investigate whether anion gap (AG) can act as a potentially predictive biomarker in recoveries of neurological and cognitive functions. PATIENTS AND METHODS: A total of 89 patients with intracerebral hemorrhage (ICH) were recruited. Of these, 68 and 21 patients were categorized into screening cohort and validation cohort, respectively. In the screening cohort, patients were categorized into three groups, according to the serum AG levels at admission. We dynamically recorded AG levels. Neurological and cognitive functions were assessed using Glasgow coma scale (GCS), Glasgow outcome scale (GOS) and mini-mental state examination (MMSE) scale at different time points. Furthermore, in the validation cohort, 9 patients with increased AG level underwent interventions to rectify the electrolyte imbalance. RESULTS: In the screening cohort, statistical differences were observed for respiratory diseases (p=0.029) among the three groups. The number of patients in the ≥16 mmol/L group (59.3%) was higher than that in the other groups. The mean scores of GCS in the ≥16 mmol/L group were lower than those in the other groups. The AG levels at admission had significant associations with 180-day GOS (p=0.043) and 180-day MMSE (p=0.001). Among them, the mean scores of the 180-day GOS and 180-day MMSE were lower in the ≥16 mmol/L group than in the other groups. In the validation cohort, AG intervention promoted recoveries of neurological and cognitive functions when compared to those without AG interventions. CONCLUSIONS: AG is a potentially predictive biomarker for the long-term outcomes of ICH patients, and rectifying AG at admission improves the outcomes.
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Equilíbrio Ácido-Base , Hemorragia Cerebral , Hemorragia Cerebral/diagnóstico , Cognição , Escala de Coma de Glasgow , Hospitalização , HumanosRESUMO
Magnetic fields have an important role in the evolution of interstellar medium and star formation1,2. As the only direct probe of interstellar field strength, credible Zeeman measurements remain sparse owing to the lack of suitable Zeeman probes, particularly for cold, molecular gas3. Here we report the detection of a magnetic field of +3.8 ± 0.3 microgauss through the H I narrow self-absorption (HINSA)4,5 towards L15446,7-a well-studied prototypical prestellar core in an early transition between starless and protostellar phases8-10 characterized by a high central number density11 and a low central temperature12. A combined analysis of the Zeeman measurements of quasar H I absorption, H I emission, OH emission and HINSA reveals a coherent magnetic field from the atomic cold neutral medium (CNM) to the molecular envelope. The molecular envelope traced by the HINSA is found to be magnetically supercritical, with a field strength comparable to that of the surrounding diffuse, magnetically subcritical CNM despite a large increase in density. The reduction of the magnetic flux relative to the mass, which is necessary for star formation, thus seems to have already happened during the transition from the diffuse CNM to the molecular gas traced by the HINSA. This is earlier than envisioned in the classical picture where magnetically supercritical cores capable of collapsing into stars form out of magnetically subcritical envelopes13,14.
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Myostatin (MSTN) is primarily expressed in skeletal muscle and plays an important role in the regulation of muscle growth and development as well as fat deposition; however, little is known about the molecular mechanism through which MSTN regulates body fat deposition. Therefore, in this study, we sought to identify the signaling pathways through which MSTN regulates fat accumulation in pigs. MSTN knockout (MSTN-/-) pigs showed increased muscle mass, decreased fat mass, and a leaner body composition. In this study, we found that the adipose tissue of MSTN-/- pigs exhibits the characteristics of beige adipose tissue, and the mRNA expression levels of beige adipose marker genes, including UCP3, Cidea, and CD137, were significantly increased. Remarkably, the observed beige phenotype was not adipocyte autonomous but rather caused by muscle-secreted myokine interleukin (IL)-6. This occurrence results in increased AMP-activated protein kinase (AMPK) phosphorylation in adipose tissue, which subsequently activates peroxisome proliferator-activated receptor gamma coactivator 1α and the conversion of white adipocytes to beige in pigs. Therefore, we concluded that MSTN deficiency leads to increased IL-6 secretion in skeletal muscle and activates AMPK in adipocytes, thereby increasing the beige adipose tissue in MSTN-/- pigs.
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Tecido Adiposo Bege , Miostatina , Tecido Adiposo/metabolismo , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Técnicas de Inativação de Genes/veterinária , Interleucina-6/genética , Músculo Esquelético/metabolismo , Miostatina/genética , SuínosRESUMO
OBJECTIVE: Renal injury caused by sepsis is a difficult point in the field of critical care medicine today, which seriously endangers the health of patients. The aim of our paper was to study the role of irisin in the inflammation and apoptosis of renal injury caused by sepsis and its potential mechanism of action. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was utilized to establish an acute kidney injury model. HK-2 cells were divided into 3 groups: control group, LPS group, LPS+irisin group. The expression of TNF-α, IL-1ß, Bcl-2, and Bax were detected using Western blot. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to detect the levels of TNF-α, IL-6, and IL-1ß in the cell supernatant. The LDH content was detected to observe cell damage. TUNEL staining and flow cytometry were to investigate the apoptosis in three groups. The viability of HK-2 cells was detected using Cell Counting Kit-8 (CCK-8) assay. RESULTS: After HK-2 cells were treated with LPS, the LDH content in the cell supernatant was greatly increased, and the expression of TNF-α, IL-6, and IL-1ß was also significantly increased. However, after treatment with irisin, LDH content and expression of inflammatory factors were significantly suppressed. Similarly, LPS treatment greatly elevated the levels of TNF-α, IL-1ß, Bax, p65 and IκKα, as well as inhibited the expression of Bcl-2 and IκB-α. However, irisin treatment reversed these situations. In addition, the number of TUNEL-positive cells and the apoptotic rate were also greatly decreased in LPS+irisin group compared with those in LPS group. CONCLUSIONS: Irisin could inhibit inflammation and apoptosis of HK-2 cells treated with LPS via the NF-κB pathway.
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Injúria Renal Aguda/metabolismo , Fibronectinas/metabolismo , NF-kappa B/metabolismo , Sepse/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos , Sepse/induzido quimicamente , Sepse/patologia , Transdução de SinaisRESUMO
OBJECTIVE: To discuss the role and mechanism of ß4GalT1 both in vivo and in vitro glioma, observe whether pathophysiological processes of glioma can be improved after ß4GalT1 is knocked down, and study whether ß4GalT1 plays a role in malignant biological processes of glioma by regulating the apoptosis and immune processes. PATIENTS AND METHODS: Firstly, the distribution difference of ß4GalT1 in tumor tissues and normal tissues was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) tumor analysis system to deduce the possible role of ß4GalT1 in glioma. Secondly, whether the malignant degree of glioma was related to the expression of ß4GalT1 and its immunity using human tumor tissues and blood lymphocyte subsets was analyzed. Thirdly, interfere lentivirus vector with ß4GalT1 and knockdown ß4GalT1 was analyzed to observe whether the malignant degree of glioma has changed. Fourthly, interfere lentivirus vector with recombinant ß4GalT protein and ß4GalT1 was analyzed to verify the effect of ß4GalT in vitro test. Fifth, interfere lentivirus vector with recombinant ß4GalT protein and ß4GalT1 was analyzed to verify effect of ß4GalT in vivo test. Finally, we discuss whether ß4GalT is involved in the biological process of glioma through inflammatory reaction. RESULTS: In the GEPIA tumor analysis system, the expression in tumor was significantly higher than that in normal tissues. The expression of ß4GalT1 in glioma tissues was higher than that in normal tissues, and the higher the malignancy of the tumor, the higher the expression of ß4GalT1 in the glioma tissues, and the lower the immune level was. The expression of IDH1, MGMT, and ki-67 was reduced, and the survival rate of the mice with glioma was improved after ß4GalT1 was knocked down. In vitro tests, the activity of tumor cells and their reproductive ability can be reduced after ß4GalT1 was knocked down, the immune level of the body can be improved, and the level of tissue apoptosis can be reduced. After recombinant ß4GalT1 was given alone, the result was opposite to that of ß4GalT1 knocked down group. In vivo tests, gross tumor volume can be reduced after ß4GalT1 was knocked down, the immune level of the body can be improved, and the level of tissue apoptosis can be reduced. After recombinant ß4GalT1 was given alone, the result was opposite to that of ß4GalT1 knocked down group. After knocking down ß4GalT1, the expression of inflammatory factors can be reduced both in vivo and in vitro, and the inflammatory microenvironment of tumors can be improved. After recombinant ß4GalT1 was given alone, the result was opposite to that of ß4GalT1 knocked down group. CONCLUSIONS: The level of ß4GalT1 expression in tumor tissues was increased. The malignant degree of glioma is related to the expression of ß4GalT1 and its immunity. The level of tumor marker can be decreased, and the survival rate of glioma model mice can be increased after ß4GalT1 is knocked down. Apoptosis and immune injury caused by tumor can be improved and gross tumor volume can be deduced after ß4GalT1 is knocked down. During the development of glioma, ß4GalT1 may play a malignant biological role through inflammatory response.
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Neoplasias do Sistema Nervoso Central/enzimologia , Galactosiltransferases/metabolismo , Glioma/enzimologia , Animais , Células Cultivadas , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Experimentais/enzimologiaRESUMO
OBJECTIVE: Ovarian cancer (OC) is a common tumor in women, and the development of chemoresistance is the major obstacle to its treatment. Long non-coding RNAs (LncRNAs) have been linked to chemoresistance in many cancers. However, the function of lncRNA urothelial carcinoma associated1 (UCA1) in paclitaxel (PTX) resistance of OC is not well elucidated. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of UCA1, microRNA-654-5p (miR-654-5p) and salt inducible kinase 2 (SIK2). Cell PTX resistance and proliferation were evaluated by 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The abilities of apoptosis, migration and invasion were measured by Flow cytometry and Transwell assays, respectively. Dual-luciferase reporter assay was used to verify the interaction among UCA1, miR-654-5p and SIK2. Besides, Western blot analysis was performed to assess the protein level of SIK2. RESULTS: UCA1 was markedly upregulated in OC tissues and PTX-resistant OC cells. Silencing of UCA1 restrained the PTX resistance, reduced the proliferation, migration, invasion and enhanced the apoptosis of PTX-resistant OC cells. MiR-654-5p could be sponged by UCA1, and the inhibitory effect of its overexpression on the progression of PTX-resistant OC cells could be reversed by overexpressed-UCA1. Moreover, SIK2 was a target of miR-654-5p. Silencing of SIK2 could hinder the PTX resistance and suppress the progression of PTX-resistant OC cells, while miR-654-5p inhibitor could invert this inhibitory effect. Also, the expression of SIK2 was regulated by miR-654-5p and UCA1 expression. CONCLUSIONS: LncRNA UCA1 plays an active role in PTX resistance of OC and is crucial to maintain the development of PTX resistance in OC, which provides a new therapeutic target for the study of OC chemoresistance.
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Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , MicroRNAs/biossíntese , Neoplasias Ovarianas/metabolismo , Paclitaxel/uso terapêutico , Proteínas Serina-Treonina Quinases/biossíntese , RNA Longo não Codificante/biossíntese , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Células Cultivadas , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Humanos , MicroRNAs/antagonistas & inibidores , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidoresRESUMO
OBJECTIVE: The aim of this study was to investigate the effect of microRNA-214-5p (miR-214-5p) on spinal cord injury (SCI) and to explore the mechanism of action in pathophysiological relevance. MATERIALS AND METHODS: The model of SCI was successfully established in rats aged 6-8 weeks. The levels of the locomotor function recovery in rats of the miR-379-5p group and SCI group were detected one month later by Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Biochemical indexes were measured by Western blotting and real time-PCR, respectively. In addition, rat astrocytes were cultured to verify the effect of miR-379-5p on activated astrocytes in vitro. RESULTS: Compared with the SCI group, the rats in the miR-379-5p group showed prominent improvement in the locomotor function in vivo. MiR-379-5p attenuated the activation of astrocytes and significantly suppressed the expressions of the nerve growth inhibitors. Furthermore, the down-regulation of endothelin-1 (ET-1) ameliorated the spinal cord ischemia, thereby reducing apoptosis and oxidative stress. Compared with the pentylenetetrazol (PTZ) group, ET-1 and chondroitin sulfate poly-glycoprotein (CSPG) in miR-379-5p group decreased significantly in the astrocytes transfected with miR-214-5p in vitro. CONCLUSIONS: MiR-379-5p retarded the neurofilament regeneration block effect by inhibiting endothelin 1 and the expression of the astrocytes after SCI. Furthermore, it might relieve nerve structure destruction, resist oxidative stress, and inhibit apoptosis, eventually promoting functional recovery.
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Astrócitos/metabolismo , Endotelina-1/metabolismo , Locomoção , MicroRNAs/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Modelos Animais de Doenças , Endotelina-1/antagonistas & inibidores , Endotelina-1/genética , Feminino , Locomoção/efeitos dos fármacos , MicroRNAs/genética , Estresse Oxidativo/efeitos dos fármacos , Pentilenotetrazol/farmacologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologiaRESUMO
OBJECTIVE: To uncover the influence of plasmacytoma variant translocation 1 (PVT1) on aggravating the progression of glioma via downregulating UPF1. PATIENTS AND METHODS: The relative levels of PVT1 and UPF1 in glioma tissues were determined. PVT1 level in glioma patients in stage I+II and stage III+IV, and either with metastasis or not was examined as well. The Kaplan-Meier curves were depicted for assessing the survival in glioma patients expressing a high and low level of PVT1. The regulatory effects of PVT1 and UPF1 on the proliferative and migratory abilities of U87 and LN229 cells were evaluated. The subcellular distributions of PVT1 and UPF1 were analyzed, and their interaction was investigated by performing RNA immunoprecipitation (RIP) assay. At last, the mRNA level of UPF1 was determined in U87 and LN229 cells overexpressing PVT1 treated with 50 µM α-amanitin. RESULTS: PVT1 was upregulated in glioma tissues relative to controls. Its level was higher in glioma patients with advanced stage or accompanied by metastasis. The glioma patients with a high level of PVT1 suffered a worse prognosis. The overexpression of PVT1 accelerated proliferative and migratory abilities of U87 and LN229 cells. UPF1 was conversely downregulated in glioma patients. Its level was negatively correlated to that of PVT1. The overexpression of UPF1 attenuated the proliferative and migratory abilities of U87 and LN229 cells. Both PVT1 and UPF1 were mainly enriched in the cytoplasm. The interaction between PVT1 and UPF1 was identified in the RIP assay. PVT1 prolonged the half-life of UPF1 and inhibited its synthesis. CONCLUSIONS: PVT1 accelerates the proliferative and migratory abilities of glioma via downregulating UPF1.
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Neoplasias Encefálicas/patologia , Regulação para Baixo , Glioma/patologia , RNA Helicases/genética , RNA Longo não Codificante/genética , Transativadores/genética , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , Estadiamento de Neoplasias , Análise de SobrevidaRESUMO
OBJECTIVE: G protein-coupled receptors (GPCRs) constitute the largest membrane proteins superfamily. However, the interactions between them and the coupled heterotrimeric G proteins were little known. To get a deeper view of how the receptor bound to the G protein, we carried out the molecular dynamics' simulations of human Beta2 adrenoceptors (ß1 and ß2) and G protein (s and I) alpha subunit complexes by homology modeling. MATERIALS AND METHODS: For homology modeling, the program modeller 9.11 was used with automodel module. Before dynamics simulation, the homology models were prepared by Protein Preparation Wizard module in Maestro 9.3. The Desmond program was used to perform molecular minimization and molecular dynamics simulation under OPLS-All atom 2005 force field with default parameters. RESULTS: The results offered us the mechanism vividly in molecular level: (1) GPCR-G protein complex can be simulated without specific nanobody; (2) the G protein activation ability of GPCR can be explained by molecular dynamics simulation. CONCLUSIONS: It is suggested that we could do molecular dynamics simulation of complex of GPCR-G protein without bound nanobody. Secondly, the simulation time reduced greatly by using homology modeling to generate complex of proteins. Thirdly, the molecular dynamics simulation will help us to know or even predict further protein-protein interactions.
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Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/metabolismo , Receptores Adrenérgicos beta 2/química , Receptores Adrenérgicos beta 2/metabolismo , Sítios de Ligação , Biologia Computacional/métodos , Humanos , Modelos Moleculares , Simulação de Dinâmica Molecular , Ligação Proteica , Conformação Proteica , Sódio/metabolismo , Homologia Estrutural de ProteínaRESUMO
OBJECTIVE: The aim of this study was to investigate the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in juvenile rats with nephrotic syndrome, and to explore its effects on inflammatory changes and renal injury. MATERIALS AND METHODS: 24 Sprague-Dawley (SD) rats were randomly divided into the normal group (n=12) and model group (n=12). Rats in the normal group were intraperitoneally injected with normal saline. Meanwhile, rats in the model group were given azithromycin hydrochloride injection to establish the model of nephrotic syndrome. After 24 h of modeling, the samples were collected. The expression of NF-κB was detected via immunohistochemistry. Moreover, the protein expression of NF-κB was determined through Western blotting. Quantitative Polymerase Chain Reaction (qPCR) was used to measure the messenger ribonucleic acid (mRNA) expression levels of interleukin-1 (IL-1) and IL-6. Meanwhile, the content of IL-1 and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA). The serum levels of urea nitrogen and serum creatinine were measured by an automatic biochemical analyzer. Furthermore, the correlation between NF-κB protein with IL-1 and IL-6 were studied via Pearson analysis. RESULTS: Compared with the normal group, rats in the model group exhibited significantly increased expression and protein expression of NF-κB (p<0.05). Meanwhile, the mRNA expression levels and content of IL-1 and IL-6 (p<0.05), as well as the serum levels of urea nitrogen and creatinine (p<0.05) of the model group were markedly higher than those of the normal group. Furthermore, NF-κB protein was positively correlated with IL-1 and IL-6 contents. CONCLUSIONS: NF-κB is highly expressed in juvenile rats with nephrotic syndrome, which promotes the expressions of inflammatory factors (IL-1 and IL-6) and aggravates the renal injury.
Assuntos
Rim/patologia , NF-kappa B/metabolismo , Síndrome Nefrótica/patologia , Animais , Azitromicina/toxicidade , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Feminino , Interleucina-1/análise , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-6/análise , Interleucina-6/genética , Interleucina-6/metabolismo , Rim/metabolismo , Masculino , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: The factors contributing to the eosinophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain elusive. This study was designed to investigate the inflammatory patterns and tissue remodeling of CRSwNP in patients from central China at two time points over 14 years apart and the influence of age. METHODS: One hundred and eight CRSwNP patients enrolled in 2000 and 2001 (group A), and 134 CRSwNP patients enrolled in 2014 and 2015 (group B) were retrospectively studied. Hematoxylin-eosin stained tissue sections were used to study characteristics of inflammation and tissue remodeling. Immunohistochemistry was used to further evaluate the cells positive for eosinophil cationic protein (ECP), IL-5, IgE, tryptase or myeloperoxidase (MPO). Time- and age-related difference was analyzed. RESULTS: The number of eosinophils and proportion of eosinophilic CRSwNP were increased, whereas the numbers of total inflammatory cells and lymphocytes were decreased in group B as compared with group A. Group B had severer epithelial squamous metaplasia and basement membrane thickening, and a lower number of mucosal glands than group A. Higher numbers of ECP plus, IL-5 plus and IgE plus cells were detected in group B than those in group A. The elderly (60 yrs or older) and non-elderly (less than 60 yrs) had a comparable number of eosinophils and ratio of eosinophilic CRSwNP. CONCLUSION: Eosinophilic inflammation has been significantly augmented over time, which is associated with increased Th2 response and IgE production, and accompanied by exaggerated epithelium remodeling in CRSwNP patients from central China. Age has no significant influence on eosinophilic inflammation.
Assuntos
Pólipos Nasais , Rinite , Adulto , Idoso , China , Doença Crônica , Citocinas , Eosinófilos , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/patologia , Estudos Retrospectivos , Rinite/complicaçõesRESUMO
BACKGROUND: Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. PATIENTS AND METHODS: A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients' PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. RESULTS: RS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 [95% confidence interval (CI) 0.923-0.993], 0.941 (95% CI 0.904-0.977), 0.928 (95% CI 0.886-0.971), and 0.920 (95% CI 0.862-0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability. CONCLUSION: CT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.