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1.
Gene ; 851: 147000, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36283605

ABSTRACT

Pancreatic stellate cell (PSC) activation is a major cause of chronic pancreatitis and pancreatic cancer, yet the mechanisms by which PSCs switch from quiescent to activated state are poorly studied. In this study, we identified JUN, a key transcription factor that maintains the quiescent state of PSCs, by integrating single-cell sequencing data from multiple pancreatic tissues and using WGCNA and SCENIC algorithms, and demonstrated that the expression and activity of JUN is a major regulator of the quiescent state of PSCs through cellular experiments and multiple pancreatic-related disease bulk RNAseq data. This study explores the main mechanism of PSC activation and provides a theoretical basis for the treatment of multiple pancreatic injury-related diseases caused by PSCs.


Subject(s)
Pancreatic Neoplasms , Pancreatitis, Chronic , Humans , Pancreatic Stellate Cells/metabolism , Transcription Factors/metabolism , Pancreatic Neoplasms/genetics , Pancreatitis, Chronic/metabolism , Pancreas/metabolism , Cells, Cultured
2.
Front Pediatr ; 9: 706012, 2021.
Article in English | MEDLINE | ID: mdl-34621711

ABSTRACT

Circular RNAs (circRNAs) generated by back-splicing are the vital class of non-coding RNAs (ncRNAs). Circular RNAs are highly abundant and stable in eukaryotes, and many of them are evolutionarily conserved. They are blessed with higher expression in mammalian brains and could take part in the regulation of physiological and pathophysiological processes. In addition, premature birth is important in neurodevelopmental diseases. Brain damage in preterm infants may represent the main cause of long-term neurodevelopmental disorders in surviving babies. Until recently, more and more researches have been evidenced that circRNAs are involved in the pathogenesis of encephalopathy of premature. We aim at explaining neuroinflammation promoting the brain damage. In this review, we summarize the current findings of circRNAs properties, expression, and functions, as well as their significances in the neurodevelopmental impairments, white matter damage (WMD) and hypoxic-ischemic encephalopathy (HIE). So we think that circRNAs have a direct impact on neurodevelopment and brain injury, and will be a powerful tool in the repair of the injured immature brain. Even though their exact roles and mechanisms of gene regulation remain elusive, circRNAs have potential applications as diagnostic biomarkers for brain damage and the target for neuroprotective intervention.

3.
J Diabetes Res ; 2021: 6626627, 2021.
Article in English | MEDLINE | ID: mdl-34557552

ABSTRACT

BACKGROUND: Circulating endothelial progenitor cells (EPCs) play important roles in vascular repair. However, the mechanisms of high-glucose- (HG-) induced cord blood EPC senescence and the role of B2 receptor (B2R) remain unknown. METHODS: Cord blood samples from 26 patients with gestational diabetes mellitus (GDM) and samples from 26 healthy controls were collected. B2R expression on circulating CD34+ cells of cord blood mononuclear cells (CBMCs) was detected using flow cytometry. The plasma concentrations of 8-isoprostaglandin F2α (8-iso-PGF2α) and nitric oxide (NO) were measured. EPCs were treated with HG (40 mM) alone or with bradykinin (BK) (1 nM). The B2R and eNOS small interfering RNAs (siRNAs) and the PI3K antagonist LY294002 were added to block B2R, eNOS, and PI3K separately. To determine the number of senescent cells, senescence-associated ß-galactosidase (SA-ß-gal) staining was performed. The level of mitochondrial reactive oxygen species (ROS) in EPCs was assessed by Mito-Sox staining. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assays. Mitochondrial DNA (mtDNA) copy number and the relative length of telomeres were detected by real time-PCR. The distribution of human telomerase reverse transcriptase (hTERT) in the nucleus, cytosol, and mitochondria of EPCs was detected by immunofluorescence. The expression of B2R, p16, p21, p53, P-Ser473AKT, T-AKT, eNOS, and hTERT was demonstrated by Western blot. RESULTS: B2R expression on circulating CD34+ cells of CBMCs was significantly reduced in patients with GDM compared to healthy controls. Furthermore, B2R expression on circulating CD34+ cells of CBMCs was inversely correlated with plasma 8-iso-PGF2α concentrations and positively correlated with plasma NO levels. BK treatment decreased EPC senescence and ROS generation. Furthermore, BK treatment of HG-exposed cells led to elevated P-Ser473AKT and eNOS protein expression compared with HG treatment alone. BK reduced hTERT translocation in HG-induced senescent EPCs. B2R siRNA, eNOS siRNA, and antagonist of the PI3K signalling pathway blocked the protective effects of BK. CONCLUSION: BK, acting through PI3K-AKT-eNOS signalling pathways, reduced hTERT translocation, increased the relative length of telomeres while reducing mtDNA copy number, and finally protected against EPC senescence induced by HG.


Subject(s)
Bradykinin/pharmacology , Cellular Senescence/drug effects , Endothelial Progenitor Cells/drug effects , Receptor, Bradykinin B2/metabolism , Case-Control Studies , Cells, Cultured , DNA, Mitochondrial/genetics , Diabetes, Gestational , Dinoprost/analogs & derivatives , Dinoprost/blood , Endothelial Progenitor Cells/cytology , Female , Fetal Blood , Gene Dosage , Glucose/pharmacology , Humans , Infant, Newborn , Nitric Oxide/blood , Nitric Oxide Synthase Type III/metabolism , Pregnancy , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Telomerase , Telomere
4.
Rev. bras. med. esporte ; 27(2): 201-206, Apr.-June 2021. tab, graf
Article in English | LILACS | ID: biblio-1280061

ABSTRACT

ABSTRACT Introduction: We applied three-dimensional gait analysis to assess the effects of enhanced active contraction of the transversus abdominis (EACTA) during walking. We sought to evaluate the effect of EACTA during walking in order to improve walking quality. Methods: Thirty college students were recruited and trained to perform EACTA during walking. We examined gait parameters under different conditions, including EACTA and habitual ACTA (natural walking with mild contraction of the feedforward mechanism of ACTA, HACTA) during walking using three-dimensional gait analysis. We compared differences in gait parameters under the two walking conditions using SPSS 16.0 statistical software. Results: The following gait parameters were significantly lower under EACTA conditions than under HACTA conditions (P < 0.05): stance phase, 59.151% ± 1.903% vs. 59.825% ± 1.495%; stride time, 1.104 s ± 0.080 s vs. 1.134 s ± 0.073 s:; stance time, 0.656 s ± 0.057 s vs. 0.678 s ± 0.053 s; and swing time, 0.447 s ± 0.028 s vs. 0.454 s ± 0.031 s, respectively. Gait parameters single support phase and mean velocity were significantly higher for EACTA than for HACTA conditions (both P < 0.05). Conclusions: Overall, the results revealed that EACTA during walking can improve gait. This method is simple, and EACTA training during walking to improve gait quality in daily life could provide a positive basis for people to strengthen the transverse abdominal muscle. Level of evidence III; Retrospective comparative study .


RESUMEN Introducción: Aplicamos el análisis tridimensional de la marcha para evaluar los efectos del aumento de la contracción activa del músculo transverso del abdomen (EACTA) durante la caminata. Buscamos evaluar el efecto del EACTA durante la caminata para mejorar su calidad. Métodos: Treinta estudiantes universitarios fueron reclutados y entrenados para realizar el EACTA durante la caminata. Examinamos los parámetros de la marcha en diferentes condiciones, incluyendo EACTA y ACTA habitual (caminata natural con leve contracción del mecanismo de feedforward del ACTA, HACTA) durante la caminata usando análisis tridimensional de la marcha. Comparamos las diferencias en los parámetros de la marcha en las dos condiciones de caminata en el software estadístico SPSS 16.0. Resultados: Los siguientes parámetros de marcha fueron significativamente más bajos en la condición EACTA que en condiciones HACTA (P <0,05): fase de apoyo 59,151 ± 1,903% vs 59,825 ± 1,495%, tiempo de zancada 1,104 s ± 0,080 s vs 1,134 s ± 0,073 s, tiempo de apoyo 0,656 s ± 0,057 s vs 0,678 s ± 0,053 s y tiempo de balance 0,447 s ± 0,028 s vs 0,454 s ± 0,031 s, respectivamente. Los parámetros de la marcha, fase de apoyo simple y velocidad promedio fueron significativamente mayores en el EACTA que en las condiciones HACTA (ambos P <0,05). Conclusiones: En general, los resultados revelaron que el EACTA durante la caminata puede mejorar la marcha. Este método es simple, y el entrenamiento del EACTA durante la caminata para mejorar la calidad de la marcha en la vida diaria puede ser una base positiva para el fortalecimiento del músculo transverso del abdomen. Nivel de evidencia III; Estudio retrospectivo comparativo .


RESUMO Introdução: Aplicamos a análise tridimensional da marcha para avaliar os efeitos do aumento da contração ativa do músculo transverso do abdome (EACTA) durante a caminhada. Procuramos avaliar o efeito do EACTA durante a caminhada para melhorar sua qualidade. Métodos: Trinta estudantes universitários foram recrutados e treinados para realizar o EACTA durante a caminhada. Examinamos os parâmetros da marcha em diferentes condições, incluindo EACTA e ACTA habitual (caminhada natural com leve contração do mecanismo de feedforward do ACTA, HACTA) durante a caminhada usando análise tridimensional da marcha. Comparamos as diferenças nos parâmetros da marcha nas duas condições de caminhada no software estatístico SPSS 16.0. Resultados: Os seguintes parâmetros da marcha foram significativamente mais baixos na condição EACTA do que em condições HACTA (P < 0,05): fase de apoio 59,151 ± 1,903% vs. 59,825 ± 1,495%, tempo de passada 1,104 s ± 0,080 s vs. 1,134 s ± 0,073 s, tempo de apoio 0,656 s ± 0,057 s vs. 0,678 s ± 0,053 s e tempo de balanço 0,447 s ± 0,028 s vs. 0,454 s ± 0,031 s, respectivamente. Os parâmetros da marcha fase de apoio simples e velocidade média foram significativamente maiores no EACTA do que nas condições HACTA (ambos P < 0,05). Conclusões: No geral, os resultados revelaram que o EACTA durante a caminhada pode melhorar a marcha. Esse método é simples, e o treinamento do EACTA durante a caminhada para melhorar a qualidade da marcha na vida diária pode ser uma base positiva para o fortalecimento do músculo transverso do abdome. Nível de evidência III; Estudo retrospectivo comparativo .


Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Abdominal Muscles/physiology , Gait , Muscle Contraction/physiology , Imaging, Three-Dimensional , Gait Analysis
5.
Trials ; 18(1): 297, 2017 06 28.
Article in English | MEDLINE | ID: mdl-28659162

ABSTRACT

BACKGROUND: Type-2 diabetes has become a major disease and is known to seriously impair people's health worldwide. Prediabetes includes impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and is the most critical period for preventing type-2 diabetes, as it can be identified and reversed. Studies in the past decade have indicated that acupuncture and Chinese herbal medicine may be beneficial for treating prediabetes. However, a randomized controlled trial (RCT) should be conducted to obtain more clinical evidence on this topic. METHODS/DESIGN: An RCT will be implemented in this study, using a72-week study period (24 weeks for the intervention and 48 weeks for follow-up). Participants will be recruited from the Fifth Affiliated Hospital of Guangzhou Medical University in China. Eighty participants will be randomized to the treatment group (acupuncture plus herbal medicine and health education) or the control group (health education only), 40 participants in each. People included in this study must have been diagnosed with prediabetes using Western medicine criteria. The endpoint indices include the incidence of diabetes mellitus and the reversion rate. The primary outcome is fasting plasma glucose (FPG) level, 2-h plasma glucose (2-hPG) level after a 75-g oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) level. Secondary outcomes include the following: Body Mass Index (BMI); hemorheology, including shear rates of whole-blood viscosity and plasma viscosity. Safety indices include hepatic (ALT, AST) and renal function (BUN, Cr) and records of adverse events, including diarrhoea, colds, pharyngitis, and sleep disorders. Quality control will be implemented, including quality control of the laboratory, researchers, participants, investigational drugs, data and documents, occurrence of bias, supervision, among others, according to uniform standard operating procedures (SOPs) which have been established by the Good Clinical Practice (GCP) office of the Fifth Affiliated Hospital of Guangzhou Medical University. DISCUSSION: The aim of this study is to evaluate the efficacy and safety of acupuncture paired with herbal medicine for the treatment of patients with prediabetes. TRIAL REGISTRATION: Chinese clinical trials register ChiCTR-INR-16008891 . Registered on 23 July 2016.


Subject(s)
Acupuncture Therapy , Drugs, Chinese Herbal/therapeutic use , Hypoglycemic Agents/therapeutic use , Prediabetic State/therapy , Acupuncture Therapy/adverse effects , Adolescent , Adult , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , China , Clinical Protocols , Combined Modality Therapy , Drugs, Chinese Herbal/adverse effects , Female , Glucose Tolerance Test , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/adverse effects , Male , Middle Aged , Patient Education as Topic , Prediabetic State/blood , Prediabetic State/diagnosis , Research Design , Risk Reduction Behavior , Time Factors , Treatment Outcome , Young Adult
6.
Zhen Ci Yan Jiu ; 39(6): 466-71, 2014 Dec.
Article in Chinese | MEDLINE | ID: mdl-25632571

ABSTRACT

OBJECTIVE: To observe the effect of acupuncture therapy on 14-3-3, Bcl-2 and Bax expression levels in the cerebral cortex in neonatal rats with hypoxic-ischemic brain damage(HIBD). METHODS: Timed pregnant Sprague-Dawley rat dams were delivered either vaginally (normal group), or by C-section (sham-operation group) or by C-section with 5 min of global anoxia (anoxia group), with 8 rats in each group. The rat pups of the anoxia group were randomly divided into model group and acupuncture group (n =8). Acupuncture stimulation of "Naosanzhen" "Niesanzhen" and "Zhisanzhen" acupoints was given begin- ning from the 14th day after birth, once daily for 7 consecutive days. All rat pups were killed by decapitation on day 21 after birth, and then 14-3-3, Bcl-2 and Bax immunoactivity (expression) in the cerebral cortex were detected by immunohistochemistry. RESULTS: In comparison with the normal group, the expression level of cerebral cortical 14-3-3 was significantly decreased, and that of Bax remarkably increased in the model group (P<0. 01, P<0. 05). Compared to the model group, cortical 14-3-3 and Bcl-2 expression levels were markedly up-regulated in the acupuncture group (P<0.01, P<0.05). Compared to the normal group, cortical 14-3-3 expression level was obviously lower, but Bax expression level significantly higher in the sham-operation group (P<0. 05, P<0. 01). No significant differences were found between the model and normal groups in the expression levels of Bcl-2, and between the acupuncture and model groups in the expression levels of Bax (P>0. 05). CONCLUSION: Acupuncture intervention can increase the expression of 14-3-3 and Bcl-2 in the cerebral cortex in HIBD rats.


Subject(s)
14-3-3 Proteins/analysis , Acupuncture Therapy , Cerebral Cortex/chemistry , Hypoxia-Ischemia, Brain/therapy , Animals , Female , Hypoxia-Ischemia, Brain/metabolism , Proto-Oncogene Proteins c-bcl-2/analysis , Rats , Rats, Sprague-Dawley , bcl-2-Associated X Protein/analysis
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