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Aim: To comprehensively evaluate the association and impact of nutritional status and immune function on the severity of pulmonary tuberculosis (PTB). Methods: This descriptive cross-sectional study involved 952 participants who were diagnosed with active PTB. Severe PTB involves three or more lung field infections based on chest radiography. Nutritional status was evaluated using various indicators, including body mass index (BMI), the nutritional risk screening score (NRS-2002), total protein (TP), prealbumin (PA), transferrin (TRF), and serum albumin (ALB) levels and the prognostic nutritional index (PNI). Immune dysfunction was defined as a CD4+ count <500 cells/µl or a CD4+/CD8+ ratio <1. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were also calculated. Multivariate logistic and generalized linear regression were used to assess the associations between nutritional status, immune function, the severity of PTB, and the number of infected lung fields, adjusting for age, sex, and diabetes. Mediation analysis was conducted to evaluate the extent to which immune function mediated the impact of nutritional status on the severity of PTB. Sensitivity analysis was performed to enhance the robustness of the results. Results: Compared to those in the general PTB group, patients in the severe PTB group tended to be older men with diabetes. Higher nutritional risk, higher proportion of immune dysfunction and lower lymphocyte counts were observed in the severe group. BMI and the PNI were found to be protective factors, while PLR was identified as a risk factor for disease severity. Immune dysfunction and the PLR are mediators of the relationship between nutritional status and PTB severity. When BMI, the PNI, and the PLR were combined with traditional clinical indicators, these parameters showed promising diagnostic value, and the AUC reached 0.701 (95% CI: 0.668-0.734). Conclusion: The findings suggest that nutritional status is significantly associated with the severity of PTB, and immune function mediates the effects of nutritional status on the severity of PTB. Maintaining adequate BMI, PNI levels, and immune function or reducing PLR levels helps reduce the risk of severe PTB.
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Estado Nutricional , Índice de Severidad de la Enfermedad , Tuberculosis Pulmonar , Humanos , Masculino , Femenino , Tuberculosis Pulmonar/inmunología , Persona de Mediana Edad , Estudios Transversales , Adulto , Anciano , Evaluación Nutricional , Neutrófilos/inmunología , Índice de Masa Corporal , Factores de RiesgoRESUMEN
BACKGROUND: Hypoxic-ischaemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although hypothermia therapy offers some neuroprotection, the recovery of neurological function is limited. Therefore, new synergistic therapies are necessary to improve the prognosis. Mesenchymal stem cell-based therapy is emerging as a promising treatment option for HIE. In this study, we studied the therapeutic efficacy of human placenta-derived mesenchymal stem cells (PD-MSCs) in the HIE rat model and analyzed the underlying therapeutic mechanisms. METHODS: Rats were divided into 6 groups (n = 9 for each) as follows: control, HIE model, HIE + normal saline, and HIE + PD-MSC transplantation at days 7, 14 and 28 postpartum. Following PD-MSC transplantation, neurological behavior was evaluated using rotarod tests, traction tests, and the Morris water maze test. The degree of brain tissue damage was assessed by histological examination and Nissl staining. Expression levels of apoptosis-related proteins and inflammatory factors were quantified by Western blotting and enzyme-linked immunosorbent assays. Immunofluorescence was used to investigate the ability of PD-MSCs to repair the morphology and function of hippocampal neurons with hypoxic-ischaemic (HI) injury. RESULTS: PD-MSC transplantation enhanced motor coordination and muscle strength in HIE rats. This treatment also improved spatial memory ability by repairing pathological damage and preventing the loss of neurons in the cerebral cortex. The most effective treatment was observed in the HIE + PD-MSC transplantation at day 7 group. Expression levels of microtubule-associated protein-2 (MAP-2), B-cell lymphoma-2 (BCL-2), interleukin (IL)-10, and transforming growth factor (TGF -ß1) were significantly higher in the HIE + PD-MSC treatment groups compared to the HIE group, whereas the levels of BCL-2-associated X protein (BAX), BCL-2-associated agonist of cell death (BAD), IL-1ß and tumour necrosis factor α (TNF-α) were significantly lower. CONCLUSIONS: We demonstrated that intravenous injection of PD-MSC at 7, 14 and 28 days after intrauterine HI damage in a rat model could improve learning, memory, and motor function, possibly by inhibiting apoptosis and inflammatory damage. These findings indicate that autologous PD-MSC therapy could have potential application for the treatment of HIE.
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Apoptosis , Hipoxia-Isquemia Encefálica , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Placenta , Ratas Sprague-Dawley , Animales , Femenino , Trasplante de Células Madre Mesenquimatosas/métodos , Embarazo , Hipoxia-Isquemia Encefálica/terapia , Humanos , Placenta/citología , Células Madre Mesenquimatosas/citología , Ratas , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Inflamación/terapia , Neuronas/metabolismo , MasculinoRESUMEN
Long term exposure to silica particles leads to various diseases, among which silicosis is of great concern. Silicosis is an interstitial lung disease caused by inhalation of silica particles in production environments. However, the mechanisms underlying silicosis remains unclear. Our previous studies revealed that progranulin (Pgrn) promoted the expression of pro-inflammatory factors in alveolar macrophages treated with silica particles and the secretion of extracellular matrix of pulmonary fibroblasts. Nevertheless, the role of Pgrn in silica particles-induced silicosis in vivo was unknown. This study found that silica particles increased Pgrn expression in silicosis patients. Pgrn deficiency reduced lung inflammation and fibrosis in silica particles-induced silicosis mouse models. Subsequently, based on transcriptional sequencing and interleukin (Il) -6 knockout mouse models, results demonstrated that Pgrn deficiency might decrease silicosis inflammation by reducing the production of Il-6, thereby modulating pulmonary fibrosis in the early stage of silicosis mouse models. Furthermore, another mechanism through which Pgrn deficiency reduced fibrosis in silicosis mouse models was the regulation of the transforming growth factor (Tgf) -ß1/Smad signaling pathway. Conclusively, Pgrn contributed to silicosis inflammation and fibrosis induced by silica particles, indicating that Pgrn could be a promising therapeutic target.
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Neumonía , Silicosis , Animales , Humanos , Ratones , Fibrosis , Inflamación , Interleucina-6 , Progranulinas/uso terapéutico , Dióxido de Silicio , Silicosis/tratamiento farmacológico , Silicosis/etiología , Silicosis/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/uso terapéuticoRESUMEN
Silicosis is a severe worldwide occupational hazard, characterized with lung tissue inflammation and irreversible fibrosis caused by crystalline silicon dioxide. As the most common and abundant internal modification of messenger RNAs or noncoding RNAs, N6-methyladenosine (m6A) methylation is dysregulated in the chromic period of silicosis. However, whether m6A modification is involved in the early phase of silica-induced pulmonary inflammation and fibrosis and its specific effector cells remains unknown. In this study, we established a pulmonary inflammation and fibrosis mouse model by silica particles on day 7 and day 28. Then, we examined the global m6A modification level by m6A dot blot and m6A RNA methylation quantification kits. The key m6A regulatory factors were analyzed by RTqPCR, Western blot, and immunohistochemistry (IHC) in normal and silicosis mice. The results showed that the global m6A modification level was upregulated in silicosis lung tissues with the demethylase FTO suppression after silica exposure for 7 days and 28 days. METTL3, METTL14, ALKBH5, and other m6A readers had no obvious differences between the control and silicosis groups. Then, single-cell sequencing analysis revealed that thirteen kinds of cells were recognized in silicosis lung tissues, and the mRNA expression of FTO was downregulated in epithelial cells, endothelial cells, fibroblasts, and monocytes. These results were further confirmed in mouse lung epithelial cells (MLE-12) exposed to silica and in the peripheral blood mononuclear cells of silicosis patients. In conclusion, the high level of global m6A modification in the early stage of silicosis is induced by the downregulation of the demethylase FTO, which may provide a novel target for the diagnosis and treatment of silicosis.
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Neumonía , Fibrosis Pulmonar , Silicosis , Animales , Humanos , Ratones , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Células Endoteliales/metabolismo , Leucocitos Mononucleares/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , Metilación de ARN , Dióxido de Silicio/toxicidad , Dióxido de Silicio/metabolismo , Silicosis/genéticaRESUMEN
Fibroblast growth factor receptor 1 (FGFR1) is a core component of the FGFs/FGFR pathway that activates multiple signalling pathways, including ERK1/2, PI3K/AKT, PLCγ, and NF-κB. Aberrant expression of FGFR1 due to gene amplification, chromosome rearrangement, point mutation, and epigenetic deregulations, have been reported in various cancers. FGFR1 overexpression has also been reported in prostate cancer (PCa), but the underlining mechanisms are not clear. Here we report a novel circular RNA, circFGFR1int2, derived from intron 2 of FGFR1 gene, which is overexpressed in PCa and associated with tumor progression. Importantly, we show that circFGFR1int2 facilitates FGFR1 transcription by recruiting transcription activators P65/FUS and by interacting with FGFR1 promoter. Moreover, we show that circFGFR1int2 suppresses post-transcriptional inhibitory effects of miR-4687-5p on FGFR1 mRNA. These mechanisms synergistically promote PCa cell growth, migration, and invasion. Overexpression of circFGFR1int2 is significantly correlated with higher tumor grade, Gleason score, and PSA level, and is a significant unfavorable prognosticator for CRPC-free survival (CFS) (RR = 3.277, 95% confidence interval: 1.192-9.009; P = 0.021). These findings unravelled novel mechanisms controlling FGFR1 gene expression by intronic circRNA and its potential clinicopathological utility as a diagnostic or therapeutic target.
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MicroARNs , Neoplasias de la Próstata , Masculino , Humanos , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , ARN Circular/genética , Intrones/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/patología , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteína FUS de Unión a ARN/genética , Proteína FUS de Unión a ARN/metabolismoRESUMEN
The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is overexpressed in a variety of malignancies including prostate cancer (PCa) and may play important roles in tumor progression. Gene copy number gains, enhanced transcription, and a few circRNAs have been reported to upregulate EZH2. It was not known whether EZH2 itself generates circRNAs that promote its own expression. We here report the identification of circEZH2E2/E3 that is derived from exons 2 and 3 of the EZH2 gene and overexpressed in PCa. We show that circEZH2E2/E3 functions as a dual inhibitor for both miR363 and miR708 that target the EZH2 3'UTR and CDS, respectively, resulting in the upregulation of EZH2 expression and hence the downregulation of EZH2-repressed genes (e.g., CDH1 and DAB2IP), and enhancement of PCa cell proliferation, migration, invasion, and xenograft PCa growth. Overexpression of circEZH2E2/E3 is significantly correlated with higher tumor grade, tumor progression, and unfavorable progression-free and disease-specific survival in PCa patients. These findings show a novel autoenhancing EZH2-circEZH2E2/E3 -miR363/miR708-EZH2 regulatory loop, by which circEZH2E2/E3 plays important roles in PCa tumorigenesis and progression by upregulating EZH2, and may have potential diagnostic, prognostic, and therapeutic uses in PCa management.
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MicroARNs , Neoplasias de la Próstata , Masculino , Humanos , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Complejo Represivo Polycomb 2/genética , Complejo Represivo Polycomb 2/metabolismo , ARN Circular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata/patología , Proliferación Celular/genética , Proteínas Activadoras de ras GTPasa/metabolismo , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
BACKGROUND: The homeodomain-containing transcription factor NANOG is overexpressed in prostate adenocarcinoma (PCa) and predicts poor prognosis. The SOX family transcription factor SOX9, as well as the transcription co-activator HMGB3 of the HMGB family, are also overexpressed and may play pivotal roles in PCa. However, it is unknown whether SOX9 and HMGB3 interact with each other, or if they regulate NANOG gene transcription. METHODS: We identified potential SOX9 responsive elements in NANOG promoter, and investigated if SOX9 regulated NANOG transcription in co-operation with HMGB3 by experimental analysis of potential SOX9 binding sites in NANOG promoter, reporter gene transcription assays with or without interference or artificial overexpression of SOX9 and/or HMGB3, and protein-binding assays of SOX9-HMGB3 interaction. Clinicopathologic and prognostic significance of SOX9-HMGB3 overexpression in PCa was analyzed. RESULTS: SOX9 activated NANOG gene transcription by preferentially binding to a highly conserved consensus cis-regulatory element (-573 to -568) in NANOG promoter, and promoted the expression of NANOG downstream oncogenic genes. Importantly, HMGB3 functioned as a partner of SOX9 to co-operatively enhance transactivation of NANOG by interacting with SOX9, predominantly via the HMG Box A domain of HMGB3. Overexpression of SOX9 and/or HMGB3 enhanced PCa cell survival and cell migration and were significantly associated with PCa progression. Notably, Cox proportional regression analysis showed that co-overexpression of both SOX9 and HMGB3 was an independent unfavorable prognosticator for both CRPC-free survival (relative risk [RR] = 3.779ï¼95% confidence interval [CI]: 1.159-12.322, p = 0.028) and overall survival (RR = 3.615ï¼95% CI: 1.101-11.876, p = 0.034). CONCLUSIONS: These findings showed a novel SOX9/HMGB3/NANOG regulatory mechanism, deregulation of which played important roles in PCa progression.
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Proteína HMGB3 , Proteína Homeótica Nanog , Neoplasias de la Próstata , Factor de Transcripción SOX9 , Humanos , Masculino , Regulación de la Expresión Génica , Proteína HMGB3/genética , Proteína HMGB3/metabolismo , Proteína Homeótica Nanog/genética , Proteína Homeótica Nanog/metabolismo , Procesos Neoplásicos , Próstata/metabolismo , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: Thyroid function is widely considered a lipid metabolism regulator. However, studies on lipid metabolism in pregnant women with low free thyroxine (FT4) levels are limited and inconclusive. Furthermore, the association between maternal FT4 deficiency and adverse lipid metabolic parameters is unknown. Therefore, we aimed to investigate this association and the effects of levothyroxine (L-T4) treatment on these metabolic indicators. METHODS: This retrospective study included 164 patients with isolated hypothyroidism (IH) (FT4 levels below the 5th percentile with normal thyroid stimulating hormone levels according to the gestational-specific reference range) and 407 euthyroidism patients (control group who had regular antenatal examinations at Zhejiang Provincial People's Hospital, Hangzhou, China) between January 1, 2019, and December 31, 2020. Patients with IH were divided into levothyroxine (L-treatment group, n = 77) and dietary iodine supplement treatment groups (dietary treatment group, n=87) according to the hospital's treatment policy and clinical experience. The intervention lasted for at least 8 weeks. Metabolic indicators, including thyroid function and lipid parameters, were collected at least twice before and after the intervention. Other data collected included maternal age, history of abortion, prepregnancy BMI, and gestational weight gain (Fig. 1). RESULTS: Compared with the control group, Patients with IH had a higher degree of dyslipidemia, reflected in elevated total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) levels. In IH patients, an inverse correlation was found between FT4 and TG levels, which remained after adjusting for prepregnancy BMI. The L-treatment group demonstrated a significantly slower rate of hypercholesterolemia progression during pregnancy than the dietary treatment group. In addition, there was a relationship between the therapeutic effect and the degree of disease, with the main factors being FT4, TSH and TG levels prior to starting treatment. CONCLUSIONS: Low FT4 levels were associated with elevated blood lipid levels. Serum FT4 and lipid levels in patients could be improved by medical intervention.
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Hipotiroidismo , Tiroxina , Humanos , Femenino , Embarazo , Tiroxina/uso terapéutico , Estudios Retrospectivos , Tirotropina/uso terapéutico , Hormonas Tiroideas , Hipotiroidismo/tratamiento farmacológico , Lípidos , LDL-ColesterolRESUMEN
Objective: To identify the active chemical in Wenshen Huatan Quyu Decotion (WHQD) and to explore its possible network interactions with the polycystic ovary syndrome (PCOS). Methods: The Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP) and the Bioinformatics Analysis Tool for Molecular Mechanisms in Chinese Medicine (BATMAN-TCM) were used to decompose compound formulations, detect active chemicals and their corresponding target genes, and then convert them into UniProt gene symbols. Meanwhile, PCOS-related target genes were collected from GeneCards to construct a protein-protein interaction (PPI) network, which was further analyzed by STRING online database. Gene Ontology (GO) functional analysis was also performed afterwards to construct the component-target gene-disease network to visualize the correlation between WHQD and PCOS. We then performed an in silico molecular docking study to validate the predicted relationships. Results: WHQD consists of 14 single drugs containing a total of 67 chemical components. 216 genes were predicted as possible targets. 123 of the 216 target genes overlapped with PCOS. GO annotation analysis revealed that 1968 genes were associated with biological processes, 145 with molecular functions, and 71 with cellular components. KEGG analysis revealed 146 pathways involved PPI, and chemical-target gene-disease networks suggest that PGR, AR, ADRB2, IL-6, MAPK1/8, ESR1/2, CHRM3, RXRA, PPARG, BCL2/BAX, GABRA1, and NR3C2 may be key genes for the pharmacological effects of WHQD on PCOS. Molecular docking analysis confirmed that hydrogen bonding was the main interaction between WHQD and its targets. Conclusion: WHQD exerts its pharmacological effects by improving insulin sensitivity, subfertility, and hormonal imbalance, increasing ovulation rates, which in turn may increase pregnancy rates in patients with significant efficacy.
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Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel, which is involved in the endogenous stress adaptation mechanism for protection of the heart as well as the occurrence and development of some heart diseases. Although the effect of activation of the TRPV1 channel on different types of non-neural cells in the heart remains unclear, most data show that stimulation of sensory nerves expressing TRPV1 or stimulation/overexpression of the TRPV1 channel has a beneficial role in heart disease. Some studies have proven that TRPV1 has an important relationship with pathological myocardial hypertrophy, but the specific mechanism and effect are not clear. In order to help researchers better understand the relationship between TRPV1 and pathological myocardial hypertrophy, this paper aims to summarize the effect of TRPV1 and the related mechanism in the occurrence and development of pathological myocardial hypertrophy from the following three points of view: 1) role of TRPV1 in alleviation of pathological myocardial hypertrophy; 2) role of TRPV1 in aggravation of pathological myocardial hypertrophy; and 3) the point of view of our team of researchers. It is expected that new therapies can provide potential targets for pathological myocardial hypertrophy.
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PURPOSE: To evaluate the efficacy of intravitreal conbercept injections in patients with treatment-resistant neovascular age-related macular degeneration (nvAMD). METHODS: Retrospective review of patients with resistance (persistent exudation) to ranibizumab (0.5 mg) that were switched to treatment with 3 monthly intravitreal injections of conbercept (0.5 mg), followed by dosing on an as-needed basis. The demographic data, visual acuities, central retinal thickness (CRT), and the maximum pigment epithelial detachment (PED) height were reviewed. RESULTS: Outcomes observed in 34 eyes from 26 patients with a mean of 7.68 (range 6-14) previous ranibizumab injections were compiled. Twelve months after switching to conbercept, there were significant reductions of CRT (402.59 ± 163.85 vs. 473.18 ± 164.84 µm, p = 0.002) and maximum PED height (218.59 ± 106.89 vs. 295.32 ± 179.80 µm, p = 0.006) compared with the baseline. No statistical change in visual acuity logarithm of the minimal angle of resolution occurred after 12 months (0.68 ± 0.48 vs. 0.78 ± 0.63 letters, p = 0.17) despite 27 of 34 eyes (79.41%) remaining stable or having improvement visual acuity. CONCLUSIONS: Intravitreal injections of conbercept appear to be beneficial in patients with nvAMD who exhibit persistent fluid despite previous treatment with ranibizumab.
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Inhibidores de la Angiogénesis/administración & dosificación , Neovascularización Coroidal/tratamiento farmacológico , Degeneración Macular/tratamiento farmacológico , Proteínas Recombinantes de Fusión/administración & dosificación , Anciano , Anciano de 80 o más Años , Neovascularización Coroidal/fisiopatología , Femenino , Humanos , Inyecciones Intravítreas , Degeneración Macular/fisiopatología , Masculino , Persona de Mediana Edad , Ranibizumab/uso terapéutico , Retina/patología , Estudios Retrospectivos , Agudeza Visual/fisiologíaRESUMEN
OBJECTIVE: To explore the role of HIF1α gene in prostate cancer cell line DU145 by knocking it out with a novel gene-editing tool CRISPR/cas9 system. METHODS: A CRISPR/cas9 system with two sgRNAs targeting exon 1 of the HIF1α gene was constructed for the knock out experiment. CCK8 assay and transwell experiment were carried out to assess the effect of the knock out on the proliferation, migration and invasiveness of DU145 cells. RESULTS: The efficiency of gene-targeting was measured through a T7E1 assaying and sequence analysis, which confirmed that the partial knock out was successful and has led to a significant decrease in the expression of HIF1α and inhibition of cell proliferation, migration and invasiveness. CONCLUSION: A CRISPR/cas9 system for the knock out of HIF1α has been successfully constructed, which could inhibit the proliferation and migration of DU145 cells. The system can facilitate further studies of the HIF1α gene and its roles in tumorigenesis.
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Sistemas CRISPR-Cas/genética , Edición Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias de la Próstata/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Masculino , Invasividad NeoplásicaRESUMEN
BACKGROUND: The ERK signaling pathway is frequently deregulated in tumorigenesis, mostly by classical mechanisms such as gene mutation of its components (eg, RAS and RAF). However, whether and how multiple key components of ERK pathway are regulated by microRNAs are not clear. METHODS: We firstly predicted post-transcriptional regulation of multiple key components of the ERK signaling pathway by miR181c through bioinformatics analysis, and then confirmed the post-transcriptional regulation by dual luciferase reporter gene assays and Western blot analysis. The biological effects of miR181c on prostate cancer cell proliferation, apoptosis, migration, and invasion were measured by CCK-8 assay, flow cytometry, wound scratch assay, transwell cell migration, and invasion assays. RESULTS: miR181c post-transcriptionally regulated multiple key members of the ERK signaling pathway, including extracellular signal-regulated kinase 2 (ERK2), ribosomal S6 kinase 2 (RSK2), serum response factor (SRF), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Ectopic expression of miR181c mimics effectively suppressed prostate cancer cell proliferation, migration, and invasion, but promoted cell apoptosis. Furthermore, miR181c treatment combined with the multi-kinase inhibitor sorafenib significantly enhanced these anti-tumor effects. CONCLUSIONS: Downregulation of miR181c results in deregulated ERK signaling and promotes prostate cancer cell growth and metastasis.
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Sistema de Señalización de MAP Quinasas , MicroARNs/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Procesos de Crecimiento Celular/fisiología , Línea Celular Tumoral , Regulación hacia Abajo , Humanos , Masculino , MicroARNs/genética , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Invasividad Neoplásica , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/patología , Proteínas Quinasas S6 Ribosómicas 90-kDa/antagonistas & inhibidores , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Factor de Respuesta Sérica/antagonistas & inhibidores , Factor de Respuesta Sérica/metabolismo , Sorafenib/farmacologíaRESUMEN
OBJECTIVE: To improve evidence-based care in the management of tuberculosis, we retrospectively analyzed the bacterial types and drug sensitivity test results of mycobacteria in Guangzhou over the past twelve years (from July 1998 to March 2010). METHODS: Over these twelve years, a total of 14 095 mycobacterial strains isolated from different samples were subjected to type identification and drug sensitivity tests according to the Standard Protocols of Laboratory Diagnostics for Tuberculosis by the Chinese Antituberculosis Association. Chi-square test was performed for statistical analyses for comparisons between groups. RESULTS: Of 14 095 strains of mycobacteria isolated, 10 844 strains (76.84%) were MTB, and 3251 strains (23.16%) were non-tuberculosis mycobacteria (NTM). Compared with the result of the fourth national survey of tuberculosis epidemiology, which showed 11.1% of NTM, the one of our study was significantly different (χ(2) = 69.79, P < 0.001). Drug sensitivity tests of MTB showed tolerance rates of 28.99% (2729/9413), 21.75% (2047/9413), 17.45% (1643/9413) and 11.53% (1085/9413) against isoniazid, rifampin, streptomycin and ethambutol, respectively. CONCLUSION: An increasing trend was observed in MTB drug tolerance against streptomycin, rifampin and isoniazid, whereas more and more NTM strains were isolated in recent years. These findings are worthy of note for clinicians.
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Farmacorresistencia Bacteriana , Mycobacterium/efectos de los fármacos , Mycobacterium/aislamiento & purificación , Tuberculosis/microbiología , Antituberculosos/farmacología , Técnicas de Tipificación Bacteriana , China/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Mycobacterium/clasificación , Tuberculosis/epidemiologíaRESUMEN
The aim of this study was to characterize 160 clinical Mycobacterium tuberculosis isolates from Guangdong with respect to their drug susceptibility phenotypes to three common anti-tuberculosis drugs, isoniazid (INH), rifampin (RIF) and streptomycin (SM), and with respect to genetic mutations in the most commonly corresponding resistance genes (katG, rpoB and rpsL). The drug susceptibility profiles were evaluated by the absolute concentration method, and genetic mutations in the corresponding resistance genes were identified by DNA sequencing. Among these isolates, 33.1% (53/160) were drug-resistant. The percentages of isolates resistant to INH, RIF and SM were 21.9% (35/160), 16.9% (27/160) and 15.6% (25/160), respectively. Twenty-five of 35 (71%) INH-resistant isolates, 22 of 27 (81.5%) RIF-resistant isolates and 19 of 25 (76%) SM-resistant isolates were found to have mutations in the analyzed katG, rpoB and rpsL gene fragments. The most frequent mutation patterns for the three drugs were as follows: INH, Ser315Thr (68.6%) in katG; RIF, Ser531Leu (55.6%) in rpoB; and SM, Lys43Arg (72%) in rpsL. These findings provide useful data on the mutation types of drug-resistant genes in M. tuberculosis isolates from Guangdong province in China.
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Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Proteínas Bacterianas/genética , Catalasa/genética , China , ADN Bacteriano/química , ADN Bacteriano/genética , ARN Polimerasas Dirigidas por ADN , Humanos , Isoniazida/farmacología , Pruebas de Sensibilidad Microbiana , Mutación Missense , Mycobacterium tuberculosis/genética , Proteínas Ribosómicas/genética , Rifampin/farmacología , Análisis de Secuencia de ADN , Estreptomicina/farmacologíaRESUMEN
Mycobacterium tuberculosis and Mycobacterium bovis are pathogenic bacterial species in the genus Mycobacterium and the causative agents of most cases of tuberculosis (TB). Detection of M. tuberculosis and M. bovis using conventional culture- and biochemical-based assays is time-consuming and laborious. Therefore, a simple and sensitive method for rapid detection has been anxiously awaited. In the present study, a visual loop-mediated isothermal amplification (LAMP) assay was designed from the rimM (encoding 16S rRNA-processing protein) gene sequence and used to rapidly detect M. tuberculosis and M. bovis from clinical samples in South China. The visual LAMP reaction was performed by adding calcein and manganous ion, allowing the results to be read by simple visual observation of color change in a closed-tube system, and which takes less than 1 h at 65 degrees C. The assay correctly identified 84 M. tuberculosis isolates, 3 M. bovis strains and 1 M. bovis BCG samples, but did not detect 51 non-tuberculous mycobacteria (NTM) isolates and 8 other bacterial species. Sensitivity of this assay for detection of genomic DNA was 1 pg. Specific amplification was confirmed by the ladder-like pattern of gel electrophoresis and restriction enzyme HhaI digestion. The assay successfully detected M. tuberculosis and M. bovis not only in pure bacterial culture but also in clinical samples of sputum, pleural fluid and blood. The speed, specificity, sensitivity of the rimM LAMP, the lack of a need for expensive equipment, and the visual readout show great potential for clinical detection of M. tuberculosis and M. bovis.
Asunto(s)
Mycobacterium bovis/aislamiento & purificación , Mycobacterium tuberculosis/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Tuberculosis/diagnóstico , Sangre/microbiología , China , Color , Femenino , Fluoresceínas/metabolismo , Calor , Humanos , Masculino , Manganeso/metabolismo , Derrame Pleural/microbiología , Proteínas Ribosómicas/genética , Sensibilidad y Especificidad , Esputo/microbiología , Factores de TiempoRESUMEN
OBJECTIVE: To explore the effects of systemic glucocorticoid treatment on tuberculous pleural effusion. METHODS: Ninety Wistar rats were intrapleurally injected with 0.03 mg of standard human Mycobacterium tuberculosis to establish models of tuberculous pleural effusions and then were randomly divided into 2 equal groups both without anti-tuberculosis treatment: glucocorticoids group (GG) undergoing intramuscular injection of 0.3 mg triamcinolone acetonide in the right thigh 24 h after intrapleural injection, and control group (CG) received nothing as control. 8, 24, 32, and 48 hours, and 3, 5, 7, 10, and 15 days after intramuscular injection 5 rats from each group were killed. The thorax was opened, the amount of pleural effusion (PE) was recorded, and the pleural cavity, histopathology of pleura and lung parenchyma were examined. The white blood cell (WBC) count and differential leukocyte count, and levels of total protein (TP), glucose (GLU), and lactic dehydrogenase (LDH) in the PE were determined. Bioassays were used to detect the PE levels of soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta1 (TGF-beta1), and interferon gamma (IFN-gamma). RESULTS: The PE volumes of GG 8 - 48 h after the intramuscular injection were significantly lower than those of CG (P < 0.05, P < 0.01), and PE completely disappeared on day 3. The WBC in PE 24 - 48 h after and the percentages of neutrophils 8 - 48 h after the intramuscular injection of GG were all significant lower than those of CG (all P < 0.01). The TP levels 32 and 48 h after the intramuscular injection of GG were both significantly higher than those of CG (both P < 0.01). The LDH level of GG within 24 h after the intramuscular injection was significantly lower than that of CG (P < 0.01). Both the sICAM-1 and TGF-beta1 levels of GG were higher 8 h after the intramuscular injection, but lower 48 h after the intramuscular injection than those of CG (both P < 0.01). The IFN-gamma levels 8 - 48 h after the intramuscular injection of GG were all higher than those of CC (all P < 0.01). The IFN-gamma/TGF-beta1 ratios at different time points of GG were all higher than those of CG, and there were significant differences in those 8 - 48 h after the intramuscular injection between these 2 groups (all P < 0.01). Pathologically, the mean thickness of pleura in GG was significantly less than that in CG. Congestion and edema in subpleural and pulmonary interstitium were less in GG than in CG. CONCLUSION: Early use of glucocorticoids helps reduce the inflammatory response in pleural cavity in tuberculous pleurisy accelerate the absorption of pleural effusion and decrease the thickness of pleura.