RESUMEN
INTRODUCTION/AIMS: Previous studies have suggested that treatments targeting the neuromuscular junction (NMJ) may play a role in the treatment of amyotrophic lateral sclerosis (ALS). However, factors impacting repetitive nerve stimulation (RNS), a technique to evaluate NMJ function, have yet to be fully elucidated. We aimed to identify independent factors contributing to the decremental response of the accessory nerve and evaluated its value in ALS clinical practice. METHODS: A total of 626 patients who were diagnosed with ALS and underwent 3 Hz RNS tests on the accessory nerve were enrolled. Data on their clinical and electrophysiological indicators were divided into a training set (collected from June 2016 to December 2022) and a test set (collected from January to August 2023). Stepwise regression was used in independent variable selection and model building. RESULTS: Forty-two percent of patients had a decrement larger than 10% and 24% had a decrement larger than 15%. Onset age, sex, onset site, forced vital capacity (FVC) and motor unit potential (MUP) duration were independent factors contributing to the results of the RNS test. MUP duration had the greatest impact on decremental response, followed by FVC and onset age. The decremental response in females was larger than in males. Upper limb onset was found to contribute more to the decrement than lower limb or bulbar onset. DISCUSSION: In patients with ALS, NMJ safety factor is reduced during re-innervation. Decremental response is affected by multiple factors, which needs to be considered in clinical trials targeting the NMJ in these patients.
Asunto(s)
Esclerosis Amiotrófica Lateral , Humanos , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Estimulación Eléctrica/métodos , Unión Neuromuscular/fisiopatología , Electromiografía/métodosRESUMEN
PURPOSE: Chronic Obstructive Pulmonary Disease (COPD) is regarded as an accelerated aging disease. Aging-related genes in COPD are still poorly understood. METHOD: Data set GSE76925 was obtained from the Gene Expression Omnibus (GEO) database. The "limma" package identified the differentially expressed genes. The weighted gene co-expression network analysis (WGCNA) constructes co-expression modules and detect COPD-related modules. The least absolute shrinkage and selection operator (LASSO) and the support vector machine recursive feature elimination (SVM-RFE) algorithms were chosen to identify the hub genes and the diagnostic ability. Three external datasets were used to identify differences in the expression of hub genes. Real-time reverse transcription polymerase chain reaction (RT-qPCR) was used to verify the expression of hub genes. RESULT: We identified 15 differentially expressed genes associated with aging (ARDEGs). The SVM-RFE and LASSO algorithms pinpointed four potential diagnostic biomarkers. Analysis of external datasets confirmed significant differences in PIK3R1 expression. RT-qPCR results indicated decreased expression of hub genes. The ROC curve demonstrated that PIK3R1 exhibited strong diagnostic capability for COPD. CONCLUSION: We identified 15 differentially expressed genes associated with aging. Among them, PIK3R1 showed differences in external data sets and RT-qPCR results. Therefore, PIK3R1 may play an essential role in regulating aging involved in COPD.
Asunto(s)
Envejecimiento , Enfermedad Pulmonar Obstructiva Crónica , Máquina de Vectores de Soporte , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Envejecimiento/genética , Perfilación de la Expresión Génica , Fosfatidilinositol 3-Quinasa Clase Ia/genética , Algoritmos , Bases de Datos Genéticas , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Biomarcadores/metabolismo , Redes Reguladoras de GenesRESUMEN
Urolithiasis is one of the most prevalent benign urological disorders globally with a high incidence rate. Male Sprague-Dawley rats were chemically induced to have urolithiasis and treated with triptonide and the standard antiurolithic drug cystone. Kidney weight was measured to detect calculi formation, and urinary parameters such as pH, 24-h urine volume, and protein content were measured to analyze the urolithiasis induction in rats. The inorganic ions, organic solutes, antioxidant levels, and inflammatory cytokines were measured in the experimental rats. Triptonide treatment significantly modulated the urinary pH, decreased the protein concentration, and increased the urinary outflow in urolithiasis induced rats. It also significantly decreased the urinary excretion of calcium and phosphorous and increased the excretion of magnesium, potassium, sodium, creatinine, and uric acid. SOD, CAT, and GPx levels were increased in triptonide-treated rats, and it significantly reduced the MDA levels. Triptonide treatment also decreased the levels of inflammatory cytokines and prevented the renal tissue from inflammation. To conclude, our results prove that triptonide significantly prevents calculi formation and protects renal tissue from urolithiasis-induced damage in rats. Further studies may prove triptonide a potent alternative to currently available antiurolithic drugs.
RESUMEN
BACKGROUND: Previous studies have assessed the association between antidiabetic drugs and stroke risk, but the results are inconsistent. Mendelian randomization (MR) was used to assess effects of antidiabetic drugs on stroke risk. METHODS: We selected blood glucose-lowering variants in genes encoding antidiabetic drugs targets from genome-wide association studies (GWAS). A two-sample MR and Colocalization analyses were applied to examine associations between antidiabetic drugs and the risk of stroke. For antidiabetic agents that had effect on stroke risk, an independent blood glucose GWAS summary data was used for further verification. RESULTS: Genetic proxies for sulfonylureas targets were associated with reduced risk of any stroke (OR=0.062, 95% CI 0.013-0.295, P=4.65×10ï¼4) and any ischemic stroke (OR=0.055, 95% CI 0.010-0.289, P=6.25×10ï¼4), but not with intracranial hemorrhage. Colocalization supported shared casual variants for blood glucose with any stroke and any ischemic stroke within the encoding genes for sulfonylureas targets (KCNJ11 and ABCC8) (posterior probability>0.7). Furthermore, genetic variants in the targets of insulin/insulin analogues, glucagon-like peptide-1 analogues, thiazolidinediones, and metformin were not associated with the risk of any stroke, any ischemic stroke and intracranial hemorrhage. The association was consistent in the analysis of sulfonylureas with stroke risk using an independent blood glucose GWAS summary data. CONCLUSIONS: Our findings showed that genetic proxies for sulfonylureas targets by lowering blood glucose were associated with a lower risk of any stroke and any ischemic stroke. The study might be of great significance to guide the selection of glucose-lowering drugs in individuals at high risk of stroke.
Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Glucemia , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Compuestos de Sulfonilurea/farmacología , Compuestos de Sulfonilurea/uso terapéutico , Insulina , Accidente Cerebrovascular/genética , Hemorragias IntracranealesRESUMEN
BACKGROUND: Currently, miRNAs are involved in the development of amyotrophic lateral sclerosis (ALS), and identifying circulating miRNAs that are causally associated with ALS risk as biomarkers is imperative. METHODS: We performed a two-sample Mendelian randomization study to evaluate the causal relationship between miRNAs and ALS. Our analysis was conducted using summary statistics from miRNA expression quantitative loci (eQTL) data of the Framingham Heart Study and ALS genome-wide association studies data. Another independent miRNA data was used to further validate. RESULTS: We identified eight unique miRNAs that were causally associated with ALS risk. Using expression data of miRNAs from an independent study, we validated three high-confidence miRNAs, namely hsa-miR-27b-3p, hsa-miR-139-5p, and hsa-miR-152-3p, which might have a potential causal effect on ALS risk. CONCLUSION: We suggested that higher levels of hsa-miR-27b-3p and hsa-miR-139-5p had protective effects on ALS, whereas higher levels of hsa-miR-152-3p might act as a risk factor for ALS. The analytical framework presented in this study helps to understand the role of miRNAs in the development of ALS and to identify the biomarkers for ALS risk.
Asunto(s)
Esclerosis Amiotrófica Lateral , MicroARN Circulante , MicroARNs , Humanos , Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/genética , Estudio de Asociación del Genoma Completo , MicroARNs/genética , MicroARNs/metabolismo , MicroARN Circulante/genética , BiomarcadoresRESUMEN
Dansyl chloride fluorophore exhibits typical aggregation induced fluorescence emission behavior in acetone/water solution. To realize the integration of detective and adsorptive functions, dansyl chloride is covalently immobilized on cellulose substrate to fabricate an efficient adsorbent for mercury ions in water. The as-prepared material exhibits excellent fluorescence sensing performance exclusively for Hg (II) with the presence of other metal ions. A sensitive and selective fluorescence quenching across the concentration range of 0.1-8.0 mg/L is observed with a detection limit of 8.33 × 10-9 M as a result of the inhibition of aggregation induced emission caused by the coordination between adsorbent and Hg (II). Besides, the adsorption properties for Hg (II) including the influence of initial concentration and contact time are investigated. Langmuir model and pseudo-second-order kinetics are demonstrated to fit well with the adsorption experiment for the uptake of Hg (II) by the functionalized adsorbent, also, intraparticle diffusion kinetic model is proved to aptly describe the Hg (II) removal in aqueous solution. In addition, the recognition mechanism is considered to originate from the Hg (II) triggered structural reversals of naphthalene ring units which are verified by the X-ray photoelectron spectroscopy and density functional theory calculation. Moreover, the synthesis method used in this work also provides a strategy for the sensing application of organic sensor molecules with AIE properties in which the aggregated behavior could be appropriately realized.
Asunto(s)
Mercurio , Contaminantes Químicos del Agua , Purificación del Agua , Mercurio/química , Celulosa/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Concentración de Iones de Hidrógeno , Agua/química , Cinética , Adsorción , IonesRESUMEN
BACKGROUND: The preoperative use of mineralocorticoid receptor antagonists (MRA) in patients with unilateral forms of primary aldosteronism (PA) is not standardized. The current Endocrine Society Guidelines do not specifically recommend MRA treatment before surgery. It is unclear whether preoperative MRA can optimize perioperative blood pressure and potassium control, and reduce the incidence of postoperative hyperkalaemia. OBJECTIVE: This study aimed to investigate the effect of MRA on the incidence of postoperative hyperkalaemia in addition to perioperative blood pressure and potassium concentration in patients undergoing unilateral adrenalectomy for the treatment of PA. DESIGN: Retrospective cohort study. SETTING: Tertiary referral centres, Victoria, Australia. PATIENTS: A total of 96 patients who were diagnosed with unilateral forms of PA: 73 patients ('MRA' group) received preoperative MRA while 23 patients ('No-MRA' group) did not. RESULTS: The prevalence of postoperative hyperkalaemia was significantly higher in the 'No-MRA' group at 2-4 weeks after surgery, compared to the 'MRA' group (35% vs. 11%, p = .014). In a logistic regression, the use of MRA significantly predicted a lower incidence of postoperative hyperkalaemia after adjusting for age, sex, baseline aldosterone-to-renin ratio, potassium and preoperative eGFR. Before surgery, patients in the 'MRA' group had normalized blood pressure and potassium concentration requiring fewer antihypertensive medications and no potassium supplements. CONCLUSION: Preoperative MRA use was associated with optimal perioperative blood pressure and normalized serum potassium in addition to a lower incidence of postoperative hyperkalaemia. MRA should be considered standard treatment for patients awaiting surgery for PA.
Asunto(s)
Hiperaldosteronismo , Hiperpotasemia , Adrenalectomía , Humanos , Hiperaldosteronismo/tratamiento farmacológico , Hiperaldosteronismo/cirugía , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Estudios Retrospectivos , VictoriaRESUMEN
BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is a type of paraneoplastic syndrome that may initially manifest itself with proximal weakness and gait abnormalities. Approximately up to 50% of LEMS patients have a primary autonomic dysfunction. CASE PRESENTATION: We present here a case of a 75-year-old male with symmetric proximal muscle weakness, dry mouth and constipation. The cutaneous response to scratch and upright tilt-table testing were positive. A repetitive nerve stimulation test showed that there was a decremental response of compound muscle action potential (CMAP) amplitude at 3 Hz while an incremental response at 20 Hz. The presence of antibodies against voltage-gated calcium channels (VGCC) confirmed the diagnosis. Because of the prominent symptom of autonomic disorder, the patient further underwent the test of skin sympathetic response (SSR). Lower amplitude and longer response duration were found in palms, while it evoked no response in soles. CONCLUSIONS: In this case, we present the detailed results of SSR test on a patient suffering LEMS with autonomic disorder. Since autonomic dysfunction has a significant impact on clinical management and SSR test is an effective detection method, we recommend that SSR test be performed on patients with LEMS regularly.
Asunto(s)
Síndrome Miasténico de Lambert-Eaton , Síndromes Paraneoplásicos , Disautonomías Primarias , Anciano , Humanos , Síndrome Miasténico de Lambert-Eaton/complicaciones , Síndrome Miasténico de Lambert-Eaton/diagnóstico , MasculinoRESUMEN
A novel microwave (MW) catalytic oxidation denitrification method was developed, which can deeply oxidize NO into nitrate/nitrite with little NO2 yield. A molecular-sieve-supported oxygen-vacancy-enriched Fe2O3-MnO2 catalyst (Ov-Fe-Mn@MOS) was fabricated. Physicochemical properties of the catalyst were revealed by various characterization methods. MW irradiation was superior to the conventional heating method in NO oxidation (90.5 vs 70.6%), and MW empowered the catalyst with excellent low-temperature activity (100-200 °C) and good resistance to H2O and SO2. Ion chromatography analysis demonstrated that the amount of nitrate/nitrite accounted for over 90.0% of the N products, but the main product gradually varied from nitrate to nitrite as the reaction proceeded because of the switching of the main reaction path of NO removal. Mechanism analyses clarified that NO oxidation was a non-radical catalytic reaction: (i) the chemisorbed NO on ≡Mn(IV) reacted with O2* to produce nitrate and (ii) the excited NO* due to MW irradiation reacted with the active O* generated from Ov···O2 to form nitrite. Density functional theory calculations combined with electron paramagnetic resonance tests revealed the promotional effects of Fe2O3 in (i) boosting the Ov's quantity; (ii) facilitating O2 adsorption; (iii) increasing the nitrite formation; and (iv) alleviating the suppression of SO2.
Asunto(s)
Microondas , Óxidos , Catálisis , Compuestos de Manganeso , Nitratos , Nitritos , Óxidos de Nitrógeno , Oxidación-Reducción , Oxígeno/químicaRESUMEN
The genetic factors of tuberculosis (TB) susceptibility have been widely recognized. Here we performed a two-stage study in 616 TB patients and 709 healthy controls to systematically identify the genetic markers of TB susceptibility. In the discovery stage, we identified 93 single nucleotide polymorphisms (SNPs) and 3 human leucocyte antigen (HLA) class II alleles that had potential associations with TB susceptibility. In the validation stage, we confirmed that 6 nominally significant SNPs, including 2 novel missense variants at RAB17 and DCTN4 (odds ratio (OR) = 1.40, P = 4.98 × 10-3 and OR = 2.30, P = 3.17 × 10-2 respectively), were associated with the predisposition to TB. Moreover, our study found that HLA-II allele DQA1*05:05 (P = 0.0011, OR = 1.44, 95%CI = 1.15-1.77) was a TB susceptibility locus for the first time. This study comprehensively investigated the genetic variants that were associated with TB susceptibility and provided insight into the tuberculosis pathogenesis.
Asunto(s)
Estudio de Asociación del Genoma Completo , Tuberculosis , Alelos , Estudios de Casos y Controles , China , Predisposición Genética a la Enfermedad , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Polimorfismo de Nucleótido Simple , Tuberculosis/genéticaRESUMEN
The mammalian target of rapamycin complex 1 (mTORC1) is a crucial regulator of adipogenesis and systemic energy metabolism. Its dysregulation leads to a diversity of metabolic diseases, including obesity and type 2 diabetes. DEP-domain containing 5 (DEPDC5) is a critical component of GATOR1 complex that functions as a key inhibitor of mTORC1. So far, its function in adipose tissue remains largely unknown. Herein we evaluated how persistent mTORC1 activation in adipocyte via Depdc5 knockout modulates adiposity in vivo. Our data indicated that adipocyte-specific knockout of Depdc5 in aged mice led to reduced visceral fat, aggravated insulin resistance and enhanced adipose tissue inflammation. Moreover, we found that Depdc5 ablation resulted in upregulation of adipose triglyceride lipase (ATGL) in adipocytes and elevated levels of serum free fatty acids (FFAs). Intriguingly, rapamycin treatment did not reverse insulin resistance but alleviated adipose tissue inflammation caused by Depdc5 deletion. Taken together, our findings revealed that mTORC1 activation caused by Depdc5 deletion promotes lipolysis process and further exacerbates insulin resistance and adipose tissue inflammation in mice.
Asunto(s)
Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Proteínas Activadoras de GTPasa/genética , Inflamación/genética , Resistencia a la Insulina/genética , Adipogénesis/genética , Tejido Adiposo/patología , Factores de Edad , Animales , Western Blotting , Dieta Alta en Grasa/efectos adversos , Proteínas Activadoras de GTPasa/deficiencia , Inflamación/metabolismo , Grasa Intraabdominal/metabolismo , Lipasa/genética , Lipasa/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones Noqueados , Ratones Transgénicos , Obesidad/etiología , Obesidad/genética , Obesidad/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/genéticaRESUMEN
Chloroplast gene expression involves the participation of hundreds of pentatricopeptide repeat (PPR) RNA binding proteins, and proteins in the PLS subfamily typically specify sites of RNA editing, whereas those in the P-subfamily typically stabilize RNA, activate translation, or promote intron splicing. Several P-type PPR proteins include a small MutS-related (SMR) domain, but the biochemical contribution of the SMR domain remains enigmatic. Here, we describe a rice (Oryza sativa) mutant, osatp4, lacking the ortholog of ATP4, a PPR-SMR protein in maize (Zea mays). osatp4 mutants were chlorotic and had a plastid-ribosome deficiency when grown in the cold. Like maize ATP4, OsATP4 was required for the accumulation of dicistronic rpl16-rpl14 transcripts. Surprisingly, OsATP4 was also required for the editing of a specific nucleotide in the ribosomal protein S8 transcripts, rps8, and this function was conserved in maize. By contrast, rps8 RNA was edited normally in the maize PROTON gradient regulation3 mutant, pgr3, which also lacks rpl16-rpl14 transcripts, indicating that the editing defect in atp4 mutants is not a secondary effect of altered rpl16-rpl14 RNA metabolism. Expression of the edited rps8 isoform in transgenic osatp4 mutants complemented the cold-sensitive phenotype, indicating that a rps8 expression defect accounts for the cold-sensitivity. We suggest that ATP4 stimulates rps8 editing by facilitating access of a previously characterized PLS-type RNA editing factor to its cognate cis-element upstream of the edited nucleotide.
Asunto(s)
Cloroplastos/genética , Productos Agrícolas/genética , Oryza/genética , Edición de ARN , ARN Mensajero/genética , ARN de Planta/genética , Zea mays/genética , Regulación de la Expresión Génica de las Plantas , Variación Genética , Genotipo , Mutación , Plantas Modificadas GenéticamenteRESUMEN
Kidney stones, also known as calcium oxalate (CaOx) nephrolithiasis, are often asymptomatic, leading to kidney injury and renal failure complications. Corilagin is a gallotannin found in various plants and is known to elicit various biological activities. The present study aimed to elucidate the renoprotective effect of corilagin against the rats' renal stones deposition. The rats were induced for nephrolithiasis (CaOx deposition) using 0.75% ethylene glycol in their drinking water. Then, they were treated with corilagin at 50 and 100 mg/kg/day for 4 weeks. At the end of the experimental period, the rats were killed; blood and renal tissues were collected for various histological, biochemical, and gene expression analyses. The results demonstrated that the rats had renal calculi displaying a significant increase in serum creatinine (59.39 µmol/L) and blood urea nitrogen (19.03 mmol/L) levels compared with controls. Moreover, the malondialdehyde (13.29 nmol/mg) level was found to increase with a profound reduction in antioxidants' activities with upregulated inflammatory cytokines. In contrast, the RT-PCR and immunohistochemistry analysis demonstrated a substantial reduction in cell survival markers PPAR-γ and PI3K/Akt with an apparent increase in apoptosis markers genes expressions in rats suffering from renal stones. Thus, the present study results suggest that corilagin could suppress renal CaOx crystal-induced oxidative stress, inflammatory response, and apoptosis via PPAR-γ and PI3K/Akt-mediated pathway.
Asunto(s)
Oxalato de Calcio/antagonistas & inhibidores , Glucósidos/farmacología , Taninos Hidrolizables/farmacología , Inflamación/tratamiento farmacológico , Sustancias Protectoras/farmacología , Animales , Apoptosis/efectos de los fármacos , Oxalato de Calcio/farmacología , Cristalización , Inflamación/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , PPAR gamma/antagonistas & inhibidores , PPAR gamma/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Epidemiological evidence concerning dietary fiber on newly-diagnosed type 2 diabetes mellitus (T2DM) is sparse. Therefore, the purpose of this study was to investigate the relationship between dietary fiber intake and newly-diagnosed T2DM in a middle-aged Chinese population. METHODS: Using data from the Hangzhou Nutrition and Health Survey collected between June 2015 and December 2016, we investigated the associations between dietary patterns and the risk of chronic non- communicable diseases. Anthropometric measurements and samples collection for biochemical assays are conducted by the well-trained staff and nurse, respectively. Multivariable logistic regression analysis was used to analyze the effect of dietary fiber intake on the risk of newly-diagnosed T2DM in crude and adjusted models. RESULTS: Among 3250 participants, 182 (5.6%) people were identified as newly-diagnosed T2DM. Pearson correlation coefficients revealed a significant inverse association of total dietary fiber with BMI, SBP, DBP, HbA1c and LDL-C in all participants, participants with and without T2DM (P < 0.05). Compared with the study participants in the first quartile (Q1, the lowest consumption)of dietary fiber intake, participants in the fourth quartile (Q4) had a lower prevalence of newly-diagnosed T2DM(OR = 0.70; 95%CI:0.49-1.00; P < 0.05), after adjustment for potential confounders. CONCLUSIONS: In this middle-aged Chinese population, higher intake of dietary fiber was significantly associated with lower risk of newly-diagnosed T2DM. However, our findings need to be confirmed in future large-scale prospective studies.
Asunto(s)
Diabetes Mellitus Tipo 2 , China/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Fibras de la Dieta , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
Plastid-encoded genes are coordinately transcribed by the nucleus-encoded RNA polymerase (NEP) and the plastid-encoded RNA polymerase (PEP). Resulting primary transcripts are frequently subject to RNA editing by cytidine-to-uridine conversions at specific sites. The physiological role of many editing events is largely unknown. Here, we have used the CRISPR/Cas9 technique in rice to knock out a member of the PLS-DYW subfamily of pentatricopeptide repeat (PPR) proteins. We found that OsPPR16 is responsible for a single editing event at position 545 in the chloroplast rpoB messenger RNA (mRNA), resulting in an amino acid change from serine to leucine in the ß-subunit of the PEP. In striking contrast to loss-of-function mutations of the putative orthologue in Arabidopsis, which were reported to have no visible phenotype, knockout of OsPPR16 leads to impaired accumulation of RpoB, reduced expression of PEP-dependent genes, and a pale phenotype during early plant development. Thus, by editing the rpoB mRNA, OsPPR16 is required for faithful plastid transcription, which in turn is required for Chl synthesis and efficient chloroplast development. Our results provide new insights into the interconnection of the finely tuned regulatory mechanisms that operate at the transcriptional and post-transcriptional levels of plastid gene expression.
Asunto(s)
Proteínas de Arabidopsis , Oryza , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cloroplastos/genética , Cloroplastos/metabolismo , ARN Polimerasas Dirigidas por ADN/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Regulación de la Expresión Génica de las Plantas , Oryza/genética , Oryza/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Edición de ARN/genéticaRESUMEN
Runt related transcription factors as trans-acting elements play critical roles in the developmental control of cell fate, hematopoiesis, bone formation and cancers. In previous study, the homologue of runt related transcription factor PmRunt has been identified from pearl oyster Pinctada fucata martensii and considered to play an important role in nacre formation. In this study, we used the same samples to perform RNA-seq to detect the global effects after the decrease of PmRunt expression. The transcription levels of several nacre shell matrix protein (NSMP) genes were significantly changed and the potential compensatory effect could happen internal gene families. Downregulation of PmRunt could also influence the biosynthesis of NSMPs through affecting amino acid metabolism, translation, protein processing and export. The inhibition of PmRunt also possibly affected the expression of caspases, IAPs and C1qs that related to apoptosis and immune. In addition, PmRunt highly expressed at 12â¯h and 12â¯d after transplantation in hemolymph, which was corresponded to transplantation immunity immune response and the morphology of pearl sac, suggested the cross-talk of biomineralization-immune regulation in hemocytes. Furthermore, a lincRNA (LncRunt) that co-located with PmRunt was identified and showed a significantly relative expression with PmRunt, which suggested the potential regulation. Therefore, these findings provided new idea to find the regulation targets of runt-related transcription factors and offers evidence of lncRNAs in potential biomineralization-immune regulation.
Asunto(s)
Pinctada/genética , ARN Largo no Codificante/genética , Factores de Transcripción/genética , Animales , Regulación de la Expresión Génica/inmunología , Pinctada/inmunología , Pinctada/metabolismo , ARN Largo no Codificante/metabolismo , Análisis de Secuencia de ARN , Factores de Transcripción/metabolismo , Transcripción Genética/inmunologíaRESUMEN
BACKGROUND: Globally, there is increased clinical interest and uptake of hemodiafiltration (HDF) for increased removal of uremic toxins. To date, there has been no epidemiological analysis of HDF in China. We present HDF practice patterns and associated mortality risk in Shanghai. METHODS: This is an observational, prospectively collected, retrospective analysis of 9351 Chinese patients initiating hemodialysis in Shanghai from 2007 to 2014. The primary exposure was hemodialysis sub-modality at inception, classified into hemodiafiltration (HDF) and hemodialysis (HD), with adjustment for concommitant hemoperfusion. The primary outcome was patient mortality. We used Cox proportional hazards regression and Fine and Gray's proportional subhazards regression, with multiple imputation of missing co-variates by the chained equation method, adjusting for demographic and clinical variables. RESULTS: Overall, patients in the cohort were younger, with a more males, and with a lower body mass index when compared to corresponding non-Asian cohorts. Mortality rate was low although it doubled over the period of observation. HDF utilization increased from 7% of patients in 2007 to 42% of patients in 2014. The majority of patients received HDF once a week. The adjusted hazard ratio of death (95% confidence intervals) for HDF versus HD was 0.85 (0.71-1.03), and corresponding sub-hazard ratio 0.86 (0.71-1.03). There was strong effect modification by age. In those aged 40-60 years, the hazard ratio (95% confidence intervals) was 0.65 (0.45-0.94), and sub-hazard ratio also 0.65 (0.45-0.95). CONCLUSIONS: Our study has certain limitations resulting from the limited number of co-variates available for modelling, missing data for some co-variates, and the lack of verification of data against source documentation. Notwithstanding, there is evidence of clinical benefit from HDF in China, and potential to improve patient outcomes through the greater removal of middle and larger uremic solutes.
Asunto(s)
Hemodiafiltración/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Distribución por Edad , Anciano , Tamaño Corporal , China , Femenino , Hemodiafiltración/métodos , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos Biológicos , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Albúmina Sérica/análisis , Distribución por Sexo , Resultado del TratamientoRESUMEN
BACKGROUND: Studies investigating the association between the methylenetetrahydrofolate reductase (MTHFR) gene 1298A>C polymorphism and the risk of breast cancer have reported inconsistent results. So, we performed this updated meta-analysis and tried to give a more precise estimation of association between MTHFR gene 1298A>C polymorphism and breast cancer susceptibility. METHODS: Relevant studies published before 1 January 2016 were identified by searching PubMed and EMBASE. The strength of relationship between the MTHFR gene 1298A>C polymorphism and breast cancer susceptibility was assessed using odds ratio (OR) and corresponding 95 % confidence interval (95 % CI). The meta-analysis was performed using Stata 11.0 software. RESULTS: A total number of 38 case-control studies including 18,686 cases and 22,299 controls were identified. No association was found in five genetic models (dominant model: OR = 0.99, 95 % CI 0.99-1.00, P = 0.218; recessive model: OR = 1.00, 95 % CI 0.97-1.02, P = 0.880; homozygote genetic model: OR = 0.99, 95 % CI 0.98-1.01, P = 0.390; heterozygote genetic model: OR = 0.99, 95 % CI 0.97-1.00, P = 0.138; and allele contrast genetic model: OR = 0.99, 95 % CI 0.98-1.01) for MTHFR gene 1298 A>C polymorphism and breast cancer susceptibility. In the subgroup analysis stratified by source of control, decreased risk of breast cancer was found in studies with hospital-based controls in dominant model (OR = 0.98, 95 % CI 0.96-1.00, P = 0.037). CONCLUSIONS: Our meta-analysis suggested that there is no significant association between MTHFR gene 1298A>C polymorphism and breast cancer susceptibility for overall population.
Asunto(s)
Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Estudios de Casos y Controles , Femenino , Humanos , Modelos Genéticos , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Flemingia stricta Roxb. ex Ait. 1812 belongs to the Phaseoleae tribe within the Fabaceae family and has significant pharmaceutical value. In this study, we reported the complete chloroplast genome of F. stricta using the Illumina DNA sequencing data. The chloroplast genome was 152,940 bp and encoded 111 unique genes, including 77 protein-coding genes (PCGs), 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. The phylogenetic analysis confirmed that F. stricta was closely related to Flemingia prostrata and Flemingia macrophylla. The chloroplast genome of F. stricta could provide critical information for the molecular breeding of F. stricta and be used as a reference genome for other species of Phaseoleae.
RESUMEN
BACKGROUND: Chylopericardium is a rare condition characterized by the accumulation of chyle in the pericardial space. It is most commonly caused by thoracic duct injury. Chylopericardium following esophagectomy is extremely rare but can cause life-threatening complications. This report presents a case of chylopericardium post-esophagectomy, resulting in cardiac tamponade and cardiac arrest. A systematic literature review was also conducted to facilitate the understanding of this rare condition. CASE PRESENTATION: A 41-year-old male was admitted to our hospital with intermediate to highly differentiated squamous cell carcinoma of the mid-thoracic esophagus (clinical T4NxM0). He underwent thoracoscopic-laparoscopic esophagectomy with cervical anastomosis. On postoperative day 1, patient had a cardiac arrest secondary to cardiac tamponade, requiring emergency ultrasound-guided drainage. The drained fluid was initially serous but became chylous after the administration of enteral nutritional emulsion. As a result of significant daily pericardial drainage, patient subsequently underwent thoracic duct ligation. The amount of drainage was substantially reduced post-thoracic duct ligation. Over a period of 2 years and 7 months, patient recovered well and tolerated full oral diet. A comprehensive literature review was conducted and 4 reported cases were identified. Among these cases, three patients developed pericardial tamponade secondary to chylopericardium post-esophagectomy. CONCLUSION: Chylopericardium is a rare but serious complication post-esophagectomy. Prompt echocardiography and thorough pericardial fluid analysis are crucial for diagnosis. Thoracic duct ligation has been shown to be an effective management approach for this condition.