Edmondsonbrowne4371
Our results demonstrated for the first time that lncRNA 4344 regulates NLRP3-related neuroinflammation and cognitive impairment by targeting miR-138-5p, providing a possible target for the treatment of diseases characterized by a cognitive deficit.
Our results demonstrated for the first time that lncRNA 4344 regulates NLRP3-related neuroinflammation and cognitive impairment by targeting miR-138-5p, providing a possible target for the treatment of diseases characterized by a cognitive deficit.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with several complications. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) represent an emerging type of MSCs with high plasticity and immunoregulatory capabilities and are useful for treating inflammation-related disorders such as T2DM. However, the pathogenic microenvironment of T2DM may affect their therapeutic potential. selleck chemical We aimed to examine the impact of the diabetic milieu on the immunomodulatory/anti-inflammatory potential of AT-MSCs.
We assessed the proliferation potential, cell surface expression of MSC-characteristic markers and immunomodulatory markers, along with the gene expression and protein secretion of pro-inflammatory and anti-inflammatory cytokines and adipokines in AT-MSCs derived from T2DM patients (dAT-MSCs) vs. those derived from non-diabetic volunteers (ndAT-MSCs). Furthermore, we evaluated the IFN-γ priming effect on both groups.
Our data revealed comparable proliferative activities in both groupsards a proinflammatory phenotype which may restrain their autologous therapeutic use. Furthermore, our findings indicate that IFN-γ priming could be a useful strategy for enhancing dAT-MSC anti-inflammatory potential.
Chronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous disease, which is caused by biological heterogeneity. The purpose of our study is to determine the association between the single nucleotide polymorphisms (SNPs) of miRNAs (miR-8079 and miR-5007) and the susceptibility to COPD in Chinese population.
We conducted a 'case-control' study involving 315 COPD patients and 314 healthy individuals. Three SNPs of miR-8079 (rs9533803, rs9525927, rs7981875) and three SNPs of miR-5007 (rs9527345, rs2252932, rs2997119) were selected, then we used logistic regression to analyze the association between candidate SNPs and COPD susceptibility under different genetic models. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction of "SNP-SNP" in COPD risk studies. Finally, we used univariate and ANOVA to analyze the differences in clinical characteristics among different genotypes.
Our results showed that miR-8079-rs9525927 was significant associated with COPD susceptibility whether in overall and stratified analysis. miR-5007-rs2997119 was associated with the increased risk of COPD in women under multiple genetic models; miR-8079-rs9525927 and miR-5007-rs9527345 had a certain association with clinical indicator Fev_1 of COPD patients; rs9527345 or rs2252932 on miR-5007 was associated with the risk of COPD with wheezing dyspnea or wheezing.
Our results suggested that the genetic polymorphisms of miR-8079 or miR-5007 were potentially associated with COPD risk, of which miR-8079-rs9525927 was more prominent.
Our results suggested that the genetic polymorphisms of miR-8079 or miR-5007 were potentially associated with COPD risk, of which miR-8079-rs9525927 was more prominent.Wet granulation lines in pharmaceutical manufacturing facilities typically comprise a dryer that removes the excess moisture content after wet granulation. In this study, a semi-continuous dryer installed in the ConsiGma 25 wet granulation line was investigated. The goal was to highlight specific characteristics of this type of dryer, utilizing the available process data and the corresponding data obtained via material characterization. This paper addresses typical effects and issues associated with the dryer's setup and operation (e.g., unexpected cell temperature profiles, the effects of air flow and temperature on the granule properties, variations in the granule moisture between the dryer cells). Since in many situations the liquid-to-solid ratio is based on the properties of granules after the granulation step, the selection of inlet air flow rate and the inlet air temperature of the dryer as well as the overall line throughput (affecting the cell fill level in the dryer) are of particular interest from a practical point of view. This paper discusses these issues and provides suggestions on how to address them when setting up the process. A novel approach for characterizing the fluidization inside the dryer by means of quantifying the "smoothness" of the temperature profile is proposed. The paper should be viewed as a hands-on guideline, which highlights possible pitfalls during the process setup and offers solutions.Rapamycin insensitive companion of mechanistic target of Rapamycin (Rictor), the key component of mTOR complex 2 (mTORC2), controls both β-cell proliferation and function. We sought to study whether long chain acyl-CoA synthetase 4 (Acsl4) worked downstream of Rictor/mTORC2 to maintain β-cell functional mass. We found Acsl4 was positively regulated by Rictor at transcriptional and posttranslational levels in mouse β-cell. Infecting adenovirus expressing Acsl4 in β-cell-specific-Rictor-knockout (βRicKO) islets and Min6 cells knocking down Rictor with lentivirus-expressing siRNA-oligos targeting Rictor(siRic), recovered the β-cell dysplasia but not dysfunction. Cell bioenergetic experiment performed with Seahorse XF showed that Acsl4 could not rescue the dampened glucose oxidation in Rictor-lacking β-cell, but further promoted lipid oxidation. Transposase-Accessible Chromatin (ATAC) and H3K27Ac chromatin immunoprecipitation (ChIP) sequencing studies reflected the epigenetic elevated molecular signature for β-cell dedifferentiation and mitigated oxidative defense/response. These results were confirmed by the observations of elevated acetylation and ubiquitination of FoxO1, increased protein levels of Gpx1 and Hif1an, excessive reactive oxygen species (ROS) production and diminished MafA in Acsl4 overexpressed Rictor-lacking β-cells. In these cells, antioxidant treatment significantly recovered MafA level and insulin content. Inducing lipid oxidation alone could not mimic the effect of Acsl4 in Rictor lacking β-cell. Our study suggested that Acsl4 function in β-cell was context dependent and might facilitate β-cell dedifferentiation with attenuated Rictor/mTORC2 activity or insulin signaling via posttranslational inhibiting FoxO1 and epigenetically enhancing ROS induced MafA degradation.
Acute hypoxemic respiratory failure (ARF) is characterized by both lower arterial oxygen and carbon dioxide tensions in the blood. First line treatment for ARF includes oxygen therapy - intially administered non invasively using nasal prongs, high flow nasal cannulae (HFNC) or masks. Invasive mechanical ventilation (IMV) is usually reserved for patients who are unable to maintain their airway, those with worsening hypoxemia, or those who develop respiratory muscle fatigue and consequent hypercapnia. Inhaled nitric oxide (iNO) gas is known to improve oxygenation in patients with ARF by manipulating ventilation-perfusion matching. Addition of iNO may potentially alleviate the need for IMV in selected patients.
In this article we report our preliminary experience of using HFNC to deliver oxygen and nitric oxide gas in patients with hypoxemic ARF as a strategy to potentially avoid IMV in selected patients.
This article demonstrates the feasibility of this technique based on our experience of patients with hypoxemic ARF and generates hypothesis for future studies.
This article demonstrates the feasibility of this technique based on our experience of patients with hypoxemic ARF and generates hypothesis for future studies.Nutcracker syndrome refers to the compression of the left renal vein between the abdominal aorta and the superior mesenteric artery. The subsequent venous congestion of the left kidney, when symptomatic, could be associated with left flank pain, hematuria, varicocele, dyspareunia, dysmenorrhea, and proteinuria. Here we describe a 42-year-old female patient with simultaneous Dunbar syndrome and a rare variant of nutcracker syndrome in which the left renal vein (LRV) compression is secondary to the unusual path of the vein between the right renal artery and the proper hepatic artery. For both the nutcracker syndrome and the Dunbar syndrome, open approach by median mini-laparotomic access for transposition of LRV, and resection of the diaphragmatic pillars and arcuate ligament was attempted. During the intervention, due to anatomical issues, the LRV transposition was converted to endovascular stenting of the LRV, moreover the implanted stent was transfixed with an external non-absorbable suture to avoid migration. At the 12 months follow-up the patient was asymptomatic, and the duplex scan confirmed the patency of the celiac trunk without re-stenosis and a correct position of the LRV stent with no proximal or distal migration.
Brachial artery aneurysms constitute 0.5% of peripheral aneurysms. These can be true or secondary to trauma or arteriovenous fistulas. These present as an asymptomatic pulsatile mass or may cause symptoms due to compression of adjacent neurological structures.
We present a review of the literature on clinical, histological, and therapeutic characteristics of true brachial aneurysms, motivated by the case of a 67-year-old woman with an asymptomatic pulsatile mass dependent on the brachial artery of the left arm who underwent open surgical correction with resection of the aneurysmal sac and interposition of great saphenous vein graft with adequate postoperative results.
We present a review of the literature on clinical, histological, and therapeutic characteristics of true brachial aneurysms, motivated by the case of a 67-year-old woman with an asymptomatic pulsatile mass dependent on the brachial artery of the left arm who underwent open surgical correction with resection of the aneurysmal sac and interposition of great saphenous vein graft with adequate postoperative results.
To present a novel means of overcoming a deviation when treating an aortic arch aneurysm with a physician-modified fenestrated stent-graft.
A 78-year-old man presented with sharp chest pain. Computed tomography angiography showed a rapidly expanding aortic arch aneurysm, and the limited landing zone required the use of a fenestrated/branched arch endograft. Physician-modified fenestrated stent-grafts are considered suitable for patients in an acute setting. Informed consent was obtained from the patient, and the procedure was approved by the local ethics committee. The device became malrotated in a clockwise direction during deployment; therefore, cannulation of the first inner branch using a through-and-through wire technique was needed. The final angiogram showed a good result. The 3-month computed tomography angiogram showed no endoleak.
Thoracic endovascular repair of an aortic arch aneurysm using a through-and-through technique can be considered for high-risk patients in an acute setting.
Thoracic endovascular repair of an aortic arch aneurysm using a through-and-through technique can be considered for high-risk patients in an acute setting.