Mchughnieves0636

To clarify the effect of miR-181b on the biological function of small-cell lung cancer (SCLC) and explore the effect of clinical resistance on SCLC.

Blood samples were collected from 30 SCLC patients and 30 non-SCLC patients in our department from 2017 to 2019 to detect the expression level of miR-181b.The expression level of miR-181b was detected in SCLC cells by RT-PCR, and screening of downstream target genes by gene chip, verification with luciferase, and Western blotting. In addition, collect the general data of 30 SCLC patients and 30 non-SCLC patients (control group), the patients were diagnosed by pathology and undergoing EC protocol in the Department of Thoracic Surgery and Oncology of our hospital to detect the expression level of mir-181b in different periods. Furthermore, in the SCLC cell line, EC chemotherapy was administered to detect the sensitivity of drug resistance and nondrug resistance.

miR-181b in SCLC patients was lower than in normal people as well as the drug-sensitive cell line. ACE2 was verified as a downstream target of miR-181b by gene chip screening. First-line chemotherapy can promote the recovery of miR-181b, but cannot repair to normal levels. miR-181b can enhance the drug sensitivity of SCLC drug-resistant cells.

miR-181b directly targets ACE2 to affect the biological characteristics of SCLC. The expression level of miR-181b is highly related to the drug resistance of SCLC, which suggests that miR-181b could be a potential biomarker candidate for treatment efficacy of SCLC.

miR-181b directly targets ACE2 to affect the biological characteristics of SCLC. The expression level of miR-181b is highly related to the drug resistance of SCLC, which suggests that miR-181b could be a potential biomarker candidate for treatment efficacy of SCLC.

Few studies have focused on the role of adverse childhood experiences (ACEs) in relation to genetic susceptibility to obesity.

We aimed to examine the interaction between the presence of ACEs (i.e., physical, psychological and sexual abuse) before the age of 18 and BMI polygenic score.

Data came from the National Longitudinal Study of Adolescent to Adult Health (Add Health) Wave IV (2007/2008) where saliva samples were collected for DNA genotyping and information on BMI and ACEs were obtained from 5854 European American (EA), 2073 African American (AA) and 1448 Hispanic American (HA) participants aged 24 to 32 years old. Polygenic scores were calculated as the sum of the number of risk alleles of BMI-related SNPs which were weighted by effect size. A race/ethnicity-stratified mixed-effects linear regression model was used to test for differential association between BMI polygenic score and BMI by the presence of ACEs.

We did not find any evidence of significant interaction between ACEs and polygenic score in relation to BMI among EA (p=0.289), AA (p=0.618) or HA (p=0.870). In main effects models, polygenic score was positively associated with BMI in all race/ethnic groups, yet the presence of ACEs was associated with increased BMI only among EA.

We did not find any evidence that ACEs exacerbate genetic predisposition to increased BMI in early adulthood.

We did not find any evidence that ACEs exacerbate genetic predisposition to increased BMI in early adulthood.

Macrophages are associated with metabolic complications to obesity including fatty liver disease and impaired hepatic and muscle insulin sensitivity (IS). Bariatric surgery induces weight loss and improves IS. We investigated associations between the macrophage activation marker soluble (s)CD163, alanine-aminotransferase (ALT), and IS before and after Roux-en-Y Gastric Bypass (RYGB).

We analyzed sCD163 from 10 type 2 diabetes (T2D) and 10 obese patients with normal glucose tolerance (NGT) undergoing RYGB for associations with hepatic, adipose tissue, and muscle IS and ALT after 1-week, 3, and 12months postoperatively. IS was evaluated by hyperinsulinemic-euglycemic clamp in combination with glucose tracer technique.

Preoperative sCD163 correlated with ALT (r=0.58, p=0.007) and tended to associate inversely with hepatic (r=-0.39, p=0.1) and adipose tissue (r=-0.39, p=0.09), but not muscle IS. Following RYGB, sCD163 decreased significantly in all patients. The decrease in sCD163 during the first 3months correlated inversely with the improvement of hepatic IS (r=-0.65, p=0.01) and tended to be associated with changes in muscle IS (r=-0.45, p=0.09). After 3months sCD163remained associated with ALT (r=0.75, p<0.001) and inversely with hepatic IS (r=-0.39, p=0.1), but not muscle or adipose tissue IS. One year after RYGB, sCD163 correlated with ALT (r=0.61, p=0.007), but not with hepatic, adipose tissue, or muscle IS.

Macrophage activation is associated with liver injury and hepatic IS in obese patients. Improvements in these measures correlate during the first 3months following RYGB, supporting a link between macrophages and hepatic IS in severe obesity and diabetes.

Macrophage activation is associated with liver injury and hepatic IS in obese patients. Improvements in these measures correlate during the first 3 months following RYGB, supporting a link between macrophages and hepatic IS in severe obesity and diabetes.3D printed porous titanium alloy implants is an advanced orthopedic material for joint replacement. However, the high risk of aseptic loosening and periprosthetic infection is difficult to avoid, and the declined autophagy of osteoporosis-derived bone marrow mesenchymal stem cells (OP-BMSCs) further severely impairs the osseointegration under the osteoporotic circumstance. It is thus becoming urgently significant to develop orthopedic materials with autophagy regulation and antibacterial bioactivity. In this regard, a novel class of multifunctional hydrogel-integrated 3D printed bioactive prosthetic interfaces is engineered for in situ osseointegration in osteoporosis. The hydrogel is fabricated from the dynamic crosslinking of synthetic polymers, natural polymers, and silver nanowires to deliver autophagy-regulated rapamycin. Therefore, the resultant soft material exhibits antibacterial ability, biocompatibility, degradability, conductive, self-healing, and stimuli-responsive abilities. In vitro experiments demonstrate that the hydrogel-integrated 3D printed bioactive prosthetic interfaces can restore the declined cellular activities of OP-BMSCs by upregulating the autophagy level and show excellent antibacterial activity against S. aureus and MRSA. More remarkably, the multifunctional 3D printed bioactive prosthetic interfaces significantly improve osseointegration and inhibit infection in osteoporotic environment in vivo. This study provides an efficient strategy to develop novel prosthetic interfaces to reduce complications after arthroplasty for patients with osteoporosis.Postbariatric outcomes may improve by providing an additional preconditioning program (APP) in targeted patients. However, APPs are a demand for health resources while only little and inconsistent evidence consists to support their effectiveness. This cohort study aims to evaluate the effectiveness of APP, by comparing outcomes of patients with and without such APP. We carried out a retrospective single-centre cohort study in a before-after design. Patients signing up for primary gastric bypass or sleeve gastrectomy and eligible for surgery were included if screened as vulnerable patients. Vulnerable patients screened between September 2017 and March 2018 followed an APP and formed the APP-group. Due to a policy change, APPs were no longer performed since September 2018. Vulnerable patients screened between September 2018 and March 2019 thus did not receive an APP (comparator-group). Multidisciplinary follow-up remained unchanged. Endpoints included percentage total weight loss (%TWL), bodyweight, evolution of comorbidities, protein intake, and number of no-shows. The APP-group comprised 231 patients and the comparator-group 153. %TWL differed statistically significantly at 7 (Δ1.5%, p = .01) and 12 months postoperative (Δ2.8%, p  less then  .01) in favour of the comparator-group, as did bodyweight 12 months postoperative (Δ1.8 kg, p  less then  .01). Statistically significant differences were also found in the evolution of comorbidities, protein intake, and the number of no-shows, most in favour for the comparator-group. APP proofed not to be superior to Non-App. JAK Inhibitor I in vitro It is debatable whether statically significant differences are clinically relevant given their small magnitude. A care pathway without an APP seems at least as effective as a care pathway without.Our previous work using a melanoma progression model composed of melanocytic cells (melanocytes, primary and metastatic melanoma samples) demonstrated various deregulated genes, including a few known lncRNAs. Further analysis was conducted to discover novel lncRNAs associated with melanoma, and candidates were prioritized for their potential association with invasiveness or other metastasis-related processes. In this sense, we found the intergenic lncRNA U73166 (ENSG00000230454) and decided to explore its effects in melanoma. For that, we silenced the lncRNA U73166 expression using shRNAs in a melanoma cell line. Next, we experimentally investigated its functions and found that migration and invasion had significantly decreased in knockdown cells, indicating an essential association of lncRNA U73166 for cancer processes. Additionally, using naïve and vemurafenib-resistant cell lines and data from a patient before and after resistance, we found that vemurafenib-resistant samples had a higher expression of lncRNA U73166. Also, we retrieved data from the literature that indicates lncRNA U73166 may act as a mediator of RNA processing and cell invasion, probably inducing a more aggressive phenotype. Therefore, our results suggest a relevant role of lncRNA U73166 in metastasis development. We also pointed herein the lncRNA U73166 as a new possible biomarker or target to help overcome clinical vemurafenib resistance.The novel approach of thoracic normothermic regional perfusion (TA-NRP) for in-situ preservation of organs prior to removal presents a new series of ethical questions about donation after circulatory determination of death (DCD) procedures. This manuscript describes the framework used for the analysis of ethical acceptability of DCD donation and analyzes the specific practice of TA-NRP DCD within that framework to demonstrate that TA-NRP DCD can be performed within the ethical boundaries of DCD donation. We argue that TA-NRP DCD organ procurements meet the ethical standards of informed consent, non-maleficence, adherence to the dead donor rule, and irreversibility, and as such, are ethically acceptable. We also describe the potential benefits of TA-NRP DCD procedures that result from higher organ yields and better recipient outcomes. Finally, we call for open and transparent support of TA-NRP DCD by professional organizations as a necessary cornerstone for the advancement of TA-NRP DCD procedures.Atherosclerosis is the main cause of cardiovascular diseases. The Fat-1 gene can express the n-3 fatty acid desaturase, which converts n-6 polyunsaturated fatty acids (PUFA) to n-3 PUFAs. The role of n-3 PUFAs in atherosclerosis is widely debated. This study explored the effect of n-3 PUFAs on atherosclerosis in rabbits. In this study, atherosclerosis was induced in Fat-1 transgenic rabbits and their littermate (WT) rabbits by feeding a high-cholesterol diet containing 0.3% cholesterol and 3% soybean oil for 16 weeks. Plasma lipid, fatty acid and pathological analyses of atherosclerotic lesions were conducted. Fatty acid composition in the liver and muscle showed that n-3 PUFAs increased and n-6 PUFAs decreased in the Fat-1 group. Plasma high-density lipoprotein cholesterol (HDL-C) levels were significantly increased in the Fat-1 group, and the atherosclerotic lesion area of the aortic arch in Fat-1 transgenic rabbits was significantly reduced. Histological analysis showed that smooth muscle cells (SMCs) in atherosclerotic lesions decreased significantly.