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Rosenkilde Ebbesen posted an update 1 month, 2 weeks ago
Human guanine nucleotide binding protein like 1 (GNL1) is an evolutionary conserved putative nucleolar GTPase belonging to the HSR1_MMR1 subfamily of GTPases. GNL1 was found to be highly up-regulated in various cancers. Here, we report for the first time that GNL1 inhibits apoptosis by modulating the expression of Bcl2 family of proteins and the cleavage of caspases 7 and 8. Furthermore, Elafibranor protects colon cancer cells from chemo-drug-induced apoptosis. Interestingly, GNL1 up-regulates the expression of p53 and its transcriptional target, p21 but the up-regulation of p21 was found to be p53 dependent as well as independent mechanisms. Our results further demonstrate that GNL1 promotes cell growth and survival by inducing cytoplasmic retention and stabilization of p21 through AKT-mediated phosphorylation. #link# In addition, GNL1 failed to inhibit apoptosis under p21 knockdown conditions which suggests the critical role of p21 in GNL1-mediated cell survival. Finally, an inverse correlation of GNL1, p21, and AKT expression in primary colon and breast cancer with patient survival suggests their critical role in tumorigenesis. Collectively, our study reveals that GNL1 executes its antiapoptotic function by a novel mechanism and suggests that it may function as a regulatory component of the PI3K/AKT/p21 signaling network to promote cell proliferation and survival in cancers.Background The photo reflection method (PRM) is used to measure light reflected from particles released from dry powder inhalers (DPIs). This simple method depicts time trajectories of released drugs; however, it underestimates the number of particles at high peak inhalation flow rates (PIFs). In this study, we aimed to correct this underestimation and clarify whether long inhalation is necessary for capsule-type DPIs, using this unique method. Methods To establish quantitative measurements using the PRM, several types of DPIs were inhaled with square-wave inhalations at different PIFs using an inhalation simulator, and the total emitted dose (TED) and the release time of the TED (TTED) were measured. Next, capsule-type DPIs were inhaled using inhalation patterns of patients with chronic obstructive pulmonary disease (COPD), and particle release time trajectories were recorded. Results For all DPIs, except for Turbuhaler® (TBH), both TED and TTED were hyperbolically decreased with an increase in the PIF of square-wave inhalations. TED correction using the TTED showed flat TED changes at high PIF ranges. The patient inhalation analysis showed that the corrected TEDs of seven COPD inhalation patterns were not significantly different. The PRM further revealed that the inhaled flow rate and release time of all seven patterns were sufficient to release particles in the capsule. Conclusions The inhaled flow rate and TTED that exceeded specific conditions enabled complete particle release from the DPIs except for TBH. Therefore, an extremely long inhalation is not required for capsule-type DPIs. Our corrected time trajectory analysis using the PRM provides a new strategy for the particle release analysis of DPIs.Maternal dysglycemia-including diabetes, impaired glucose tolerance, and impaired fasting glucose-affects one in six pregnancies worldwide and represents a significant health risk to the mother and the fetus. Maternal dysglycemia is an independent risk factor for perinatal mortality, major congenital anomalies, and miscarriages. Furthermore, it increases the longer-term risk of type 2 diabetes mellitus, metabolic syndrome, cardiovascular morbidity, malignancies, and ophthalmic, psychiatric, and renal diseases in the mother. The most commonly encountered form of maternal dysglycemia is gestational diabetes. Currently, international consensus does not exist for diagnostic criteria defining gestational diabetes at 24-28 weeks gestation, and potential diagnostic glucose thresholds earlier in gestation require further investigation. Likewise, recommendations regarding the timing and modality (e.g., lifestyle or pharmacological) of treatment vary greatly. Because a precise diagnosis determines the appropriate treatment and outcome of the pregnancy, it is imperative that a better definition of maternal dysglycemia and its treatment be achieved. This article will address some of the controversies related to diagnosing and managing maternal dysglycemia. In addition, the article will discuss the impact of maternal dysglycemia on complications experienced by the mother and infant, both at birth and in later life.Background Minimally invasive abdominal wall reconstruction, utilizing transversus abdominis release (TAR), has been described and shown to be beneficial for ventral hernia repair (VHR). Limited literature is available surrounding the hybrid robotic TAR (h-rTAR) approach, which combines robotic dissection and component separation with open fascial defect closure and mesh deployment. In this study, we describe our h-rTAR technique and present our center’s postoperative and patient-reported outcomes (PROs). Methods h-rTAR VHRs performed between 2013 and 2018 were examined. The h-rTAR technique was described. Patient characteristics and operative variables were analyzed. Perioperative results were presented according to European Hernia Society (EHS) classifications. Pre- and post-operative hernia-specific quality-of-life (QoL) assessments were conducted. Results Twenty patients who underwent an h-rTAR were included in this study. All hernias were incisional. A bilateral TAR needed in 90% of patients. The average hospital stay was 1.8 days. Two patients experienced medical complications and 5 patients experienced surgical site events. None of the patients experienced a hernia recurrence throughout a mean postoperative follow-up period of 319 days. PROs showed improvement in all domains, especially cosmetic. Conclusion The h-rTAR technique combines the benefits of robotic and open techniques when used for large incisional VHR with improvement in patient-reported QoL.Zirconia is the preferred material for dental restorations; however, dental restorations are usually affected by zirconia fractures due to chipping and delamination of the veneer ceramic. One effective solution for repairing chemically inert zirconia frameworks is to strongly chemically bond them with the composite resin via surface modification. Thus, the bonding strength between the zirconia and composite resin determines the performance of dental restoration. Herein, we investigate the shear bond strength between zirconia ceramic and two ceramic repair systems before and after thermal cycling based on different surface pretreatments, including air-abrasion and a novel silane coupling agent. When treated with combined sandblasting, novel silane and 10-methacryloyloxydecyl hydrogen phosphate act as a bonding agent for the zirconia surface, and the maximum shear bond strength achieves 27.5 MPa, as measured by a universal testing machine through the average of 16 separate measurements. The results show that the combined treatment resists the interface damage caused by expansion and contraction during thermal cycling.