Pramanicin analog induces apoptosis in human colon cancer cells: critical roles for Bcl-2, Bim, and p38 MAPK signaling

Pramanicin (PMC) is an antifungal agent that was previously demonstrated to exhibit antiangiogenic and anticancer properties in a few in vitro studies. We initially screened a number of PMC analogs for their cytotoxic effects on HCT116 human colon cancer cells. PMC-A, the analog with the most potent antiproliferative effect was chosen to further interrogate the underlying mechanism of action. PMC-A led to apoptosis through activation of caspase-9 and -3. The apoptotic nature of cell death was confirmed by abrogation of cell death with pretreatment with specific caspase inhibitors. Stress-related MAPKs JNK and p38 were both activated concomittantly with the intrinsic apoptotic pathway. Moreover, pharmacological inhibition of p38 proved to attenuate the cell death induction while pretreatment with JNK inhibitor did not exhibit a protective effect. Resistance of Bax -/- cells and the protective nature of caspase-9 inhibition indicate that mitochondria play a central role in PMC-A induced apoptosis. Early post-exposure elevation of cellular Bim and Bax was followed by a marginal Bcl-2 depletion and Bid cleavage. Further analysis revealed that Bcl-2 downregulation occurs at the mRNA level and is critical to mediate PMC-A induced apoptosis, as ectopic Bcl-2 expression substantially spared the cells from death. Conversely, forced expression of Bim proved to significantly increase cell death. In addition, analyses of p53-/- cells demonstrated that Bcl-2/Bim/Bax modulation and MAPK activations take place independently of p53 expression. Taken together, p53-independent transcriptional Bcl-2 downregulation and p38 signaling appear to be the key modulatory events in PMC-A induced apoptosis

Design of a robot-assisted exoskeleton for passive wrist and forearm rehabilitation

This paper presents a new exoskeleton design for wrist and forearm rehabilitation. The contribution of this study is to offer a methodology which shows how to adapt a serial manipulator that reduces the number of actuators used on exoskeleton design for the rehabilitation. The system offered is a combination of end-effector- and exoskeleton-based devices. The passive exoskeleton is attached to the end effector of the manipulator, which provides motion for the purpose of rehabilitation process. The Denso VP 6-Axis Articulated Robot is used to control motion of the exoskeleton during the rehabilitation process. The exoskeleton is designed to be used for both wrist and forearm motions. The desired moving capabilities of the exoskeleton are flexion–extension (FE) and adduction–abduction (AA) motions for the wrist and pronation–supination (PS) motion for the forearm. The anatomical structure of a human limb is taken as a constraint during the design. The joints on the exoskeleton can be locked or unlocked manually in order to restrict or enable the movements. The parts of the exoskeleton include mechanical stoppers to prevent the excessive motion. One passive degree of freedom (DOF) is added in order to prevent misalignment problems between the axes of FE and AA motions. Kinematic feedback of the experiments is performed by using a wireless motion tracker assembled on the exoskeleton. The results proved that motion transmission from robot to exoskeleton is satisfactorily achieved. Instead of different exoskeletons in which each axis is driven and controlled separately, one serial robot with adaptable passive exoskeletons is adequate to facilitate rehabilitation exercises.</p

The effects of maternal smoking on fetal cranial development. Findings from routine midtrimester sonographic anomaly screening

The aim of this study was to assess the effect of continued smoking before and during pregnancy on mid-trimester fetal head development. A total of 250 pregnant women enrolled in the study. All participants were confirmed to be smokers or non-smokers by verifying breath carbon monoxide readings. Biparietal diameter (BPD), head circumference (HC), lateral ventricle (LV), and cisterna magna (CM) were evaluated by ultrasound between 20-22 weeks of pregnancy. Gender and gestational age-adjusted BPD z- scores were not statistically different between smokers and non-smokers (-0.75 ± 1.6 vs -0.51 ± 1, p = .3). HC measurements and z- scores were significantly lower in the smoking group than in the non-smoking groups (183.38 ± 14.56 vs. 189.28 ± 12.53, p = .003, 0.18 ± 1.39 multiple of median (MoM) vs. 0.56 ± 0.92, respectively, p = .023). At linear regression analysis, maternal smoking was the only independent factor associated with fetal HC z score (p = .041). In conclusion, continued smoking during pregnancy reduces fetal HC and has no effect on BPD, LV, or CM measurements at mid-gestation.IMPACT STATEMENTWhat is already known on this subject? Smoking during pregnancy is one of the most common environmental factors affecting fetal and neonatal growth and well-being. Despite the well-known effects of smoking on somatic growth, current studies have shown that it selectively affects some parts of the fetal brain, even in appropriately growing fetuses.What do the results of this study add? Continued smoking during pregnancy reduces fetal HC and has no effect on BPD, LV or CM measurements at mid-gestation. Since smoking is well known for its early and late childhood behavioral and neurological consequences, smaller mid-trimester fetal HC measurements should bring maternal smoking to mind as one of the potentially reversible causes.What are the implications of these findings for clinical practice and/or further research? The harmful effects of smoking start before the third trimester and antenatal counseling should be started early in the gestation. Every effort should be made to quit smoking before or early in pregnancy

The Role of the Urine Dipstick Test in the Detection of Abnormal Proteinuria Using Different Cut-off Levels in Hypertensive Pregnancies Hipertansif Gebeliklerde Farklı Kesim Değerleri Kullanılarak Anormal Proteinüri Saptanmasında Spot İdrar Protein Ölçümünün Rolü

© 2022, Duzce University Medical School. All rights reserved.Aim: The aim of this study was to determine the diagnostic accuracy of different urine dipstick protein threshold levels in predicting the presence of abnormal proteinuria in pregnant women with hypertension. Material and Methods: A total of 326 singleton pregnant women who underwent 501 urine protein tests and who had suspected preeclampsia were included in this retrospective study. Patient data was taken including medical and obstetric history. The results of dipstick urinalysis and concurrent 24-hour urine protein excretion measurements were compared to determine the accuracy of urinalysis. Results: A dipstick result of 1+ was found to be the best cut-off to predict 500 mg of protein excretion per day, with sensitivity and specificity of 62.09% and 88.97%, respectively. A 2+ proteinuria dipstick cut-off had high specificity and positive predictive value (PPV) (99.05% and 98.84%, respectively) for the prediction of 300 mg of protein excretion per day; this cut-off had low sensitivity (21.46%). A cut-off of 1+ also provided satisfactory specificity and PPV (91.43% and 94.48%, respectively) for the detection of 300 mg of protein excretion per day, but sensitivity was compromised (38.89%). Among 301 patients with negative dipstick results, 212 had a 24-hour urine protein extraction greater than 300 mg, with a false negative rate of 70.43%. Conclusion: The results suggest that the urine protein dipstick measurement has limited quantitative ability for the prediction of abnormal proteinuria. Additionally, the use of 500 mg 24-hours protein excretion as a cut-off value for abnormal proteinuria may provide useful data

The Correlation of the SLAP II Lesion Findings Between Physical Examination, Magnetic Resonance Imaging, and Arthroscopic Surgery

Objectives The aim of this study is to demonstrate the importance of clinical diagnosis by comparing with preoperative physical examination and magnetic resonance imaging (MRI) images in patients who were arthroscopically diagnosed as having Superior Labrum Anterior-Posterior (SLAP) II lesions. Materials and Methods 134 patients, arthroscopically diagnosed as SLAP II, established the study group, and 200 patients who underwent shoulder arthroscopy for the other pathologies established the control group. Preoperative clinical examination of the patients, MRI findings, and the arthroscopic findings of the patients were recorded. Results Out of the patients diagnosed with a SLAP II lesion, 107 (79.9) of those had an MRI finding while only 60 (30\%) of the control group had it. The O'Brien test results of the patients diagnosed with SLAP were positive in 111 (82.8\%) while those diagnosed with intact superior labrum were positive in 132 (66\%). Of the 134 patients with a SLAP II lesion, 89 (66.4\%) had both O'Brien test positiveness and MRI finding, and 129 (96\%) had at least one positive result of the O'Brien test or MRI examination Conclusion The O'Brien test and MRI examination are not capable enough to indicate a SLAP lesion one by one, because of the low sensitivity and specificity. But, combining the test with MRI findings provides more trustable information about the superior labrum