Distinct MAPK signaling pathways, p21 up-regulation and caspase-mediated p21 cleavage establishes the fate of U937 cells exposed to 3-hydrogenkwadaphnin: differentiation versus apoptosis

Despite the depth of knowledge concerning the pathogenesis of acute myeloblastic leukemia (AML), long-term survival remains unresolved. Therefore, new agents that act more selectively and more potently are required. In that line, we have recently characterized a novel diterpene ester, called 3-hydrogenkwadaphnin (3-HK), with capability to induce both differentiation and apoptosis in various leukemia cell lines. These effects of 3-HK were mediated through inhibition of inosine 5′-monophosphate dehydrogenase, a selective up-regulated enzyme in cancerous cells, especially leukemia. However, it remains elusive to understand how cells display different fates in response to 3-HK. Here, we report the distinct molecular signaling pathways involved in forcing of 3-HK-treated U937 cells to undergo differentiation and apoptosis. After 3-HK (15 nM) treatment, a portion of U937 cells adhered to the culture plates and showed macrophage criteria while others remained in suspension and underwent apoptosis. The differentiated cells arrested in G₀/G₁ phase of cell cycle and showed early activation of ERK1/2 pathway (3 h) along with ERK-dependent p21^Cip/WAF1 (p21) up-regulation and expression of p27^Kip1 and Bcl-2. In contrast, the suspension cells underwent apoptosis through Fas/FasL and mitochondrial pathways. The occurrence of apoptosis in these cells were accompanied with caspase-8-mediated p21 cleavage and delayed activation (24 h) of JNK1/2 and p38 MAPK. Taken together, these results suggest that distinct signaling pathways play a pivotal role in fates of drug-treated leukemia cells, thus this may pave some novel therapeutical utilities.     

A Systematic Review on Overall Survival and Disease-Free Survival Following Total Pelvic Exenteration

Backgrounds: Total Pelvic Exenteration (TPE) is a radical operation for malignancies in which all of the organs inside the pelvic cavity, including the female reproductive organs, the lower urinary tract, and a part of the rectosigmoid are removed. In this study, we aimed to conduct a systematic review to assess the overall survival (OS) and disease-free survival (DFS) following TPE. Methods: This systematic review is composed of a comprehensive review of PubMed and Scopus databases with various related keywords to synthesis the overall survival and disease-free survival following TPE. The Synthesis Without Meta-analysis guideline was used to summarize the results. Results: We included the results of 39 primary studies and the results revealed that one-year OS of gynecological cancer in patients who have undergone TPE ranged from 50.0% to 72.0% and the 5-years OS ranged from 6.0% to 64.6%. The one-year survival rate of colorectal cancer patients was reported to be over 80% in almost all studies. The 3-year survival rate of patients varied from 25% to 75% and the lowest 5-year survival rate was 8% and the highest survival rate was 92%. To synthesis the disease-free survival rate in colorectal cancer, ten studies were included and one-year recurrence rate was 9.1% and the one-year DFS was reported as 61.0%. Three-year recurrence rate study was 20.4% and 3 and 5-year DFS ranged from 22.0% to 78.0%. Conclusions: The results suggested that DFS in primary advanced cancers is higher than locally recurrence tumors. This review showed that patient overall survival and disease-free survival rates have increased over time, especially at high volume centers that are more experienced and possibly better equipped. Therefore, it can be suggested that the attitude towards PE as a palliative surgery can be turned into curative surgery.     

Liver of ovariectomized rats is resistant to resorption of lipids

Ovarian hormones have been shown to regulate liver lipid accumulation in rats. The present study was designed to evaluate liver lipid resorption in ovariectomized (Ovx) rats. Ovx and sham-operated (Sham) rats were submitted to a high-fat (HF; 43% kcal fat as energy) diet for 5 weeks and then either maintained on this diet or switched to a standard (SD; 12.5% kcal fat as energy) diet till weeks 8 and 13 (n=8 rats/group). Body weight, energy intake, liver and intra-abdominal fat accumulation and plasma metabolic profile were determined. Body weight was significantly (P<0.01) higher in Ovx than in Sham groups at all times and switching diet did not alter the body weight pattern. The weight of the intra-abdominal fat depots and plasma leptin levels, along with liver triacylglycerol (TAG) concentrations, were significantly higher (P<0.01) in Ovx than in Sham rats. Switching diet reduced intra-abdominal fat depot weight and plasma leptin in all groups. Switching diet also resulted in a decrease in liver fat accumulation in Sham rats at all times. However, 8 weeks after the diet switch (week 13) liver fat accumulation was as high in Ovx rats as those maintained on the HF diet. When liver TAG values measured at week 13 were compared to initial pre-switching values (week 5), liver TAG levels in Ovx animals were maintained at the same level independently of the diet switch, while in Sham rats switching to a SD diet reduced liver TAG accumulation (P<0.05). The same comparisons with plasma TAG levels revealed an opposite relationship. These data suggest that liver lipid resorption in Ovx animals is more related to the ovarian hormone status than to the type of ingested diet.     

Serum salusin-β levels in patients with systemic lupus erythematosus

Clinical Rheumatology - Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-β...     

Design and usability evaluation of a mobile-based-self-management application for caregivers of children with severe burns

Paediatric burns are a major public health issue because of long-term physical, psychological and social consequences and the high cost of treatment. The aim of this study was to design and evaluate a mobile-based self-management application for caregivers of children with severe burns. A participatory design technique was employed to develop the Burn application, which included three main phases: the determination of application requirements, the design and evaluation of the low-fidelity prototype, and the design and evaluation of the high-fidelity prototypes. In the first phase, application requirements were determined via validated paper questionnaires using the Delphi technique. In the second step, a low-fidelity prototype was prepared using conceptual models and evaluated through a focus group with specialists. Seven specialists reviewed the application and evaluated how this prototype meets functional requirements and objectives. The third phase was performed in three stages. First, the high-fidelity prototype was designed and developed by the JAVA programming language. Second, a cognitive walk-through was carried out to show how users can interact with the mobile application and how it works. Third, this program was installed on the mobile phones of 28 caregivers of burned children, eight IT experts, and two general surgeries, and the prototype's usability was evaluated. In the present study, most caregivers of children with burns stated that after discharge, they face problems regarding infection control and wound care (4.07) and how to perform physical activity (4.12). User registration, educational materials, caregiver-clinician communication, chat box, and appointment booking, safe login were the most important characteristic of the Burn application. Mean usability evaluation scores were in the range of 7.92 ± 0.238 to 8.10 ± 0.103, which is considered at a “good” level. From the Burn program design experience, it can be concluded that co-design with health care specialists can significantly support and meet the specialists' and patients' needs and ensure the program's usefulness. In addition, application evaluation by users involved and not involved in the application design process can help enhance usability.