A preliminary study of the anti-proliferative effect of Aronia Melanocarpa extract on human colon cancer cells and its relation with human TERT protein

Aim: Aronia melanocarpa is a fruit exhibiting antioxidant, anti-inflammatory, antidiabetic, hypolipidemic, and anticarcinogenic properties. Telomerase is a critical factor in the development of colon cancer, and it is being looked at as a target for cancer treatments. In the present study, we aimed to examine the potential effect of Aronia melanocarpa extract on cell viability and protein concentration of the human telomerase reverse transcriptase (hTERT) in the human colon cancer cell line (HT-29) and the non-tumorigenic human umbilical vein endothelial cell line (HUVEC). Methods: Cell lines were treated with different concentrations of Aronia extract (50-750 μg/ml) for 48 h. The cytotoxic activity of Aronia extract was determined using the MTT assay. hTERT protein concentration (pg/ml) was measured using a sandwich ELISA. Results: The MTT assay test showed that Aronia extract induces 50% cell death (IC50) at a concentration of 186 μg/mL at 48 h post-treatment in the HT-29 cell line. Cytotoxicity results showed a dose-dependent decrease in cell viability in the HT-29 cell line. However, increasing Aronia extract concentrations showed no similar effect on the HUVEC cell line. The hTERT protein concentration in HT-29 cells was 1.9-fold higher than that of HUVEC cells. Increasing concentrations of Aronia extract was linked with a significant decrease in hTERT protein level in HT-29 cells, whereas the hTERT protein concentration in HUVEC cells did not change significantly. Conclusions: Our results suggest that A. melanocarpa may be a potential therapeutic agent for anticarcinogenic activity. Also, the anti-proliferative effects of Aronia extract may be attributed, at least partly, to the decreased hTERT protein level of HT-29 cells.&nbsp

Lets Talk about Race: Identity, Chatbots, and AI

Why is it so hard for chatbots to talk about race? This work explores how the biased contents of databases, the syntactic focus of natural language processing, and the opaque nature of deep learning algorithms cause chatbots difficulty in handling race-talk. In each of these areas, the tensions between race and chatbots create new opportunities for people and machines. By making the abstract and disparate qualities of this problem space tangible, we can develop chatbots that are more capable of handling race-talk in its many forms. Our goal is to provide the HCI community with ways to begin addressing the question, how can chatbots handle race-talk in new and improved ways

Magnetic resonance imaging based kidney volume assessment for risk stratification in pediatric autosomal dominant polycystic kidney disease

IntroductionIn the pediatric context, most children with autosomal dominant polycystic kidney disease (ADPKD) maintain a normal glomerular filtration rate (GFR) despite underlying structural kidney damage, highlighting the critical need for early intervention and predictive markers. Due to the inverse relationship between kidney volume and kidney function, risk assessments have been presented on the basis of kidney volume. The aim of this study was to use magnetic resonance imaging (MRI)-based kidney volume assessment for risk stratification in pediatric ADPKD and to investigate clinical and genetic differences among risk groups.MethodsThis multicenter, cross-sectional, and case-control study included 75 genetically confirmed pediatric ADPKD patients (5–18 years) and 27 controls. Kidney function was assessed by eGFR calculated from serum creatinine and cystatin C using the CKiD-U25 equation. Blood pressure was assessed by both office and 24-hour ambulatory measurements. Kidney volume was calculated from MRI using the stereological method. Total kidney volume was adjusted for the height (htTKV). Patients were stratified from A to E classes according to the Leuven Imaging Classification (LIC) using MRI-derived htTKV.ResultsMedian (Q1-Q3) age of the patients was 6.0 (2.0–10.0) years, 56% were male. There were no differences in sex, age, height-SDS, or GFR between the patient and control groups. Of the patients, 89% had PKD1 and 11% had PKD2 mutations. Non-missense mutations were 73% in PKD1 and 75% in PKD2. Twenty patients (27%) had hypertension based on ABPM. Median htTKV of the patients was significantly higher than controls (141 vs. 117 ml/m, p = 0.0003). LIC stratification revealed Classes A (38.7%), B (28%), C (24%), and D + E (9.3%). All children in class D + E and 94% in class C had PKD1 variants. Class D + E patients had significantly higher blood pressure values and hypertension compared to other classes (p > 0.05 for all).DiscussionThis study distinguishes itself by using MRI-based measurements of kidney volume to stratify pediatric ADPKD patients into specific risk groups. It is important to note that PKD1 mutation and elevated blood pressure were higher in the high-risk groups stratified by age and kidney volume. Our results need to be confirmed in further studies

C-REACTIVE PROTEIN/ALBUMIN RATIO IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Type 2 diabetes mellitus (T2DM) is an inflammatory condition. C-reactive protein (CRP) is a well-known inflammatory marker for demonstrating systemic inflammation in T2DM. We aimed to compare the diagnostic value of CRP and C-reactive protein to albumin ratio (CAR) in discriminating T2DM patients and healthy controls and to investigate the association of CAR and glycemic control markers. This cross-sectional retrospective study included 173 T2DM patients and 104 healthy control subjects. Serum albumin and CRP levels were measured with spectrophotometric and nephelometric methods, respectively. CAR was calculated by dividing CRP level by albumin level. The median (interquartile range, IQR) CAR in the T2DM patients was significantly higher than those in the controls (0.15 (0.26) vs. 0.06 (0.20), p = 0.002, respectively). In receiver operating characteristics curve analysis (ROC), CAR > 0.0653 had 77.21% sensitivity and 52.44% specificity in discriminating T2DM. The area under ROC curve for CAR was 0.623 (95% CI =0.544-0.701, p=0.002), which was similar to CRP. A positive correlation was found between CAR and body mass index, fasting blood glucose and HbA1c levels. As a result, CAR demonstrated poor sensitivity and specificity for discriminating T2DM patients from healthy subjects and it has little diagnostic utility in diabetes

Forced expression of Wnt antagonists sFRP1 and WIF1 sensitizes chronic myeloid leukemia cells to tyrosine kinase inhibitors

Chronic myeloid leukemia is a clonal myeloproliferative disorder that arises from the neoplastic transformation of the hematopoietic stem cell, in which the Wnt/-catenin signaling pathway has been demonstrated to play an important role in disease progression. However, the role of Wnt signaling antagonists in therapy resistance and disease progression has not been fully investigated. We aimed to study the effects of Wnt/-catenin pathway antagonistssecreted frizzled-related protein 1 and Wnt inhibitory factor 1on resistance toward tyrosine kinase inhibitors in chronic myeloid leukemia. Response to tyrosine kinase inhibitors was analyzed in secreted frizzled-related protein 1 and Wnt inhibitory factor 1 stably transfected K562 cells. Experiments were repeated using a tetracycline-inducible expression system, confirming previous results. In addition, response to tyrosine kinase inhibitor treatment was also analyzed using the secreted frizzled-related protein 1 expressing, BCR-ABL positive MEG01 cell line, in the presence and absence of a secreted frizzled-related protein 1 inhibitor. Our data suggests that total cellular -catenin levels decrease in the presence of secreted frizzled-related protein 1 and Wnt inhibitory factor 1, and a significant increase in cell death after tyrosine kinase inhibitor treatment is observed. On the contrary, when secreted frizzled-related protein 1 is suppressed, total -catenin levels increase in the cell and the cells become resistant to tyrosine kinase inhibitors. We suggest that Wnt antagonists carry the potential to be exploited in designing new agents and strategies for the advanced and resistant forms of chronic myeloid leukemia

sFRP1 Expression Regulates Wnt Signaling in Chronic Myeloid Leukemia K562 Cells

Background: Wnt signaling cascades play important roles in cell fate decisions and their deregulation has been documented in many diseases, including malignant tumors and leukemia. One mechanism of aberrant Wnt signaling is the silencing of Wnt inhibitors through epigenetic mechanisms. The sFRPs are one of the most studied Wnt inhibitors; and the sFRP1 loss is known in many hematological malignancies. Therefore, we aimed to compare the expression of Wnt related genes in the presence and absence of sFRP1 in a chronic myeloid leukemia (CML) cell line. Objective: It is important to understand how sFRP1 and sFRP1 perform their effects on CML to design new agents and strategies for resistant and advanced forms of CML. Materials and Methods: We used K562 cells, which normally do not express sFRP1 and its sFRP1 expressing subclone K562s. Total RNA was isolated from K562 and K562s cell lines and converted to cDNA. PCR Array experiments were performed using Human Wnt Signaling Pathway Plus RT2 Profiler (TM) kit. Wnt signaling pathway activation was studied by western blot for downstream signaling targets. Results: The WNT3, LRP6, PRICKLE1 and BTRC expressions were significantly decreased in the presence of sFRP1; while WNT5B increased. The sFRP1 expression inhibited stabilization of total beta-catenin protein and downstream effector phosphorylation of noncanonical Wnt/PCP signaling; whereas Ca2+/PKC signaling remained active. Conclusion: The results suggest that sFRP1 could be a promising therapeutic anticancer agent. Defining these pathway interactions is crucial for designing new agents resistant and advanced forms of CML

A retrospective study on traumatic diaphragmatic hernias in cats

Besalti, Omer/0000-0002-7819-9094WOS: 000307987700005The purpose of the study was to evaluate the clinical and surgical findings of traumatic diaphragmatic hernia in 52 cats and to determine the association with mortality rate. The medical and surgical records of fifty two cats that underwent surgical repair for traumatic diaphragmatic hernia were reviewed retrospectively. Survival rate was 82.7% (43/52) in cats. The most frequently herniated organ was liver (81%). This was followed by small intestines (67%), stomach (48%), omentum (38.5%), spleen (25%), pancreas (13.5%) and large intestines (8%) respectively. Thirty-one cases had acute and 21 cases had chronic diaphragmatic hernia and mortality rate was 16.1% and 19% respectively. Although the majority of the rupture was in the right side, death was not recorded in these cases. The mortality rates according to the rupture sites were 57% in central, 24% in ventral and 19% in the left side. On the other hand, it was recorded that the mortality rate was associated with the amount of organ herniation. The more excessive amount of organ herniation resulted in higher mortality rate. It was concluded that mortality rate could be related to the location of hernia, amount of herniated organs and time from trauma to the surgery

Clinical and Surgical Evaluation of Perineal Hernia in Dogs: 41 Cases

Besalti, Omer/0000-0002-7819-9094;WOS: 000278958100007The purpose of the study was to report the clinical and surgical records of perineal hernia and associated rectal pathology with epidural morphine analgesia in 41 dogs. Fourty one dogs suffered from perineal hernia were included into the study with the age varied from 4.5 to 16 years. Eleven dogs had bilateral while the other 30 had unilateral (17 right, 13 left) perineal hernia. The clinical signs were perianal swelling (n=41), severe tenesmus (n=19), dyschesia (n=9), proctitis (n=7), fecal incontinence (n=4), stranguria (n=2) and hematuria (n=1). Associated rectal pathologies were diverticulation (n=15), dilatation (n=4), deviation (n=3) and sacculation (n=1). The rectal diverticulum was corrected by extraluminal plication (n=12) or rectal resection (n=3). Internal obturator muscle flap transposition was used to repair the hernia in all cases. Postoperative pain was subjectively evaluated and scores were "no pain" in 10 cases, mild in 28 cases, moderate in 3 cases. Mean follow-up time was 27.3 months (range 4 months to 5 years) and the recurrence was observed only in three cases postoperatively. In conclusion, combined perineal herniorraphy with internal obturator muscle transposition and rectal wall repairment can be carried out at the same time and epidural morphine administration provide adequate analgesia for these operations

Forced expression of Wnt antagonists sFRP1 and WIF1 sensitizes chronic myeloid leukemia cells to tyrosine kinase inhibitors

Chronic myeloid leukemia is a clonal myeloproliferative disorder that arises from the neoplastic transformation of the hematopoietic stem cell, in which the Wnt/-catenin signaling pathway has been demonstrated to play an important role in disease progression. However, the role of Wnt signaling antagonists in therapy resistance and disease progression has not been fully investigated. We aimed to study the effects of Wnt/-catenin pathway antagonistssecreted frizzled-related protein 1 and Wnt inhibitory factor 1on resistance toward tyrosine kinase inhibitors in chronic myeloid leukemia. Response to tyrosine kinase inhibitors was analyzed in secreted frizzled-related protein 1 and Wnt inhibitory factor 1 stably transfected K562 cells. Experiments were repeated using a tetracycline-inducible expression system, confirming previous results. In addition, response to tyrosine kinase inhibitor treatment was also analyzed using the secreted frizzled-related protein 1 expressing, BCR-ABL positive MEG01 cell line, in the presence and absence of a secreted frizzled-related protein 1 inhibitor. Our data suggests that total cellular -catenin levels decrease in the presence of secreted frizzled-related protein 1 and Wnt inhibitory factor 1, and a significant increase in cell death after tyrosine kinase inhibitor treatment is observed. On the contrary, when secreted frizzled-related protein 1 is suppressed, total -catenin levels increase in the cell and the cells become resistant to tyrosine kinase inhibitors. We suggest that Wnt antagonists carry the potential to be exploited in designing new agents and strategies for the advanced and resistant forms of chronic myeloid leukemia