Langstonparsons8087

This work is about synergy of theory and experiment in revealing mechanism of binding of dipeptidyl peptidase III (DPP III) and Kelch-like ECH-associated protein 1 (KEAP1), the main cellular sensor of oxidative stress. The NRF2 ̶ KEAP1 signaling pathway is important for cell protection, but it is also impaired in many cancer cells where NRF2 target gene expression leads to resistance to chemotherapeutic drugs. DPP III competitively binds to KEAP1 in the conditions of oxidative stress and induces release of NRF2 and its translocation into nucleus. The binding is established mainly through the ETGE motif of DPP III and the Kelch domain of KEAP1. However, although part of a flexible loop, ETGE itself is firmly attached to the DPP III surface by strong hydrogen bonds. Using combined computational and experimental study, we found that DPP III ̶ Kelch binding is a two-step process comprising the endergonic loop detachment and exergonic DPP III ̶ Kelch interaction. Substitution of arginines, which keep the ETGE motif attached, decreases the work needed for its release and increases DPP III ̶ Kelch binding affinity. Interestingly, mutations of one of these arginine residues have been reported in cBioPortal for cancer genomics, implicating its possible involvement in cancer development. Communicated by Ramaswamy H. Sarma.

Although acute pancreatitis (AP) is a self-limited disease under supportive and medical treatment, it can have life-threatening potential in some patients. Results of studies reporting outcomes of AP-associated pancreatic malignancy are controversial. The aim of this study was to evaluate the severity and prognosis of pancreatic cancer (PC)-related AP by modified Balthazar score.

A total of 354 patients hospitalized and followed up in our clinic between 2013 and 2019 were included in the study. Demographic data of all patients were recorded. The etiology of all cases was determined. According to the etiology, the cases were divided into 2 groups AP related to pancreatic malignancy and AP due to nonmalignant causes. The patients underwent computed tomography of the abdomen within the first 12 hours of admission and after 3 to 7 days. Patients were evaluated and classified by modified Balthazar classification.

Malignancy-related AP was detected in 18 (5.1%) patients. A total of 336 cases (94.9%) were related to nonmalignant causes. There was no statistically significant difference in the severity of AP in both groups at admission and after 3 days (

> 0.05). The changes (regression, progression, or no change) in the disease severity at the first and the subsequent imaging were examined. There was no significant relationship between the 2 groups (

> 0.05).

AP may be the clinical manifestation of PC or PC may induce AP in various ways. It was shown that the underlying malignancy did not adversely affect the severity and course of AP.

AP may be the clinical manifestation of PC or PC may induce AP in various ways. It was shown that the underlying malignancy did not adversely affect the severity and course of AP.

To compare the sociodemographic, diagnostic, clinical, and treatment-related characteristics and outcomes of patients with breast cancer in two hospitals in Mexico according to type of healthcare coverage.

A retrospective cohort study of women with breast cancer according to public or private healthcare coverage in two hospitals was done. Selleck NVP-BHG712 Patients were treated by the same group of physicians and healthcare infrastructure. Groups were compared using the chi-square test for categorical variables, Mann-Whitney U-test and Student's t-test for quantitative variables, and Kaplan-Meier estimator and log-rank test for time dependent outcomes (including recurrence-free and overall survival). A value of p < 0.05 was considered statistically significant.

A total of 282 women were included. Mean age at diagnosis was 52 years. Women with public healthcare coverage were diagnosed more frequently with self-detected tumors (82.8% vs 47.9%, p < 0.001) and advanced clinical stage (III and IV) (31.1% vs 17.8%, p = 0er, trends suggesting worse survival for patients with public medical coverage with stage III and triple-negative disease should encourage close follow-up.

Strategies to promote preventive medicine, diagnostic mammograms, and prompt diagnosis of breast cancer in Mexican women with public health coverage are needed. Access to the main treatment modalities by Seguro Popular and good quality care by an experienced group of physicians likely explains the similar outcomes between patients with private and public healthcare coverage. However, trends suggesting worse survival for patients with public medical coverage with stage III and triple-negative disease should encourage close follow-up.A method for the simultaneous determination in mussel of 8 polychlorinated biphenyls (PCBs), 23 organochlorine pesticides (OCPs), and 35 polycyclic aromatic hydrocarbons (PAHs), including alkyl-PAHs, was optimised using ultrasound-assisted cloudy extraction and gas chromatography-tandem mass spectrometry (GC-MS/MS). Optimal selection of the extraction solvent and the dispersing solvent contributed to a high extraction yield and a clean extract. The ranges of the lower limits of detection of PCBs, OCPs and PAHs were 0.012-0.058, 0.01-0.29 and 0.01-0.5 μg kg-1, respectively. The feasibility of the proposed method was validated by analysing standard reference materials of mussel with satisfactory results. The precision achieved by this method was in the range of 0.677-2.69% (PCBs), 1.14-6.60% (OCPs) and 0.694-7.46% (PAHs), and its accuracy was in the range of 101-104% (PCBs), 99.6-106% (OCPs) and 101-110% (PAHs). The advantages of the method include the simultaneous measurement of 66 analytes and the simplicity, low cost and high sensitivity of the procedure. When the proposed method was used to analyse the target compounds in 11 mussel samples, the analytical results displayed a concentration range of 0.41-0.45 µg kg-1 for PCBs, 0.26-6.49 µg kg-1 for OCPs, and 3.48-30.69 µg kg-1 for PAHs.We have developed a robust procedure for the visual on-site detection of zinc, cadmium and mercury metal ions in an aqueous medium using a polymeric hydrogel matrix-based colorimetric sensor. Zn2+, Cd2+and Hg2+, owing to their biological significant value and environmental harm, have attracted more attention. The selective detection of Zn2+, Cd2+and Hg2+ metal ions has always been challenging due to their closed-shell d10 electronic configuration which makes them spectroscopically silent. A polyacrylamide/carboxymethyl guargum polymeric hydrogel-based metal ion sensor was synthesized by in situ embedding 11, 16-bis (phenyl)-6, 6, 21, 21-tetramethyl-m-benzi-6,21-porphodimethene (meta-BPDM) in a host hydrogel. The meta-BPDM-embedded hydrogel shows high stability, sensitivity and selectivity when it is dipped into the aqueous solutions of Zn2+, Cd2+and Hg2+ metal ions. During detection, the binding of these metal ions in hydrogel causes hydrogel to change from red to bluish-green which was visually detected and confirmed by UV-visible spectroscopy.