Design, synthesis and biological evaluation of a new thieno[2,3-d]pyrimidine-based urea derivative with potential antitumor activity against tamoxifen sensitive and resistant breast cancer cell lines

Breast cancer (BC) and endocrine resistance to chemotherapy are challenging problems where angiogenesis plays fundamental roles. Thus, targeting of VEGFR-2 signalling pathway has been an attractive approach. In this study, we synthesised a new sorafenib analogue, thieno[2,3-d]pyrimidine based urea derivative, KM6. It showed 65% inhibition of VEGF2 tyrosine kinase activity and demonstrated a potential antitumor activity in TAM-resistant, LCC2, and its parental MCF7 BC cells. KM6 retained the sensitivity of LCC2 through upregulation of key enzymes of apoptosis and proteins of cell death including caspases 3, 8, 9, P53, BAX/BCL-2 ratio and LDH in media. It downregulated mRNA expression of Ki-67, survivin, Akt, and reduced levels of ROS and glucose uptake. Moreover, KM6 reduced the levels of inflammation markers PGE2, COX2, IL-1β and IL6 and metastasis markers MMP-2 and MMP-9. In conclusion, KM6 is a promising compound for ER + and TAM-resistant BC with many potential antitumor and polypharmacological mechanisms

Enhancing PM_2.5 Prediction Using NARX-Based Combined CNN and LSTM Hybrid Model

In a world where humanity’s interests come first, the environment is flooded with pollutants produced by humans’ urgent need for expansion. Air pollution and climate change are side effects of humans’ inconsiderate intervention. Particulate matter of 2.5 µm diameter (PM2.5) infiltrates lungs and hearts, causing many respiratory system diseases. Innovation in air pollution prediction is a must to protect the environment and its habitants, including those of humans. For that purpose, an enhanced method for PM2.5 prediction within the next hour is introduced in this research work using nonlinear autoregression with exogenous input (NARX) model hosting a convolutional neural network (CNN) followed by long short-term memory (LSTM) neural networks. The proposed enhancement was evaluated by several metrics such as index of agreement (IA) and normalized root mean square error (NRMSE). The results indicated that the CNN–LSTM/NARX hybrid model has the lowest NRMSE and the best IA, surpassing the state-of-the-art proposed hybrid deep-learning algorithms

Rebound increase in microRNA levels at the end of 5-FU-based therapy in colorectal cancer patients

Abstract Treatment with 5-fluorouracil (5-FU) based therapy is still used for colorectal cancer (CRC). Epigenetics has become a focus of study in cancer because of its reversibility besides its known regulatory functions. In this study, we will monitor the change in microRNAs (miRNAs) levels with 5-FU-based therapy at baseline and after 3 and 6 months of treatment to be correlated with their prognostic potential. The expression levels of 5 miRNAs, namely miRNA223-3p, miRNA20a-5p, miRNA17-5p, miRNA19a-3p, and miRNA7-5p, were measured in the peripheral blood of 77 CRC patients, along with the expression of 3 proteins PTEN, ERK, and EGFR. At baseline, CRC patients had significantly higher levels of circulating miRNAs than healthy controls. This level was reduced after 3 months of 5-FU-based therapy, then increased after 6 months significantly in responder patients compared to non-responders. MiRNA19a-3p showed that significant pattern of change in the subgroups of patients with high ERK, EGFR, and PTEN protein levels, and its 6 months level after 5-FU-based therapy showed significance for the hazard of increased risk of disease recurrence and progression

Changes in digital cast measurements related with two types of rapid maxillary expanders, tooth-borne versus hybrid one: A retrospective cohort study

Objectives: This study compared digital study casts from tooth-borne and hybrid Rapid Maxillary Expansion (RME) using 3D virtual models scanned with a 3Shape laser scanner. Methods: A total of thirty patients with narrow maxilla were distributed into two equal groups using sequential randomization. The hybrid hyrax group (11 females and 4 males) had a mean age of 14.5 years, whereas the conventional hyrax group (10 females and 5 males) had a mean age of 13.96 years. Cone beam computed tomography and orthodontic casts were obtained before expansion and six months after the last activation. Eight parameters were measured, and the data was analyzed. Results: A paired t-test was used to evaluate the mean differences between pre-expansion and post-expansion measurements. Interdental distance (IDD) and rotations at first molar and premolars showed a statistically significant increase post-treatment compared to preoperative values, whereas arch depth and incisor inclination showed a statistically significant decrease. Furthermore, group B had statistically significant higher postoperative values and a greater IDD change (P≤0.05). Conclusion: RME with hybrid hyrax achieved skeletal effects and broaden the arch with only a slight increase in IDD compared to traditional RME. Regardless of the appliance, arch depth may be decreased following RME

Egyptian pediatric clinical practice adapted guidelines: evidence-based [2] steroid-resistant nephrotic syndrome (SRNS) 2022

Abstract Background Nephrotic syndrome is one of the most common chronic kidney diseases in children. Steroid sensitive type (SSNS) constitutes about 85–90%, whereas steroid-resistant type (SRNS) only 15–20% (Mickinney et al. Pediatr Nephrol 16:1040-1044, 2001). While MCD is the most common histopathology in SS type, children with SRNS have MCD, mesangial proliferative glomerulonephritis, or focal and segmental glomerulosclerosis (FSGS) (International Study Kidney Disease in children, Kidney Int 20;765-771, 1981). SRNS is defined as those who do not show remission after 6 weeks and standard dose of oral steroids ± 3 IV MPD doses (Trautmann et al. Pediatr Nephrol 35:1529-1561, 2020). Objectives These national adapted guidelines aim to frame evidence-based recommendations adopted or adapted from the IPNA 2020, KDIGO 2021, and Japanese 2014 de novo guidelines for diagnosis and management of nephrotic children to be presented in two manuscripts: (1) steroid sensitive (SSNS) and (2) steroid-resistant nephrotic syndrome (SRNS). Methodology Formulation of key questions was followed with a review of literature guided by our appraised guidelines using AGREE plus appraisal tool. Virtual monthly meetings all through the year 2021 were activated  for reviewing and validation of final adaptation evidence-based draft, considering all comments of external reviewers including KDIGO assigned reviewer. Discussion Rationale behind the selection of adopted statements and tailoring of others to suit our local facilities, expertise, and our local disease profile was discussed in the text with reasons. Conclusion The provided guidelines aim to optimize patient care and outcome and suggest research areas lacking validated research recommendations