Design, Synthesis and Molecular Modeling of Pyrazolo[1,5-]pyrimidine Derivatives as Dual Inhibitors of CDK2 and TRKA Kinases with Antiproliferative Activity.

Background: The increasing prevalence of drug resistance in cancer therapy underscores the urgent need for novel therapeutic approaches. Dual enzyme inhibitors, targeting critical kinases such as CDK2 and TRKA, represent a promising strategy. The goal of this investigation was to design, synthesize, and evaluate a set of pyrazolo[1,5-]pyrimidine derivatives for their dual inhibition potential toward CDK2 and TRKA kinases, along with their potential antiproliferative against cancer cell lines.

Management of Ventilator-Associated Pneumonia Caused by and Organisms in a Pediatric Center: A Randomized Controlled Study.

A dangerous infection contracted in hospitals, ventilator-associated pneumonia is frequently caused by bacteria that are resistant to several drugs. It is one of the main reasons why patients in intensive care units become ill or die. This research aimed to determine the most effective empirical therapy of antibiotics for better ventilator-associated pneumonia control and to improve patient outcomes by using the minimal inhibitory concentration method and the Ameri-Ziaei double antibiotic synergism test and by observing the clinical responses to both single and combination therapies.

Exploring the antiproliferative and proapoptotic activities of new pyridopyrimidine derivatives and their analogs.

This study investigates a series of newly synthesized compounds, including pyridopyrimidine derivatives (9a-g), tricyclic pyridotriazolopyrimidine analogs (18a-d), and dihydropyrimidinones (22a-i), as apoptotic inducers and inhibitors of phosphatidylinositol-3-kinase α (PI3Kα), with potential anticancer activity. An initial in vitro screening of 60 cancer cell lines identified pyridopyrimidine derivatives 9a-g as promising broad-spectrum anticancer agents, with compound 9e demonstrating the strongest inhibitory activity, particularly against T-47D breast cancer cells. Notably, the antitumor potency of compound 9e surpassed that of Pictilisib, inducing G2-M phase cell cycle arrest and initiating apoptosis through the intrinsic apoptotic pathway.

Sulfonamide-Pyrazole derivatives as next-generation Cyclooxygenase-2 enzyme inhibitors: From molecular design to in vivo efficacy.

The current research focuses on the design and synthesis of celecoxib analogues incorporating sulphonamide and pyrazole moieties (4, 5, 6a-e, and 7a-f) with the aim of achieving a broad range of COX-2 selectivity in vitro. Among these, compounds 6b-d, 7a, 7e, and 7d exhibited potent inhibition, with IC values ranging between 0.05 and 0.

Tailoring nursing interventions to empower patients: personal coping strategies and self-management in type 2 diabetes care.

Background: Diabetes is one of the most common chronic diseases that severely reduce a patient's quality of life. Effective self-care and management are critical for maintaining blood glucose levels and preventing complications.

Aim: This study evaluates the effectiveness of a structured diabetes self-management education program on patients' self-management behaviors, empowerment, and activation levels.

Perception, knowledge, and factors influencing Saudi nursing students toward practicing testicular self-examination: A cross-sectional study.

Background: Testicular cancer poses a substantial health burden globally, and early detection through testicular self-examination (TSE) is vital for improving prognosis. The study aims to assess the perception, awareness, knowledge, and factors associated with TSE among Saudi nursing students.

Materials And Methods: A structured questionnaire was distributed to 418 participants.

Design, synthesis, and evaluation of novel benzofuran and pyrazole-based derivatives as dual AChE/BuChE inhibitors with antioxidant properties for Alzheimer's disease management.

As a complicated neurodegenerative disorder with several clinical hallmarks, Alzheimer's disease (AD) requires multi-target treatment medicines to address multiple elements of disease progression. In this study, we reported two novel series of compounds: benzofuran-based donepezil analogs (9a-i) and their pyrazole-based counterparts (11a-i) as potential dual inhibitors of AChE and BuChE with additional antioxidant properties, aiming to address multiple pathological aspects of AD simultaneously. The design strategy employed bioisosteric replacement, substituting donepezil's indanone motif with a benzofuran ring in series (9a-i) to maintain crucial hydrogen bonding interactions with the Phe295 residue in the enzyme's active site.

4-(Pyrazolyl)benzenesulfonamide Ureas as Carbonic Anhydrases Inhibitors and Hypoxia-Mediated Chemo-Sensitizing Agents in Colorectal Cancer Cells.

Hypoxia in tumors contributes to chemotherapy resistance, worsened by acidosis driven by carbonic anhydrases (CA IX and XII). Targeting these enzymes can mitigate acidosis, thus enhancing tumor sensitivity to cytotoxic drugs. Herein, novel 4-(pyrazolyl)benzenesulfonamide ureas () were developed and evaluated for their inhibitory activity against CA IX and XII.

Spiro-fused indoline-quinazoline hybrids as smart bombs against TNF-α-mediated inflammation.

Inflammation is central to numerous diseases, highlighting the need for new anti-inflammatory agents. This study explores the potential of novel spirofused indoline-quinazoline hybrids (4a-p) as anti-inflammatory compounds, inspired by a spiroisatin analogue (VI) that showed modest TNF-α inhibition. We aimed to enhance activity by modifying the isatin scaffold: first, introducing N-alkylation (propyl, butyl, or isobutyl) to improve hydrophobic interactions within the TNF-α dimer active site; second, adding halogens (F, Cl, Br) at the 5-position to increase lipophilicity.

Synthesis of S-alkylated oxadiazole bearing imidazo[2,1-b]thiazole derivatives targeting breast cancer: In vitro cytotoxic evaluation and in vivo radioactive tracing studies.

Breast cancer is the most common invasive cancer diagnosed in women, accounting for most cancer-related fatalities globally. Numerous investigations have revealed that breast cancer is characterized by abnormal expression and maintenance of EGFR levels. In terms of structural study and optimization of several EGFR inhibitors, two series of oxadiazole bearing imidazo[2,1-b]thiazole derivatives were designed and synthesized as potential EGFR inhibitors and assessed for their antitumor activity at NCI-USA.

Molecular docking, DFT and antiproliferative properties of 4-(3,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine as potent anticancer agent with CDK2 and PIM1 inhibition potency.

Due to the limited effeteness and safety concerns associated with current cancer treatments, there is a pressing need to develop novel therapeutic agents. 4-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine (3) was synthesized and Initially screened on 59 cancer cell lines showed promising anticancer activity, so, it was chosen for a 5-dose experiment by the NCI/USA. The GI values ranged from 1.

Empowering Wellness: A Comprehensive Narrative Review of Cancer Prehabilitation from Treatment Onset to Surveillance.

Cancer prehabilitation, defined as a process occurring between cancer diagnosis and the onset of acute treatment, is highlighted for its ability to enhance physical and mental health results while decreasing overall healthcare costs. This summary introduces the concept of cancer prehabilitation and emphasises the crucial role of oncology nurses in rehabilitation care. The cancer treatment plan of prehabilitation requires timely and efficient assessment across the care continuum, focusing on enhancing outcomes at every stage of cancer.

Effect of Comprehensive Educational Program on Preeclamptic Women's Risk Perception of Cardiovascular Disease, Self-Efficacy, and Adherence to Healthy Lifestyle Behaviors.

Purpose: To evaluate the effect of a comprehensive educational program on preeclamptic women's knowledge, risk perception of cardiovascular disease, self-efficacy, and adherence to healthy lifestyle behaviors.

Patients And Methods: This study employed a pretest-posttest design. One hundred and two women who previously had preeclampsia were enrolled from July 2022 to December 2022 from outpatient obstetrics, gynecology, and family planning clinics.

Design, synthesis, and molecular dynamic simulations of some novel benzo[d]thiazoles with anti-virulence activity against Pseudomonas aeruginosa.

Inhibition of quorum sensing (QS) is an impending approach for targeting bacterial infection. Fourteen benzo[d]thiazole and 2-pyrazolo[1,5-a]pyrimidin-3-yl)benzo[d]thiazoles analogues were designed and synthesized as promising LasR antagonists with QS inhibition activity. Among the investigated compounds, compounds 3c, 3e, and 8d exhibited the highest percentage inhibition in biofilm formation (77 %, 63.

Identification of indole-grafted pyrazolopyrimidine and pyrazolopyridine derivatives as new anti-cancer agents: Synthesis, biological assessments, and molecular modeling insights.

In the current medical era, developing new PIM-1 inhibitors stands as a significant approach to cancer management due to the pivotal role of PIM-1 kinase in promoting cell survival, proliferation, and drug resistance in various cancers. This study involved designing and synthesizing new derivatives of pyrazolo[1,5-a]pyrimidines (6a-i) and pyrazolo[3,4-b]pyridines (10a-i) as potential anti-cancer agents targeting PIM-1 kinase. The cytotoxicity was screened on three cancer cell lines: A-549 (lung), PANC-1 (pancreatic), and A-431 (skin), alongside MRC5 normal lung cells to assess selectivity.

Development of new LSM-83177 analogues as anti-tumor agents against colorectal cancer targeting p53-MDM2 interaction.

LSM-83177, a phenoxy acetic acid derivative, is a small molecule reported for its promising anti-tumor properties. Via inhibiting the interaction between MDM2 and p53, LSM-83177 can elevate the active p53 levels within cells, thereby promoting apoptosis and inhibiting tumor growth. Also, LSM-83177 has been shown to inhibit GST activity in colorectal cancer HT29 cells.

Knowledge, Attitude, and Practice on Cervical Cancer Prevention among Female University Students in AlKharj, Saudi Arabia.

Background: Cervical Cancer (CC) is the fourth most frequent malignancy worldwide among females with significant death rates. It ranks as the 8 most frequent cancer in Saudi female. CC is preventable, with likelihood of full treatment by early detection, because of its long pre-invasive period.

Mitigating the resistance of MCF-7 cancer cells to Doxorubicin under hypoxic conditions with novel coumarin based carbonic anhydrase IX and XII inhibitors.

In the present study, the design and synthesis of novel coumarin derivatives 8a-h, 11a-d and 16a-c as potential selective inhibitors for the tumor associated human carbonic anhydrase isoforms (hCA IX and XII) was reported. All the newly synthesized derivatives showed potent to mild activity against the targeted CA IX (K = 0.08-9.

From Insights to Impact: Understanding Cancer Screening Choices through Mixed-Methods.

Objective: The main objective of this comprehensive mixed-methods investigation conducted in Jordan were to explore and understand men's engagement in cancer screening.

Methods: The research employed a mixed-methods approach, combining a survey with 209 participants and focus group interviews with 30 individuals. The survey involved quantitative data collection methods to gather information on cancer screening participation rates among men in Amman.

Balancing confidentiality and care coordination: challenges in patient privacy.

Background: In the digital age, maintaining patient confidentiality while ensuring effective care coordination poses significant challenges for healthcare providers, particularly nurses.

Aim: To investigate the challenges and strategies associated with balancing patient confidentiality and effective care coordination in the digital age.

Methods: A cross-sectional study was conducted in a general hospital in Egypt to collect data from 150 nurses across various departments with at least six months of experience in patient care.

Novel imidazo[2,1-b]thiazoles and imidazo[1,2-a]pyridines tethered with indolinone motif as VEGFR-2 inhibitors and apoptotic inducers: Design, synthesis and biological evaluations.

The current study investigates the anticancer and VEGFR-2 inhibitory activities of 16 novel indolinone-grafted imidazo[2,1-b]thiazole and imidazo[1,2-a]pyridine derivatives (6a-h and 10a-h). The structures of these target compounds were confirmed using elemental and spectral analyses. All compounds were evaluated for their VEGFR-2 inhibitory activity in vitro, with eight compounds demonstrating promising results, exhibiting IC values in the sub-micromolar range (0.