Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?

Targeting oncogenes and their interactive partners is an effective approach to developing novel targeted therapies for cancer and other chronic diseases. We and others have long suggested the MDM2 oncogene being an excellent target for cancer therapy, based on its p53-dependent and -independent oncogenic activities in a variety of cancers. The MYC family proteins are transcription factors that also regulate diverse biological functions.

Advancing Therapeutic Strategies with Polymeric Drug Conjugates for Nucleic Acid Delivery and Treatment.

The effective clinical translation of messenger RNA (mRNA), small interfering RNA (siRNA), and microRNA (miRNA) for therapeutic purposes hinges on the development of efficient delivery systems. Key challenges include their susceptibility to degradation, limited cellular uptake, and inefficient intracellular release. Polymeric drug conjugates (PDCs) offer a promising solution, combining the benefits of polymeric carriers and therapeutic agents for targeted delivery and treatment.

Antibiofilm and Anticancer Activity of Multi-Walled Carbon Nanotubes Fabricated with Hot-Melt Extruded Astaxanthin-Mediated Synthesized Silver Nanoparticles.

Purpose: Multi-walled carbon nanotubes (MWCNTs) were used as carriers for silver nanoparticles (AgNPs). In this process, MWCNTs were coated with mesoporous silica (MWCNT-Silica) for uniform and regular loading of AgNPs on the MWCNTs. In addition, astaxanthin (AST) extract was used as a reducing agent for silver ions to enhance the antioxidant, antibiofilm, and anticancer activities of AgNPs.

Development of Solid Self-Nanoemulsifying Drug Delivery System of Rhein to Improve Biopharmaceutical Performance: Physiochemical Characterization, and Pharmacokinetic Evaluation.

Introduction: Rhein, a natural bioactive lipophilic compound with numerous pharmacological activities, faces limitations in clinical application due to poor aqueous solubility and low bioavailability. Thus, this study aimed to develop a rhein-loaded self-nano emulsifying drug delivery system (RL-SNEDDS) to improve solubility and bioavailability.

Methods: The RL-SNEDDS was prepared by aqueous titration method with eucalyptus oil (oil phase), tween 80 (surfactant), and PEG 400 (co-surfactant) and optimization was performed by 3 factorial design.

Exploring the various functions of PHD finger protein 20: beyond the unknown.

Over the last decade, the functions of PHD finger protein 20 (PHF20) in several signaling processes have been studied, including those of protein kinase B (PKB)-mediated phosphorylation, p53 regulation, muscle differentiation, and histone modification including histone H3 lysine 4 (H3K4) methylation. One PHF20 human mutation lacks the first nonspecific lethal complex of the component that binds to H3K4me2 to facilitate cancer cell survival. In carcinoma cells, PHF20 expression is regulated by PKB; PHF20 becomes phosphorylated when DNA is damaged, thus inhibiting the p53 activity that maintains cancer cell survival.

Enhancement of renal fibrosis in PHF20 transgenic mice.

Plant homeodomain finger protein 20 (PHF20) plays a crucial role in various biological processes, but its involvement in renal fibrosis remains unclear. This study investigated the role of PHF20 in renal fibrosis using a unilateral ureteral obstruction (UUO) mouse model, a widely accepted model for chronic kidney disease. PHF20 transgenic (PHF20-TG) and wild-type (WT) mice were utilized to explore how PHF20 influences renal inflammation and fibrosis.

Rocaglamide-A mitigates LPS-induced hepatic inflammation by modulating JNK/AP-1 signaling cascade and ROS production in hepatocytes.

Unlabelled: Lipopolysaccharide (LPS), a gut-derived endotoxin, is a recognized risk factor for both Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Rocaglamide-A (Roc-A), a natural compound derived from the genus Aglaia, is known for its pharmacological and immunosuppressive effects on various cell types. Although our recent investigations have unveiled Roc-A's anti-adipogenic role in adipocytes, its mechanism in hepatic inflammation remains elusive.

Quinine inhibits myogenic differentiation by disrupting AKT signaling pathway.

Sarcopenia is a disease characterized by decreased muscle fibers and mass. Although it mainly affects the older adults, it can also occur in various age groups as a secondary effect of medications used for treating certain diseases, such as cancer and diabetes. With population aging, sarcopenia has drawn significant attention owing to its increasing prevalence.

Axatilimab.

Each month, subscribers to receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy and Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services.

Trace level detection of Pb ion using organic ligand as fluorescent-on probes in aqueous media.

In this study, an optical sensor, JA/(2,6-di((E)-benzylidene)cyclohexan-1-one), was synthesized and characterized using H NMR and FT-IR spectroscopy. The sensor exhibited high efficiency and selectivity in detecting Pb ions, even in the presence of potential interfering ions such as Mn, Cu, Co, Cr, Ni, Ce, Hg, and Cd in aqueous solutions. The interaction of JA with Pb resulted in a significant enhancement of fluorescence intensity, suggesting the formation of a stable complex.

Doctors' satisfaction with the rehabilitation system for anti-terrorist operation participants: A factor analysis.

Background: A war has a catastrophic effect on veterans' health. However, there is a knowledge gap about the veterans' rehabilitation system, requirements, and the satisfaction of doctor-organizers. The present study aims to assess the level of satisfaction of the doctor-organizers of health care with the existing rehabilitation system for anti-terrorist operation (ATO) veterans in Ukraine.

Changes in Cardiovascular Health at Midlife and Subsequent Cardiovascular Outcomes in Individuals With Diabetes.

Background: Whether improvements in cardiovascular health (CVH) in midlife mitigate cardiovascular disease (CVD) risk in patients with diabetes remains underexplored.

Objectives: The aim of the study was to examine the relationships between changes in CVH during midlife and subsequent risks of CVD events and all-cause mortality among individuals with and without diabetes.

Methods: The study utilized data from the Atherosclerosis Risk in Communities Study.

Burden of diabetes in correctional facilities: A global systematic review and meta-analysis.

Background: Diabetes mellitus presents significant public health challenges worldwide. While its prevalence and management in the general population have been extensively studied, comprehensive research on diabetes among incarcerated individuals is lacking. This study aims to conduct a systematic review and -analysis to determine the prevalence of diabetes within the prison population.

Research on unintroduced new drugs in South Korea from 2011 to 2020: approaches to prioritization and strategy.

In recent years, with the experience of the COVID-19 pandemic, countries around the world have realized that improving patient access to new medicines can have a significant impact on public health and economic stability. The aim of this study was to identify new drugs that are urgently needed among those not yet available in South Korea from 2011 to 2020, and to develop strategies to improve access by analyzing the causes of delay. Through a 3-step screening process that included a literature review of new drugs, surveys of domestic clinicians and academics, and consideration of expedited review status by regulatory authorities, 34 out of 244 unreleased new drugs were prioritized for rapid introduction.

Validation of the Arabic Version of Asthma Numeracy Questionnaire (ANQ) Among Parents of Asthmatic Children: Factor and Rasch Analyses Study.

Background: The increasing global prevalence of asthma necessitates effective disease management, with patients and their families playing a central role. Enhancing health literacy (HL) among caregivers is critical to improving asthma outcomes.

Purpose: This study aimed to validate the Arabic version of the Asthma Numeracy Questionnaire (Ar-ANQ) to address the gap in HL assessment tools for Arabic-speaking populations.

Cardiovascular Considerations During Cancer Therapy: Gaps in Evidence and Expert Panel Recommendations.

The administration of certain cancer therapies can be associated with the development of cardiovascular toxicity or complications. This spectrum of toxicities is broad and requires nuanced approaches for prevention, identification, and management. This expert panel summarizes the consensus of opinions of diverse health care professionals in several key areas: 1) cardioprotection involves strategies aimed at the primary prevention of cancer therapy-related cardiovascular toxicity; 2) surveillance entails monitoring for cancer therapy-related cardiovascular toxicity during cancer therapy; 3) permissive cardiotoxicity is the informed continuation of cancer therapy in the presence of cardiovascular toxicity, along with the implementation of mitigating cardiovascular treatments; and 4) special considerations include the invasive management of severe cardiovascular disease in patients receiving treatments for advanced cancer and the exploration of drug-drug interactions in cardio-oncology.

Assessing intention to use mobile phone-based self-management support among adults with type 2 diabetes in Saudi Arabia: A cross-sectional study.

Introduction: The use of mobile phone technology for chronic illness self-management is growing, and it may help people with type 2 diabetes mellitus (T2DM). Innovative methods are needed to improve patient involvement and disease management in the Kingdom of Saudi Arabia due to the high incidence of T2DM.

Objective: The purpose of this study was to explore how the T2DM patients in KSA utilizes their mobile phones for self-management.

Is Thermal Pulsation Therapy Effective for Dry Eyes Before and After Cataract Surgery? A Systematic Review and Meta-Analysis.

Background: Meibomian gland dysfunction (MGD) is a primary cause of evaporative dry eye disease (DED), which is often exacerbated by cataract surgery due to surgical trauma and inflammation. Thermal pulsation therapy (TPT) aims to enhance meibomian gland function and relieve dry eye symptoms. We conducted a systematic review and meta-analysis to evaluate the effectiveness of TPT in managing dry eye symptoms associated with cataract surgery.

Angiotensin III activates ERK1/2 mitogen activated protein kinases and proliferation of rat vascular smooth muscle cells.

The proliferative effects of angiotensin (Ang) II in vascular smooth muscle cells (VSMCs) through its ability to stimulate extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway have been established. The main goal of this study was to explore whether Ang III induces ERK1/2 MAPK and VSMC proliferation in cultured Wistar VSMCs. Further, the Ang III actions were compared to those observed in VSMCs derived from the spontaneously hypertensive rat (SHR).

Selective Crystallization Separation of Uranium(VI) Complexes from Lanthanides.

The limited availability of uranium (U) resources poses significant challenges to the advancement of nuclear energy. Recycling uranium from spent fuel is critical, but the coexistence of lanthanides (Ln) complicates the extraction process significantly. Here, we present an N/O ligand, ()-'-(pyridin-2-ylmethylene) picolinohydrazide (), designed for the selective recovery of U(VI) over Ln(III/IV) in acidic environments.

Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry.

Background And Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.

Factors Associated With the Recovery of Left Ventricular Ejection Fraction in Patients With Anthracycline-Induced Left Ventricular Dysfunction.

Background: Neurohormonal blocking drugs, like beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), are recommended for treating anthracycline-induced left ventricular dysfunction (AILVD). However, there is limited evidence supporting their benefit. Therefore, this study evaluated associations of neurohormonal blockers and other clinical factors with recovery of left ventricular ejection fraction (LVEF) in patients with AILVD.

Repurposing bosentan as an anticancer agent: EGFR/ERK/c-Jun modulation inhibits NSCLC tumor growth.

Drug repurposing of well-established drugs to be targeted against lung cancer has been a promising strategy. Bosentan is an endothelin 1 (ET-1) blocker widely used in pulmonary hypertension. The current experiment intends to inspect the anticancer and antiangiogenic mechanism of bosentan targeting epidermal growth factor receptor (EGFR) /extra-cellular Signal Regulated Kinase (ERK) /c-Jun/vascular endothelial growth factor (VEGF) carcinogenic pathway.

Effect of Combined Treatment with Levofloxacin and Metformin on Diabetes-the Diabetes Related Behavioral and Biochemical Alterations.

Objectives: The current experiment was conducted to investigate the combined effect of levofloxacin (LVX) and metformin treatment on blood glucose levels, malondialdehyde (MDA),nitrite levels, and anxiety in streptozotocin (STZ)+ nicotine adenine dinucleotide (NAD)-induced diabetic rats.

Materials And Methods: In this study, Wistar rats have been used. After receiving a single dose of STZ + NAD (45 mg/kg, + 50 mg/kg, ), the rats developed diabetes.