METTL3/MYCN cooperation drives neural crest differentiation and provides therapeutic vulnerability in neuroblastoma.

Neuroblastoma (NB) is the most common extracranial childhood cancer, caused by the improper differentiation of developing trunk neural crest cells (tNCC) in the sympathetic nervous system. The N-methyladenosine (mA) epitranscriptomic modification controls post-transcriptional gene expression but the mechanism by which the mA methyltransferase complex METTL3/METTL14/WTAP is recruited to specific loci remains to be fully characterized. We explored whether the mA epitranscriptome could fine-tune gene regulation in migrating/differentiating tNCC.

Identifying novel inhibitors targeting Exportin-1 for the potential treatment of COVID-19.

The nuclear export protein 1 (XPO1) mediates the nucleocytoplasmic transport of proteins and ribonucleic acids (RNAs) and plays a prominent role in maintaining cellular homeostasis. XPO1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses. In our earlier study, we proved the inhibition of XPO1 as a therapeutic strategy for managing SARS-COV-2 and its variants.

Discovery of novel acetylcholinesterase inhibitors through integration of machine learning with genetic algorithm based screening approaches.

Introduction: Alzheimer's disease (AD) is the most studied progressive eurodegenerative disorder, affecting 40-50 million of the global population. This progressive neurodegenerative disease is marked by gradual and irreversible declines in cognitive functions. The unavailability of therapeutic drug candidates restricting/reversing the progression of this dementia has severed the existing challenge.

Development of machine learning models for the screening of potential HSP90 inhibitors.

Heat shock protein 90 (Hsp90) is a molecular chaperone playing a significant role in the folding of client proteins. This cellular protein is linked to the progression of several cancer types, including breast cancer, lung cancer, and gastrointestinal stromal tumors. Several oncogenic kinases are Hsp90 clients and their activity depends on this molecular chaperone.

Combining structure-based pharmacophore modeling and machine learning for the identification of novel BTK inhibitors.

Bruton's tyrosine kinase (BTK) is a critical enzyme which is involved in multiple signaling pathways that regulate cellular survival, activation, and proliferation, making it a major cancer therapeutic target. We applied the novel integrated structure-based pharmacophore modeling, machine learning, and other in silico studies to screen the Korean chemical database (KCB) to identify the potential BTK inhibitors (BTKi). Further evaluation of these inhibitors on three different human cancer cell lines showed significant cell growth inhibitory activity.

Nanomedicine for glioblastoma: Progress and future prospects.

Glioblastoma is the most aggressive form of brain tumor, accounting for the highest mortality and morbidity rates. Current treatment for patients with glioblastoma includes maximal safe tumor resection followed by radiation therapy with concomitant temozolomide (TMZ) chemotherapy. The addition of TMZ to the conformal radiation therapy has improved the median survival time only from 12 months to 16 months in patients with glioblastoma.

Investigating the Mechanism of Inhibition of Cyclin-Dependent Kinase 6 Inhibitory Potential by Selonsertib: Newer Insights Into Drug Repurposing.

Cyclin-dependent kinases (CDKs) play significant roles in numerous physiological, and are considered an attractive drug target for cancer, neurodegenerative, and inflammatory diseases. In the present study, we have aimed to investigate the binding affinity and inhibitory potential of selonsertib toward CDK6. Using the drug repurposing approach, we performed molecular docking of selonsertib with CDK6 and observed a significant binding affinity.

Probing the Interaction of Selonsertib with Human Serum Albumin: In silico and In vitro Approaches.

Introduction: Selonsertib, the most recently developed selective inhibitor of apoptosis signal-regulating kinase 1. We elucidated the binding characteristics, mechanism of interaction, and dynamic behaviors of selonsertib with human serum albumin (HSA), a major circulatory transport protein.

Methods: Different biophysical approaches (fluorescence quenching and isothermal titration calorimetry (ITC) were combined with various in silico techniques to examine the binding of selonsertib to HSA.

Computational screening of camostat and related compounds against human TMPRSS2: A potential treatment of COVID-19.

The global coronavirus pandemic has burdened the human population with mass fatalities and disastrous socio-economic consequences. The frequent occurrence of these new variants has fueled the already prevailing challenge. There is still a necessity for highly effective small molecular agents to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Silk Cocoon-Derived Protein Bioinspired Gold Nanoparticles as a Formidable Anticancer Agent.

We synthesized bioinspired sericin encapsulated gold nanoparticles (SGNPs) using HAuCl₄ as the starting material in a bottom-up approach. Further, two-dimensional (2D) and three-dimensional (3D) conformational changes (folding and unfolding) in sericin were studied using circular dichroism (CD) and fluorescence spectroscopy, respectively, during and after the synthesis of particles. Finally, the synthesized SGNPs were characterized using several physical techniques to ensure their correct synthesis and study the size, stability, and charge over the surface of particles.

Prediction of Bacteremia Based on 12-Year Medical Data Using a Machine Learning Approach: Effect of Medical Data by Extraction Time.

Early detection of bacteremia is important to prevent antibiotic abuse. Therefore, we aimed to develop a clinically applicable bacteremia prediction model using machine learning technology. Data from two tertiary medical centers' electronic medical records during a 12-year-period were extracted.

Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight.

The recent emergence of novel SARS-CoV-2 variants has threatened the efforts to contain the COVID-19 pandemic. The emergence of these "variants of concern" has increased immune escape and has supplanted the ancestral strains. The novel variants harbored by the B.

Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study.

The COVID-19 outbreak continues to spread worldwide at a rapid rate. Currently, the absence of any effective antiviral treatment is the major concern for the global population. The reports of the occurrence of various point mutations within the important therapeutic target protein of SARS-CoV-2 has elevated the problem.

Screening of inhibitors against SARS-CoV-2 spike protein and their capability to block the viral entry mechanism: A viroinformatics study.

SARS-CoV-2, previously named 2019 novel coronavirus (2019-nCoV), has been associated with the global pandemic of acute respiratory distress syndrome. First reported in December 2019 in the Wuhan province of China, this new RNA virus has several folds higher transmission among humans than its other family member (SARS-CoV and MERS-CoV). The SARS-CoV-2 spike receptor-binding domain (RBD) is the region mediating the binding of the virus to host cells via Angiotensin-converting enzyme 2 (ACE2), a critical step of viral.

Screening of drug databank against WT and mutant main protease of SARS-CoV-2: Towards finding potential compound for repurposing against COVID-19.

Although several pharmacological agents are under investigation to be repurposed as therapeutic against COVID-19, not much success has been achieved yet. So, the search for an effective and active option for the treatment of COVID-19 is still a big challenge. The Spike protein (S), RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro) are considered to be the primary therapeutic drug target for COVID-19.

Deciphering the Role of Autophagy in Treatment of Resistance Mechanisms in Glioblastoma.

Autophagy is a process essential for cellular energy consumption, survival, and defense mechanisms. The role of autophagy in several types of human cancers has been explicitly explained; however, the underlying molecular mechanism of autophagy in glioblastoma remains ambiguous. Autophagy is thought to be a "double-edged sword", and its effect on tumorigenesis varies with cell type.

Use of Natural Compounds as a Potential Therapeutic Agent Against COVID-19.

The current 2019-nCoV outbreak is becoming extremely harmful and has affected the whole world. Its control is challenging because there is no effective vaccine or drug available for coronavirus disease. The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), previously named as 2019 novel coronavirus (2019-nCoV), primarily targets the human respiratory system to lung lesions and lethal pneumonia.

Identification of High-Affinity Inhibitors of Cyclin-Dependent Kinase 2 Towards Anticancer Therapy.

Cyclin-dependent kinase 2 (CDK2) is an essential protein kinase involved in the cell cycle regulation. The abnormal activity of CDK2 is associated with cancer progression and metastasis. Here, we have performed structure-based virtual screening of the PubChem database to identify potent CDK2 inhibitors.

ASK1 and its role in cardiovascular and other disorders: available treatments and future prospects.

: Apoptosis signal-regulating kinase 1 (ASK1), also known as MAP3K5, is a member of mitogen-activated protein kinase kinase kinase (MAP3K) family and is well reported as crucial in the regulation of the JNK and P38 pathways. ASK1 is activated in response to a diverse array of stresses such as endoplasmic reticulum stress, lipopolysaccharides, tumor necrosis factor alpha, and reactive oxygen species. The activation of ASK1 induces various stress responses.

Early Detection of Bacteraemia Using Ten Clinical Variables with an Artificial Neural Network Approach.

An adequate model for predicting bacteraemia has not yet been developed. This study aimed to evaluate the performance of an artificial neural network (ANN)-based prediction model in comparison with previous statistical models. The performance of multi-layer perceptron (MLP), a representative ANN model, was verified via comparison with a non-neural network model.

The relationship between employment status and insulin resistance in the Korean elderly population.

Background/aims: This study aimed to investigate the relationship between employment status and insulin resistance in the Korean elderly population.

Methods: The study included 2325 healthy participants (862 men and 1463 women) who did not have diabetes, were 60-74 years old, and participated in the 2007-2010 Korea National Health and Nutrition Examination Survey. Their employment status was categorized as employed or unemployed.

Dose-Dependent Effect of Cotinine-Verified Tobacco Smoking on Serum Immunoglobulin E Levels in Korean Adult Males.

Background: Smoking is one of the risk factors to exacerbate allergic diseases, and it may affect serum immunoglobulin E (IgE) levels. However, few studies have relied on an objective biomarker to examine the effect of tobacco smoking on serum IgE levels.

Method: A nationwide cross-sectional study was conducted to examine the relationship between urinary cotinine (Ucot) concentrations and IgE levels in 973 males using data from the 2010 Korean National Health and Nutrition Examination Survey (KNHANES).

Association between the triglyceride to high-density lipoprotein cholesterol ratio and insulin resistance in Korean adolescents: a nationwide population-based study.

Background: Studies have suggested the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) as a surrogate marker of insulin resistance. However, few studies have examined the association between TG/HDL-C and insulin resistance in the general adolescent population. This study aimed to examine the association between TG/HDL-C and insulin resistance in a nationally representative sample of Korean adolescents.