Martinostat as a novel HDAC inhibitor to overcome tyrosine kinase inhibitor resistance in chronic myeloid leukemia.

Background: Chronic myeloid leukemia (CML) remains a therapeutic challenge, particularly in patients who develop resistance to standard tyrosine kinase inhibitors (TKIs) such as imatinib. Here, we present the first demonstration of the potent anti-leukemic activity of the histone deacetylase (HDAC) inhibitor martinostat in both TKI-sensitive and TKI-resistant CML.

Methods And Results: Structural and biochemical analyses confirmed the efficient and selective binding of martinostat to HDAC isoenzyme ligand-binding pockets, resulting in histone and tubulin hyperacetylation in both imatinib-sensitive and resistant CML cells, outperforming vorinostat, a clinically used HDAC inhibitor (HDACi).

A haploinsufficiency restoration strategy corrects neurobehavioral deficits in Nf1+/- mice.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations of the NF1 tumor suppressor gene resulting in the loss of function of neurofibromin, a GTPase-activating protein (GAP) for Ras. While the malignant manifestations of NF1 are associated with loss of heterozygosity of the residual WT allele, the nonmalignant neurodevelopmental sequelae, including autism spectrum disorder (ASD) and/or attention deficit hyperactivity disorder (ADHD) are prevalent morbidities that occur in the setting of neurofibromin haploinsufficiency. We reasoned that augmenting endogenous levels of WT neurofibromin could serve as a potential therapeutic strategy to correct the neurodevelopmental manifestations of NF1.

Tetrahydrobenzimidazole TMQ0153 targets OPA1 and restores drug sensitivity in AML via ROS-induced mitochondrial metabolic reprogramming.

Background: Acute myeloid leukemia (AML) is a highly aggressive cancer with a 5-year survival rate of less than 35%. It is characterized by significant drug resistance and abnormal energy metabolism. Mitochondrial dynamics and metabolism are crucial for AML cell survival.

Potential of histone deacetylase 6 inhibitors in alleviating chemotherapy-induced peripheral neuropathy.

Background: Histone deacetylase 6 (HDAC6), belonging to class IIb of histone deacetylases, regulates the acetylation of the cytoplasmic protein α-tubulin. The overexpression of HDAC6 is linked to the development of tumors, and inhibiting HDAC6 is known to trigger apoptosis in multiple myeloma cells. In addition to its application in cancer treatment, bortezomib, a proteasome inhibitor, is widely used in managing multiple myeloma and has shown effectiveness in patients with both newly diagnosed and relapsed disease.

The Role of Pentacyclic Triterpenoids in Non-Small Cell Lung Cancer: The Mechanisms of Action and Therapeutic Potential.

Lung cancer remains a major global health problem because of its high cancer-related mortality rate despite advances in therapeutic approaches. Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is more amenable to surgical intervention in its early stages. However, the prognosis for advanced NSCLC remains poor, owing to limited treatment options.

Nationwide distribution and factors related to indoor fine particulate matter concentrations in subway stations in Korea: Results of first-year measurement.

This study assessed the seasonal distribution and factors associated with PM in nationwide subway stations in Korea. A total of 229,644 data points collected over one year were used to determine one-day PM concentrations from 642 subway stations. The geometric mean of indoor PM concentrations was 26.

Association Between Time From Surgery to Radiation Therapy and Multimodality Treatment Outcomes in HPV+ Head and Neck Cancer: A Multi-Institutional Cohort Experience.

Purpose: Oropharyngeal squamous cell cancers (OPSCCs) are traditionally managed with surgery and, if indicated, adjuvant radiation therapy (RT) with or without chemotherapy. NCCN recommends keeping the time from surgery to the start of RT (TSRT) within 6 weeks to avoid possibly compromising patient outcomes. HPV+ OPSCCs behave more favorably than HPV- OPSCCs.

Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.

Background: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1 manifestations (eg, neurocognitive function, growth reduction, and café-au-lait spots) are unknown.

Methods: This open-label, phase II trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥3 cm).

Regulation of Hippo-YAP signaling axis by Isoalantolactone suppresses tumor progression in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a devastating malignancy characterized by aggressive tumor growth and limited treatment options. Dysregulation of the Hippo signaling pathway and its downstream effector, Yes-associated protein (YAP), has been implicated in CCA development and progression. In this study, we investigated the effects of Isoalantolactone (IALT) on CCA cells to elucidate its effect on YAP activity and its potential clinical significance.

One-Year Safety Evaluation of New Hyaluronic Acid Fillers (YYS Series): A Prospective, Multicenter, Observational Study.

Background: With the continuous increasing availability of new filler products, each hyaluronic acid filler brand has distinctive pharmacokinetics, which may be associated with different complications. Therefore, the long-term safety of new generations of fillers should be evaluated.

Objective: This prospective, multicenter, observational, postmarketing study ( ClinicalTrials.

ECT12, an YTH-domain protein, is a potential mRNA mA reader that affects abiotic stress responses by modulating mRNA stability in Arabidopsis.

N-methyladenosine (mA), the most abundant modification found in eukaryotic mRNAs, is interpreted by mA "readers," thus playing a crucial role in regulating RNA metabolism. The YT521-B homology-domain (YTHD) proteins, also known as EVOLUTIONARILY CONSERVED C-TERMINAL REGION (ECT), are recognized as mA reader proteins in plants and animals. Among the 13 potential YTHD family proteins in Arabidopsis thaliana, the functions of only a few members are known.

Correlation Between Articulatory Diadochokinetic Parameters and Dysphagia Parameters in Subacute Stroke Patients.

Objective: To determine correlations of alternation motor rate (AMR), sequential motor rate (SMR), and maximum phonation time (MPT) with the severity of dysphagia in subacute stroke patients.

Methods: This was a retrospective chart review study. Data of 171 subacute stroke patients were analyzed.

Cold anesthesia for pain reduction during intralesional steroid injection for nodulocystic acne.

Background: In any dermatologic procedure, patient acceptance of treatment is heavily influenced by intraprocedural pain. Intralesional triamcinolone injections are very important in keloid scar and nodulocystic acne treatment. However, the main problem of needle-stick procedures is pain.

Viral detection from negative mumps cases with respiratory symptoms in Gwangju, South Korea in 2021.

Mumps is the second-most reported infectious disease in South Korea; however, due to the low pathogen confirmation rate in laboratory diagnoses, we proposed a method for reevaluating the high incidence rate via the laboratory verification of other viral diseases. In 2021, 63 cases of pharyngeal or cheek mucosal swabs of suspected mumps cases in Gwangju, South Korea, were assessed for causative pathogens using massive simultaneous pathogen testing. More than one respiratory virus was detected in 60 cases (95.

A Randomized, Prospective, Split-Face Pilot Study to Evaluate the Safety and Efficacy of 532-nm and 1,064-nm Picosecond-Domain Neodymium:Yttrium-Aluminum-Garnet Lasers Using a Diffractive Optical Element for Non-Ablative Skin Rejuvenation: Clinical and Histological Evaluation.

Background: The advent of fractionated picosecond (ps) lasers has provided an opportunity to explore new ways of creating microinjuries in the skin to induce skin rejuvenation.

Objective: To compare the efficacy and safety of diffractive optical element (DOE)-assisted ps neodymium: yttrium-aluminum-garnet (Nd:YAG) lasers with 532-nm and 1,064-nm wavelengths (532-nm and 1,064-nm Nd:YAG P-DOE) using a novel fractional handpiece for the treatment of photoaged skin.

Methods: An guinea pig skin experiment was performed by evaluating the histology of the skin after 532-nm Nd:YAG P-DOE irradiation.

A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients.

Efficacy and Safety of Cold-Induced Noninvasive Targeted Fat Reduction in Pseudogynecomastia.

Background: Treatment options for pseudogynecomastia are limited, and the demand for noninvasive breast fat reduction is increasing.

Objective: We evaluated the efficacy and safety of a cold-induced lipolysis device for treating pseudogynecomastia.

Methods: In this 16-week prospective trial, a total of 15 male patients with pseudogynecomastia were treated twice with cryolipolysis.

Arabidopsis N6-methyladenosine methyltransferase FIONA1 regulates floral transition by affecting the splicing of FLC and the stability of floral activators SPL3 and SEP3.

N 6-methyladenosine (m6A) RNA methylation has been shown to play a crucial role in plant development and floral transition. Two recent studies have identified FIONA1 as an m6A methyltransferase that regulates the floral transition in Arabidopsis through influencing the stability of CONSTANS (CO), SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), and FLOWERING LOCUS C (FLC). In this study, we confirmed that FIONA1 is an m6A methyltransferase that installs m6A marks in a small group of mRNAs.

MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer.

Background: The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC.

Methods: We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma.

Exosomes as novel player in dermatologic field.

Exosomes are nano-sized extracellular vesicles released by the majority of the cell types. Exosomes play a major role in intercellular communication via transferring cargoes between cells and altering specific functions of the target cells. The interest in the biological activities of exosomes has been increasing and their therapeutic role has already been demonstrated in various diseases.

Genetic Aspects of Small for Gestational Age Infants Using Targeted-Exome Sequencing and Whole-Exome Sequencing: A Single Center Study.

Background: The etiology of small for gestational age (SGA) is multifactorial and includes maternal/uterine-placental factors, fetal epigenetics, and genetic abnormalities. We evaluated the genetic causes and diagnostic effectiveness of targeted-panel sequencing (TES) or whole-exome sequencing (WES) in SGA infants without a known cause.

Methods: A prospective study was conducted on newborn infants born with a birth weight of less than the 10th percentile for gestational age between January 2019 and December 2020 at the Pusan National University Hospital.

Quantitative Evaluation of Volume Augmentation and Durational Changes in the Anteromedial Cheek with Hyaluronic Acid Fillers Using Three-Dimensional Measurement: 2-Year Results from a Comparative Split-Face Study.

Summary: Hyaluronic acid fillers are widely used for the augmentation of facial soft tissues. Hyaluronic acid fillers can be monophasic or biphasic and have different characteristics, especially regarding volumetric effects and maintenance potential. However, there is paucity of long-term quantitative and objective data on clinical outcomes following hyaluronic acid injection.

Explicating Child-Driven Patterns of Parent-Child Responsivity in Fragile Families: A Longitudinal Approach.

It has been well-established that development occurs in the context of a transactional framework, with bidirectional parent-child interactions influencing both proximal and distal outcomes. In particular, child vocabulary development is sensitive to parenting qualities including warmth, sensitivity, and control as well as parental stimulation including language input and access to learning enrichment activities. Similarly, these parenting qualities are influenced by and influence children's development of pro-social behaviors.