Therapy-induced senescent cancer cells contribute to cancer progression by promoting ribophorin 1-dependent PD-L1 upregulation.

Conventional chemotherapy- and radiotherapy-induced cancer senescence, which is characterized by poor proliferation, drug resistance, and senescence-associated secretory phenotype, has gained attention as contributing to cancer relapse and the development of an immunosuppressive tumor microenvironment. However, the association between cancer senescence and anti-tumor immunity is not fully understood. Here, we demonstrate that senescent cancer cells increase the level of PD-L1 by promoting its transcription and glycosylation.

PD-L1: From cancer immunotherapy to therapeutic implications in multiple disorders.

The PD-L1/PD-1 signaling pathway is the gold standard for cancer immunotherapy. Therapeutic antibodies targeting PD-1, such as nivolumab (Opdivo) and pembrolizumab (Keytruda), and PD-L1, including atezolizumab (Tecentriq), durvalumab (Imfinzi), and avelumab (Bavencio) have received Food and Drug Administration approval and are currently being used to treat various cancers. Traditionally, PD-L1 is known as an immune checkpoint protein that binds to the PD-1 receptor on its surface to inhibit the activity of T cells, which are the primary effector cells in antitumor immunity.

PPIH as a poor prognostic factor increases cell proliferation and m6A RNA methylation in hepatocellular carcinoma.

RNA-binding proteins (RBPs) play a crucial role in the biological processes of liver hepatocellular carcinoma (LIHC). Peptidyl-prolyl cis-trans isomerase H (PPIH), an RBP, possesses prolyl isomerase activity and functions as a protein chaperone. The relationship between PPIH and LIHC has not yet been fully elucidated.

Developmental screening of neurodevelopmental disorders before age 6: a nationwide health screening program.

Background: We aimed to investigate the association between developmental screening before 24 months of age and neurodevelopmental disorders (NDDs) at 4-6 years of age.

Methods: We included 922,899 newborn born between 2014 and 2016 registered in National Health Insurance Service (NHIS). Developmental screening was administered at 9-12 and 18-24 months old with the Korean Developmental Screening Test for Infants & Children (K-DST).

TESC associated with poor prognosis enhances cancer stemness and migratory properties in liver cancer.

Liver cancer stem cells (LCSCs) are responsible for recurrence, metastasis, and drug resistance in liver cancer. However, the genes responsible for inducing LCSCs have not been fully identified. Based on our previous study, we found that tescalcin (TESC), a calcium-binding EF hand protein that plays a crucial role in chromatin remodeling, transcriptional regulation, and epigenetic modifications, was up-regulated in LCSCs of spheroid cultures.

NAMPT-Driven M2 Polarization of Tumor-Associated Macrophages Leads to an Immunosuppressive Microenvironment in Colorectal Cancer.

Nicotinamide phosphoribosyltransferase (NAMPT) is a metabolic enzyme with key roles in inflammation. Previous studies have examined the consequences of its upregulated expression in cancer cells themselves, but studies are limited with respect to its role in the other cells within the tumor microenvironment (TME) during colorectal cancer (CRC) progression. Using single-cell RNA sequencing (scRNA-seq) data, it is founded that NAMPT is highly expressed in SPP1 tumor-associated macrophages (TAMs), a unique subset of TAMs associated with immunosuppressive activity.

The risk of pediatric cardiovascular diseases in offspring born to mothers with systemic lupus erythematosus: a nationwide study.

Background: Systemic lupus erythematosus (SLE), a common autoimmune disease predominantly affecting women, has been linked to various complications during pregnancy. The transfer of anti-Ro/SSA antibodies from SLE-affected mothers to their offspring can lead to neonatal lupus and cardiac issues. This study investigated the association between maternal SLE and the risk of pediatric cardiovascular disorders.

Rapid weight gain in early life is associated with central precocious puberty in girls, not in boys - a nationwide population-based study in Korea.

Objectives: This study aimed to investigate the effect of rapid weight gain (RWG) on the incidence of central precocious puberty (CPP) using nationwide population-based data.

Methods: A total of 253,967 children (101,841 boys and 152,126 girls) who underwent regular health consultations under the National Health Insurance Service from 2007 to 2010 were followed up until the age of 10 years for boys and 9 years for girls. We calculated differences in the weight Z-scores from 4-6 months to 9-12 months (infancy) and from 9-12 months to 18-24 months or 30-36 months (toddlerhood) using the lambda-mu-sigma method.

Learning-Based Longitudinal Prediction Models for Mortality Risk in Very-Low-Birth-Weight Infants: A Nationwide Cohort Study.

Introduction: Prediction models assessing the mortality of very-low-birth-weight (VLBW) infants were confined to models using only pre- and perinatal variables. We aimed to construct a prediction model comprising multifactorial clinical events with data obtainable at various time points.

Methods: We included 15,790 (including 2,045 in-hospital deaths) VLBW infants born between 2013 and 2020 who were enrolled in the Korean Neonatal Network, a nationwide registry.

Multivalent Carbohydrate Nanocomposites for Tumor Microenvironment Remodeling to Enhance Antitumor Immunity.

Current cancer immunotherapeutic strategies mainly focus on remodeling the tumor microenvironment (TME) to make it favorable for antitumor immunity. Increasing attention has been paid to developing innovative immunomodulatory adjuvants that can restore weakened antitumor immunity by conferring immunogenicity to inflamed tumor tissues. Here, a galactan-enriched nanocomposite (Gal-NC) is developed from native carbohydrate structures through an optimized enzymatic transformation for effective, stable, and biosafe innate immunomodulation.

Feeding practice during infancy is associated with attention-deficit/hyperactivity disorder and autism spectrum disorder: a population-based study in South Korea.

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are representative neurodevelopmental disorders. Using a nationwide database, we aimed to investigate whether feeding practices in infancy (breastfeeding and the timing of supplementary food introduction) could impact ADHD or ASD development. We evaluated 1,173,448 children aged 4-6 months who were included in the National Screening Program for Infants and Children (NHSPIC) between 2008 and 2014.

Immunogenic cell death in cancer immunotherapy.

Cancer immunotherapy has been acknowledged as a new paradigm for cancer treatment, with notable therapeutic effects on certain cancer types. Despite their significant potential, clinical studies over the past decade have revealed that cancer immunotherapy has low response rates in the majority of solid tumors. One of the key causes for poor responses is known to be the relatively low immunogenicity of solid tumors.

A combination of BR101801 and venetoclax enhances antitumor effect in DLBCL cells via c-Myc/Bcl-2/Mcl-1 triple targeting.

Double hit diffuse large B-cell lymphoma (DLBCL) with rearrangement and overexpression of both c-Myc and Bcl-2 responds poorly to standard R-CHOP therapy. In a recent phase I study, Venetoclax (ABT-199) targeting Bcl-2 also exhibited disappointing response rates in patients with relapsed/refractory DLBCL, suggesting that targeting only Bcl-2 is not sufficient for achieving successful efficacy due to the concurrent oncogenic function of c-Myc expression and drug resistance following an increase in Mcl-1. Therefore, co-targeting c-Myc and Mcl-1 could be a key combinatorial strategy to enhance the efficacy of Venetoclax.

T-cell exhaustion and stemness in antitumor immunity: Characteristics, mechanisms, and implications.

T cells play a crucial role in the regulation of immune response and are integral to the efficacy of cancer immunotherapy. Because immunotherapy has emerged as a promising treatment for cancer, increasing attention has been focused on the differentiation and function of T cells in immune response. In this review, we describe the research progress on T-cell exhaustion and stemness in the field of cancer immunotherapy and summarize advances in potential strategies to intervene and treat chronic infection and cancer by reversing T-cell exhaustion and maintaining and increasing T-cell stemness.

An undefined cystatin CsCPI1 from tea plant Camellia sinensis harbors antithrombotic activity.

Tea consumption has been linked to a decreased risk of cardiovascular disease (CVD) mortality, which imposes a heavy burden on the healthcare system; however, which components in tea cause this beneficial effect is not fully understood. Here we uncovered a cystatin (namely CsCPI1), which is a cysteine proteinase inhibitor (CPI) of the tea plant (Camellia sinensis) that promotes antithrombotic activity. Since thrombosis is a common pathogenesis of fatal CVDs, we investigated the effects of CsCPI1, which showed good therapeutic effects in mouse models of thrombotic disease and ischemic stroke.

Protective Effect of Breastfeeding Against Febrile Seizure: A Nationwide Study in Korea.

Background: Breastfeeding is known to protect against febrile seizure (FS). Whether its impact continues throughout the childhood period is still controversial. Our objective was to investigate the protective effect of breastfeeding against FS stratified by age.

Cystic Periventricular Leukomalacia Worsens Developmental Outcomes of Very-Low-Birth Weight Infants with Intraventricular Hemorrhage-A Nationwide Cohort Study.

Cystic periventricular leukomalacia (cPVL) is a major brain injury involving periventricular white matter that leads to neurodevelopmental impairment in very-low-birth weight (VLBW) infants. We investigated the neurodevelopmental outcomes (motor, cognition, visual, and hearing) of 5734 VLBW infants born between 2013 and 2019 and enrolled in the Korean Neonatal Network. Cranial ultrasound results were stratified by the presence of cPVL and severity of intraventricular hemorrhage (IVH) (no, low-grade [I/II], high-grade [III]).

Impact of Preterm Birth on Neurodevelopmental Disorders in South Korea: A Nationwide Population-Based Study.

Neurodevelopmental disorder (NDD) in preterm infants has become of great interest. We aimed to investigate the impact of preterm birth on the proportion of NDD using nationwide data provided by the Korean National Health Insurance Service. We included 4894 extremely preterm or extremely low-birth-weight (EP/ELBW; <28 weeks of gestation or birth weight < 1000 g) infants, 70,583 other preterm or low-birth-weight (OP/LBW; 28−36 weeks of gestation or birth weight < 2500 g) infants, and 264,057 full-term infants born between 2008 and 2015.

Altered microstructure of the splenium of corpus callosum is associated with neurodevelopmental impairment in preterm infants with necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) is a devastating disease in preterm infants with significant morbidities, including neurodevelopmental impairment (NDI). This study aimed to investigate whether NEC is associated with (1) brain volume expansion and white matter maturation using diffusion tensor imaging analysis and (2) NDI compared with preterm infants without NEC.

Methods: We included 86 preterm infants (20 with NEC and 66 without NEC) with no evidence of brain abnormalities on trans-fontanelle ultrasonography and magnetic resonance imaging at term-equivalent age (TEA).