Peptides as multifunctional players in cancer therapy.

Peptides exhibit lower affinity and a shorter half-life in the body than antibodies. Conversely, peptides demonstrate higher efficiency in tissue penetration and cell internalization than antibodies. Regardless of the pros and cons of peptides, they have been used as tumor-homing ligands for delivering carriers (such as nanoparticles, extracellular vesicles, and cells) and cargoes (such as cytotoxic peptides and radioisotopes) to tumors. Additionally, tumor-homing peptides have been conjugated with cargoes such as small-molecule or chemotherapeutic drugs via linkers to synthesize peptide-drug conjugates. In addition, peptides selectively bind to cell surface receptors and proteins, such as immune checkpoints, receptor kinases, and hormone receptors, subsequently blocking their biological activity or serving as hormone analogs. Furthermore, peptides internalized into cells bind to intracellular proteins and interfere with protein-protein interactions. Thus, peptides demonstrate great application potential as multifunctional players in cancer therapy.

Steady-state memory-phenotype conventional CD4+ T cells exacerbate autoimmune neuroinflammation in a bystander manner via the Bhlhe40/GM-CSF axis.

Memory-phenotype (MP) CD4+ T cells are a substantial population of conventional T cells that exist in steady-state mice, yet their immunological roles in autoimmune disease remain unclear. In this work, we unveil a unique phenotype of MP CD4+ T cells determined by analyzing single-cell transcriptomic data and T cell receptor (TCR) repertoires. We found that steady-state MP CD4+ T cells in the spleen were composed of heterogeneous effector subpopulations and existed regardless of germ and food antigen exposure. Distinct subpopulations of MP CD4+ T cells were specifically activated by IL-1 family cytokines and STAT activators, revealing that the cells exerted TCR-independent bystander effector functions similar to innate lymphoid cells. In particular, CCR6high subpopulation of MP CD4+ T cells were major responders to IL-23 and IL-1ß without MOG35-55 antigen reactivity, which gave them pathogenic Th17 characteristics and allowed them to contribute to autoimmune encephalomyelitis. We identified that Bhlhe40 in CCR6high MP CD4+ T cells as a key regulator of GM-CSF expression through IL-23 and IL-1ß signaling, contributing to central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis. Collectively, our findings reveal the clearly distinct effector-like heterogeneity of MP CD4+ T cells in the steady state and indicate that CCR6high MP CD4+ T cells exacerbate autoimmune neuroinflammation via the Bhlhe40/GM-CSF axis in a bystander manner.

Seroprevalence and disease burden of acute hepatitis A in adult population in South Korea.

BACKGROUND: Adult seroprevalence of HAV is decreasing in developed countries including South Korea, due to general sanitation improvement. Although hepatitis A vaccination was introduced in South Korea more than 20 years ago, recent infection rates have not decreased. In this study, we investigate the seroprevalence of anti-HAV IgG, and estimate the national disease burden of acute hepatitis A in adult population. METHODS: Seroprevalence data were collected from health promotion center of Korea University Guro Hospital, in Seoul, Korea from 2010 to 2014. Data from adults (≥20-years) being tested for anti-HAV IgG were included. In addition, epidemiological and clinical data of patients diagnosed with acute hepatitis A from 2009 to 2013, were collected from Korean Statistical Information Service (KOSIS) and the National Health Insurance Service (NHIS) database. Data were stratified and compared by age groups. RESULTS: A total of 11,177 subjects were tested for anti-HAV IgG from 2010 to 2014. Age-related seroprevalence showed relatively low seropositivity in young adults. Incidence of acute hepatitis A was highest in 2009 and lowest in 2013. When categorized by age group, adults in their 20s and 30s had more HAV infections and related-admissions than older adults. However, ICU admission rate and average insurance-covered cost was high in older adults. CONCLUSION: The anti-HAV IgG seropositivity in Korean younger adult population was low while the incidence of acute hepatitis A was high, especially in the 20-39 aged. However, a substantial number of older adults were infected, and required more intensive procedures and incurred higher insurance-covered medical costs.

Disease burden of hospitalized community-acquired pneumonia in South Korea: Analysis based on age and underlying medical conditions.

Pneumonia is a leading cause of hospitalization and mortality worldwide. Despite recognition of the importance of community-acquired pneumonia (CAP) in adults, limited epidemiologic information is available in South Korea. This study aimed to evaluate the disease burden of hospitalized CAP in adults aged ≥19 years and its epidemiologic trend using Health Insurance and Review Assessment (HIRA) data.This is a retrospective study using the HIRA database from year 2009 to 2013. We estimated the incidence rate and direct medical cost of hospitalized CAP in adults aged ≥19 years in South Korea. These were further analyzed with respect to age and underlying medical conditions.During 2009 to 2013, 1216,916 hospitalizations were recorded. On average, the annual age-adjusted incidence rate of hospitalized CAP was 626 per 100,000 persons, with the rate increasing with age. When stratified by age- and risk groups, elderly people ≥75 years showed the highest incidence rate of hospitalized CAP over 5-year study periods. With respect to the risk groups based on underlying medical conditions, incidence rate ratios were 2.04 to 5.86 for the high-risk group versus the low-risk group and 1.28 to 5.49 for the moderate-risk group versus the low-risk group. Overall, mean direct medical cost for hospitalized CAP was 1851 USD per capita during the 5-year period: 1263 USD in the low-risk group, 2353 USD in the moderate-risk group, and 2841 USD in the high-risk group.This study shows that the incidence and medical cost of hospitalized CAP were consistently high over the 5-year study period. In particular, elderly people and adults with underlying medical conditions were at increased risk for hospitalized CAP.

Prevalence, antibiotic susceptibility, and virulence factors of Yersinia enterocolitica and related species from ready-to-eat vegetables available in Korea.

A total of 673 ready-to-eat vegetable samples were collected in Korea from 2001 to 2002 and analyzed for the presence of Yersinia spp. We analyzed biotypes, serotypes, and susceptibility to 12 antibiotics and tested for virulence genes of pathogenic Yersinia enterocolitica isolates by PCR assay. Among the samples, 27 (4.0%) were found to be contaminated with Yersinia spp. Among the 27 strains of Yersinia spp. isolates, 18 strains (66.7%) of Y. enterocolitica, 5 strains (18.5%) of Y. frederiksenii, 3 strains (11.1%) of Y. intermedia, and 1 strain (3.7%) of Y. kristensenii were identified. According to the serotypes of Y. enterocolitica isolates, O:3 (11.1%) and O:5 (11.1%) were the most predominant, followed by O:8 (5.6%) and others (72.2%). For biotypes of Y. enterocolitica isolates, 1A (77.8%) was the most predominant, followed by 3B (11.1%), 3 (5.6%), and 5A (5.6%). Also, an antibiotic susceptibility test showed that Y. enterocolitica isolates were very susceptible to the antibiotics tested but highly resistant to ampicillin (94%), cephalothin (100%), and carbenicillin (83%). PCR assays with specific primers derived from yst and ail genes of Y. enterocolitica were applied to confirm the presence of pathogenic Y. enterocolitica. Among the 18 strains of Y. enterocolitica isolates, only 3 strains (O:3/1A, UT/3B, and UT/1A isolated from Chinese cabbage, onion, and spinach, respectively) were shown to have a virulence gene.