Impact of the conjugation of antibodies to the surfaces of polymer nanoparticles on the immune cell targeting abilities

Antibodies have been widely used to provide targeting ability and to enhance bioactivity owing to their high specificity, availability, and diversity. Recent advances in biotechnology and nanotechnology permit site-specific engineering of antibodies and their conjugation to the surfaces of nanoparticles (NPs) in various orientations through chemical conjugations and physical adhesions. This study proposes the conjugation of poly(lactic-co-glycolic acid) (PLGA) NPs with antibodies by using two distinct methods, followed by a comparison between the cell-targeting efficiencies of both techniques. Full-length antibodies were conjugated to the PLGA-poly(ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) NPs through the conventional carbodiimide coupling reaction, and f(ab')2 antibody fragments were conjugated to the PLGA-poly(ethylene glycol)-maleimide(PLGA-PEG-Mal) NPs through interactions between the f(ab')2 fragment thiol groups and the maleimide located on the nanoparticle surface. The results demonstrate that the PLGA nanoparticles conjugated with the f(ab')2 antibody fragments had a higher targeting efficiency in vitro and in vivo than that of the PLGA nanoparticles conjugated with the full-length antibodies. The results of this study can be built upon to design a delivery technique for drugs through biocompatible nanoparticles.ope

New insights into the microbiota of wild mice

Laboratory mice have long been an invaluable tool in biomedical science and have made significant contributions in research into life-threatening diseases. However, the translation of research results from mice to humans often proves difficult due to the incomplete nature of laboratory animal-based research. Hence, there is increasing demand for complementary methods or alternatives to laboratory mice that can better mimic human physiological traits and potentially bridge the translational research gap. Under these circumstances, the natural/naturalized mice including "wild", "dirty", "wildling", and "wilded" systems have been found to better reflect some aspects of human pathophysiology. Here, we discuss the pros and cons of the laboratory mouse system and contemplate how wild mice and wild microbiota are able to help in refining such systems to better mimic the real-world situation and contribute to more productive translational research.ope

치약 내 불소의 생리적 가용능 평가

Objectives : The aims of this study were to determine the total fluoride concentration and bioavailable fluoride concentration in different toothpastes, based on a newly suggested method by the International Organization for Standardization (ISO), and to compare the measured concentrations with the concentrations written on the packaging. Methods : The concentrations of total fluoride (TF) and bioavailable fluoride (BF) were measured in six toothpastes. For the TF measurement, 1 g of each toothpaste was mixed with dipotassium hydrogen phosphate (K2HPO4), and hydrogen chloride (HCl) was placed. After 24 hours, the samples were centrifuged and total ionic strength adjustment buffer (TISAB) solution was added. For the BF measurement, the toothpaste was mixed with K2HPO4 for only 1 minute. The samples were centrifuged, and then HCl was placed and allowed to stand for 24 hours. The TISAB solution was added subsequently. The concentration of fluoride ions was measured using a fluoride ion-selective electrode and calculated against a standard curve. Results : The six toothpastes were composed of different fluoride compounds and abrasives. The measured TF concentration ranged from 624.99 ppm to 1,353.00 ppm, and the similarity to the declared fluoride concentration ranged from 53.48% to 93.31%. The measured BF concentration ranged from 587.61 ppm to 1,360.05 ppm, and the similarity to the expected fluoride concentration ranged from 41.97% to 93.80%. Two samples were clearly separated when the samples were centrifuged, whereas the remaining four samples had unclear supernatants. The clearly separated toothpastes (i.e., toothpastes 5 and 6) had BF concentrations that were similar to or lower than the declared fluoride concentrations and the measured TF concentrations. However, the unclearly separated toothpastes showed inconsistent relationships between the measured TF and BF concentrations. Conclusions : The measured TF and BF concentrations of the six toothpastes did not reach the expected fluoride concentration. This finding resulted from the different compositions and forms of the toothpastes. Therefore, the properties of toothpastes need to be considered when measuring their fluoride concentrations.ope

Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4+ T cells

Children with autism spectrum disorders often display dysregulated immune responses and related gastrointestinal symptoms. However, the underlying mechanisms leading to the development of both phenotypes have not been elucidated. Here, we show that mouse offspring exhibiting autism-like phenotypes due to prenatal exposure to maternal inflammation were more susceptible to developing intestinal inflammation following challenges later in life. In contrast to its prenatal role in neurodevelopmental phenotypes, interleukin-17A (IL-17A) generated immune-primed phenotypes in offspring through changes in the maternal gut microbiota that led to postnatal alterations in the chromatin landscape of naive CD4+ T cells. The transfer of stool samples from pregnant mice with enhanced IL-17A responses into germ-free dams produced immune-primed phenotypes in offspring. Our study provides mechanistic insights into why children exposed to heightened inflammation in the womb might have an increased risk of developing inflammatory diseases in addition to neurodevelopmental disorders.ope

치태의 산생성 능력을 이용한 새로운 우식활성검사법의 임상적 활용 가능성 평가

Objectives : This study was aimed at evaluating the clinical usability of a new caries activity test (Cariview®), which was based on the acidogenic potential of plaque by evaluating it's correlation with the DMFT index and comparing the results of Cariview® with those of previous caries activity tests in an adult group. Methods : Teeth of 74 subjects were examined, and the DMFT index was calculated according to World Health Organization (WHO) criteria to determine the past caries experience. Caries activity tests were performed according to manufacturer's instructions. For Cariview® test, plaque samples were collected from the tooth surface by using a sterile cotton swab and incubated at 37℃ for 48 h; an indicator was added to observe the color changes according to the plaque acidogenicity. The subjects were classified into three groups (Low, Moderate, High) according to the level of caries risk. The data were assessed using one-way ANOVA to compare the caries experiences of risk groups according to the caries activity test results, and the relationships between the caries activity tests and the DMFT index were evaluated. Results : The overall mean DMFT index was 5.70±4.42. There was a significant difference in the DMFT index among the caries risk groups (Low, Moderate, High) according to the Cariview® test result (P=0.036). Further, there was a positive correlation between the Cariview® score and the DMFT index (r=0.23, P=0.047) and between the Cariview® score and the previous caries activity tests score (P<0.01). Conclusions : The new caries activity test (Cariview®) can be easily used at dental clinics and enables precise caries risk assessment.ope

Usefulness of Dental Hygiene Education Curriculum in the Public Oral Health Service Performance in Korea

The purpose of this study was to evaluate the usefulness of dental hygiene education curriculum such as oral prophylaxis, preventive dentistry, public oral health, oral health statistics, oral health education in the public oral health service performance. Questionnaire survey was posed to 96 dental hygienists working in health centers and health subcenters. The relativity among frequency of task, usefulness, importance, and reinforcement of the education curriculum in the health centers, and the effect of current dental hygiene education curriculum on public oral health service were studied. The results were follows; 1. Sealant was performed the most frequently in the health centers and health subcenters, and it was also the most useful content in the education curriculum. And the tooth brushing method was considered the most important in the curriculum. Therefore, oral health education was considered as factor which required the most reinforcement. However, the issues of school water fluoridation and water fluoridation in the public oral health were barely brought up as a matter of subject. 2. In the relationship between the frequency of task and the usefulness of curriculum, it showed that the more frequency of task was more useful. In the relationship between importance and reinforcements of curriculum, it showed that the more importance of the education curriculum requires more reinforcement. And more frequently performed task should be more strengthened. 3. According to the education course hours, current education curriculum course hours were 532.4 hours, which is 42.9 hours more spent than the original curriculum guideline. Lecture hours were 205.4 hours, which is 50.6 hours less, and the practice hours were 327 hours, which is 93.5 hours more than the original curriculum guideline. 4. Because of the insufficient course hours of curriculum compared to the frequency of the task, the oral health education, oral prophylaxis, and preventive dentistry should be reinforced more than now. But the oral health statistics and public oral health curriculum were not only emphasized, but also any reinforced compared to other tasks.ope

Bioinspired DNase-I-Coated Melanin-Like Nanospheres for Modulation of Infection-Associated NETosis Dysregulation

The current outbreak of the beta-coronavirus (beta-Cov) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in December 2019. No specific antiviral treatments or vaccines are currently available. A recent study has reported that coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with neutrophil-specific plasma membrane rupture, and release excessive neutrophil extracellular traps (NETs) and extracellular DNAs (eDNAs). This mechanism involves the activation of NETosis, a neutrophil-specific programmed cell death, which is believed to play a crucial role in COVID-19 pathogenesis. Further progression of the disease can cause uncontrolled inflammation, leading to the initiation of cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. Herein, it is reported that DNase-I-coated melanin-like nanospheres (DNase-I pMNSs) mitigate sepsis-associated NETosis dysregulation, thereby preventing further progression of the disease. Recombinant DNase-I and poly(ethylene glycol) (PEG) are used as coatings to promote the lengthy circulation and dissolution of NET structure. The data indicate that the application of bioinspired DNase-I pMNSs reduce neutrophil counts and NETosis-related factors in the plasma of SARS-CoV-2 sepsis patients, alleviates systemic inflammation, and attenuates mortality in a septic mouse model. Altogether, the findings suggest that these nanoparticles have potential applications in the treatment of SARS-CoV-2-related illnesses and other beta-CoV-related diseases.ope

3'-Sialyllactose Prebiotics Prevents Skin Inflammation via Regulatory T Cell Differentiation in Atopic Dermatitis Mouse Models

3'-Sialyllactose (3'-SL), a natural prebiotic, maintains immune homeostasis and exerts anti-inflammatory and anti-arthritic effects. Although regulatory T cells (Tregs) prevent excessive inflammation and maintain immune tolerance, the effect of 3'-SL on Treg regulation is unclear. This study aimed to investigate the effect of 3'-SL on Treg responses in atopic dermatitis (AD) pathogenesis. Oral administration of 3'-SL reduced AD-like symptoms such as ear, epidermal, and dermal thickness in repeated topical application of house dust mites (HDM) and 2,4-dinitrochlorobenzene (DNCB). 3'-SL inhibited IgE, IL-1β, IL-6, and TNF-α secretion and markedly downregulated AD-related cytokines including IL-4, IL-5, IL-6, IL-13, IL-17, IFN-γ, TNF-α, and Tslp through regulation of NF-κB in ear tissue. Additionally, in vitro assessment of Treg differentiation revealed that 3'-SL directly induced TGF-β-mediated Treg differentiation. Furthermore, 3'-SL administration also ameliorated sensitization and elicitation of AD pathogenesis by suppressing mast cell infiltration and production of IgE and pro-inflammatory cytokines in mouse serum by mediating the Treg response. Furthermore, Bifidobacterium population was also increased by 3'-SL administration as prebiotics. Our data collectively show that 3'-SL has therapeutic effects against AD progression by inducing Treg differentiation, downregulating AD-related cytokines, and increasing the Bifidobacterium population.ope

Gut Microbial Metabolites on Host Immune Responses in Health and Disease

Intestinal microorganisms interact with various immune cells and are involved in gut homeostasis and immune regulation. Although many studies have discussed the roles of the microorganisms themselves, interest in the effector function of their metabolites is increasing. The metabolic processes of these molecules provide important clues to the existence and function of gut microbes. The interrelationship between metabolites and T lymphocytes in particular plays a significant role in adaptive immune functions. Our current review focuses on 3 groups of metabolites: short-chain fatty acids, bile acids metabolites, and polyamines. We collated the findings of several studies on the transformation and production of these metabolites by gut microbes and explained their immunological roles. Specifically, we summarized the reports on changes in mucosal immune homeostasis represented by the Tregs and Th17 cells balance. The relationship between specific metabolites and diseases was also analyzed through latest studies. Thus, this review highlights microbial metabolites as the hidden treasure having potential diagnostic markers and therapeutic targets through a comprehensive understanding of the gut-immune interaction. © 2023, Korean Association of Immunologists. All rights reserved.ope

Ets1 suppresses atopic dermatitis by suppressing pathogenic T cell responses

Atopic dermatitis (AD) is a complex inflammatory skin disease mediated by immune cells of both adaptive and innate types. Among them, CD4+ Th cells are one of major players of AD pathogenesis. Although the pathogenic role of Th2 cells has been well characterized, Th17/Th22 cells are also implicated in the pathogenesis of AD. However, the molecular mechanisms underlying pathogenic immune responses in AD remain unclear. We sought to investigate how the defect in the AD susceptibility gene, Ets1, is involved in AD pathogenesis in human and mice and its clinical relevance in disease severity by identifying Ets1 target genes and binding partners. Consistent with the decrease in ETS1 levels in severe AD patients and the experimental AD-like skin inflammation model, T cell-specific Ets1-deficient mice (Ets1ΔdLck) developed severe AD-like symptoms with increased pathogenic Th cell responses. A T cell-intrinsic increase of gp130 expression upon Ets1 deficiency promotes the gp130-mediated IL-6 signaling pathway, thereby leading to the development of severe AD-like symptoms. Functional blocking of gp130 by selective inhibitor SC144 ameliorated the disease pathogenesis by reducing pathogenic Th cell responses. Our results reveal a protective role of Ets1 in restricting pathogenic Th cell responses and suggest a potential therapeutic target for AD treatment.ope