• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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• pp.88-94
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• 2018

Background: We strived to evaluate the status of nivolumab use and associated factors on the clinical efficacy of the drug. Methods: The study was retrospectively conducted in patients who had been administered nivolumab at least once at the cancer center of Seoul National University Hospital from June 2015 to April 2017. Data were collected from electronic medical records. A medication-use evaluation was performed based on the American Society of Health-System Pharmacists mediation-use guidelines. Results: Sixty-six of the 74 patients (89.2%) showed indications approved for nivolumab use by the Korean Ministry of Food and Drug Safety (MFDS; n=55) or the US Food and Drug Administration (FDA; n=11). Approximately 73.0% of the patients were administered the approved dose of 3 mg/kg but 25.7% were administered an unapproved fixed dose of 100 mg. The overall response rate was 21.7%, and the response rate of non-small cell lung cancer patients, who accounted for the largest number of indications, was 18.8%. Adverse reactions were found in 90.1% of the patients and were mostly mild (86%). The expression of programmed death-ligand 1 (PD-L1) was analyzed as a factor affecting treatment response (p=0.028, odds ratio [OR]=11.331). Conclusion: PD-L1 expression was found to affect treatment response. However, caution is required while using an unapproved dosage and in the absence of monitoring for effectiveness and safety. Therefore, an effective protocol or instruction manual for the proper use of nivolumab should be considered.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.5
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• pp.492-499
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• 2021

Purpose: Celiac disease (CD) is an autoimmune disorder of the small intestine caused by an abnormal immune response to gluten proteins and is often characterized by gastrointestinal symptoms. Food allergy (FA) is an adverse immune sensitivity to ingested food proteins leading to inflammation in various organs including the gastrointestinal tract. The relationship between CD and FA remains unclear. This study aimed to assess the prevalence and clinical relevance of immunoglobulin E (IgE)-mediated food sensitization in children with CD. Methods: Fifty-nine children diagnosed with CD were reviewed for clinical symptoms and evidence of IgE-sensitization to food and airborne allergens using the PolyCheck method. Results: IgE-mediated sensitization has been diagnosed in 20.3% of children with CD (CD/A). In the CD/A group, 58.3% of children were sensitized to food and 66.7% to airborne allergens. Further, 41.7% of patients with CD and allergy reported gastrointestinal tract symptoms associated with the ingestion of sensitizing foods. Analysis of the clinical status revealed that the incidence of other allergic disorders in the CD/A group was as follows: atopic dermatitis (33.3%), asthma (25.0%), and allergic rhinitis (16.7%). The percentage of eosinophils was significantly higher in the CD/A group than in the CD group (0.33±0.25 vs. 0.11±0.09; p=0.006). Conclusion: The diagnosis of CD does not exclude FA. The gastrointestinal symptoms in children with CD may be the result of both CD and FA; therefore, children with CD should be evaluated for the presence of FA regardless of age.

• Molecules and Cells
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• v.42 no.7
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• pp.503-511
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• 2019

As sessile organisms, plants have developed sophisticated system to defend themselves against microbial attack. Since plants do not have specialized immune cells, all plant cells appear to have the innate ability to recognize pathogens and turn on an appropriate defense response. The plant innate immune system has two major branches: PAMPs (pathogen associated molecular patterns)-triggered immunity (PTI) and effector-triggered immunity (ETI). The ability to discriminate between self and non-self is a fundamental feature of living organisms, and it is a prerequisite for the activation of plant defenses specific to microbial infection. Arabidopsis cells express receptors that detect extracellular molecules or structures of the microbes, which are called collectively PAMPs and activate PTI. However, nucleotidebinding site leucine-rich repeats (NB-LRR) proteins mediated ETI is induced by direct or indirect recognition of effector molecules encoded by avr genes. In Arabidopsis, plasmamembrane localized multifunctional protein RIN4 (RPM1-interacting protein 4) plays important role in both PTI and ETI. Previous studies have suggested that RIN4 functions as a negative regulator of PTI. In addition, many different bacterial effector proteins modify RIN4 to destabilize plant immunity and several NB-LRR proteins, including RPM1 (resistance to Pseudomonas syringae pv. maculicola 1), RPS2 (resistance to P. syringae 2) guard RIN4. This review summarizes the current studies that have described signaling mechanism of RIN4 function, modification of RIN4 by bacterial effectors and different interacting partner of RIN4 in defense related pathway. In addition, the emerging role of the RIN4 in plant physiology and intercellular signaling as it presents in exosomes will be discussed.

• Journal of Animal Science and Technology
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• v.63 no.2
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• pp.211-247
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• 2021

Livestock species experience several stresses, particularly weaning, transportation, overproduction, crowding, temperature, and diseases in their life. Heat stress (HS) is one of the most stressors, which is encountered in livestock production systems throughout the world, especially in the tropical regions and is likely to be intensified due to global rise in environmental temperature. The gut has emerged as one of the major target organs affected by HS. The alpha- and beta-diversity of gut microbiota composition are altered due to heat exposure to animals with greater colonization of pathogenic microbiota groups. HS also induces several changes in the gut including damages of microstructures of the mucosal epithelia, increased oxidative insults, reduced immunity, and increased permeability of the gut to toxins and pathogens. Vulnerability of the intestinal barrier integrity leads to invasion of pathogenic microbes and translocation of antigens to the blood circulations, which ultimately may cause systematic inflammations and immune responses. Moreover, digestion of nutrients in the guts may be impaired due to reduced enzymatic activity in the digesta, reduced surface areas for absorption and injury to the mucosal structure and altered expressions of the nutrient transport proteins and genes. The systematic hormonal changes due to HS along with alterations in immune and inflammatory responses often cause reduced feed intake and production performance in livestock and poultry. The altered microbiome likely orchestrates to the hosts for various relevant biological phenomena occurring in the body, but the exact mechanisms how functional communications occur between the microbiota and HS responses are yet to be elucidated. This review aims to discuss the effects of HS on microbiota composition, mucosal structure, oxidant-antioxidant balance mechanism, immunity, and barrier integrity in the gut, and production performance of farm animals along with the dietary ameliorations of HS. Also, this review attempts to explain the mechanisms how these biological responses are affected by HS.

• Animal Bioscience
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• v.35 no.4
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• pp.587-595
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• 2022

Objective: The present study was conducted to evaluate the effects of dietary supplementation with Bifidobacterium animalis, Agave fructans, and symbiotic of both encapsulated on growth performance, feed efficiency, blood parameters, and immune status in broiler chickens, and to compare these with diets including antibiotic growth promoters and without additives. Methods: A comparative experimental study was carried out with 135 male Ross 308 broiler chickens. Each trial was divided into 5 equal groups. Control group (CON) received a standard diet without growth promoter; GPA, a standard diet with colistin sulfate and zinc bacitracin (0.25 g/kg of feed); PRE, a standard diet with 1% Agave fructans; PRO, a standard diet with Bifidobacterium animalis (11.14±0.70 log CFU/g); SYM, a standard diet with B. animalis and Agave fructans. Results: A significant decrease in food consumption was found for the GPA, PRE, and SYM, compared to the CON group. The results show a better feed conversion index in PRE and GPA with respect to the CON group with the highest conversion index. Interestingly, the weight of the gastrointestinal tract shows a statistically significant difference between GPA and PRE groups. Moreover, the length of the gastrointestinal tract of the GPA group was less than the PRE group. In the total leukocyte count, there was a statistically significant increase in the GPA group compared to the CON, PRE, and PRO groups, and the heterophiles-lymphocytes index was lower in PRO. Regarding the cytokines, interleukin 10 (IL-10) decreased in PRO compared to CON and PRE, while IL-1β increased in the SYM group. Conclusion: Alternative treatments were shown to achieve similar productive results as growth-promoting antibiotics and showed improvement over diet without additives; however, they have immunomodulatory properties and improved the development of the gastrointestinal tract compared to the treatment of growth-promoting antibiotics.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.39.1-39.18
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• 2021

The high virulent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that emerged in China at the end of 2019 has generated novel coronavirus disease, coronavirus disease 2019 (COVID-19), causing a pandemic worldwide. Every country has made great efforts to struggle against SARS-CoV-2 infection, including massive vaccination, immunological patients' surveillance, and the utilization of convalescence plasma for COVID-19 therapy. These efforts are associated with the attempts to increase the titers of SARS-CoV-2 neutralizing Abs (nAbs) generated either after infection or vaccination that represent the body's immune status. As there is no standard therapy for COVID-19 yet, virus eradication will mainly depend on these nAbs contents in the body. Therefore, serological nAbs neutralization assays become a requirement for researchers and clinicians to measure nAbs titers. Different platforms have been developed to evaluate nAbs titers utilizing various epitopes sources, including neutralization assays based on the live virus, pseudovirus, and neutralization assays utilizing recombinant SARS-CoV-2 S glycoprotein receptor binding site, receptor-binding domain. As a standard neutralization assay, the plaque reduction neutralization test (PRNT) requires isolation and propagation of live pathogenic SARS-CoV-2 virus conducted in a BSL-3 containment. Hence, other surrogate neutralization assays relevant to the PRNT play important alternatives that offer better safety besides facilitating high throughput analyses. This review discusses the current neutralization assay platforms used to evaluate nAbs, their techniques, advantages, and limitations.

• Korean Journal of Poultry Science
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• v.8 no.1
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• pp.15-24
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• 1981

A study was conducted to determine whether the vaccination programs for the control of New castle disease (ND) would affect the immune status of birds against the disease. Twenty-six poultry flocks in the epizootic area of ND were surveyed to investigate the level of urn antibody against ND virus and the programs used for the vaccination of birds. The mortality rates and vaccination status of birds during the epizootic of ND were also examined in the infected poultry flocks to elucidate the immune effect against the epizootic with particular regard to various vaccination programs used in the field. The results obtained are summerized as follows: 1. Of 26 poultry flocks investigated, 22 flocks were immunized with live and killed vaccines, their haemagglutination-inhibition (HI) antibody titer being 146 and 50, respectively. Among 22 farms using live and killed vaccines two flocks which showed the lowest HI titer of 10 and 23 had the disease later on. However, no cases of ND were recorded in the killed vaccine groups, although their HI titers were in the range of 38 to 64. 2. Of 14 infected flecks, one flock was not vaccmated against ND while all the remaining 13 flocks were vaccinated against the disease, of which 8 flocks were vaccinated with live vaccine only and the other 5 flocks with both live and killed vaccines. The mortality rate of 8 infected flocks which had been vaccinated with only live vaccine was as high as 32.5% while that of 5 flocks with both live and killed vaccines was as low as 5.1%. 3. It was found that in majority of flocks B$_1$vaccine was used via drinking water and in a few flocks the vaccine was administered via intramuscular route or method of dipping mouth, nose and eye of birds into vaccine solution.

• Korean Journal of Poultry Science
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• v.48 no.1
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• pp.13-22
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• 2021

The present experiment was conducted to evaluate the effect of stocking density on the growth performance, immune status, and meat quality of broilers. In total, 385 one-day-old Ross 308 broilers were randomly assigned to one of four distinct stocking densities: 26 birds/㎡, 22 birds/㎡, 19 birds/㎡, and 16 birds/㎡. They were fed the diet ad libitum for 5 weeks. Immunoglobulin (Ig) and corticosterone levels were evaluated, and growth performance, blood parameters, and breast meat quality were determined. It was observed that the weight gain and feed intake of growers (21~35 d) and broilers (0~35 d) were significantly reduced as the stocking density increased (P<0.05). However, the feed intake of starters (0~21 d) significantly increased as the stocking density increased (P<0.05). There were no significant differences in the biochemical profiles among the four different stock densities. Furthermore, no significant differences were observed in the stress parameters: (heterophils / lymphocytes ratio and corticosterone), IgA, and IgM; however, IgG significantly increased with stocking density (P<0.05). The pH, water holding capacity, and cooking loss of the muscle were all unaffected by the stocking density, but the shear force (tenderness) increased slightly as the density increased. The findings of this study suggest that a lower stocking density (16 birds/㎡) significantly improved the shear force of breast meat and IgG in broilers.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.5
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• pp.661-666
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• 2005

The effects of pre-partum feeding management in terms of birth weight, growth, metabolic profile and immunity of calves were studied using 24 crossbred (Bos taurus${\times}$Bos indicus) cows, divided into three equal groups. The dietary treatments included feeding of either 3.0 kg concentrate/head/d throughout the 60 d pre-partum (T$_1$), or 3.0 kg concentrate during 60-22 d pre-partum and thereafter at an increased allowance at 0.25 kg/d during the next 21 d till it reached 1% of live weight (T$_2$). The third group of cows was fed similar to T$_2$, except that the concentrate feeding during 60-22 d pre-partum was reduced to 2.0 kg (T$_3$). All the groups had access to ad libitum green fodder throughout. The results revealed that the mean daily dry matter (DM) intake by the cows was similar (p>0.05) among the three groups during the 60 days of the pre-partum but T2 animals tended to gain more live weight (41.25 kg) than T$_1$ (38.12 kg) and T$_3$ (36.25 kg). The body condition score of the cows did not change appreciably over the experimental period. The mean birth weight of the calves was 24.00${\pm}$1.10, 24.63${\pm}$1.17 and 23.25${\pm}$1.19 kg for the three groups, respectively, with the corresponding average daily gain of 154.2, 155.0 and 169.7 g during the subsequent 60 days; both these parameters did not vary significantly ascribable to prepartum feeding regimens of their dams. The total immunoglobulin (Ig) concentration in the colostrum was 6.31${\pm}$0.34, 5.80${\pm}$0.21 and 6.13${\pm}$0.30 g/dl for the three groups, respectively, showing no influence of dietary treatments. The mean serum Ig levels (T$_1$ 2.10${\pm}$0.09, T$_2$ 2.05${\pm}$0.09 and T$_3$ 2.10${\pm}$0.12 g/dl) of calves at 5 d of age were similar among the dietary groups as was the case with various serum biochemical constituents. It is concluded that the variations in pre-partum dietary management elicited no significant influence on the calf performance including the immune status.

• Nutrition Research and Practice
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• v.14 no.2
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• pp.117-126
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• 2020

BACKGROUND/OBJECTIVES: Vitamin D and zinc are recognized for their roles in immune-modulation, and their deficiencies are suggested to be important risk factors for childhood infections. This study, therefore, undertook to assess the occurrence of infections in rural Indian schoolchildren, subsequent to daily supplementation with vitamin D-calcium or zinc for 6 months. SUBJECTS/METHODS: This was a randomized, double-blind, placebo-controlled trial in apparently healthy 6-12 year-old rural Indian children, recruited to 3 study arms: vitamin D arm (1,000 IU D3 - 500 mg calcium, n = 135), zinc arm (10 mg, n = 150) and placebo arm (n = 150). The infection status was assessed using a validated questionnaire, and the biochemical parameters of serum 25(OH)D and serum zinc were measured by ELISA and colorimetry, respectively. The primary outcome variable was occurrence of infections (upper respiratory and total infections). RESULTS: Serum 25(OH)D concentration in the vitamin D arm improved significantly by 34%, from 59.7 ± 10.9 nmol/L to 80 ± 23.3 nmol/L (P < 0.0001), but no improvement was observed for serum zinc concentration. While there was significant increase in the percentage of children reporting no or mild upper respiratory tract infections (URTI) and total infections (TI) in all three groups, improvements in the supplemented groups were similar to the placebo group. However, the vitamin D arm reported lower URTI and TI status in the vitamin D sufficient versus insufficient children. Also, URTI and TI status were found to be significantly (P < 0.0001) lower in children with improved 25(OH)D versus unchanged 25(OH)D. CONCLUSIONS: Vitamin D-calcium supplementation helped to improve the vitamin D status but exerts no effect on the occurrence of infections when compared to the placebo group. Improvement in the serum 25(OH)D concentrations and attainment of vitamin D sufficiency may exert a beneficial effect on the infection status and needs to be investigated further. To evaluate the efficacy of zinc supplementation, higher dosages need to be administered in future studies.