• Current Optics and Photonics
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• v.1 no.4
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• pp.412-420
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• 2017

Multinucleated bone resorptive osteoclasts differentiate from bone marrow-derived monocyte/macrophage precursor cells. During osteoclast differentiation, mononuclear pre-osteoclasts change their morphology and biochemical characteristics. In this study, Raman spectroscopy with multivariate techniques such as Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were used to extract biochemical information related to various cellular events during osteoclastogenesis. This technique allowed for label-free and noninvasive monitoring of differentiating cells, and clearly discriminated four different time points during osteoclast differentiation. The Raman band intensity showed significant time-dependent changes that increased up to day 4. The results of Raman spectroscopy agreed with results from atomic force microscopy (AFM) and tartrate-resistant acid phosphatase (TRAP) staining, a conventional biological assay. Under AFM, normal spindle-like mononuclear pre-osteoclasts became round and smaller at day 2 after treatment with a receptor activator of nuclear $factor-{\kappa}B$ ligand and they formed multinucleated giant cells at day 4. Thus, Raman spectroscopy, in combination with PCA-LDA, may be useful for noninvasive label-free quality assessment of cell status during osteoclast differentiation, enabling more efficient optimization of the bioprocesses.

• Tuberculosis and Respiratory Diseases
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• v.38 no.1
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• pp.25-33
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• 1991

The immune staus is known to be decreased in malignant disease and radiation therapy (RT), used as a therapeutic tool, further decrease this-attenuated immune status. We measured the number of peripheral lymphocytes, its subsets and lymphoblast transformation for PPD, PHA, monoclonal antibodies including anti-CD3 and anti-CD2 before and after RT in 19 patients with squamous cell lung cancer to search the fine mechanism behind the RT-induced attenuation of lymphoblast transformtion for mitogens and antigen. The results were as follows; 1) The number of lymphocytes and its subsets decreased significantly after RT, but the percentages of lymhocyte subsets did not change aftr RT except interleukin-2 receptor positive T lymphocytes. 2) The function of lymphoctes, measured by lymphoblast tranformation for PHA and PPD, decrased after RT and the compositions of PBMC used for lymphoblast transformtion were not different before and after RT. 3) The mitosis of lymphocytes to anti-CD2 or anti-CD3 decreased significantly after RT. And IL-2 plus anti-CD3 increased the mitosis than that of anti-CD3 only after RT, but before RT there was no difference. In conclusion, we suggested the fine mechanism behind the RT-induced attenuation of immune response might be the dysfunction of lymphocytes in terms of impaired synthesis of IL-2 rather than the decrease of circulating lymphocyte numbers.

• Journal of Embryo Transfer
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• v.29 no.4
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• pp.375-383
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• 2014

Klotho (KL) is a single transmembrane protein composed of KL1 and KL2 repeats possessing ${\beta}$-glucuronidase activity and maintains calcium homeostasis in physiological state. It has been implicated in pigs that calcium is important for the establishment and maintenance of pregnancy, and our previous study has shown that transient receptor potential vanilloid type 6 (TRPV6), a calcium ion transporter, is predominantly expressed in the uterine endometrium during pregnancy in pigs. However, expression and function of KL in the uterine endometrium has not been determined in pigs. Thus, the present study determined expression and regulation of KL in the uterine endometrium during the estrous cycle and pregnancy in pigs. Real-time RT-PCR analysis showed that levels of KL mRNA decreased between Days 12 to 15 of the estrous cycle, and its expression showed a biphasic manner during pregnancy. KL mRNA was expressed in conceptuses and in chorioallantoic tissues during pregnancy. Explant culture study showed that expression levels of KL were not affected by treatment of steroid hormones or interleukin-1beta during the implantation period. Furthermore, levels of KL mRNA in the uterine endometrium from gilts carrying somatic cell nuclear transfer (SCNT)-derived embryos were significantly lower than those from gilts carrying natural mating-derived embryos on Day 12 of pregnancy. These results exhibited that KL was expressed at the maternal-conceptus interface in a pregnancy status- and stage-specific manner, and its expression was affected by SCNT procedure, suggesting that KL may play an important role in the establishment and maintenance of pregnancy in pigs.

• Nutritional Sciences
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• v.9 no.4
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• pp.295-300
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• 2006

Iron bound to heme appears to be more bioavailable than iron salts. A clinical study was performed to investigate the absorption efficiency of heme-iron and iron-salt products available. Heme-iron and nonheme-iron supplements have become available in Korea. We performed iron absorption studies to compare the absorption of heme-iron polypeptide (HIP) products made from digested hemoglobin, produced in Korea (HIPk) and imported from Japan (HIj), with that of iron salts. In the study, 80 subjects were divided into 5 groups (n=56): placebo group; 12 mg glucose, HIPk group; 12 mg iron as HIPk, HIj group; 12 mg iron as HIj, iron-salt group 1; 12 mg of iron as ferrous aminoacetate, and iron-salt group 2; 100 mg iron as ferrous aminoacetate. Changes in serum iron levels were measured at 3 and 5 hours post ingestion. Absorption of iron in HIPk was higher compared to HIj, iron-salt or placebo. There was a significant inverse correlation between low serum iron levels $(<80{\mu}g/dl)$ and iron absorption from HIPk. These results demonstrated that HIPk was more bioavailable, even taken with a meal, and would have potential advantages over iron salt or HIj as an iron supplement. Our results indicate that heme-iron absorption is regulated by iron status through a heme receptor, whereas iron-salt absorption is unregulated.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.2
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• pp.290-296
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• 2019

Objective: Pigs share many physiological, anatomical and genomic similarities with humans, which make them suitable models for biomedical researches. Understanding the genetic status of Yucatan miniature pigs (YMPs) and their association with human diseases will help to assess their potential as biomedical model animals. This study was performed to identify non-synonymous single nucleotide polymorphisms (nsSNPs) in selective sweep regions of the genome of YMPs and present the genetic nsSNP distributions that are potentially associated with disease occurrence in humans. Methods: nsSNPs in whole genome resequencing data from 12 YMPs were identified and annotated to predict their possible effects on protein function. Sorting intolerant from tolerant (SIFT) and polymorphism phenotyping v2 analyses were used, and gene ontology (GO) network and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed. Results: The results showed that 8,462 genes, encompassing 72,067 nsSNPs were identified, and 118 nsSNPs in 46 genes were predicted as deleterious. GO network analysis classified 13 genes into 5 GO terms (p<0.05) that were associated with kidney development and metabolic processes. Seven genes encompassing nsSNPs were classified into the term associated with Alzheimer's disease by referencing the genetic association database. The KEGG pathway analysis identified only one significantly enriched pathway (p<0.05), hsa04080: Neuroactive ligand-receptor interaction, among the transcripts. Conclusion: The number of deleterious nsSNPs in YMPs was identified and then these variants-containing genes in YMPs data were adopted as the putative human diseases-related genes. The results revealed that many genes encompassing nsSNPs in YMPs were related to the various human genes which are potentially associated with kidney development and metabolic processes as well as human disease occurrence.

• Animal Bioscience
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• v.35 no.1
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• pp.22-28
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• 2022

Objective: Endoplasmic reticulum (ER) stress engages the unfolded protein response (UPR) that serves as an important mechanism for modulating hepatic fatty acid oxidation and lipogenesis. Chronic fasting in mice induced the UPR activation to regulate lipid metabolism. However, there is no direct evidence of whether negative energy balance (NEB) induces ER stress in the liver of cows. This study aimed to elucidate the relationship between the NEB attributed to feed deprivation and ER stress in bovine hepatocytes. Methods: Blood samples and liver biopsy tissues were collected from 6 non-lactating cows before and after their starvation for 48 h. The blood non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA) and glucose level were analyzed. Real-time quantitative polymerase chain reaction and Western blotting were used to explore the regulation of genes associated with UPR and lipid metabolism. Results: The starvation increased the plasma BHBA and NEFA levels and decreased the glucose level. Additionally, the starvation caused significant increases in the mRNA expression level of spliced X-box binding protein 1 (XBP1s) and the protein level of phosphorylated inositol-requiring kinase 1 alpha (p-IRE1α; an upstream protein of XBP1) in the liver. The mRNA expression levels of peroxisome proliferator-activated receptor alpha and its target fatty acid oxidation- and ketogenesis-related genes were significantly upregulated by the starvation-mediated NEB. Furthermore, we found that the mRNA expression levels of lipogenic genes were not significantly changed after starvation. Conclusion: These findings suggest that in the initial stage of NEB in dairy cows, the liver coordinates an adaptive response by activating the IRE1 arm of the UPR to enhance ketogenesis, thereby avoiding a fatty liver status.

• Animal Bioscience
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• v.36 no.2
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• pp.284-294
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• 2023

Objective: This study investigated the effects of in ovo feeding of γ-aminobutyric acid (GABA) and embryonic thermal manipulation (ETM) on growth performance, organ indices, plasma biochemical parameters, hepatic antioxidant levels, and expression of lipid metabolism-related genes in broilers. Methods: Two hundred and fifty eggs were assigned to one of four treatments: control eggs incubated under standard conditions (CON); eggs that received an in ovo injection of 10% GABA on day 17.5 of incubation (G10); thermally manipulated eggs between days 10 and 18 of incubation at 39.6°C for 6 h daily (TM); and eggs that received both treatments during incubation (G10+TM). After 28 days of rearing, five birds per treatment were selected for blood and organ sampling. Results: No differences were found in hatchability or growth parameters among different treatment groups. Hepatic gene expression of catalase (CAT) and glutathione peroxidase 1 (GPx1) was upregulated (p = 0.046 and p = 0.006, respectively) in the G10+TM group, while that of nuclear factor erythroid 2-related factor 2 (NRF2) was upregulated (p = 0.039) in the G10 group. In addition, the relative gene expression of NADPH oxidase 1 (NOX1) was significantly lower (p = 0.007) in all treatment groups than that in the CON group. Hepatic fatty acid synthase (FAS) levels and average daily feed intake (ADFI) of last week showed a positive correlation (r = 0.50, p = 0.038). In contrast, the relative gene expression of the extracellular fatty acid-binding protein (EXFAB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were positively correlated (r = 0.48, p = 0.042 and r = 0.50, p = 0.031) with the overall ADFI of birds. Conclusion: Taken together, the results of this study suggest that the combination of in ovo feeding of GABA and ETM can enhance hepatic antioxidant function in broilers.

• Journal of Gastric Cancer
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• v.22 no.4
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• pp.408-417
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• 2022

Purpose: Treatment options are limited after the failure of first-and second-line treatments in patients with HER2⁺ metastatic gastric cancer (mGC). The present study aimed to explore the efficacy, safety, and prognostic factors of apatinib efficacy as a third-line therapy for patients with human epithelial growth factor receptor 2-positive (HER2⁺) mGC. Materials and Methods: A total of 59 HER2⁺ mGC patients who received apatinib as third-line therapy were retrospectively enrolled in this two-center, single-arm, cohort study; the clinical response, survival data, and adverse events were retrieved. Results: The median progression-free survival (PFS) was 5.2 months (95% confidence interval [CI], 3.9-6.5), and the median overall survival (OS) was 8.2 months (95% CI, 6.6-9.8) Furthermore, forward stepwise multivariate Cox regression analysis showed that a higher Eastern Cooperative Oncology Group performance status score and multiple metastases were independently correlated with decreased PFS and OS (both P<0.05). The main adverse events were leukopenia (45.8%), hypertension (44.1%), thrombocytopenia (39.0%), hand-foot syndrome (37.3%), and elevated transaminase (33.9%). Grade 3 adverse events mainly included hypertension (5.1%) and neutropenia (5.1%); grade 4 adverse events did not occur. Conclusions: Apatinib is efficient and well tolerated in patients with HER2⁺ mGC as a third-line treatment, suggesting that it may be a candidate of choice for these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.117-122
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• 2014

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. Materials and Methods: We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively Results: A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). Conclusions: All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2501-2504
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• 2014

Background: Capecitabine is an oral fluoropyrimidine derivative which is frequently used alone or in combination regimens for the treatment of metastatic breast cancer. Although overall and progression free survivals have increased in recent years with the use of new generation drugs, predictive factors that would further improve the outcomes are needed. Previous studies have demonstrated the relation between post-treatment increase in mean corpuscular volume (MCV) and predicting therapy response as well as survival. The present study investigated the clinical impact of MCV elevation in metastatic breast cancer patients treated with capecitabine. Materials and Methods: The data of a total of 82 patients from three centers followed between June 2005 and June 2013 were retrospectively analyzed. The demographic data and hormone receptor status of the patients, as well as initial examination before and after treatment and data concerning progression were recorded. MCV ${\geq}100$ fl was considered as macrocytosis. Capecitabine was given at a dose of $2500mg/m^2$ daily for 14 days every three weeks. Pre-treatment and post-treatment MCV and other parameters of complete blood count were recorded. Post-treatment initial evaluation was performed after 2 cycles of therapy. Results: The median age of the patients was 46.5 years (range 26-72 years) and 54% were premenopausal. Performance status was ECOG 0 and 1 in 81 (99%) patients. The median number of cycles for capecitabine therapy was 5 (min-max: 2-18). The median ${\Delta}MCV$ level (post-treatment values at sixth week - baseline) was 6.4. Whilst ${\Delta}MCV$ was ${\geq}6.4$ in 42 patients, it was <6.4 in 40 patients. Clinical benefit (complete response+partial response+stable disease) was observed in 37 (88%) of 42 patients with a median ${\Delta}MCV$ ${\geq}6.4$ and in 30 (75%) of 40 patients with ${\Delta}MCV$ <6.4 with no statistically significant difference (p=0.158). No significant difference was determined between the group with ${\Delta}MCV$ ${\geq}6.4$ and the group with ${\Delta}MCV$ <6.4 in terms of progression-free survival (11 vs 12 months) (p=0.55) and overall survival (20 months vs. 24 months) (p=0.11). Conclusions: The identification of new predictive markers in metastatic breast cancer is very important. In some recent studies, increase in MCV has been suggested as a marker in tumor response. In the present study, however, no significant difference was determined between tumor response and increase in MCV. Further studies including higher numbers of patients are needed to determine whether increase in MCV is a predictive marker or not.