The purpose of this study was to investigate the lesions of a mouse collagen antibody-induced arthritis (CAIA) model using fluorescence bioimaging and micro-computed tomography (micro-CT) and to compare it with histopathological examination. Twelve mice were randomly divided into three groups: group 1 (G1) as control, group 2 (G2) as fluorescence probe control and group 3 (G3) as collagen antibodyinduced arthritis. The mice of G3 intravenously received anti-type II collagen 5-clone antibody cocktail (2 mg/mouse) on day 0 and intraperitoneally received lipopolysaccharide (50 μg/mouse) on day 3. On the while, the mice of G1 and G2 received 0.9% saline in equal volumes at equivalent times. Fluorescence bioimaging and micro-CT analysis were carried out to assess arthritis. Treatment with the collagen antibody cocktail increased the paw thickness of mice compared to those in both the control and probe-treated groups. Fluorescence bioimaging using a near infrared imaging agent showed high intensity in the joints of collagen antibody- treated mice, whereas those of control mice showed no signal. Micro-CT analysis of the knee joints of collagen antibody-treated mice showed rough and irregular articular appearance, whereas those of control mice showed normal appearance. Histopathological examination of the knee joints of collagen antibody-treated mice revealed destruction of cartilage and bony structure, synovial hyperplasia and infiltration of inflammatory cells. No cartilage destruction or inflammation was observed in control or probe control mice. Taken together, it is concluded that analyses of fluorescent bioimaging made it possible to evaluate CAIA lesions, comparable with those by micro-CT and histopathological examination in mice.
Adhesive capsulitis of the shoulder is a common cause of pain that occurs during shoulder movement, thereby restricting shoulder rotation in clinical practice. Although most patients respond to pain relief treatment (NSAID or corticosteroids) by improving their range of motion, it remains poorly understood without any definitive treatment algorithm. In addition to immune cells, synoviocytes, chondrocytes and osteoblasts in the joint are known to produce pro-inflammatory mediators such as reactive oxygen species (ROS), inflammatory cytokines and lipid mediators, presumably contributing to the pathogenesis of osteoarthritis (OA) and adhesive capsulitis. Although inflammation and also fibrosis are proposed to be the basic pathological changes of a frozen shoulder, there is a lack of information regarding the downstream targets of the pro-inflammatory ROS signaling pathway in the synoviocytes and also how these ROS targets are modulated at the transcription level by a corticosteroid - dexamethasone. In this study, we used human fibroblast like synoviocytes (HFLS) to characterize the signaling targets of ROS by employing a human DNA microarray tool and studied the role of dexamethasone in this process. Our data suggest that several genes such as FOS, FOSB and NFkBIZ, which are known to be involved in pro- or anti- inflammation response, are modulated at the transcription level by ROS and dexamethasone.
Excessive iron can promote the production of free radicals, thereby leading to harmful effects on cancer and aging. Ascorbic acid is not only an antioxidant but also a co-factor of iron absorption. The effect of iron-overload with ascorbic acid on experimental colon carcinogenesis was investigated in male ICR mice. Animals were treated weekly with azoxymethane (AOM, 10 mg/kg b.w.) at 0, 1, and 2 week and then drunk 2% dextran sodium sulfate (DSS)-containing water for the next 1 week. There were four experimental groups: carboxymethylcellulose (CMC) alone (control), CMC + ascorbic acid (AA), CMC + Fe, CMC + Fe + AA. The animals fed on AIN-76A purified rodent diet for six weeks. AA or Fe2O3 at the dose of 450 mg/kg b.w. were daily and orally treated for 6 weeks. The colonic mucosa was stained with methylene blue and then aberrant crypt foci (ACF) and polyps were counted. Thiobarbituric acid-reactive substances (TBARS) in serum and liver were determined. Iron concentration in liver was measured by inductively coupled plasma spectrophotometer. Fe-overload with AA strongly increased liver iron contents compared to control or Fe group (p<0.05). There were no significant differences in the number of ACF or polyps among all groups, although ironoverloaded groups had slightly higher numbers compared with the control or AA group. TBARS values in the liver were increased in the iron-overloaded groups compared to control and AA only group (p<0.05), but serum TBARS values were not changed. These results indicate that the excessive iron treatment did not affect the experimental colon carcinogenesis regardless of presence of AA in mice.
Electroconvulsive therapy (ECT) has been used in the treatment of psychiatric disorders such as schizophrenia and major depressive disorders which are resistant to pharmacologic therapy. Seizure duration is a major determinant of treatment efficacy in ECT. Patients requiring ECT need effective sedation and neuromuscular blockade to prevent discomfort and the possibility of fractures of bones during ECT. The Bispectral Index (BIS) reflects the clinical degrees of consciousness during sedation and hypnosis with intravenous and inhalational anesthesia. This study was performed to investigate if there is any correlation between the BIS and seizure duration in the patients with psychiatric disorders during ECT under propofol and succinylcholine anesthesia. A total of 11 patients with schizophrenia and major depressive disorders were monitored for BIS, electroencephalogram (EEG) and seizure duration. Seizure was detected using isolated forearm technique (IFT). The BIS was recorded at four specific time points (baseline before the start of anesthetic induction, before ECT (Pre-ECT BIS), at eye opening to verbal command and at 5 minutes after eye opening). Awake baseline value of the BIS showed significant changes depending on the depth of anesthesia at specific time points after propofol was administered. Pre-ECT BIS was positively correlated with seizure duration.
Breast cancer is of enormous concern worldwide and linked with age, sex, hormonal factors, and family history. The treatment of early breast cancer includes treating the disease locally with surgery, radiation therapy, or both and treating microscopic systemic disease with either one or a combination of chemotherapy, endocrine therapy, or biologic therapy. Doxorubicin is a well-known anthracycline antibiotic and antineoplastic drug usually administered to breast cancer patients. However, there have been some reports suggesting that doxorubicin causes side effects such as cardiotoxicity. Furthermore, breast cancer patients on doxorubicin treatment are commonly prescribed steroid suppression therapy. In addition, it has been previously reported that lack of estrogen elevates cardiotoxicity. In this study, we evaluated whether the steroid suppression therapy might influence the cardiotoxicity of doxorubicin. We hypothesized that the presence of a steroid hormone, particularly estrogen, is closely related to doxorubicin action. To investigate the effect of estrogen, mice were divided into four groups: control group, doxorubicin-treated group, ovariectomized group, and ovariectomized plus doxorubicin-treated group. We observed upregulation of inflammatory cytokine gene and downregulation of apoptotic genes in the groups treated with doxorubicin, particularly in the ovariectomized plus doxorubicin-treated group. This suggests that administration of doxorubicin under a non-steroid condition can excessively damage the heart. In summary, combination treatment of hormonal and doxorubicin therapy for breast or many different types of cancer patients must be prescribed with requisite precautions.
It became possible to perform genomic predictions using single nucleotide polymorphism (SNP) with advancements in genomics technology, not only in human but in livestock as well. There are strong interests in improving economical traits in livestock through identifying causative mutation, genes or predicting genomic breeding values. We present the current status of genome prediction studies for phenotype estimation of economic traits in livestock from various perspectives based on the genomic area. First, we introduce theoretical background of genomic prediction methods and newest development on SNP information. Thanks to develop sequencing technology, multi-omics data can be used to predict phenotypes associated with the economic traits. In particular, many studies show that genomic prediction accuracy of genomic partitioning data based on the biological information is higher than that of commercial SNP chip. Therefore, multi-omics data can be useful for genomic prediction studies. It is also important that researchers should consider factors affecting genomic prediction accuracy such as heritability, Quantitative Trait Loci (QTL) and marker density, size and structure of reference population. We also introduce genomic prediction studies based on the integration of multi-omics data that shows improvement of prediction accuracy than typical Genomic Best Linear Unbiased Prediction (GBLUP) models. We concluded that genomic prediction studies can be expanded to apply social issues, new phenotypes, or precision agriculture such as diseases, climate change, and metabolism including economic traits with multi-omics data using high-throughput technologies.