Background: Lung transplantation is the definitive therapy for end stage lung disorders. The success of allogenic lung transplantation has led to an increasing shortage of donor lungs from humans, including cadavers, and attention has now turned to transplantation of lungs from other species. However, there are many biological hurdles when using organs from other species because of hyperacute rejection after discordant xenotransplantation. Material and Method: Pigs (n=6, weighing $20{\sim}30kg$ each) for the donors and mongrel dogs (n=6, weighing $20{\sim}28kg$ each) for the recipients were used in this experiment. The left kidney of a pig was perfused to a mongrel dog for 30 minutes through the femoral artery and vein of the dog, and the right kidney was perfused for 30 minutes sequentially. Then, both lungs of the pig were perfused to the dog through the pulmonary artery and left atrium with using the same time intervals. The levels of IgM and IgG were measured from the blood and specimens of the kidney and lung. Result: The average levels of serum IgM gradually decreased after the perfusion, but the average levels of serum IgG did not charge from before to after perfusion. The immunohistochemical findings revealed decreased deposition of IgG and IgM after the perfusion. Conclusion: We conclude that the levels of the serum natural antibodies would be decreased with pre-transplantation xenograft perfusion in the recipient and the occurrence rate of hyperacute rejection after transplantation would be decreased.
Background : Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. The current evidence has indicated a critical role of HO-1 in cytoprotection and also in other, more diverse biological functions. It is known that the high expression of HO-1 occurs in various tumors, and that HO-1 has an important role in rapid tumor growth because of its antioxidative and antiapoptotic effects. Therefore, the role of HO-1 was analyzed in human lung cancer cell lines, and especially in the A549 cell line. Material and Methods : Human lung cancer cell lines, i.e., A549, NCI-H23, NCI-H157 and NCI-H460, were used for this study. The expression of HO-1 in the untreated state was defined by Western blotting. ZnPP, which is the specific HO inhibitor we used, and the viability of cells were tested for by conducting MTT assaysy. The HO enzymatic activity, as determined via the bilirubin level, was also indirectly measured. Moreover, the generation of intracellular hydrogen peroxide (H2O2) was monitored fluorimetrically with using a scopoletin-horse radish peroxidase (HRP) assay and 2',7'-dichlorofluorescein diacetate (DCFH-DA). We have also transfected small HO-1 interfering RNA (siRNA) into A549 cells, and the apoptotic effects were evaluated by flow cytometric analysis and Western blotting. Results : The A549 cells had a greater expression of HO-1 than the other cell lines, whereas ZnPP significantly decreased the viability of the A549 cells more than the viability of the other lung cancer cells in a dose-dependant fashion. Consistent with the viability, the HO enzymatic activity also was decreased. Moreover, intracellular H2O2 generation via ZnPP was induced in a dose-dependent manner. Apoptotic events were, then induced in the HO-1 siRNA transfected A549 cells. Conclusion : HO-1 provides new important insights into the possible molecular mechanism of the antitumor therapy in lung cancer.
Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.
Ha, Jun Young;Kim, Mi Kyeong;Lee, Jun Young;Choi, Eun Bi;Hong, Chang Oh;Lee, Byong Won;Bae, Chang Hwan;Kim, Keun Ki
Journal of Life Science
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v.25
no.1
/
pp.53-61
/
2015
In this study, we tried to separate the photosensitizer that induces apoptosis of leukemia cells (U937) from perilla leaves. Perilla leaves (Perilla frutescens Britt var. japonica Hara) are a popular vegetable in Korea, being rich in vitamins (A and E), GABA, and minerals. Dried perilla leaves were extracted with methanol to separate the photosensitizer by various chromatographic techniques. The structure of the isolated compound (PL9443) was identified by 1D-NMR, 2D-NMR, and FAB-mass spectroscopy. Absorbance of the UV-Vis spectrum was highest at 410 nm and was confirmed by the 330, 410, and 668 nm. PL9443 compound was determined to be pheophorbide, an ethyl ester having a molecular weight of 620. It was identified as a derivative compound of pheophorbide structure when magnesium comes away from a porphyrin ring. Observation of morphological changes in U937 cells following cell death induced by treated PL9443 compound revealed representative phenomena of apoptosis only in light irradiation conditions (apoptotic body, vesicle formation). Results from examining the cytotoxicity of PL9443 substance against U937 cells showed that inhibition rates of the cell growth were 99.9% with the concentration of 0.32 nM PL9443. Also, the caspase-3/7 activity was 99% against U937 cells with the concentration of 0.08 nM of PL9443 substance. The result of the electrophoresis was that a DNA ladder was formed by the PL9443. The PL9443 compound is a promising lead compound as a photosensitizer for photodynamic therapy of cancer.
Exercise-induced anaphylaxis (EIA) is a physical allergy, sometimes severe, triggered by exertion following specific food intake. It was defined for the first time in 1980. EIA is associated with different kinds of exercise. The clinical manifestations progress from itching, erythema and urticaria to some combination of cutaneous angioedema and vascular collapse. Mast cell participation in the pathogenesis of this syndrome has been proved by the findings of an elevated serum histamine level during exhaustive exercise. As predisposing factors of EIA, a specific or even nonspecific sensitivity to food has been reported. Food-dependent exercise-induced anaphylaxis (FDEIA) is a distinct form of food allergy induced by physical exercise. It is typified by the onset of anaphylaxis during exercise which was preceded by the ingestion of the causal food allergens. The diagnosis of FDEIA is heavily dependent on clinical history. Allergy tests may need to be performed using a broad panel of food and food additives. As with food allergies, FDEIA diagnosis is based on interview, biological test and skin test. Prophylaxis aims to prevent a recurrence; the patient should be given an emergency kit to deal with any recurrent episodes. After the food allergen has been identified, it should be avoided for at least 4 to 5 hours before any exercise. Two cases of EIA are presented (EIA to circumstances; FDEIA) in this paper, The diagnosis, pathophysiology and therapy of FDEIA are also reviewed.
The ultimate goal of periodontal therapy is the regeneration of periodontal tissue which has been lost due to destructive periodontal disease. To achieve periodontal regeneration, various kinds of methods have been investigated and developed, including guided tissue regeneration and bone graft. Bone graft can be catagorized into autografts, allografts, xenografts, bone substitutes. And materials of all types have different biological activity and the capacity for periodontal regeneration, but ideal graft material has not been developed that fits all the requirement of ideal bone graft material. Recently, bioactive glass that has been utilized in plastic surgery is being investigated for application in dental practice. But, there has not been any long-term assessment of bioactive glass when used in periodontal intrabony defects. The present study evaluates the long-term effects of bioactive glass on the periodontal regeneration in intrabony defects of human and the effect of plaqu control on long term treatment results after dividing patients into those who underwent 3-month regular check-up and those who didn't under go regular check-up The clinical effect on 74sites from 17 infrabony pockets of 11 patients were analyzed 36months after treatment. 51 sites which underwent regular check up were classified as the Follow-up group(F/U group), and 23 sites which did not undergo regular check up were classified as Non Follow-up group(Non F/U group). After comparing the probing depth, attachment loss, bone probing depth before and 36months after treatment, the following results could be concluded. 1. The changes of probing pocket depth showed a statistically significant decrease between after baseline and 36 months after treatment in F/U group(1.79${\pm}$0.68mm) and did no show astatistically significant decrease between after baseline and 36months after treatment in Non F/U group(0.61${\pm}$0.54mm) (P<0.05). 2. The changes of loss of attachment showed a statistically significant decrease between after baseline and 36 months after treatment in F/U group(1.44${\pm}$0.74mm) and did no show astatistically significant decrease between after baseline and 36months after treatment in Non F/U group(1.18${\pm}$1.54) (P<0.05). 3. The changes of bone probing depth showed a statistically significant decrease between after baseline and 36 months after treatment in both F/U(1.35${\pm}$0.28) and Non F/U group(0.78${\pm}$0.55mm) (P<0.05). The results suggest that treatment of infrabony defects with bioactive glass resulted in significan reduction of attachment loss and bone probing depth 36months after the treatment. The use of bioactive glass in infrabony defects, combined with regular check-up and proper plaque control generally shows favorable clinical results. This measn that bioactive glass could be a useful bone substitute.
Ji, Seon Yeong;Kim, Min Yeong;Hwangbo, Hyun;Lee, Hyesook;Hong, Su Hyun;Cha, Hee-Jae;Kim, Heui-Soo;Kim, Suhkmann;Choi, Yung Hyun
Journal of Life Science
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v.31
no.9
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pp.818-826
/
2021
5-Aminolevulinic acid phosphate (5-ALA-p) is a substance obtained by eluting 5-ALA (a natural delta amino acid) with aqueous ammonia, adding phosphoric acid to the eluate, and then adding acetone to confer properties suitable for use in photodynamic therapy applications. However, its pharmacological efficacy, including potential mechanisms of antioxidant and anti-inflammatory reactions, remains unclear. This study aimed to investigate the effects of 5-ALA-p on oxidative and inflammatory stresses in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our data showed that 5-ALA-p significantly inhibited excessive phagocytic activity via LPS and attenuated oxidative stress in LPS-treated RAW 264.7 cells. Furthermore, 5-ALA-p improved mitochondrial biogenesis reduced by LPS, suggesting that 5-ALA-p restores mitochondrial damage caused by LPS. Additionally, 5-ALA-p significantly suppressed the release of nitric oxide (NO) and pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, which are associated with the inhibition of inducible NO synthase and respective cytokine expression. Furthermore, 5-ALA-p reduced the nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited phosphorylation of mitogen-activated protein kinases (MAPKs), indicating that the anti-inflammatory effect of 5-ALA-p is mediated through the suppression of NF-κB and MAPK signaling pathways. Based on these results, 5-ALA-p may serve as a potential candidate to reduce inflammation and oxidative stress.
Chun Mison;Kang Seunghee;Kil Hoon-Jong;Oh Young-Taek;Sohn Jeong-Hye;Jung Hye-Young;Ryu Hee Suk;Lee Kwang-Jae
Radiation Oncology Journal
/
v.20
no.4
/
pp.343-352
/
2002
Purpose : Radiotherapy is the main treatment modality for uterine cervix cancer. Since the rectum is in the radiation target volume, rectal bleeding is a common late side effect. This study evaluates the risk factors of radiation induced rectal bleeding and discusses its optimal management. Materials and Methods : total of 213 patients who completed external beam radiation therapy (EBRT) and intracavitary radiation (ICR) between September 1994 and December 1999 were included in this study. No patient had undergone concurrent chemo-radiotherapy. Ninety patients received radiotherapy according to a modified hyperfractionated schedule. A midline block was placed at a pelvic dose of between 30.6 Gy to 39.6 Gy. The total parametrial dose from the EBRT was 51 to 59 Gy depending on the extent of their disease. The Point A dose from the HDR brachytherapy was 28 Gy to 30 Gy $(4\;Gy\times7,\;or\;5\;Gy\times6)$. The rectal point dose was calculated either by the ICRU 38 guideline, or by anterior rectal wall point seen on radiographs, with barium contrast. Rectal bleeding was scored by the LENT/SOMA criteria. For the management of rectal bleeding, we opted for observation, sucralfate enema or coagulation based on the frequency or amount of bleeding. The median follow-up period was 39 months $(12\~86\;months)$. Results : The incidence of rectal bleeding was $12.7\%$ (27/213); graded as 1 in 9 patients, grade 2 in 16 and grade 3 in 2. The overall moderate and severe rectal complication rate was $8.5\%$. Most complications $(92.6\%)$ developed within 2 years following completion of radiotherapy (median 16 months). No patient progressed to rectal fistula or obstruction during the follow-up period. In the univariate analysis, three factors correlated with a high incidence of bleeding an icruCRBED greater than 100 Gy $(19.7\%\;vs.\;4.2\%)$, an EBRT dose to the parametrium over 55 Gy $(22.1\%\;vs.\;5.1\%)$ and higher stages of III and IV $(31.8\%\;vs.\;10.5\%)$. In the multivariate analysis, the icruCRBED was the only significant factor (p>0.0432). The total parametrial dose from the EBRT had borderline significance (p=0.0546). Grade 1 bleeding was controlled without further management (3 patients), or with sucralfate enema 1 to 2 months after treatment. For grade 2 bleeding, sucralfate enema for 1 to 2 months reduced the frequency or amount of bleeding but for residual bleeding, additional coagulation was peformed, where immediate cessation of bleeding was achieved (symptom duration of 3 to 10 months). Grade 3 bleeding lasted for 1 year even with multiple transfusions and coagulations. Conclusion : Moderate and several rectal bleeding occurred in $8.5\%$ of patients, which is comparable with other reports. The most significant risk factor for rectal bleeding was the accumulated dose to the rectum (icruCRBED), which corrected with consideration to biological equivalence. Prompt management of rectal bleeding, with a combination of sucralfate enema and coagulation, reduced the duration of the symptom, and minimized the anxiety/discomfort of patients.
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