Yoon, Byung Gyu;Kim, Hee Na;Han, Ui Joung;Jang, Hae In;Han, Dong Kyun;Baek, Hee Jo;Hwang, Tai Ju;Kook, Hoon
Clinical and Experimental Pediatrics
/
v.57
no.3
/
pp.125-134
/
2014
Purpose: The aim of this study was to characterize Korean patients with Fanconi anemia (FA), which is a rare but very challenging genetic disease. Methods: The medical records of 12 FA patients diagnosed at Chonnam National University Hospital from 1991 to 2012 were retrospectively reviewed. Results: The median age at diagnosis was 6.2 years. All patients showed evidence of marrow failure and one or more physical stigmata. Chromosome breakage tests were positive in 9 out of 11 available patients. The median follow-up duration was 69.5 months. The Kaplan-Meier (KM) survival of all patients was 83.3% at 10 years and 34.7% at 20 years, respectively. Seven patients underwent 9 stem cell transplantations (SCTs). Among them, 5 were alive by the end of the study. Ten-year KM survival after SCT was 71.4% with a median follow-up of 3.4 years. All 5 patients treated with supportive treatment alone died of infection or progression at the median age of 13.5 years, except for one with short followup duration. Acute leukemia developed in 2 patients at 15.4 and 18.1 years of age. Among 6 patients who are still alive, 3 had short stature and 1 developed insulin-dependent diabetes mellitus. Conclusion: We provide information on the long-term outcomes of FA patients in Korea. A nation-wide FA registry that includes information of the genotypes of Korean patients is required to further characterize ethnic differences and provide the best standard of care for FA patients.
In order to investigate the effects of Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang on antitumor effects after Sarcoma-180 cells transplantation into the peritoneal cavity or left groin in mice, and immune responses in mice induced by methotrexate, the extracts of its herbal medicines were orally administered for 14 or 21 days. Experimental studies were performed for measurance of mean survival days, tumor and body weight for antitumor effects, and delayed type hypersensitivity, hemagglutinin titer, hemolysin titer, rosette forming cells, natural killer cell activity and phagocytic activity for immune responses in ICR mice. Following results were obtained : 1. Mean survival time in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly prolonged, as compared with the control group(P<0.010, P<0.005). 2. Tumor weight in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly depressed, as compared with the control group(P<0.050, P<0.050). 3. Body weight in Banhabaekchulcheonmatang-treated group was significantly increased (P<0.050), but in Banhabackchulcheonmatanggamibang-treated group was slightly increased with no effectivenes, as compared with the control group. 4. Delayed type hypersensitivity in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly increased, as compared with the control group(P<0.010, P<0.050). 5. Hemagglutinin titer in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly increased, as compared with the control group(P<0.050, P<0.050). 6. Hemolysin titer in Banhabaekchulcheonmatanggamibang-treated group was significantly increased (P<0.050), but in Banhabaekchulcheonmatanggamibang-treated group was slightly increased with no effectiveness, as compared with the control group. 7. Rosette forming cells in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was slightly increased with no effectiveness, as compared with the control group. 8. Natural Killer cell activity in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was slightly increased with no effectiveness, as compared with the control group. 9. Phagocytic activity in Banhabaekchulcheonmatanggamibang-treated group group was significantly increased (P<0.050), but in Banhabaekchulcheonmatanggamibang-treated group was increased with no effectiveness, as compared with the control group. According to the above results, it could be suggested that Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang have prominent antitumor effects, and enhance both cellular and humoral immunity.
Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-${\alpha}8$ (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-${\alpha}8$ is largely unknown. We functionally overexpressed integrin-${\alpha}8$ in MM cell lines, and surprisingly, stemness features including $HIF1{\alpha}$, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-${\alpha}8$ expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-${\alpha}8$, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.
Human adipose tissue-derived mesenchymal stem cells (hADSCs) have therapeutic potential, including the ability to self-renew and differentiate into multiple lineages. Understanding of molecular mechanisms of stem cell differentiation is important for improving the therapeutic efficacies of stem cell transplantation. In this study, we determined the role of nuclear factor of activated T cells (NFAT5) in the osteogenic differentiation of hADSCs. The down-regulation of NFAT5 expression by the transfection of a specific siRNA significantly inhibited osteogenic differentiation of hADSCs and decreased the activity of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) promoter without affecting their proliferation and adipogenic differentiation. The inhibition of NFAT5 expression inhibited the basal and Tumor Necrosis Factor ${\alpha}$ (TNF-${\alpha}$) induced activation of NF-${\kappa}B$, but it did not affect TNF-${\alpha}$-induced degradation of the $I{\kappa}B$ protein. These findings indicate that NFAT5 plays an important role in the osteogenic differentiation of hADSCs through the modulation of the NF-${\kappa}B$ pathway.
With an approach to study the anti-tumor effects and mechanism of selenium compound, we investigated the anti-tumor activity and mechanism of $Na_5SeV_5O_{18}{\cdot}3H_2O$ (NaSeVO) in K562 cells. The results showed that $0.625{\sim}20\;mg/L$ NaSeVO could significantly inhibit the proliferation of K562 cells in vitro in a time- and concentration-dependent manner as determined by microculture tetrazolium (MTT) assay, the IC50 values were 14.41 (4.45-46.60) and 3.45 (2.29-5.22) mg/L after 48 hand 72 h treatment with NaSeVO respectively. In vivo experiments demonstrated that i.p. administration of 5, 10 mg/kg NaSeVO exhibited an significant inhibitory effect on the growth of transplantation tumor sarcoma 180 (S180) and hepatoma 22 (H22) in mice, with inhibition rate 26.8% and 58.4% on S180 and 31.3% and 47.4% on H22, respectively. Cell cycle studies indicated that the proportion of G0/G1 phase was increased at 2.5 mg/L while decreased at 10 mg/L after treatment for 24, 48 h. Whereas S phase was decreased at 2.5-5 mg/L and markedly increased at 10 mg/L after treatment for 48 h. After treatment for 24 h, 10 mg/L NaSeVO also markedly increased S and G2/M phases. Take together, the result clearly showed that NaSeVO markedly increased S and G2/M phases at 10 mg/L. The study of immunocytochemistry showed that the expression bcl-2 is significantly inhibited by 10 mg/L NaSeVO, and bax increased. Morphology observation also revealed typical apoptotic features. NaSeVO also significantly caused the accumulation of $Ca^{2+}$ and $Mg^{2+}$, reactive oxygen species (ROS) and the reduction of pH value and mitochondrial membrane potential in K562 cells as compared with control by confocal laser scanning microscope. These results suggest that NaSeVO has anti-tumor effects and its mechanism is attributed partially to apoptosis induced by the elevation of intracellular $Ca^{2+}$, $Mg^{2+}$ and ROS concentration, and a reduction of pH value and mitochondria membrane potential (MMP).
Lee, So Jin;Kim, Hye Yun;Kim, Seul Ji;Yang, Jaewon;Lee, Seon Ui;Park, Chan Hum;Joo, Choun-Ki;Khang, Gilson
Polymer(Korea)
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v.38
no.3
/
pp.364-370
/
2014
The retinal pigment epithelium (RPE) plays an important role in maintaining a healthy retina and the degeneration of RPE caused a number of retinal diseases. The transplantation of RPE has recently become a possible therapeutic modality for retinal degeneration. To transplant RPE cells securely, substrates are essential, and then as a substrate, we fabricated films using silk that has unique mechanical properties and biocompatibility. After the FTIR spectra, contact angle and biodegradation of silk films were confirmed, RPE cells were seeded and the influence of RPE cells on silk films was examined. We measured the cell adhesion, cell viability, morphology and specific mRNA expression by MTT assay, SEM, immunofluorescence and RT-PCR. In this study, we confirmed that attachment, proliferation and phenotype maintenance of RPE cells cultured on silk films were great, and thereby we were able to confirm the potential applications of silk films as tissue engineering carrier for regeneration of retina.
Wi, Hayeon;Lee, Seunghoon;Kim, Youngim;No, Jin-Gu;Lee, Poongyeon;Lee, Bo Ram;Oh, Keon Bong;Hur, Tai-young;Ock, Sun A
Journal of Veterinary Science
/
v.22
no.5
/
pp.63.1-63.14
/
2021
Background: Recently, mesenchymal stem cells therapy has been performed in dogs, although the outcome is not always favorable. Objectives: To investigate the therapeutic efficacy of mesenchymal stem cells (MSCs) using dog leukocyte antigen (DLA) matching between the donor and recipient in vitro. Methods: Canine adipose-derived MSCs (cA-MSCs) isolated from the subcutaneous tissue of Dog 1 underwent characterization. For major DLA genotyping (DQA1, DQB1, and DRB1), peripheral blood mononuclear cells (PBMCs) from two dogs (Dogs 1 and 2) were analyzed by direct sequencing of polymerase chain reaction (PCR) products. The cA-MSCs were co-cultured at a 1:10 ratio with activated PBMCs (DLA matching or mismatching) for 3 days and analyzed for immunosuppressive (IDO, PTGS2, and PTGES), inflammatory (IL6 and IL10), and apoptotic genes (CASP8, BAX, TP53, and BCL2) by quantitative real-time reverse transcriptase-PCR. Results: cA-MSCs were expressed cell surface markers such as CD90+/44+/29+/45- and differentiated into osteocytes, chondrocytes, and adipocytes in vitro. According to the Immuno Polymorphism Database, DLA genotyping comparisons of Dogs 1 and 2 revealed complete differences in genes DQA1, DQB1, and DRB1. In the co-culturing of cA-MSCs and PBMCs, DLA mismatch between the two cell types induced a significant increase in the expression of immunosuppressive (IDO/PTGS2) and apoptotic (CASP8/BAX) genes. Conclusions: The administration of cA-MSCs matching the recipient DLA type can alleviate the need to regulate excessive immunosuppressive responses associated with genes, such as IDO and PTGES. Furthermore, easy and reliable DLA genotyping technology is required because of the high degree of genetic polymorphisms of DQA1, DQB1, and DRB1 and the low readability of DLA 88.
Ahn, Yong Ho;Seok, Pu Reum;Oh, Su Jin;Choi, Jin Woo;Shin, Jae-Ho
Korean Journal of Clinical Laboratory Science
/
v.51
no.3
/
pp.370-378
/
2019
The hepatic ischemic model has recently been widely used for the epidemiological study of ischemic reperfusion injury. This study was carried out to investigate the protective effect of vanillin, which is known to have antioxidant and anti-inflammatory effects, against hepatic and renal injury using an ischemia-reperfusion rat model, and we also investigated the mechanism related to vanillins' protective effect. The test material was administered at a concentration of 100 mg/kg for 3 days, followed by ligation of the liver for 60 minutes to induce ischemia reperfusion. As control groups, there was a negative control, sham control and ischemia-reperfusion-only ischemia reperfusion control, and the controls groups were compared with the drug administration group. In the vanillin group, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly inhibited compared with the AST and ALT activities of the ischemia-reperfusion group, and histopathological examination showed significant reduction of both inflammation and necrosis. The malondialdehyde (MDA) and superoxide dismutase (SOD) levels were significantly different from the ischemia-reperfusion group. In conclusion, vanillin showed a hepatocyte protective action by alleviating the cellular inflammation and cell necrosis caused by hepatic ischemia-reperfusion, and vanillin mitigated inflammatory changes in the kidney glomeruli and distal tubules. The protective effect is considered to be caused by vanillin's antioxidant function. Further studies such as on cell death and possibly vanillin's same effect on damaged tissue will be necessary for clinical applications such as organ transplantation.
The significance of the enactment of the 「Act On The Safety Of And Support For Advanced Regenerative Medicine And Advanced Biological Products」 is to break away from the regulation of the Pharmaceutical Affairs Act and expand patient treatment opportunities through a medical technology approach to regenerative medicine, which is essentially a medical practice called 'transplantation'. However, more than a year after the law was enacted, clinical study has not been activated, with not a single high-risk study approved by the Ministry of Food and Drug Safety being approved. The reason is that despite the legal purpose of expanding patient treatment opportunities, the data requirements for clinical study approval are set in connection with drug development despite the insufficient legal basis, making it difficult for many researchers to meet the data requirements. Prior to the enactment of the Act, submitted data for clinical study on cell therapy products within the Pharmaceutical Affairs Act were cosiderably exempted from quality and non-clinical test data, but with the enforcement of the Advanced Regenerative Bio Act, quality and non-clinical test data are required in accordance with pharmaceuticals when applying for approval of a clinical study plan. To rectify this, when considering the identity of clinical study on advanced regenerative medicine to expand treatment opportunities, recognize that there are limitations in connection with drug development. And it is necessary to preserve the identity of clinical study on advanced regenerative medicine, and on the other hand, in the case of drug product approval, clinical study results should be utilized while specifying usage requirements. Therefore, with the power of the market and the voluntary motive of the clinical researcher, it is necessary to prepare the necessary data by themselves rather than the basic requirements for clinical study approval.
Seongsu Kang;Seung-Hyun Jun;Jinyong Lee;Myoung Jin An;Nae Gyu Kang
Journal of the Society of Cosmetic Scientists of Korea
/
v.49
no.4
/
pp.365-373
/
2023
Since the lips are a representative facial part that can express human attraction, aesthetic interest in them has always existed in human history. However, as lips age, they tend to form wrinkles, become thinner, and lose their volume. To counteract this phenomenon, medical procedures such as fillers or fat transplantation have been suggested. In this study, we verified that the one of main effective material complex of L G H&H L IPCERIN®, combination of cedrol, a sesquiterpene found in cedarwood, and three peptides (acetyl hexapeptide-8, acetyl tetrapeptide-9, and desamidocollagen) could ameliorate the photo-aging and reduce the wrinkles through in vitro experiments. The possibility of improving collagen and elastin expression in skin fibroblasts and reducing MMP expression under photoaging conditions was verified. In addition, it was confirmed that the amount of fat tissue in the lips can be increased by promoting adipose stem cell differentiation and increasing the amount of fat produced in the in vitro adipose stem cell differentiation experiment. Two weeks of human application tests confirmed that a combination of cedrol and peptides can improve the wrinkles, texture, elasticity, and volume of the lips. This study verified that the combination of cedrol and three peptides can be used as effective cosmetic materials to decrease the various signs of aging in the lips.
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