• Childhood Kidney Diseases
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• 제24권1호
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• pp.1-13
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• 2020

Immunoglobulin (Ig)A vasculitis nephritis (IgAVN), also referred to as Henoch-Schönlein purpura nephritis, is a relatively benign disease in children. However, two 24-year European cohort studies have reported high sustained rates of hypertension, severe proteinuria, and renal dysfunction in patients with IgAVN. Notably, the incidence and exacerbation rates of proteinuria, hypertension, and renal dysfunction during pregnancy were high even in women who recovered from IgAVN before pregnancy. Patients with IgAVN need lifelong care. Trials have been performed to investigate early biomarkers and genes associated with poor prognosis to identify high-risk patients in whom IgAVN may progress to severe renal disease. Urinary IgA/cr, IgM/cr levels, and HLAB35 and angiotensinogen gene expression were shown to be predictors of progression of IgAVN to severe renal dysfunction. The 2019 Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative group published guidelines for pediatric IgAVN, following the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines established in 2012. Compared with the KDIGO guidelines, the SHARE guidelines recommend earlier corticosteroid administration in cases of mild proteinuria (>0.5 g/d). Clinical trials of targeted budesonide delivery to the distal ileum, monoclonal antibody targeting C5, eculizumab and anti-CD20 monoclonal antibody administration, among others are currently underway in patients with IgA nephropathy. It is expected that newer therapeutic agents would become available for IgAVN in the near future. This review summarizes IgAVN with emphasis on recently published literature, including possible preventive strategies, predictive biomarkers for progression of IgAVN, and various treatments.

• 생약학회지
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• 제39권3호
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• pp.165-173
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• 2008

Aldose reductase (AR), the principal enzyme of the polyol pathway, has been shown to play an important role in the diabetic complications, including diabetic cataract. The inhibitors of AR, therefore, would be potential agents for prevention of diabetic complications. As part of our ongoing project directed toward the discovery of preventive and/or treatment for diabetic complications, 48 Korean herbal medicines have been investigated with an in vitro evaluation system using aldose reductase inhibitory activities. Of these, 12 herbal medicines exhibited a significant inhibitory activity against aldose reductase. Particularly, seven herbal medicines, i.e., Eurya japonica, Chrysanthemum indicum, Akebia quinata, Saururus chinensis, Catalpa bignonioides, Lonicera japonica, Vitex rotundifolia showed two times more potent inhibitory activity than the positive control 3.3-tetramethyleneglutaric acid (TMG). In addition, Catalpa bignonioides showed the retardation of cataract-opacification of the lens of the eye under diabetic condition by xylose. Therefore, this result may provide a potential therapeutic approach for preventing and treating diabetic cataracts.

• Archives of Reconstructive Microsurgery
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• 제6권1호
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• pp.1-8
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• 1997

Recently prostaglandin $E_1(PGE_1)$ has been shown to ensure flap survival by producing vasodilation of the peripheral vessels and platelet disaggreation. However, direct observation and detailed quantitative studies of the effects of $PGE_1$ on the cutaneous microcirculation have not been reported. In the present study, we investigated cutaneous microcirculatory changes in the rabbit ear chamber(REC) with an intravital microscope following intravenous administration of $PGE_1$. The results obtained in this study indicate that $PGE_1$ administered intravenously at a rate of 200ng/kg/min might act directly on the vessels and cause dilatation of metarterioles and capillaries without affecting vasomotion and systemic blood pressure. Clinically in order to evaluate the effect of an intravenous administration of $PGE_1$ on the cutaneous microcirculation, cutaneous blood flow, skin temperature and transcutaneous $Po_2$ in the pedicle or free flap of operated patients were evaluated by the combination of several measurements following the administration of $PGE_1$. The present study suggests that improvement of cutaneous microcirculation by $PGE_1$ may enhance the survival rate of flap or replantation. Both vessel arterial ischemia and venous congestion are main factors of tissue necrosis in the flap surgery. Vasodilatory or antithrombotic agents have been used in salvage of flap necrosis. However, the therapeutic effects of those drugs are still not well elucidated. Recently prostaglandin $E_1(PGE_1)$ has been shown to ensure flap survival by producing vasodilatation of the peripheral vessels and platelet disaggregation[1-3]. Emerson and sykes[4] have obtained significant improvement in the flap survival in the rat using $PGI_2$. Suzuki et al.[5] have reported prolonged flap survival length by using $PGE_1$ in the rabbit and concluded that $PGE_1$ improved the microcircuration in the flap. However, direct observation and detailed quantitative studies of the effects of $PGE_1$ on the cutaneous microcirculation have not been reported. In the present study, we investigated microcirculatory changes in the rabbit ear chamber[6,7] with an intravital microscope following intravenous administration of $PGE_1$.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.993-1001
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• 2016

Type 2 diabetes mellitus patients are at increased risk of many forms of malignancies, especially of the pancreas, colon and hepatocellular cancer. Unfortunately, little is known of the possible interaction between antidiabetic drugs and anticancer agents. The present study investigates the influence of metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular liver carcinoma cell line (HepG2) viability and apoptosis were determined by the MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D, respectively, after treatment with EpoA, metformin or sitagliptin. The levels of nuclear factor NF-${\kappa}B$ and p53 were evaluated in the presence and absence of inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not. EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the level of NF-${\kappa}B$. Only MET enhanced the proapoptotic effect of EpoA. The EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led to apoptosis independent of p53, decreasing the level of NF-${\kappa}B$. These findings support the link between NF-${\kappa}B$ and p53 in the modulation of apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic effect on liver cancer cells than each of the compounds alone. The therapeutic advantages of the combination of EpoA with MET may be valuable in the treatment of patients with diabetes mellitus type 2 (T2DM) and liver cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3631-3636
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• 2012

Objective: To determine whether silence of $PKC-{\alpha}$ expression by small interference RNA (siRNA) might regulate MDR1 expression and reverse chemoresistance of ovarian cancer. Methods: We measured gene and protein expression of MDR1 and $PKC-{\alpha}$ in ovarian cancer cells and assessed their correlation with cell drug resistance. We also examined whether blocking $PKC-{\alpha}$ by RNA interference (RNAi) affected MDR1 expression and reversed drug resistance in drug sensitivity tests. Results: The drug resistance cell lines, OV1228/DDP and OV1228/Taxol, had higher gene and protein expression of MDR1 and $PKC-{\alpha}$ than their counterpart sensitive cell line, OV1228. SiRNA depressed $PKC-{\alpha}$ gene protein expression, as well as MDR1 and protein expression and improved the drug sensitivity in OV1228/DDP and OV1228/Taxol cells. Conclusion: These results indicated that decreasing $PKC-{\alpha}$ expression with siRNA might be an effective method to improve drug sensitivity in drug resistant cells with elevated levels of $PKC-{\alpha}$ and MDR1. A new siRNA-based therapeutic strategy targeting $PKC-{\alpha}$ gene could be designed to overcome the chemoresistance of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1297-1303
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• 2012

Aims: Primary hepatocellular carcinoma (HCC) is a common malignancy often related to hepatitis viral infection. Smad4 is known to mediate the TGF-${\beta}$ pathway to suppress tumorigenesis. However, the function of Smad4 in HCC is still controversial. In this study we compared levels of Smad4 in HCC tissues with or without hepatitis virus infection and adjacent normal-appearing liver. Methods: Samples from HCC patients were analyzed for Smad4 protein and mRNA expression by immunohistochemistry (IHC), RT-PCR and Western blotting. Results: We found that tumor tissues expressed less Smad4 mRNA and protein than the adjacent tissues. Most HCC tumor tissues were negative for Smad4 in IHC staining, while the majority of adjacent tissues were positively stained. Interestingly, protein levels were higher in HCC tissues with viral hepatitis than those without virus infection. Suppression of expression appeared closely related to HCC, so that Smad4 appears to function as a tumor suppressor gene (TSG). Conclusion: Patients with hepatitis viral infection, at higher risk for HCC, exhibited increased Smad4 protein expression suggesting hepatitis virus may modulate Smad4 expression, which is functionally distinct from its putative role as a TSG. Smad4 expression may thus be an applicable marker for diagnosis and/or a target to develop therapeutic agents for HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1395-1399
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• 2012

Background: Histone deacetylase (HDAC) inhibitors have been reported to induce cell growth arrest, apoptosis and differentiation of tumor cells. The present study aimed to examine the effects of trichostatin A (TSA), one such inhibitor, on the cell cycle, apoptosis and invasiveness of osteosarcoma cells. Methods: MG-63 cells were treated with TSA at various concentrations. Then, cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) and TUNEL assays, respectively; cell cycling was assessed by flow cytometry; invasion assays were performed with the transwell Boyden Chamber system. Results: MTT assays revealed that TSA significantly inhibited the growth of MG-63 cells in a concentration and time dependent manner. TSA treated cells demonstrated morphological changes indicative of apoptosis and TUNEL assays revealed increased apoptosis of MG-63 cells after TSA treatment. Flow cytometry showed that TSA arrested the cell cycle in G1/G2 phase and annexin V positive apoptotic cells increased markedly. In addition, the invasiveness of MG-63 cells was inhibited by TSA in a concentration dependent manner. Conclusion: Our findings demonstrate that TSA inhibits the proliferation, induces apoptosis and inhibits invasiveness of osteosarcoma cells in vitro. HDAC inhibitors may thus have promise to become new therapeutic agents against osteosarcoma.

• 한국자원식물학회지
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• 제29권5호
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• pp.620-624
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• 2016

본 연구에서 국내 자생식물 추출물중 비만관련 특허가 없는 식물원료를 대상으로 지방세포의 분화억제 효과를 Wnt/β-catenin 신호전달계 활성측정방법으로 탐색하여 비만치료를 위한 기능성소재 응용가능성을 검토하였다. HEK 293-TOP세포의 luciferase 리포터 상대적인 활성은 무 처리 대조군에 비하여 지유(전초), 측백나무(줄기)가 각각 152%, 130%로 높은 활성을 나타내었으며, 피마자(전초)는 약 90%대의 활성을, 해당화(줄기), 괴화(전초)의 경우는 약 80%, 초피나무(줄기), 칡(줄기), 까마중(전초)은 약 70%대의 높은 활성을 나타내었다. 또한, 신경줄기 세포에 대한 어떠한 독성도 보이지 않음으로써 안전한 물질인 것으로 사료되었다. 이 결과는 Wnt/β-catenin 신호전달 활성 측정방법이 향후 High throughput screening 기반기술로 활용될 수 있을 것으로 판단되며, 지방세포 분화 억제활성 후보로 선별된 식물추출물들에 대한 추가적인 실험을 통하여 항비만 소재 개발 응용 가능성을 타진할 것이다.

• 한국자원식물학회지
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• 제30권6호
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• pp.640-646
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• 2017

In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor $GSK3{\beta}$ but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through $GSK3{\beta}$-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

• 한국자원식물학회지
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• 제33권4호
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• pp.263-270
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• 2020

이상의 연구 결과로 미루어 볼 때, 댕댕이나무 잎과 가지 추추출물은 대장암 세포주 HCT116과 SW480세포의 생육을 억제하였으나 열매추출물은 억제활성이 나타나지 않았다. 잎과 가지 추출물은 cell migration과 wound healing assay를 통해 비정상적인 세포증식 억제를 확인하였으며, β-catenin과 TCF4의 단백질 수준을 감소시켜 비정상적인 Wnt 신호전달을 억제를 통해 대장암세포의 생육을 억제하는 것으로 판단된다. 따라서 댕댕이나무 잎과 가지는 항암을 위한 대체보완소재 및 천연 항암제 개발을 위한 소재로 활용이 가능할 것으로 판단된다.