• Nutrition Research and Practice
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• 제7권6호
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• pp.466-474
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• 2013

Despite the reports on safety concerns regarding the relationship between aluminum salts and neurological and bone disease, many countries continue to use aluminum as phosphate binders among patients with renal failure. In search for a diet supplement that could reduce aluminum toxicity related to renal failure, we carried out this prospective animal study in which the fenugreek seeds were assessed for their effects on rats nephrotoxicity induced by aluminum chloride ($AlCl_3$). Oral $AlCl_3$ administration during 5 months (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) led to plasma biochemical changes, an inhibition of alkaline phosphatase (ALP), a decrease of total antioxidant status (TAS), and an induction of lipid peroxidation (LPO) in the blood and brain, in addition to kidney atrophy and morphological alterations at the level of Bowman's capsule, the glomerulus and different sorts of tubules, reminiscent of some known kidney disease. The treatment with the whole fenugreek seed powder (FSP) (5% in the diet) during the last 2 months showed its effectiveness in restoring normal plasma values of urea, creatinine, ALP and glucose, as well as re-increasing the TAS, inhibiting LPO and alleviating histopathological changes in the injured kidneys. This study highlights the induced nephrotoxicicity, as well as the related toxicity in the brain and bone, by chronic oral ingestion of the aluminum salts. However, the maintenance of a diet supplemented with fenugreek seeds could offer protection for the kidney, bone and brain, at the same time.

• Animal cells and systems
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• 제15권2호
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• pp.139-146
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• 2011

Secretory leukocyte protease inhibitor (SLPI) plays an important role in promoting the invasion and metastasis of a range of cancer cells. However, there are no reports of the expression and function of SLPI in oral carcinoma cells. In this study, the oral carcinoma cell line KB was used to determine whether SLPI affects the proliferation, migration and invasion of oral carcinoma cells. RT-PCR and Western blotting revealed high levels of endogenous SLPI expression in KB cells as well as a strong increase in SLPI secretion after wounding compared to immortalized normal oral keratinocytes (INOK). The wound healing assay revealed more migration of KB cells than INOK cells, and the SLPI treatment increased the migration of KB cells. KB cell proliferation was increased significantly by the SLPI protein but decreased by SLPI-siRNA. SLPI strongly increased the migration and invasion of KB cells. On the other hand, SLPI-siRNA decreased the migration and invasion of KB cells. This suggests that SLPI plays an important role in the metastasis of oral carcinoma cells.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.342-351
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• 2021

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.

• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.2801-2804
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• 2016

It is conventionally accepted that renal cell carcinoma (RCC) occurs in older patients and the clear cell type is the most common histology. However, ethnic variations exist and this study was carried out to determine the epidemiological pattern of RCC in Oman. Ninety RCC patients who presented to a tertiary care center in the Sultanate of Oman from 2010 to 2014 were studied. The main findings were that the median age of presentation was low, more patients presented with localized stage, and there was a higher incidence of non-clear (especially papillary) histology. Data from other Gulf countries and possible reasons for the different profile are discussed.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7849-7855
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• 2014

Purpose: To investigate the effect of deacetylase inhibitory trichostatin A (TSA) on anti HepG2 liver carcinoma cells and explore the underlying mechanisms. Materials and Methods: HepG2 cells exposed to different concentrations of TSA for 24, 48, or 72h were examined for cell growth inhibition using CCK8, changes in cell cycle distribution with flow cytometry, cell apoptosis with annexin V-FTIC/PI double staining, and cell morphology changes under an inverted microscope. Expression of ${\beta}$-catenin, HDAC1, HDAC3, H3K9, CyclinD1 and Bax proteins was tested by Western blotting. Gene expression for ${\beta}$-catenin, HDAC1and HDAC3 was tested by q-PCR. ${\beta}$-catenin and H3K9 proteins were also tested by immunofluorescence. Activity of Renilla luciferase (pTCF/LEF-luc) was assessed using the Luciferase Reporter Assay system reagent. The activity of total HDACs was detected with a HDACs colorimetric kit. Results: Exposure to TSA caused significant dose-and time-dependent inhibition of HepG2 cell proliferation (p<0.05) and resulted in increased cell percentages in G0/G1 and G2/M phases and decrease in the S phase. The apoptotic index in the control group was $6.22{\pm}0.25%$, which increased to $7.17{\pm}0.20%$ and $18.1{\pm}0.42%$ in the treatment group. Exposure to 250 and 500nmol/L TSA also caused cell morphology changes with numerous floating cells. Expression of ${\beta}$-catenin, H3K9and Bax proteins was significantly increased, expression levels of CyclinD1, HDAC1, HDAC3 were decreased. Expression of ${\beta}$-catenin at the genetic level was significantly increased, with no significant difference in HDAC1and HDAC3 genes. In the cytoplasm, expression of ${\beta}$-catenin fluorescence protein was not obvious changed and in the nucleus, small amounts of green fluorescence were observed. H3K9 fluorescence protein were increased. Expression levels of the transcription factor TCF werealso increased in HepG2 cells following induction by TSA, whikle the activity of total HDACs was decreased. Conclusions: TSA inhibits HDAC activity, promotes histone acetylation, and activates Wnt/${\beta}$-catenin signaling to inhibit proliferation of HepG2 cell, arrest cell cycling and induce apoptosis.

• 대한수의학회지
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• 제43권2호
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• pp.171-180
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• 2003

Certain hexavalent chromium compounds when administered via inhalation have the potential to induce lung injury in human and experimental animals. In present study, the inhalation effect of hexavalent chromium on morphological change and weight change of rat organ were investigated. Rats were exposed to hexavalent chromium ($Na_2CrO_4{\cdot}4H_2O$) at concentration of $0.36mg/m^3$ (group 1), $1.8mg/m^3$ (group 2), ascorbic acid and $1.8mg/m^3$ (group 3) and filtered air (group 0, control group) for I week, 2 weeks and 3 weeks. The weight of lung and kidney in group 2 and group 3 significantly higher than in control group at same exposure period. The epithilial cells of bronchiole in group 1, 2, 3 were more flatten than group 0. In the lung, the number of macrophage was significantly increased and morphologically changed macrophages were observed in group 1, 2, 3. The morphological change of the lung did not significant between group 2 and group 3, however, in group 1 was milder than in group 2 and group 3. The severity of morphological change were depend on exposure period in the lung. The morphological changes by hexavalent chromium of the liver and kidney were also observed These results suggest that inhalation of hexavalent chromium effects on not only respiratory organ, but also the liver and the kidney via blood stream.

• Toxicological Research
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• 제29권2호
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• pp.91-98
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• 2013

Armeniacae semen (AS) has been considered a toxic herb in the Korean medicine as it contains hydrogen cyanide and amygdalin, especially in its endocarp. Therefore, prebrewed AS that is devoid of endocarp has been traditionally used. In the present study, amygdalin content of the prebrewed AS was significantly lower ($2.73{\pm}0.32{\mu}g/ml$; p<0.01) than the content in the extract that contained the endocarps ($28.50{\pm}6.71{\mu}g/ml$); amygdalin content corresponded to 10% of the extract in the present study. Because of single oral dose toxicity of prebrewed AS according to the recommendation of Korea Food and Drug Administration Guidelines (2009-116, 2009), which was based on single oral dose toxicity study of prebrewed AS, mortality due to toxic principles was significantly reduced. In this study, 2,000 mg/kg of prebrewed AS led to death of 1 female rat and 1 male rat at the end of 2 hr of administration. Based on these results, the 50% lethal dose in both male and female rats was determined to be 9279.5 mg/kg. Seizure, loss of locomotion, and increases in respiration and heart rate were observed as prebrewed AS treatment-related toxicological signs; these signs were restrictedly manifested in the prebrewed AS (2,000 mg/kg)-treated rats. In addition, no changes were observed in body weight, organ weight, gross features, and histopathological parameters with 2,000 mg/kg of AS in both male and female rats. These findings serve as direct evidence that amygdalin in AS is the toxic principle, which can be reduced by the traditional prebrewing method involving the exclusion of endocarp.

• 대한예방한의학회지
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• 제18권2호
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• pp.133-145
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• 2014

Objective : In this study, the addition of dried pomegranate concentrate powder (PCP) was affected the anti-climacterium activity of red clover dry extracts (RC) in ovariectomized (OVX) rats. Materials and methods : After bilateral OVX surgery, RC 40 mg/kg, PCP 20 mg/kg and RC:PCP 2:1 mixture (g/g) 120, 60 and 30 mg/kg (of body weight) were orally administered, once a day for 84 days, and then the changes on the serum estradiol levels, abdominal fat pad and uterus weights were observed for estrogenic effects. In addition, liver weights, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were also evaluated for hepatoprotective effects, and serum total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG) levels were monitored for hypolipidemic effects. Results : As a result of OVX, the estrogen-deficient climacterium symptoms, increments of abdominal fat pad weights, serum AST, ALT, TC, LDL and TG levels with decrease of uterus and liver weights, serum estradiol levels, were demonstrated. However, these estrogen-deficient climacterium symptoms induced by bilateral OVX in rats were significantly inhibited by continuous oral treatment of RC 40 mg/kg, PCP 20 mg/kg and RC:PCP 2:1 mixture (g/g) 120, 60 and 30 mg/kg, respectively. Conclusion : The results suggested that RC:PCP 2:1 mixtures synergistically increased the anti-climacterium effects of RC in OVX rats. It, therefore, is expected that RC:PCP 2:1 mixture will be promising as a new potent protective agents for relieving the climacterium symptoms.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1099-1104
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• 2014

Aims and Background: Ginsenoside Rh2, which exerts the potent anticancer action both in vitro and in vivo, is one of the most well characterized ginsenosides extracted from ginseng. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between ginsenoside Rh2 and phosphoglucose isomerase/autocrine motility factor (PGI/AMF). Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PGI/AMF was assessed by western blot analysis and reverse transcription- PCR (RT-PCR) assay after transfection of a small interfering (si)-RNA to silence PGI/AMF. The effect of PGI/AMF on proliferation was measured by typan blue assay and antibody array. A cell counting kit (CCK)-8 and flow cytometry (FCM) were adopted to investigate the effects of Rh2 on PGI/AMF. The relationships between PGI/AMF and Rh2 associated with Akt, mTOR, Raptor, Rag were detected by western blot analysis. Results: KG1${\alpha}$ cells expressed PGI/AMF and its down-regulation significantly inhibited proliferation. The antibody array indicated that the probable mechanism was reduced expression of PARP, State1, SAPK/JNK and Erk1/2, while those of PRAS40 and p38 were up-regulated. Silencing of PGI/AMF enhanced the sensibility of $KG1{\alpha}$ to Rh2 by suppressing the expression of mTOR, Raptor and Akt. Conclusion: These results suggested that ginsenoside Rh2 suppressed the proliferation of $KG1{\alpha}$, the same as down-regulation of PGI/AMF. Down-regulation of PGI/AMF enhanced the pharmacological effects of ginsenoside Rh2 on KG1${\alpha}$ by reducing Akt/mTOR signaling.

• Restorative Dentistry and Endodontics
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• 제32권5호
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• pp.459-468
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• 2007

이 연구에서는 법랑모세포 분화과정에서 APin의 기능을 알아보고자 APin-protein microarray를 시행한 후 치아발생과 관련이 있는 MEF2, Aurora kinase A, BMPR-IB와 EF-hand calcium binding protein을 분석하여 다음과 같은 결과를 얻었다. 1 CMV-APin construct를 transfection하여 APin의 과발현을 유도한 경우에는 MEF2와 Aurora kinase A 둘 모두에서 발현이 현저히 감소한 반면에, APin의 발현억제를 유도한 경우에는 둘 모두 변화가 없었다. 2. APin의 과발현을 유도한 경우에는 BMPR-IB와 EF-hand calcium binding protein 모두에서 발현이 크게 증가한 반면, APin을 발현억제 시킨 경우에는 BMPR-IB는 변화가 없었고, EF-hand calcium binding protein은 현저히 감소하였다. 위의 결과들로 보아 APin 단백질은 MEF2, Aurora kinase A, BMPR-IB, EF-hand calcium binding protein과 상호작용하여 법랑모세포의 분화와 석회화 과정 중에 중요한 역할을 하는 것으로 사료된다.