• Development and Reproduction
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• v.24 no.4
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• pp.263-275
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• 2020

The proper administration of melatonin has well been documented to induce testicular regression in seasonal breeding animals. The subcutaneous injections of melatonin in the afternoon, not in the morning, consistently occurred testicular involution in the male Syrian (golden) hamsters whose reproductive activity is regulated by the photoperiod. But the effects of daily melatonin via gavage have not been estimated. Golden hamsters housed in long photoperiod (LP) were divided into 5 groups: the control animals housed in LP or in short photoperiod (SP) and animals treated daily with low (15 ㎍), middle (150 ㎍), and high dosages (1,500 ㎍) of pure melatonin by using gavage in the evening for 8 weeks. As results, LP control animals had large testes and SP controls displayed small and entirely regressed testes. The animals treated with various dosages of melatonin showed collectively degenerating effects on the weights of testes, epididymides, and seminal vesicles in the middle and high dosage groups, with the individual differences as well. The high dosages induced testicular regression in more proportion than the middle dosages did. The low dosage had large testes like the LP control animals. The small and inactive testes shown in some animals of both middle and high groups presented the complete regression as those of the animals maintained in SP. These results strongly suggest that the administrations of melatonin lead to testicular involution in the male golden hamsters when it is administered through gavage.

• Journal of Veterinary Science
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• v.21 no.6
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• pp.81.1-81.10
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• 2020

Background: Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers. Objectives: In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity. Methods: For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats. Results: GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein. Conclusions: These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

• IMMUNE NETWORK
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• v.21 no.3
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• pp.23.1-23.16
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• 2021

Chemokines are key factors that influence the migration and maintenance of relevant immune cells into an infected tissue or a tumor microenvironment. Therefore, it is believed that the controlled administration of chemokines in the tumor microenvironment may be an effective immunotherapy against cancer. Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Here, we investigated the role of CCL3 in regulating the tumor microenvironment using a syngeneic mouse tumor model. We observed that MC38 tumors overexpressing CCL3 (CCL3-OE) showed rapid regression compared with the wild type MC38 tumors. Additionally, these CCL3-OE tumors showed an increase in the proliferative and functional tumor-infiltrating T cells. Furthermore, PD-1 immune checkpoint blockade accelerated tumor regression in the CCL3-OE tumor microenvironment. Next, we generated a modified CCL3 protein for pre-clinical use by fusing recombinant CCL3 (rCCL3) with a non-cytolytic hybrid Fc (HyFc). Administering a controlled dose of rCCL3-HyFc via subcutaneous injections near tumors was effective in tumor regression and improved survival along with activated myeloid cells and augmented T cell responses. Furthermore, combination therapy of rCCL3-HyFc with PD-1 blockade exhibited prominent effect to tumor regression. Collectively, our findings demonstrate that appropriate concentrations of CCL3 in the tumor microenvironment would be an effective adjuvant to promote anti-tumor immune responses, and suggest that administering a long-lasting form of CCL3 in combination with PD-1 blockers can have clinical applications in cancer immunotherapy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.1
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• pp.112-118
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• 2001

To study effect of non-fat components present in plant seeds on lipid metabolism, defatted safflower and perilla seed powders were used in high cholesterol diets for ovariectomized (ovx) female Sprague-Dawley rats weighing 227$\pm$15g. Experimental groups were six as follows; normal group without ovariectomy and cholesterol-free diet, sham and ovx-control groups with high cholesterol and cellulose for dietary fiber, ovx-est group with the same diet as ovx-control but with eight subcutaneous injections of 50$\mu\textrm{g}$ 17$\beta$-estradiol. ovx-safflower and ovx-perilla with 29% and 16% (w/w) of each defatted powder in high cholesterol diets at the expense of cellulose. Weight gains were lower in normal and sham groups and food efficiencies were lower in normal,ovx-est and ovx-safflower groups compared with ovx-control. Uterus weights were dramatically reduced by ovariectomy but restored completely by 17$\beta$-estradiol and partially (~5%) by defatted safflower. Plasma levels of total cholesterol were not different among ovx-control, sham, vx-est and ovx-safflower groups (90.8~95.1 mg/dL) but that was lower in ovx-perilla (80.4$\pm$6.2 mg/dL). Plasma triglyceride (TG) levels were lower in sham (76.6$\pm$7.0 mg/dL) and ovx-perilla (79.2$\pm$5.8 mg/dL) groups. Liver cholesterol levels were lower in sham, ovx-est, ovx-safflower and ovx-perilla groups (26.6~29.8 mg/g) than ovx-control (36.5$\pm$3.2 mg/g). But liver TG levels were reduced only sham and ovx-est groups compared to control group. Fecal excretions of bile acid and cholesterol were highest in ovx-safflower group (30.8$\pm$5. and 32.1$\pm$5.7 mg/g) compared with other ovx groups (20.8~23.1 and 12.1~19.5 mg/g). These results suggest that both perilla and safflower seeds contain groups (20.8~23.1 and 12.1~19.5mg/g). These results suggest that both perilla and safflower seeds contain non-fat and non-fiber components having lipid lowering effects.

• Toxicological Research
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• v.23 no.4
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• pp.321-330
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• 2007

Garlic (Allium sativum L.) with the food supplement material and medicine was used traditionally in Asia and Europe. Epidemiological studies revealed that the intake of garlic reduced incidences of various cancer including digestive system. The present study was designed to investigate the effect of garlic ethanol extract on the development of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in male F344 rats. Five-week-old rats were given four times for two weeks to subcutaneous injections by DMH (30 mg/kg body weight) to induce ACF. The animals were divided into groups that fed diet containing garlic ethanol extract at five different doses (0.1, 0.2, 0.5, 2, 5%), respectively, animals were evaluated for the total number of ACF and total aberrant crypts (AC) per colon detected from methylene blue-stained rat colon. ACF were formed in animals in DMH-treated group. The feeding suppressed potently the appearance ACF in the colon of rats. Especially, fed diet containing garlic ethanol extract at intermediate dose (0.5%) significantly reduced the number of ACF and AC per colon (p < 0.05). Garlic ethanol extract inhibited DMH-induced overexpression of Activator Protein-1 (AP-1) and ${\beta}-catenin$ genes related to cell proliferation that also upregulated the expression of p21Waf1/Cip1 mRNA, a cell cycle-regulating gene. These results suggested that garlic ethanol extract may inhibit ACF formation, ${\beta}-catenin$ gene as the early preneoplastic marker of malignant potential in the process of colon carcinogenesis.

• Journal of Oriental Physiology
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• v.14 no.2 s.20
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• pp.189-198
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• 1999

Aminoglycosides, including gentamicin, have been used as antibiotics for the various infections by gram-negative bacteria. However, there are some restrictions for using these drugs. Gentamicin, a typical aminoglycoside, has the side effect of nephrotoxicity, including polyuria, glycosuria, proteinuria, glomerulonephritis, and uremia. The aims of this study were to examine the prevention or reduction effects of Jinmootang on the gentamicin-induced nephrotoxicity and to investigate the possible mechanisms on the effect of Jinmootang. The subcutaneous injections of 60mg of gentamicin per kg of boby weight to Sprague-Dawley rats for 8 days induced typical symptoms of nephrotoxicity by aminoglycosides. 0.6ml of water extract Jinmootang (100ml/chup) was orally treated in the experimental animal. 24-hour urine was collected with the metabolic cage and plasma was sampled from the abdominal aorta. The plasma concentration of sodium was significantly decreased by the treatment of gentamicin but it was not-significantly changed by the treatment of Jinmootang to the animal. The concentration of potassium was greatly decreased in the gentamicin-treated animals. However. it was returned to the normal level in the Jinmootang-treated animals. The concentrations of creatinine and urea were increased by gentamicin treatment. But, Jinmootang reduced these concentrations. Nevertheless, the osmolalities of plasma in both group were not different from each other. Even though the plasma concentration of aldosterone was not significantly changed, the mean value was increased by the gentamicin intoxication. The concentration of aldosterone was decreased by the treatment of Jinmootang. The reduction of aldosterone level in plasma could be a factor to improve the hypokalemia. The fractional excretion of potassium was much higher than normal by the treatment of gentamicin and it was decreased by 50% in the Jinmootang-treated rats. Therefore, the reabsorption of potassium was significantly increased by the treatment of Jinmootang, even though the filtered load of potassium in the experimental group was much highter than control. Even though the concentration of plasma aldosterone was decreased by the treatment of Jinmootang, the fractional excretion of sodium was not increased, slightly lower. These data suggested that Na reabsorption was increased in the proximal tubule by Jinmootang. The filtered load of glucose in the Jinmootang-treated group was greater than in control. Nevertheless, the fractional excretion of glucose in the experimental group was not different from that in control. These results indicate that glucose reabsorption was increase in the proximal tubule by Jinmootang treatment. The results of this study suggest that Jinmootang could improve the some nephrotoxic symptoms induced by gentramicin treatment. Hypokalemia, the reduced glomerular filtration rate, and dysfunctions of renal proximal tubule and distal nephron were significantly recovered to normal level. The increase of glomerular filtration rate by Jinmootang might contribute to eliminate the waste product, including creatinine and urea, and/or gentamicin through the kidney.