• 제목/요약/키워드: translational research

검색결과 527건 처리시간 0.025초

Inhibition of Hydrogen Sulfide-induced Angiogenesis and Inflammation in Vascular Endothelial Cells: Potential Mechanisms of Gastric Cancer Prevention by Korean Red Ginseng

  • Choi, Ki-Seok;Song, Heup;Kim, Eun-Hee;Choi, Jae-Hyung;Hong, Hua;Han, Young-Min;Hahm, Ki-Baik
    • Journal of Ginseng Research
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    • 제36권2호
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    • pp.135-145
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    • 2012
  • Previously, we reported that Helicobacter pylori-associated gastritis and gastric cancer are closely associated with increased levels of hydrogen sulfide ($H_2S$) and that Korean red ginseng significantly reduced the severity of H. pylori-associated gastric diseases by attenuating $H_2S$ generation. Because the incubation of endothelial cells with $H_2S$ has been known to enhance their angiogenic activities, we hypothesized that the amelioration of $H_2S$-induced gastric inflammation or angiogenesis in human umbilical vascular endothelial cells (HUVECs) might explain the preventive effect of Korean red ginseng on H. pylori-associated carcinogenesis. The expression of inflammatory mediators, angiogenic growth factors, and angiogenic activities in the absence or presence of Korean red ginseng extracts (KRGE) were evaluated in HUVECs stimulated with the $H_2S$ generator sodium hydrogen sulfide (NaHS). KRGE efficiently decreased the expression of cystathionine ${\beta}$-synthase and cystathionine ${\gamma}$-lyase, enzymes that are essential for $H_2S$ synthesis. Concomitantly, a significant decrease in the expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase, and several angiogenic factors, including interleukin (IL)-8, hypoxia inducible factor-1a, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, was observed; all of these factors are normally induced after NaHS. An in vitro angiogenesis assay demonstrated that NaHS significantly increased tube formation in endothelial cells, whereas KRGE pretreatment significantly attenuated tube formation. NaHS activated p38 and Akt, increasing the expression of angiogenic factors and the proliferation of HUVECs, whereas KRGE effectively abrogated this $H_2S$-activated angiogenesis and the increase in inflammatory mediators in vascular endothelial cells. In conclusion, KRGE was able to mitigate $H_2S$-induced angiogenesis, implying that antagonistic action against $H_2S$-induced angiogenesis may be the mechanism underlying the gastric cancer preventive effects of KRGE in H. pylori infection.

Gypenoside XVII protects against myocardial ischemia and reperfusion injury by inhibiting ER stress-induced mitochondrial injury

  • Yu, Yingli;Wang, Min;Chen, Rongchang;Sun, Xiao;Sun, Guibo;Sun, Xiaobo
    • Journal of Ginseng Research
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    • 제45권6호
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    • pp.642-653
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    • 2021
  • Background: Effective strategies are dramatically needed to prevent and improve the recovery from myocardial ischemia and reperfusion (I/R) injury. Direct interactions between the mitochondria and endoplasmic reticulum (ER) during heart diseases have been recently investigated. This study was designed to explore the cardioprotective effects of gypenoside XVII (GP-17) against I/R injury. The roles of ER stress, mitochondrial injury, and their crosstalk within I/R injury and in GP-17einduced cardioprotection are also explored. Methods: Cardiac contractility function was recorded in Langendorff-perfused rat hearts. The effects of GP-17 on mitochondrial function including mitochondrial permeability transition pore opening, reactive oxygen species production, and respiratory function were determined using fluorescence detection kits on mitochondria isolated from the rat hearts. H9c2 cardiomyocytes were used to explore the effects of GP-17 on hypoxia/reoxygenation. Results: We found that GP-17 inhibits myocardial apoptosis, reduces cardiac dysfunction, and improves contractile recovery in rat hearts. Our results also demonstrate that apoptosis induced by I/R is predominantly mediated by ER stress and associated with mitochondrial injury. Moreover, the cardioprotective effects of GP-17 are controlled by the PI3K/AKT and P38 signaling pathways. Conclusion: GP-17 inhibits I/R-induced mitochondrial injury by delaying the onset of ER stress through the PI3K/AKT and P38 signaling pathways.

Clinical and microbiological effects of the supplementary use of an erythritol powder air-polishing device in non-surgical periodontal therapy: a randomized clinical trial

  • Park, Eon-Jeong;Kwon, Eun-Young;Kim, Hyun-Joo;Lee, Ju-Youn;Choi, Jeomil;Joo, Ji-Young
    • Journal of Periodontal and Implant Science
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    • 제48권5호
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    • pp.295-304
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    • 2018
  • Purpose: This study was undertaken to evaluate the clinical and microbiological effects of an erythritol powder air-polishing device (EPAP) as a supplement to scaling and root planing (SRP) therapy in patients with moderate chronic periodontitis. Methods: Clinical and microbiological evaluations were performed at 21 sites treated with SRP (control) and 21 sites treated with SRP+EPAP (test). All examinations were performed before treatment, 1 month after treatment, and 3 months after treatment. Results: There were no significant clinical differences between the test group and the control group. Microbiological analysis revealed that the relative expression level of Porphyromonas gingivalis was significantly lower in the test group than in the control group at 1 month after treatment. Clinical and microbiological results showed improvements at 1 month compared to baseline; in contrast, the results at 3 months after treatment were worse than those at 1 month after treatment. Conclusions: In this study, both SRP and SRP+EPAP were clinically and microbiologically effective as non-surgical periodontal treatments. In particular, the SRP+EPAP group showed an antimicrobial effect on P. gingivalis, a keystone bacterium associated with the onset of chronic periodontitis, in a short-term period. Periodic periodontal therapy, at intervals of at least every 3 months, is important for sustaining the microbiological effects of this treatment.

Protective effect and mechanism of ginsenoside Rg2 on atherosclerosis

  • Qianqian Xue;Tao Yu;Zhibin Wang;Xiuxiu Fu;Xiaoxin Li;Lu Zou;Min Li;Jae Youl Cho;Yanyan Yang
    • Journal of Ginseng Research
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    • 제47권2호
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    • pp.237-245
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    • 2023
  • Background: Ginsenoside Rg2 (Rg2) has a variety of pharmacological activities and provides benefits during inflammation, cancer, and other diseases. However, there are no reports about the relationship between Rg2 and atherosclerosis. Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to detect the cell viability of Rg2 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). The expression of inflammatory factors in HUVECs and the expression of phenotypic transformation-related marker in VSMCs were detected at mRNA levels. Western blot method was used to detect the expression of inflammation pathways and the expression of phenotypic transformation at the protein levels. The rat carotid balloon injury model was performed to explore the effect of Rg2 on inflammation and phenotypic transformation in vivo. Results: Rg2 decreased the expression of inflammatory factors induced by lipopolysaccharide in HUVECs-without affecting cell viability. These events depend on the blocking regulation of NF-κB and p-ERK signaling pathway. In VSMCs, Rg2 can inhibit the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet derived growth factor-BB (PDGF-BB)-which may contribute to its anti-atherosclerotic role. In rats with carotid balloon injury, Rg2 can reduce intimal proliferation after injury, regulate the inflammatory pathway to reduce inflammatory response, and also suppress the phenotypic transformation of VSMCs. Conclusion: These results suggest that Rg2 can exert its anti-atherosclerotic effect at the cellular level and animal level, which provides a more sufficient basis for ginseng as a functional dietary regulator.

Roles of Protein Histidine Phosphatase 1 (PHPT1) in Brown Adipocyte Differentiation

  • Kang, Joo Ae;Kang, Hyun Sup;Bae, Kwang-Hee;Lee, Sang Chul;Oh, Kyoung-Jin;Kim, Won Kon
    • Journal of Microbiology and Biotechnology
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    • 제30권2호
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    • pp.306-312
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    • 2020
  • Despite the importance of brown adipocytes as a therapeutic target for the prevention and treatment of obesity, the molecular mechanism underlying brown adipocyte differentiation is not fully understood. In particular, the role of post-translational modifications in brown adipocyte differentiation has not been extensively studied. Histidine phosphorylation is increasingly recognized an important process for protein post-translational modifications. In this study, we show that histidine phosphorylation patterns change during brown adipocyte differentiation. In addition, the expression level of protein histidine phosphatase 1 (PHPT1), a major mammalian phosphohistidine phosphatase, is reduced rapidly at the early phase of differentiation and recovers at the later phase. During white adipocyte differentiation of 3T3-L1 preadipocytes, however, the expression level of PHPT1 do not significantly change. Knockdown of PHPT1 promotes brown adipocyte differentiation, whereas ectopic expression of PHPT1 suppresses brown adipocyte differentiation. These results collectively suggest that histidine phosphorylation is closely linked to brown adipocyte differentiation and could be a therapeutic target for obesity and related metabolic diseases.

Is Level V Dissection Necessary for Low-risk Patients with Papillary Thyroid Cancer Metastasis in Lateral Neck Levels II, III, and IV

  • Yu, Wen-Bin;Tao, Song-Yun;Zhang, Nai-Song
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권9호
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    • pp.4619-4622
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    • 2012
  • Whether it is beneficial to dissect level V in papillary thyroid cancer (PTC) patients with positive lateral neck lymph nodes at levels II-IV is still controversial, especially for low risk cases. In this study, we reviewed the medical records of 47 patients who underwent 47 ipsilateral selective lateral neck dissections (levels II-IV) for previously untreated papillary thyroid carcinomas between October 2006 and October 2008 to assist in establishing the optimal strategy for lateral neck dissection in low risk PTC patients with clinically negative level V nodes. All 47 patients were confirmed to have positive lymph nodes pathologically. Seventeen (36.12%), 36 (76.6%), and 34 (72.34%) patients had positive lymph nodes in levels II, III, and IV, respectively. The mean number of pathologically positive lymph nodes was 1.7 in level II, 2.9 in level III, 2.8 in level IV. No death and distant metastasis were recorded during follow up period. Just 2 patients exhibited recurrence to lymph nodes, and only one showed nodal recurrence in ipsilateral level V, who had positive lymph nodes in all of levels II, III, and IV at initial neck surgery. In conclusion, for PTC low risk patients with clinically negative lymph nodes in level V, non-performance of level V dissection would still achieve good survival results as traditional modified radical neck dissection, with a "wait and see" strategy to be recommended.