• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제22권5호
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• pp.417-430
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• 2019

The policies developed for the treatment of Helicobacter pylori infection in adults may not be the most suitable ones to treat children and adolescents. Methods used to treat children and adolescents in Europe and North America may not be appropriate for treating children and adolescents in Korea due to differences in epidemiological characteristics of H. pylori between regions. Moreover, the agreed standard guidelines for the treatment of H. pylori infection in children and adolescents in Korea have not been established yet. In this study, the optimal treatment strategy for H. pylori infection control in children and adolescents in Korea is discussed based on these guidelines, and recent progress on the use and misuse of antimicrobial agents is elaborated. Non-invasive as well as invasive diagnostic test and treatment strategy for H. pylori infection are not recommendable in children aged less than ten years or children with body weight under 35 kg, except in cases of clinically suspected or endoscopically identified peptic ulcers. The uncertainty, whether enough antimicrobial concentrations to eradicate H. pylori can be maintained when administered according to body weight-based dosing, and the costs and adverse effects outweighing the anticipated benefits of treatment make it difficult to decide to eradicate H. pylori in a positive noninvasive diagnostic test in this age group. However, adolescents over ten years of age or with a bodyweight of more than 35 kg can be managed aggressively as adults, because they can tolerate the adult doses of anti-H. pylori therapy. In adolescents, the prevention of future peptic ulcers and gastric cancers is expected after the eradication of H. pylori. Bismuth-based quadruple therapy (bismuth-proton pump inhibitor-amoxicillin/tetracycline-metronidazole) with maximal tolerable doses and optimal dose intervals of 14 days is recommended, because in Korea, the antibiotic susceptibility test for H. pylori is not performed at the initial diagnostic evaluation. If the first-line treatment fails, concomitant therapy plus bismuth can be attempted for 14 days as an empirical rescue therapy. Finally, the salvage therapy, if needed, must be administered after the H. pylori antibiotic susceptibility test.

• Tuberculosis and Respiratory Diseases
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• 제82권4호
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• pp.306-310
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• 2019

Background: Tuberculosis (TB) is increasing in immigrants. We aimed to investigate the current status of latent tuberculosis infection (LTBI) treatment for North Korean Refugees (NKR) compared to South Koreans Contacts (SKC). Methods: TB close contacts in a closed facility of SKC and NKR who underwent LTBI screening in a settlement support center for NKR were analyzed retrospectively. Results: Among tuberculin skin test (TST) ${\geq}10mm$ (n=298) reactors, the males accounted for 72.2% in SKC (n=126) and 19.5% in NKR (n=172) (p<0.01). The mean age was higher in South Korea ($42.8{\pm}9.9years$ vs. $35.4{\pm}10.0years$, p<0.01). Additionally, the mean TST size was significantly bigger in NKR ($17.39{\pm}3.9mm$ vs. $16.57{\pm}4.2mm$, p=0.03). The LTBI treatments were initiated for all screened NKR, and LTBI completion rate was only 68.0%. However, in NKR, LTBI treatment completion rate was significantly increased by shorter 4R regimen (odds ratio [OR], 9.296; 95% confidence interval [CI], 4.159-20.774; p<0.01) and male (OR, 3.447; 95% CI, 1.191-9.974; p=0.02). Conclusion: LTBI treatment compliance must be improved in NKR with a shorter regimen. In addition, a larger study regarding a focus on LTBI with easy access to related data for NKR should be conducted.

• Biomolecules & Therapeutics
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• 제27권4호
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• pp.414-422
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• 2019

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-$1{\beta}$ and tumor-necrosis factor-${\alpha}$ in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and $NF-{\kappa}B$ in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

• 한국응용과학기술학회지
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• 제36권1호
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• pp.208-216
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• 2019

본 연구는 박하 추출물을 통해 독성검사 및 항산화, 항염증과 같은 생리활성을 평가하고자 하였다. 박하 추출은 열수 및 80% 에탄올로 추출하였으며, RAW 264.7 세포를 통해 MTT를 통해 세포 생존율을 평가하였다. 또한, LPS로 유도한 RAW 264.7 세포를 통해 활성산소(ROS), 산화질소(NO), 류코트리엔 B4($LTB_4$), 항염 또는 염증성 사이토카인($IL-1{\beta}$, IL-6, $TNF-{\alpha}$, IL-10) 등을 ELISA 및 Luminex로 측정하였다. 그 결과, 박하 추출물은 열수 및 80% 에탄올 추출물에서 세포독성이 없었으며, 80% 에탄올 추출물의 $100{\mu}g/m{\ell}$ 농도에서 활성산소의 생성을 억제하였다. 또한, NO, LTB4, 염증 또는 항염증성 사이토카인의 생성을 모든 추출물에서 농도 의존적 효능을 나타냈다. 즉, 박하 추출물은 세포독성 없이 항산화 및 항염증 활성을 나타내는 생리학적 효능이 나타났다. 이와 같은 결과는 본 연구와 관련된 증상을 개선하기 위한 새로운 건강식품 및 치료제의 원료로 개발될 수 있다.

• Biomolecules & Therapeutics
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• 제29권6호
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• pp.685-696
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• 2021

In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

• Pediatric Infection and Vaccine
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• 제28권2호
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• pp.66-81
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• 2021

코로나바이러스감염증-19는 전 세계적으로 유행하고 있으며, 2021년 7월 15일 기준으로 1.88억명 이상의 확진자와 406만명 이상의 사망자가 발생하였다. 소아청소년에서는 성인에 비해 비교적 중증 감염 발생이 낮으나, 일부에서는 SARS-CoV-2 감염 약 2-6주후소아다기관염증증후군(multisystem inflammatory syndrome in children, MIS-C)라는 합병증이 발생할 수 있다. MIS-C는 어린영아부터 청소년까지 다양한 연령에서 발생할 수 있으며, 발열을 포함하여 다양한 장기와 관련된 증상을 보일 수 있다. 소화기 및 신경계 증상이 흔하며, 많은 경우 가와사키병과 유사한 피부점막증상 등이 나타난다. 특히 심장관련 증상으로 좌심실 기능저하, 심근염 등이 나타날 수 있으며, 관상동맥확장 및 관상동맥류가 나타날 수 있다. 경우에 따라 저혈압, 쇼크를 동반하며, 중환자실 치료 및 기계환기요법을 요하나, 적절한 치료 후 대체로 회복을 보이는 것으로 보고된다. 이와 같이 MIS-C는 소아청소년에서 SARS-CoV-2 이후 드물게 발생하는 중요한 합병증으로, 임상증상을 잘 인지하고 조기에 적절한 치료를 하는 것이 중요하다. 이에 본 종설에서는 MIS-C의 역학 및 임상 증상, 추정되는 병태생리, 진단적 접근 및 치료에 대해 다루고자 한다.

• Biomolecules & Therapeutics
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• 제27권6호
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• pp.522-529
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• 2019

M1/M2 polarization of immune cells including microglia has been well characterized. It mediates detrimental or beneficial roles in neuroinflammatory disorders including cerebral ischemia. We have previously found that sphingosine 1-phospate receptor subtype 1 ($S1P_1$) in post-ischemic brain following transient middle cerebral artery occlusion (tMCAO) can trigger microglial activation, leading to brain damage. Although the link between $S1P_1$ and microglial activation as a pathogenesis in cerebral ischemia had been clearly demonstrated, whether the pathogenic role of $S1P_1$ is associated with its regulation of M1/M2 polarization remains unclear. Thus, this study aimed to determine whether $S1P_1$ was associated with regulation of M1/M2 polarization in post-ischemic brain. Suppressing $S1P_1$ activity with its functional antagonist, AUY954 (5 mg/kg, p.o.), attenuated mRNA upregulation of M1 polarization markers in post-ischemic brain at 1 day and 3 days after tMCAO challenge. Similarly, suppressing $S1P_1$ activity with AUY954 administration inhibited M1-polarizatioin-relevant $NF-{\kappa}B$ activation in post-ischemic brain. Particularly, $NF-{\kappa}B$ activation was observed in activated microglia of post-ischemic brain and markedly attenuated by AUY954, indicating that M1 polarization through $S1P_1$ in post-ischemic brain mainly occurred in activated microglia. Suppressing $S1P_1$ activity with AUY954 also increased mRNA expression levels of M2 polarization markers in post-ischemic brain, further indicating that $S1P_1$ could also influence M2 polarization in post-ischemic brain. Finally, suppressing $S1P_1$ activity decreased phosphorylation of M1-relevant ERK1/2, p38, and JNK MAPKs, but increased phosphorylation of M2-relevant Akt, all of which were downstream pathways following $S1P_1$ activation. Overall, these results revealed $S1P_1$-regulated M1/M2 polarization toward brain damage as a pathogenesis of cerebral ischemia.

• 생명과학회지
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• 제31권2호
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• pp.248-255
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• 2021

유선종양은 암컷 개에서 가장 흔한 암 중의 하나이며 종양 타입에 따라 조직학적으로 다양한 종류의 세포들이 존재한다. 특히, 복합 상피암종(complex carcinoma)의 경우 내강상피세포(luminal epithelium)와 근상피세포(myoepithelium)가 혼재되어 종양 내 세포 이형성(intra-tumoral heterogeneity)을 보인다. 하지만, 이러한 다양한 종양세포의 기원과 종양의 악성화에 미치는 영향에 대해서는 아직 밝혀진 바 없다. 최근, 여러 종류의 사람 종양에서 알려진 종양줄기세포는 종양 내 세포의 다양성(diversity)에 관여하고 악성화에도 기여할 수 있다고 보고되었다. 흥미롭게도 종양줄기세포는 자가재생능과 다분화능을 갖는 정상줄기세포와 동일한 능력을 가지고 있지만 종양 특이 유전자의 돌연변이와 줄기세포성격유지를 조절하는 신호전달체계에 문제가 있어 종양의 발생 시작부터 다른 조직으로의 전이에 관여하여 개체의 생존률에 직접적인 영향을 준다. 뿐만 아니라, 방사선 및 화학항암제에 대한 저항성을 보이기 때문에 종양 재발에 밀접하게 연관되어 있다. 본 리뷰 논문은 개 유선종양의 특성 및 종류, 종양줄기세포의 정의, 분리 방법, 임상학적 중요성에 대해서 정리하였다.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.227-233
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• 2021

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and ubiquitous environmental toxin with known harmful effects to human health. Abnormal phenotypes of keratinocytes are closely associated with their exposure to B[a]P. Resorcinol is a component of argan oil with reported anticancer activities, but its mechanism of action and potential effect on B[a]P damage to the skin is unknown. In this study, we investigated the effects of resorcinol on B[a]P-induced abnormal keratinocyte biology and its mechanisms of action in human epidermal keratinocyte cell line HaCaT. Resorcinol suppressed aryl hydrocarbon receptor (AhR) activity as evidenced by the inhibition of B[a]P-induced xenobiotic response element (XRE)-reporter activation and cytochrome P450 1A1 (CYP1A1) expression. In addition, resorcinol attenuated B[a]P-induced nuclear translocation of AhR, and production of ROS and pro-inflammatory cytokines. We also found that resorcinol increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activity. Antioxidant response element (ARE)-reporter activity and expression of ARE-dependent genes NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase-1 (HO-1) were increased by resorcinol. Consistently, resorcinol treatment induced nuclear localization of Nrf2 as seen by Western analysis. Knockdown of Nrf2 attenuated the resorcinol effects on ARE signaling, but knockdown of AhR did not affect resorcinol activation of Nrf2. This suggests that activation of antioxidant activity by resorcinol is not mediated by AhR. These results indicate that resorcinol is protective against effects of B[a]P exposure. The mechanism of action of resorcinol is inhibition of AhR and activation of Nrf2-mediated antioxidant signaling. Our findings suggest that resorcinol may have potential as a protective agent against B[a]P-containing pollutants.

• 한방비만학회지
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• 제20권2호
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• pp.88-96
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• 2020

Objectives: This study was designed to investigate the effects of Valerianae Radix et Rhizoma Methanol Extract (VRME) on serum lipid levels in a high-fat diet-induced hyperlipidemic mice. Methods: Each 8 C57BL/6 mice were randomly assigned to normal diet group, high-fat diet control group, high-fat diet plus 100 mg/kg/day of VRME group. In order to induce hyperlipidemia, high-fat diets were supplied to control group and VRME group for four weeks. Normal diet group were supplied with general feed for four weeks. After that control group supplied only high-fat diets as feed, VRME group received oral administration of VRME with high-fat diets for three weeks. and normal diet group were supplied with general feed for three weeks. After seven weeks, the changes in the body weight, the plasma levels of total cholesterol, triglyceride, high density lipoprotein-cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood glucose in serum were measured. Results: In our results, VRME did not affects weight gain, serum AST and ALT in high-fat diet-induced hyperlipidemic mice. Oral administration of VRME lowered levels of total cholesterol and triglyceride, which were elevated by induction of hyperlipidemia. and oral administration of VRME lowered blood glucose significantly. Conclusions: These results suggest that VRME could act as a potent antihyperlipidemic in therapeutics for hyperlipidemia.