• Biomolecules & Therapeutics
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• 제30권5호
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• pp.455-464
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• 2022

Efonidipine, a calcium channel blocker, is widely used for the treatment of hypertension and cardiovascular diseases. In our preliminary study using structure-based virtual screening, efonidipine was identified as a potential inhibitor of c-Jun N-terminal kinase 3 (JNK3). Although its antihypertensive effect is widely known, the role of efonidipine in the central nervous system has remained elusive. The present study investigated the effects of efonidipine on the inflammation and cell migration induced by lipopolysaccharide (LPS) using murine BV2 and human HMC3 microglial cell lines and elucidated signaling molecules mediating its effects. We found that the phosphorylations of JNK and its downstream molecule c-Jun in LPS-treated BV2 cells were declined by efonidipine, confirming the finding from virtual screening. In addition, efonidipine inhibited the LPS-induced production of pro-inflammatory factors, including interleukin-1β (IL-1β) and nitric oxide. Similarly, the IL-1β production in LPS-treated HMC3 cells was also inhibited by efonidipine. Efonidipine markedly impeded cell migration stimulated by LPS in both cells. Furthermore, it inhibited the phosphorylation of inhibitor kappa B, thereby suppressing nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 cells. Taken together, efonidipine exerts anti-inflammatory and anti-migratory effects in LPS-treated microglial cells through inhibition of the JNK/NF-κB pathway. These findings imply that efonidipine may be a potential candidate for drug repositioning, with beneficial impacts on brain disorders associated with neuroinflammation.

• Journal of Microbiology and Biotechnology
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• 제33권7호
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• pp.915-925
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• 2023

Sarcopenia is defined as loss of muscle mass and strength due to aging. Recent studies show that sarcopenia may improve via the gut-muscle axis, suggesting that gut health may affect muscle phenotypes. In this study, we aimed to investigate the ability of Lactobacillus rhamnosus JY02 as a probiotic strain isolated from kimchi to alleviate sarcopenia. L. rhamnosus JY02-conditioned medium (CM) reduced dexamethasone (DEX)-induced myotube diameter atrophy and expression of muscle degradation markers (MuRF1 and atrogin-1) in C2C12 cells. The amelioration of sarcopenia was investigated by measuring body composition (lean mass), hand grip strength, myofibril size (using histological analysis), and mRNA and protein expression of muscle-related factors in a DEX-induced mouse model. The results of these analyses showed that L. rhamnosus JY02 supplementation promoted the production of muscle-enhancement markers (MHC Iβ, MHC IIα, and Myo-D) and reduced both the production of muscle degradation markers and the symptoms of muscle atrophy (loss of lean mass and muscle strength). We also found decreased levels of pro-inflammatory cytokines (IL-6, IFN- γ) and increased levels of anti-inflammatory cytokines (IL-10) in the serum of DEX+JY02-administered mice compared to those in DEX-treated mice. Overall, these results suggest that L. rhamnosus JY02 is a potent probiotic supplement that prevents sarcopenia by suppressing muscle atrophy.

• The Korean Journal of Pain
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• 제37권4호
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• pp.310-319
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• 2024

Background: This study aimed to investigate the analgesic and preventive effect of low-level laser therapy (LLLT) on the incisional pain model and spinal nerve ligation (SNL) model in rats and identify the possible mechanisms of action. Methods: Male Sprague-Dawley rats were used, divided into different treatment groups. The single application group received LLLT before or after skin incision or SNL. The consecutive application group received LLLT for six consecutive days post-incision, three days pre-incision, or three consecutive days pre-SNL. The control group underwent skin incision or SNL without LLLT. The von Frey test was used to quantify the pain associated with mechanical allodynia. Pro-inflammatory cytokine level and alterations in nerve growth factor (NGF) expression were measured by using ELISA and immunohistochemistry, respectively in the skin, muscle of the paw, and spinal cord dorsal horn (SCDH). Results: In the incisional pain model, LLLT showed significant analgesic and preventive effect. LLLT ameliorated SNL-induced mechanical allodynia but LLLT had no preventive effect. LLLT decreased interleukin-1β (IL-1β) expression levels in the skin, muscle, and SCDH and reduced the optical density of skin and spinal cord NGF in the incisional pain model. Conclusions: LLLT alleviated incisional pain and neuropathic pain caused by SNL in rats, and reduced the levels of IL-1β and NGF in the peripheral tissue and SCDH in the incisional pain model. LLLT might be effective in patients with post-operative pain and peripheral neuropathic pain.

• 생명과학회지
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• 제19권11호
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• pp.1637-1643
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• 2009

천연생약 자초의 한 성분인 shikonin은 항염증, 항암 및 항비만 등 다양한 분야에 효과를 보여왔다. 이번 연구에서는 shikonin이유도하는 adipogenesis억제 과정에 어떤 인자들이 작용하는지 살펴보았다. Shikonin의 효과에 대한 분자적 메커니즘을 규명하기 위해, real-time PCR을 이용하여 C/EBPs, $PPAR{\gamma}$를 포함한 다양한 adipogenesis 인자들의 mRNA 발현량을 분석하였다. 그 결과, 초기 분화의 주요 조절자인 C/$EBP{\beta}$와 C/$EPB{\delta}$는 shikonin에 의해 거의 변화가 없었으나, 후기 분화의 주요 조절자인 $PPAR{\gamma}$와 C/$EPB{\alpha}$의 mRNA 발현은 유의하게 감소하였다. Shikonin에 의한 adipogenesis억제의 메커니즘을 좀 더 자세히 밝히기 위해 adipogenesis과정의 상위 단계에 위치한 조절자들의 mRNA 발현을 분석하였다. C/$EBP{\beta}$의 상위 조절자인 C/$EBP{\gamma}$, CHOP은 shikonin에 의해 영향을 받지 않았으나, KROX20의 경우 유의하게 감소하였다. 이러한 결과는 Pro-adipogenic 인자인 KROX20의 감소가 C/$EBP{\beta}$에 영향을 주기 보다는 C/$EBP{\beta}$와 독립적으로 그 하위의 인자들에게 영향을 줄 수 있음을 제시한다. $PPAR{\gamma}$의 상위 조절자로 알려져 있는 KLF 들 중에서 pro-adipogenic 인자인 KLF15의 mRNA 발현은 shikonin에 의해 급격히 감소하였으나 anti-adipogenic 인자인 KLF2는 shikonin에 의한 변화가 거의 없었다. 또 다른 pro-adipogenic 인자인 KLF5의 경우, 주로 작용하는 초기 분화에서는 shikonin에 의해 거의 변화가 없었지만, 후기 분화에서는 조금 증가하였다. 이러한 후기 분화에서의 KLF5의 변화는 KLF15에 비해 전체 분화에 크게 영향을 주지 못하는 것 같다. 결론적으로, shikonin은 pro-adipogenic 인자인, KROX20과 KLF15의 조절을 통해 $PPAR{\gamma}$ 및 C/$EPB{\alpha}$의 mRNA 발현을 억제함으로써 지방 세포의 분화를 저해한다고 사료된다.

• 한국전자현미경학회:학술대회논문집
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• 한국현미경학회 2005년도 제36차 추계학술대회 및 제4회 HVEM 이용자 워크샵
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• pp.127-129
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• 2005

Bacterial lipopolysaccharide(LPS) is can stimulate the most LPS-responsive cells in the mammalian host. The macrophage response to LPS can protect the host from infection but high levels, contribute to systemic inflammatory response syndrome and destruction of host itself, The previously study, secretory leukocyte pretense inhibitor (SLPI) was known LPS-induced product of macrophage and had the function that antagonizes their LPS-induced activation of pro-inflammation signaling factors. Purpose of this study was to identify the expression of SLPI involving the infection in various cell lines including odontoblast cell line. Therefore, we conducted in vitro researches, which treated the LPS to the MDPC-23, and compared to NIH3T3, RAW264.7. To investigate the expressionof SLPI in mRNA level, the methods was used RT-PCR and western blotting for protein expression of SLPI. Moreover, we performed the scanning electron microscopic (SEM) observation for the morphological change. This work was supported by Korea Science and Engineering Foundation.

• Biomolecules & Therapeutics
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• 제13권1호
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• pp.7-12
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• 2005

GyeongshinhaeGihwan T1 (GGT1) is a newly developed oriental medicine to help weight control. We investigated nitric oxide production and cytokine secretion in mouse peritoneal macrophages. According to recent reports, macrophages are participated in fat accumulation and closely related with obesity. In this study, using mouse peritoneal macrophages, we have examined whether GGT1 affects the production of nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interleukin (IL)-12 by the stimulation of interferon-${\gamma}$ and lipopolysaccharide (LPS). GGT1 inhibits LPS-induced NO production in a dose-dependent manner. The decrease in NO synthesis was reflected as a decreased amount of inducible NO synthese protein. We also found that GGT1 inhibits pro-inflammatory cytokines, TNF-${\alpha}$ and IL-12 production. In mouse embryo preadipocyte 3T3-L1, GGT1 reduced the viability in a dose-dependent manner. These findings suggest that GGT1 may have potential effects in preventing and controlling adipogenesis and obesity.

• Clinical and Experimental Pediatrics
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• 제48권6호
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• pp.580-587
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• 2005

New evidence is emerging that airway smooth muscle(ASM) may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, polypeptide growth factors, extracellular matrix proteins, cell adhesion receptors and co-stimulatory molecules. ASM can promote the formation of the interstitial extracellular matrix, and potentially contribute to the alterations within the extracellular matrix in asthma. In addition, extracellular matrix components can alter the proliferative, survival, and cytoskeletal synthetic function of ASM cells through integrin-directed signaling. Increased ASM mass is one of the most important features of the airway wall remodeling process in asthma. Three different mechanisms may contribute to the increased ASM mass : cell proliferation, increased migration and decreased rate of apoptosis. The major signaling pathways of cell proliferation activated by ASM mitogens are those dependent on extracellular signal-regulated kinase and phosphoinositide 3'-kinase. The key signaling mechanisms of cell migration have been identified as the p38 mitogen-activated protein kinase and the p21-activated kinase 1 pathways. ASM cells contain ${\beta}2$-adrenergic receptors and glucocorticoid receptors. They may represent a key target for ${\beta}2$-adrenergic receptor agonist/corticosteroid interactions which have antiproliferative activity against a broad spectrum of mitogens.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2613-2617
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• 2015

Radiation induced lung injury has long been considered a treatment limiting factor for patients requiring thoracic radiation. This radiation induced lung injury happens early as well as late. Radiation induced lung injury can occur in two phases viz. early (< 6 months) when it is called radiation pneumonitis and late (>6 months) when it is called radiation induced lung fibrosis. There are multiple factors that can be patient, disease or treatment related that predict the incidence and severity of radiation pneumonitis. Radiation induced damage to the type I pneumocytes is the triggering factor to initiate such reactions. Over the years, radiation therapy has witnessed a paradigm shift in radiation planning and delivery and successfully reduced the incidence of lung injury. Radiation pneumonitis is usually a diagnosis of exclusion. Steroids, ACE inhibitors and pentoxyphylline constitute the cornerstone of therapy. Radiation induced lung fibrosis is another challenging aspect. The pathophysiology of radiation fibrosis includes continuing inflammation and microvascular changes due to pro-angiogenic and profibrogenic stimuli resembling those in adult bronchiectasis. General supportive management, mobilization of airway secretions, anti-inflammatory therapy and management of acute exacerbations remains the treatment option. Radiation induced lung injury is an inevitable accompaniment of thoracic radiation.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.1-13
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• 2016

The evidence for the existence of a common pathway for health issues in men is presented in this review. Several epidemiological studies have shown that conditions like cardiovascular diseases (CVD), metabolic syndrome, diabetes, lower urinary tract symptom (LUTS), erectile dysfunction (ED), prostate cancer, hypogonadism, depression and suicide can be associated as risk factors for each other. Thus, the risk of CVD is significantly increased in men with metabolic syndrome, ED, hypogonadism, prostate cancer and/or LUTS. In addition, the above mentioned conditions are more prevalent in atherosclerotic patients. In addition, growing evidence indicates that low androgen levels can cause metabolic syndrome. In addition, obesity, dyslipidaemia and diabetes can further reduce androgen levels potentiating their adverse effect. Low testosterone levels are also associated with a higher incidence of aggressive prostate cancer on biopsy and on definitive pathology, and lower probability of abiraterone response in the metastatic setting. Several recent studies point towards diffuse endothelial dysfunction and dysregulated pro-inflammatory state as the biological link between all these disorders. Our current hypothesis is that oxidative stress caused by these dysfunctions explains the pathogenesis of each of these conditions.

• IMMUNE NETWORK
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• 제10권6호
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• pp.181-187
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• 2010

Excessive alcohol consumption is one of the critical causative factors leading to alcoholic liver disease (ALD). ALD is characterized by a wide spectrum of liver damage, ranging from simple uncomplicated liver steatosis (fatty liver) to steatohepatitis and liver fibrosis/cirrhosis. It has been believed that the obvious underlying cause for ALD is due to hepatocyte death induced by alcohol itself. However, recent sparkling studies have shown that diverse immune responses contribute to ALD because liver is enriched with numerous immune cells. Especially, a line of evidence has suggested that innate immune cells such as Kupffer cells and natural killer (NK)/NKT cells are significantly involved in the pathogenesis of ALD via production of pro-inflammatory cytokines and other mediators. Indeed, more interestingly, hepatic stellate cells (HSCs), known as a major cell inducing liver steatosis and fibrosis, can be killed by liver NK cells, which could be suppressed by chronic alcohol consumption. In this review, with the view of liver as predominant innate immune organ, we describe the pathogenesis of ALD in which what roles of innate immune cells are and how they are interacting with HSCs.