Dexmedetomidine Attenuates Neuropathic Pain by Inhibiting P2X7R Expression and ERK Phosphorylation in Rats

Jia-Piao Lin,Chao-Qin Chen,Ling-Er Huang,Na-na Li,Yan Yang,Sheng-Mei Zhu,Yong-Xing Yao 한국뇌신경과학회 2018 Experimental Neurobiology Vol.27 No.4

α2-Adrenoceptor agonists attenuate hypersensitivity under neuropathic conditions. However, the mechanisms underlying this attenuation remain largely unknown. In the present study, we explored the potential roles of purinergic receptor 7 (P2X7R)/extracellular signal-regulated kinase (ERK) signaling in the anti-nociceptive effect of dexmedetomidine in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. An animal model of CCI was adopted to mimic the clinical neuropathic pain state. Behavioral hypersensitivity to mechanical and thermal stimuli was determined by von Frey filament and Hargreaves’ tests, and the spinal P2X7R expression level and ERK phosphorylation were analyzed using western blot analysis and immunohistochemistry. In parallel with the development of mechanical and thermal hyperalgesia, a significant increase in P2X7R expression was noted in the ipsilateral spinal cord on day 7 after CCI. Intrathecal administration of dexmedetomidine (2.5 μg) for 3 days not only attenuated neuropathic pain but also inhibited the CCI-induced P2X7R upregulation and ERK phosphorylation. Intrathecal dexmedetomidine administration did not produce obvious effects on locomotor function. The present study demonstrated that dexmedetomidine attenuates the neuropathic pain induced by CCI of the sciatic nerve in rats by inhibiting spinal P2X7R expression and ERK phosphorylation, indicating the potential therapeutic implications of dexmedetomidine administration for the treatment of neuropathic pain.

p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid

Liu, Jia,Wu, Ning,Ma, Lei-Na,Zhong, Jia-Teng,Liu, Ge,Zheng, Lan-Hong,Lin, Xiu-Kun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Oleanolic acid (OA) is a nutritional component widely distributed in various vegetables. Although it has been well recognized for decades that OA exerts certain anti-tumor activity by inducing mitochondria-dependent apoptosis, it is still unclear that what molecular signaling is responsible for this effect. In this study, we employed cancer cell lines, A549, BXPC-3, PANC-1 and U2OS to elucidate the molecular mechanisms underlying OA anti-tumor activity. We found that activation of MAPK pathways, including p-38 MAPK, JNK and ERK, was triggered by OA in both a dose and time-dependent fashion in all the tested cancer cells. Activation was accompanied by cleavage of caspases and PARP as well as cytochrome C release. SB203580 (p38 MAPK inhibitor), but not SP600125 (JNK inhibitor) and U0126 (ERK inhibitor), rescued the pro-apoptotic effect of OA on A549 and BXPC-3 cells. OA induced p38 MAPK activation promoted mitochondrial translocation of Bax and Bim, and inhibited Bcl-2 function by enhancing their phosphorylation. OA can induce reactive oxygen species (ROS)-dependent ASK1 activation, and this event was indispensable for p38 MAPK-dependent apoptosis in cancer cells. In vivo, p38 MAPK knockdown A549 tumors proved resistant to the growth-inhibitory effect of OA. Collectively, we elucidated that activation of ROS/ASK1/p38 MAPK pathways is responsible for the apoptosis stimulated by OA in cancer cells. Our finding can contribute to a better understanding of molecular mechanisms underlying the antitumor activity of nutritional components.

Risk factors associated with death due to severe fever with thrombocytopenia syndrome in hospitalized Korean patients (2018–2022)

Jia Kim,Hyo-jeong Hong,Ji-hye Hwang,Na-Ri Shin,Kyungwon Hwang 질병관리본부 2023 Osong Public Health and Research Persptectives Vol.14 No.3

Objectives: Severe fever with thrombocytopenia syndrome (SFTS) has no vaccine or treatment and an extremely high fatality rate. We aimed to analyze and evaluate the risk factors for death associated with SFTS.Methods: Among reports from 2018 to 2022, we compared and analyzed 1,034 inpatients aged 18 years or older with laboratory-confirmed SFTS who underwent complete epidemiological investigations.Results: Most of the inpatients with SFTS were aged 50 years or older (average age, 67.6 years). The median time from symptom onset to death was 9 days, and the average case fatality rate was 18.5%. Risk factors for death included age of 70 years or older (odds ratio [OR], 4.82); agriculture-related occupation (OR, 2.01); underlying disease (OR, 7.20); delayed diagnosis (OR, 1.28 per day); decreased level of consciousness (OR, 5.53); fever/chills (OR, 20.52); prolonged activated partial thromboplastin time (OR, 4.19); and elevated levels of aspartate aminotransferase (OR, 2.91), blood urea nitrogen (OR, 2.62), and creatine (OR, 3.21).Conclusion: The risk factors for death in patients with SFTS were old age; agriculture-related occupation; underlying disease; delayed clinical suspicion; fever/chills; decreased level of consciousness; and elevated activated partial thromboplastin time, aspartate aminotransferase, blood urea nitrogen, and creatine levels.

In Vitro Screening for Compounds Derived from Traditional Chinese Medicines with Antiviral Activities Against Porcine Reproductive and Respiratory Syndrome Virus

( Jia Cheng ),( Na Sun ),( Xin Zhao ),( Li Niu ),( Mei Qin Song ),( Yao Gui Sun ),( Jun Bing Jiang ),( Jian Hua Guo2 ),( Yuan Sheng Bai ),( Jun Ping He ),( Hong Quan Li ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.8

Seventeen compounds derived from traditional Chinese medicines (TCMs) were tested for their antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV) in vitro. Visualization with the cytopathologic effect (CPE) assay and the 3-(4, 5-dimethyithiazol- 2-yl)-2,5-diphenyltetrazolium bromide test were used to determine the 50% cytotoxic concentration (CC50) and 50% effective concentration (EC50) in cultured Marc-145 cells. Among the tested compounds, chlorogenic acid and scutellarin showed potential anti-PRRSV activity. The EC50 values were 270.8 ± 14.6 μg/ml and 28.21 ± 26.0 μg/ml and the selectivity indexes were >5.54 and 35.5, respectively. The time-of-addition and virucidal assay indicated that the anti-PRRSV activity of the two compounds could be due to their inhibiting the early stage of virus replication and/or inactivating the virus directly. The inhibition of the virus attachment was not observed in the adsorption inhibition assay. The inhibition ratios of chlorogenic acid and scutellarin were, respectively, 90.8% and 61.1% at the maximum non-cytotoxic concentrations. The results have provided a basis for further exploration of their antiviral properties and mechanisms in vivo. We believe that the chlorogenic acid and scutellarin have a great potential to be developed as new anti-PRRSV drugs for clinical application.

New neo-lignan from Acanthopanax senticosus with protein tyrosine phosphatase 1B inhibitory activity

Jia Lin Li,Na Li,Shan-Shan Xing,Nan Zhang,BanBan Li,JianGuang Chen,안종석,Long Cui 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.11

New neo-lignan, (7S, 8R)-3-hydroxyl-4-methoxyl-balanophonin (1), together with seven known compounds(2–8)were isolated fromthe EtOAc-soluble extract ofAcanthopanax senticosus. The structure of the newneo-lignanwas elucidated with spectroscopic and physico-chemicalanalyses. All the isolates were evaluated for in vitro inhibitoryactivity against PTP1B, VHR and PP1. Among them, the newcompound (1) was found to exhibit selective inhibitoryactivity on PTP1B with IC50 value 15.2 ± 1.4 lM.

Preventive Effect of Perilla frutescens Britt Var. japonica Leaf in Dextran Sulftran Sulfate Sodium(DSS)-Induced Colitis Mice

Jia-Le Song,Na Ji,Kun-Young Park 한국식품영양과학회 2013 한국식품영양과학회 학술대회발표집 Vol.2013 No.11

Preparation of Novel Pyrrolo[2,3-b]pyridine Derivatives via a New Concise Synthetic Approach

Na Guo,Haiyong Jia,Xing You,Du Jiang,Kui Lu,Peng Yu 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.4

The pyrrolo[2,3-b]pyridine core structure, a bioisostere of quinolones, is found in several molecules that possess important biological activity. We describe here a new, concise, three-step synthesis of pyrrolo[2,3-b]pyridines starting from L-alanine. A series of 4,7-dihydro-4-oxo-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid derivatives, which have not been previously reported, were synthesized using this approach.

Diacylglycerol Acyltransferase-inhibitory Prenylated Flavonoids from Maackia amurensis Rupr

Na Li,이현선,Zhen Dong Tuo,Jia Lin Li,Pei Ge Du,Long Cui 대한화학회 2014 Bulletin of the Korean Chemical Society Vol.35 No.10

HaCaT 피부각질세포에서 들깻잎 추출물의 산화적 스트레스에 대한 항산화 효과

지나(Na Ji),송가락(Jia-Le Song),길정하(Jeung-Ha Kil),박건영(Kun-Young Park) 한국식품영양과학회 2013 한국식품영양과학회지 Vol.42 No.2

들깻잎 메탄올추출물(PLME)이 가지는 산화적 스트레스 개선효과를 확인하기 위하여 H2O2으로 유도된 산화적 스트레스에 대한 HaCaT 피부 각질세포의 보호효과를 조사하였다. 또한 PLME의 항산화 능력을 확인하기 위하여 DPPH, hydroxyl free radical 소거능 및 총 항산화물질(페놀류, 플라보노이드류 및 아스코르브산) 함량을 조사하였다. H2O2(500μM)에 의한 산화적 스트레스가 유발된 HaCaT세포에 PLME를 처리한 결과, 농도 의존적으로 세포의 생존율이 증가하였고, 세포 지질과산화물질 MDA의 생성효과는 PLME 처리에 의해 유의적으로 감소하는 것을 관찰하였다. 또한 H2O2로 인하여 세포내 항산화효소인 SOD, GSH-px와 CAT 등의 활성이 감소된 HaCaT세포에 PLME를 처리했을 때, 이들 효소의 활성이 농도 의존적으로 증가되었다. PLME의 DPPH와 hydroxyl radical 소거능을 측정한 결과, 농도 의존적으로 radical 소거능이 증가함을 알 수 있었다. 50 μg/mL 이상 농도의 PLME의 DPPH 소거능은 60%의 저해율을 나타낸 천연항산화제인 아스코르브산(50 μg/mL)과 유사한 효과를 보였고, OH radical 소거능은 아스코르브산(50 μg/mL)보다 높은 결과를 나타냈다. 또한 PLME가 함유하고 있는 항산화물질인 폴리페놀류, 플라보노이드류, 아스코르브산의 함량을 측정한 결과 총 페놀류화합물은 52.2±1.1 mg GAE/g, 총 플라보노이드화합물은 33.7±4.7 mg RUE/g, 아스코르브산의 함량은 17.0±0.5 mg AA/g으로 나타났다. HaCaT 세포에서 H2O2에 의해 발생하는 산화적 스트레스에 대한 보호 효과를 측정한 결과 PLME는 세포 사멸을 방지하고, 세포 지질과산화물질(MDA)의 생성을 억제하여 세포내 항산화효소의 활성을 증가시키는 효과를 가지는 것으로 보인다. 이상의 결과로 들깻잎 메탄올추출물은 인체 피부각질 세포에 대한 보호 작용과 in vitro에서의 항산화 능력이 있는 것으로 확인되었다. The aim of this study was to investigate the protective effects of methanolic extract from perilla (Perilla frutescens Britt var. japonica) leaves (PLME) on oxidative injury from hydrogen peroxide (H2O2) in humanm HaCaT keratinoctyes. Cells were co-incubated with various concentrations (0~200 μg/mL) of PLME for 24 hr, and then exposed to H2O2 (500 μM) for 4 hr. H2O2 significantly decreased cell viability (p<0.05). However, PLME provided protection from H2O2-induced HaCaT cell oxidation in a dose-dependent manner. To further investigate the protective effects of PLME on H2O2-induced oxidative stress in HaCaT cells, the cellular levels of lipid peroxidation, and antioxidant enzymes (including superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and catalase (CAT)) were measured. PLME decreased cellular levels of lipid peroxidation, and also increased the activities of antioxidant enzymes. In addition, the antioxidant activities of PLME were also determined by DPPH and hydroxyl (?OH) radical scavenging assay, and major antioxidant compounds of PLME were measured by colorimetric methods. DPPH and ?OH radical scavenging activities of PLME increased in a dose dependent manner and was similar to the DPPH scavenging activity of ascorbic acid at 50 μg/mL; however PLME activities were stronger than ascorbic acid (50 μg/mL) in the ?OH scavenging assay. The amounts of antioxidant compounds, including total polyphenolics, total flavonoids, and total ascorbic acid from PLME were 52.2±1.1 mg gallic acid (GAE)/g, 33.7±4.7 mg rutin (RUE)/g, and 17.0±0.5 mg ascorbic acid (AA)/g, respectively. These results suggest that PLME has a strong free radical-scavenging activity and a protective effect against H2O2-induced oxidative stress in the keratinocytes.

Diacylglycerol Acyltransferase-inhibitory Prenylated Flavonoids from Maackia amurensis Rupr

Li, Na,Lee, Hyun Sun,Tuo, Zhen Dong,Li, Jia Lin,Du, Pei Ge,Cui, Long Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.10