• Biomolecules & Therapeutics
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• 제27권2호
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• pp.160-167
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• 2019

Depression is a major mood disorder. Abnormal expression of glial glutamate transporter-1 (GLT-1) is associated with depression. Schisantherin B (STB) is one bioactive of lignans isolated from Schisandra chinensis (Turcz.) Baill which has been commonly used as a traditional herbal medicine for thousands of years. This paper was designed to investigate the effects of STB on depressive mice induced by forced swimming test (FST). Additionally, we also assessed the impairment of FST on cognitive function in mice with different ages. FST and open field test (OFT) were used for assessing depressive symptoms, and Y-maze was used for evaluating cognition processes. Our study showed that STB acting as an antidepressant, which increased GLT-1 levels by promoting PI3K/AKT/mTOR pathway. Although the damage is reversible, short-term learning and memory impairment caused by FST test is more serious in the aged mice, and STB also exerts cognition improvement ability in the meanwhile. Our findings suggested that STB might be a promising therapeutic agent of depression by regulating the GLT-1 restoration as well as activating PI3K/AKT/mTOR pathway.

• 접착 및 계면
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• 제19권4호
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• pp.154-162
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• 2018

필름 형태의 Polydimethylsiloxane (PDMS)은 표면 개질을 하기 위해 Plasma 처리 또는 Corona 처리를 하여 표면을 -OH기로 활성화시키는 공정이나, 피착제와 PDMS 필름의 접착 또는 Adhesion promoter와 축합 반응을 통해 PDMS 표면을 다른 작용기로 개질시키는 공정, Grafting polymerization을 이용하는 PDMS 개질 공정이 주로 이용된다. 그러나 Plasma나 Corona 처리 후에 친수성이 오래가지 못하고, 보관에 어려움이 있다. 따라서, 본 연구에서는 코팅 공정을 통하여서 PDMS표면 개질을 하기 위해서, 먼저 새로운 형태의 실란 기능화 아크릴 고분자 전구체를 합성하고 이를 Hydroxyl-terminated PDMS와의 축합 반응을 통해 아크릴 고분자와 PDMS 고분자가 결합된 형태의 표면 개질제를 제조한 후, 이를 PDMS 필름 위에 코팅하였다. 제조한 표면 개질제의 구조와 분자량을 확인하기 위하여 1H-NMR과 GPC를 분석하였고, 표면 개질제가 코팅된 PDMS표면 특성 변화를 확인하기 위하여 XPS, ATR, WCA를 이용하여 표면 특성을 조사하였으며, PDMS 필름과의 부착을 확인하기 위해 Cross cutting test를 진행하였다. 그 결과 PDMS 필름 표면이 아크릴 고분자층이 형성된 것으로 확인하였고, PDMS 필름과 표면 개질제와의 부착성 (4 - 5B) 또한 우수한 것을 확인하였다.

• Clinics in Shoulder and Elbow
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• 제25권1호
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• pp.73-89
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• 2022

Background: To evaluate the efficacy of autologous platelet-rich plasma (PRP) injections in the treatment of common shoulder diseases. Methods: The PubMed, Medline, and Central databases and trial registries were searched from their inception to October 2020 for randomized controlled trials of autologous PRP injections for shoulder diseases versus placebo or any control intervention. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. The primary outcome was pain intensity (visual analog scale), and secondary outcomes were changes in function and quality of life (QoL). Results: A total of 17 randomized controlled trials of PRP versus control were analyzed. From 8-12 weeks to ≥1 year, PRP injections were associated with better pain relief and functional outcomes than control interventions. PRP injections were also associated with greater QoL, with an effect size of 2.61 (95% confidence interval, 2.01-14.17) at medium-term follow-up. Compared with placebo and corticosteroid injections, PRP injections provided better pain relief and functional improvement. In subgroup analyses, trials in which PRP was prepared by the double centrifugation technique, the platelet concentration in the PRP was enriched ≥5 times, leucocyte-rich PRP was used, or an activating agent was used before application reported the most effective pain relief at 6-7 months. Conclusions: PRP injections could provide better pain relief and functional outcomes than other treatments for persons presenting with common shoulder diseases. PRP injections have a greater capacity to improve shoulder-related QoL than other interventions.

• Journal of Ginseng Research
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• 제47권1호
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• pp.65-73
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• 2023

Background: Age-related macular degeneration (AMD) is a significant visual disease that induces impaired vision and irreversible blindness in the elderly. However, the effects of ginseng berry extract (GBE) on the retina have not been studied. Therefore, this study aimed to investigate the protective effects of GBE on blue light (BL)-induced retinal damage and elucidate its underlying mechanisms in human retinal pigment epithelial cells (ARPE-19 cells) and Balb/c retina. Methods: To investigate the effects and underlying mechanisms of GBE on retinal damage in vitro, we performed cell viability assay, pre-and post-treatment of sample, reactive oxygen species (ROS) assay, quantitative real-time PCR (qRT-PCR), and western immunoblotting using A2E-laden ARPE-19 cells with BL exposure. In addition, Balb/c mice were irradiated with BL to induce retinal degeneration and orally administrated with GBE (50, 100, 200 mg/kg). Using the harvested retina, we performed histological analysis (thickness of retinal layers), qRT-PCR, and western immunoblotting to elucidate the effects and mechanisms of GBE against retinal damage in vivo. Results: GBE significantly inhibited BL-induced cell damage in ARPE-19 cells by activating the SIRT1/PGC-1α pathway, regulating NF-kB translocation, caspase 3 activation, PARP cleavage, expressions of apoptosis-related factors (BAX/BCL-2, LC3-II, and p62), and ROS production. Furthermore, GBE prevented BL-induced retinal degeneration by restoring the thickness of retinal layers and suppressed inflammation and apoptosis via regulation of NF-kB and SIRT1/PGC-1α pathway, cleavage of caspase 3 and PARP, and expressions of apoptosis-related factors in vivo. Conclusions: GBE could be a potential agent to prevent dry AMD and progression to wet AMD.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.661-673
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• 2023

Treatment of colorectal cancer (CRC) has always been challenged by the development of resistance. We investigated the antiproliferative activity of licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata, in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including pEGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of sub-G1 cells and arrested the cell cycle at the G1 phase. Taken together LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2020년도 춘계학술대회
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• pp.77-77
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• 2020

Purple loosestrife-Lythrum anceps (Koehne) Makino is a herbaceous perennial plant belonging to the Lythraceae family. It has been used for centuries in Korea and other Asian traditional medicine. It has been showed pharmacological effects, including anti-oxidant and anti-microbial effects. However, the mechanisms underlying its anti-cancer mechanisms are not yet understood. In this study, we investigated the mechanism of apoptosis signaling pathways by ethanol extract of Lythrum anceps (Koehne) Makino (ELM) in human leukemia U937 cells. Treatment with ELM significantly inhibited cell growth in a dose-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies (ApoBDs), DNA fragmentation and increased populations of sub-G1 ratio. Induction of apoptosis by ELM was connected with up-regulation of death receptor (DR) 4 and DR5, pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 protein, and inhibitor of apoptosis protein (IAP) family proteins (XIAP, cIAP-1, survivin), depending on dosage. This induction was associated with Bid truncation, mitochondrial dysfunction, proteolytic activation of caspases (-3, -8 and -9) and cleavage of poly(ADP-ribose) polymerase protein. Therefore, our data indicate that ELM suppresses U937 cell growth by activating the intrinsic and extrinsic apoptosis pathways, and thus may have applications as a potential source for an anti-leukemic chemotherapeutic agent.

• Journal of Ginseng Research
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• 제48권4호
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• pp.384-394
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• 2024

Background: Herpes simplex virus type 1 (HSV-1), known to latently infect the host's trigeminal ganglion, can lead to severe herpes encephalitis or asymptomatic infection, potentially contributing to neurodegenerative diseases like Alzheimer's. The virus generates reactive oxygen species (ROS) that significantly impact viral replication and induce chronic inflammation through NF-κB activation. Nuclear factor E2-related factor 2 (Nrf2), an oxidative stress regulator, can prevent and treat HSV-1 infection by activating the passive defense response in the early stages of infection. Methods and results: Our study investigated the antiviral effects of ginsenoside Rg5, an Nrf2 activator, on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection inhibited Nrf2 activity in host cells, induced ROS/NF-κB signaling, and triggered inflammatory cytokines. However, treatment with ginsenoside Rg5 inhibited ROS/NF-κB signaling and reduced inflammatory cytokines through NRF2 induction. Interestingly, the Nrf2 inhibitor ML385 suppressed the expression of NAD(P)H quinone oxidoreductase 1(NQO1) and enhanced the expression of KEAP1 in HSV-1 infected cells. This led to the reversal of VP16 expression inhibition, a protein factor associated with HSV-1 infection, thereby promoting HSV-1 replication. Conclusion: These findings suggest for the first time that ginsenoside Rg5 may serve as an antiviral against HSV-1 infection and could be a novel therapeutic agent for HSV-1-induced neuroinflammation.

• Journal of Animal Science and Technology
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• 제63권5호
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• pp.1126-1141
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• 2021

Recent evidence has shown that methionine (Met) supplementation can improve milk protein synthesis under hyperthermia (which reduces milk production). To explore the mechanism by which milk protein synthesis is affected by Met supplementation under hyperthermia, mammary alveolar (MAC-T) cells were incubated at a hyperthermic temperature of 42℃ for 6 h in media with different concentrations of Met. While the control group (CON) contained a normal amino acid concentration profile (60 ㎍/mL of Met), the three treatment groups were supplemented with Met at concentrations of 10 ㎍/mL (MET70, 70 ㎍/mL of Met), 20 ㎍/mL (MET80, 80 ㎍/mL of Met), and 30 ㎍/mL (MET90,90 ㎍/mL of Met). Our results show that additional Met supplementation increases the mRNA and protein levels of BCL2 (B-cell lymphoma-2, an anti-apoptosis agent), and decreases the mRNA and protein levels of BAX (Bcl-2-associated X protein, a pro-apoptosis agent), especially at an additional supplementary concentration of 20 ㎍/mL (group Met80). Supplementation with higher concentrations of Met decreased the mRNA levels of Caspase-3 and Caspase-9, and increased protein levels of heat shock protein (HSP70). The total protein levels of the mechanistic target of rapamycin (mTOR) and the mTOR signalling pathway-related proteins, AKT, ribosomal protein S6 kinase B1 (RPS6KB1), and ribosomal protein S6 (RPS6), increased with increasing Met supplementation, and peaked at 80 ㎍/mL Met (group Met80). In addition, we also found that additional Met supplementation upregulated the gene expression of αS1-casein (CSN1S1), β-casein (CSN2), and the amino acid transporter genes SLC38A2, SLC38A3 which are known to be mTOR targets. Additional Met supplementation, however, had no effect on the gene expression of κ-casein (CSN3) and solute carrier family 34 member 2 (SLC34A2). Our results suggest that additional Met supplementation with 20 ㎍/mL may promote the synthesis of milk proteins in bovine mammary epithelial cells under hyperthermia by inhibiting apoptosis, activating the AKT-mTOR-RPS6KB1 signalling pathway, and regulating the entry of amino acids into these cells.

• 생명과학회지
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• 제29권3호
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• pp.295-302
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• 2019

Liquiritigenin (LG)은 licorice 뿌리에서 분리된 chiral flavonoid이다. LG는 항산화, 항암 및 항염증 효과를 포함하여 다양한 생물학적 활성을 가지고 있다. 구강편평세포암종에서 LG의 항암 활성은 아직 밝혀지지 않았다. 본 연구에서는 구강편평상피암 세포(HN22)에서 LG의 항암 효능을 시험하였다. HN22 세포에 LG를 처리하여 MTT 분석으로 세포 생존율을 평가하였으며, Annecin V/7-Aminactinomycin D 염색, 세포주기 및 Multi-caspase 활성을 $Muse^{TM}$ cell Analyzer로 분석하여 세포사멸 유도를 확인하였다. 분석결과, 구강편평상피암 HN22 세포에 LG를 처리시 G2/M 세포주기 정지를 일으켰으며, Western blotting 통하여 cyclin B1 및 CDC2 발현 감소와 p27 발현 증가를 확인하였다. LG는 활성산소종의 생성을 유발하고, CCAAT/enhancer-binding protein homologous protein (CHOP) 및 78-kDa glucose regulated protein (GRP78)의 발현을 농도의존적으로 유도하였다. HN22 세포에 LG의 처리는 미토콘드리아 막전위의 손실(${\Delta}{\Psi}m$)을 일으켰다. LG를 처리한 HN22 세포의 단백질 분석결과 apoptotic protease activating factor-1 (Apaf-1), cleaved Poly (ADP-Ribose) Polymerase (C-PARP) 및 Bax의 발현을 증가함을 확인하였다. 따라서 우리의 결과는 LG이 구강편평상피암 세포의 세포사멸을 유도하여 항암제 역할을 할 수 있는 천연 화합물임을 시사한다.

• IMMUNE NETWORK
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• 제1권1호
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• pp.45-52
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• 2001

Background: Many types of cancer become resistant to current chemotherapeutic and radiotherapeutic intervention. To overcome this situation application of gene therapy by the introduction of suicide genes followed by their prodrugs may be promising. A viral enzyme, Herpes simplex thymidine kinase (HSV-tk), which converts ganciclovir from an inactive prodrug to a cytotoxic agent by phosphorylation, are being actively investigated for use in gene therapy for cancer. The purpose of this study was to determine whether combining prodrug-activating gene therapy and irradiation might result in enhanced antitumor effects. Methods: The HSV-tk gene was cloned into the retroviral vector, pLXSN and established the clones producing retroviruses carrying the HSV-tk gene. The carcinoma cell line, HCT116 and Huh-7 were transduced with high-titer recombinant retroviruses. These cell lines were treated with ganciclovir before or after irradiation for the defining combinational effect of suicide gene therapy and radiotherapy. Results: The titers of cloned PA3 17 amphotropic retroviruses ranged from 4 to 6 X $10^6CFU/ml4$. After selectional periods, the expression of HSV-tk was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The growth of cells expressing HSV-tk was inhibited as increase of GCV dose after 48 hr and the growth inhibitory effect of GCV was much higher after 72 hr. When the cells transduced with HSV-tk gene were exposed to radiation, the growth inhibitory effect of GCV was significantly increased, as compared with non-transduced parental cells. Conclusions: The results suggest that the addition of HSV-tk gene therapy to standard radiation therapy may improve the effectiveness of treatment for solid tumors.