Jaewan Jeon  Sungmin Lee  Hyunwoo Kim  Hyunkoo Kang  HyeSook Youn  Sunmi Jo  BuHyun Youn  Hae Yu Kim 《International journal of molecular sciences》2021,22(10)

Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs.  相似文献   

    

Shuai Guo  Xue Bai  Sai Shi  Yawen Deng  Xianjiang Kang  Hailong An 《International journal of molecular sciences》2021,22(20)

Lung cancer has the highest rate of incidence and mortality among all cancers. Most chemotherapeutic drugs used to treat lung cancer cause serious side effects and are susceptible to drug resistance. Therefore, exploring novel therapeutic targets for lung cancer is important. In this study, we evaluated the potential of TMEM16A as a drug target for lung cancer. Homoharringtonine (HHT) was identified as a novel natural product inhibitor of TMEM16A. Patch-clamp experiments showed that HHT inhibited TMEM16A activity in a concentration-dependent manner. HHT significantly inhibited the proliferation and migration of lung cancer cells with high TMEM16A expression but did not affect the growth of normal lung cells in the absence of TMEM16A expression. In vivo experiments showed that HHT inhibited the growth of lung tumors in mice and did not reduce their body weight. Finally, the molecular mechanism through which HHT inhibits lung cancer was explored by western blotting. The findings showed that HHT has the potential to regulate TMEM16A activity both in vitro and in vivo and could be a new lead compound for the development of anti-lung-cancer drugs.  相似文献   

    

Do Yoon Hyun  Raveendar Sebastin  Gi-An Lee  Kyung Jun Lee  Seong-Hoon Kim  Eunae Yoo  Sookyeong Lee  Man-Jung Kang  Seung Bum Lee  Ik Jang  Na-Young Ro  Gyu-Taek Cho 《International journal of molecular sciences》2021,22(13)

Melon (Cucumis melo L.) is an economically important horticultural crop with abundant morphological and genetic variability. Complex genetic variations exist even among melon varieties and remain unclear to date. Therefore, unraveling the genetic variability among the three different melon varieties, muskmelon (C. melo subsp. melo), makuwa (C. melo L. var. makuwa), and cantaloupes (C. melo subsp. melo var. cantalupensis), could provide a basis for evolutionary research. In this study, we attempted a systematic approach with genotyping-by-sequencing (GBS)-derived single nucleotide polymorphisms (SNPs) to reveal the genetic structure and diversity, haplotype differences, and marker-based varieties differentiation. A total of 6406 GBS-derived SNPs were selected for the diversity analysis, in which the muskmelon varieties showed higher heterozygote SNPs. Linkage disequilibrium (LD) decay varied significantly among the three melon varieties, in which more rapid LD decay was observed in muskmelon (r² = 0.25) varieties. The Bayesian phylogenetic tree provided the intraspecific relationships among the three melon varieties that formed, as expected, individual clusters exhibiting the greatest genetic distance based on the posterior probability. The haplotype analysis also supported the phylogeny result by generating three major networks for 48 haplotypes. Further investigation for varieties discrimination allowed us to detect a total of 52 SNP markers that discriminated muskmelon from makuwa varieties, of which two SNPs were converted into cleaved amplified polymorphic sequence markers for practical use. In addition to these markers, the genome-wide association study identified two SNPs located in the genes on chromosome 6, which were significantly associated with the phenotypic traits of melon seed. This study demonstrated that a systematic approach using GBS-derived SNPs could serve to efficiently classify and manage the melon varieties in the genebank.  相似文献   

    

Avner Adini  Irit Adini  Etty Grad  Yuval Tal  Haim D. Danenberg  Peter M. Kang  Benjamin D. Matthews  Robert J. D&#x;Amato 《International journal of molecular sciences》2021,22(10)

Myocardial infarction (MI) remains the leading cause of death in the western world. Despite advancements in interventional revascularization technologies, many patients are not candidates for them due to comorbidities or lack of local resources. Non-invasive approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been effective in animal models but not in humans likely due to its short half-life and systemic toxicity. Here, we tested the hypothesis that PR1P, a small VEGF binding peptide that we developed, which stabilizes and upregulates endogenous VEGF, could be used to improve outcome from MI in rodents. To test this hypothesis, we induced MI in mice and rats via left coronary artery ligation and then treated animals with every other day intraperitoneal PR1P or scrambled peptide for 14 days. Hemodynamic monitoring and echocardiography in mice and echocardiography in rats at 14 days showed PR1P significantly improved multiple functional markers of heart function, including stroke volume and cardiac output. Furthermore, molecular biology and histological analyses of tissue samples showed that systemic PR1P targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium. We conclude that PR1P is a potential non-invasive candidate therapeutic for MI.  相似文献   

    

Namhun Lee  Se-Jong Oh  Jang-Woo Park  Kyung-Rok Nam  Kyung-Jun Kang  Kyo-Chul Lee  Yong-Jin Lee  June-Seek Choi  Jeong-Ho Seok  Jae-Yong Choi 《International journal of molecular sciences》2021,22(5)

Early life stress (ELS) is strongly associated with psychiatric disorders such as anxiety, depression, and schizophrenia in adulthood. To date, biological, behavioral, and structural aspects of ELS have been studied extensively, but their functional effects remain unclear. Here, we examined NeuroPET studies of dopaminergic, glutamatergic, and serotonergic systems in ELS animal models. Maternal separation and restraint stress were used to generate single or complex developmental trauma. Body weights of animals exposed to single trauma were similar to those of control animals; however, animals exposed to complex trauma exhibited loss of body weight when compared to controls. In behavioral tests, the complex developmental trauma group exhibited a decrease in time spent in the open arm of the elevated plus-maze and an increase in immobility time in the forced swim test when compared to control animals. In NeuroPET studies, the complex trauma group displayed a reduction in brain uptake values when compared to single trauma and control groups. Of neurotransmitter systems analyzed, the rate of decrease in brain uptake was the highest in the serotonergic group. Collectively, our results indicate that developmental trauma events induce behavioral deficits, including anxiety- and depressive-like phenotypes and dysfunction in neurotransmitter systems.  相似文献   

    

Yanli Jin  Seung-Nam Jung  Mi Ae Lim  Chan Oh  Yudan Piao  Hae Jong Kim  Lihua Liu  Yea Eun Kang  Jae Won Chang  Ho-Ryun Won  Kunho Song  Bon Seok Koo 《International journal of molecular sciences》2021,22(20)

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Nipin Sp  Dong Young Kang  Jin-Moo Lee  Se Won Bae  Kyoung-Jin Jang 《International journal of molecular sciences》2021,22(9)

Hormone-specific anticancer drugs for breast cancer treatment can cause serious side effects. Thus, treatment with natural compounds has been considered a better approach as this minimizes side effects and has multiple targets. 6-Gingerol is an active polyphenol in ginger with various modalities, including anticancer activity, although its mechanism of action remains unknown. Increases in the level of reactive oxygen species (ROS) can lead to DNA damage and the induction of DNA damage response (DDR) mechanism, leading to cell cycle arrest apoptosis and tumorsphere suppression. Epidermal growth factor receptor (EGFR) promotes tumor growth by stimulating signaling of downstream targets that in turn activates tumor protein 53 (p53) to promote apoptosis. Here we assessed the effect of 6-gingerol treatment on MDA-MB-231 and MCF-7 breast cancer cell lines. 6-Gingerol induced cellular and mitochondrial ROS that elevated DDR through ataxia-telangiectasia mutated and p53 activation. 6-Gingerol also induced G0/G1 cell cycle arrest and mitochondrial apoptosis by mediating the BAX/BCL-2 ratio and release of cytochrome c. It also exhibited a suppression ability of tumorsphere formation in breast cancer cells. EGFR/Src/STAT3 signaling was also determined to be responsible for p53 activation and that 6-gingerol induced p53-dependent intrinsic apoptosis in breast cancer cells. Therefore, 6-gingerol may be used as a candidate drug against hormone-dependent breast cancer cells.  相似文献   

    

Min-Kyung Kang  Dong-Yeon Kim  Hyeongjoo Oh  Soo-Il Kim  Su-Yeon Oh  Woojin Na  Sin-Hye Park  Kyungho Park  Jun-Il Kim  Ae-Hyang Kim  Young-Hee Kang 《International journal of molecular sciences》2021,22(11)

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Eun-Jin Kim  Oh-Sang Kwon  Chang-Gi Hur  Marie Merci Nyiramana  Dong-Kun Lee  Seong-Geun Hong  Jaehee Han  Dawon Kang 《International journal of molecular sciences》2021,22(17)

The two-pore domain K⁺ (K_2P) channel, which is involved in setting the resting membrane potential in neurons, is an essential target for receptor agonists. Activation of the γ-aminobutyric acid (GABA) receptors (GABA_AR and GABA_BR) reduces cellular excitability through Cl^- influx and K⁺ efflux in neurons. Relatively little is known about the link between GABA_AR and the K⁺ channel. The present study was performed to identify the effect of GABAR agonists on K_2P channel expression and activity in the neuroblastic B35 cells that maintain glutamic acid decarboxylase (GAD) activity and express GABA. TASK and TREK/TRAAK mRNA were expressed in B35 cells with a high level of TREK-2 and TRAAK. In addition, TREK/TRAAK proteins were detected in the GABAergic neurons obtained from GABA transgenic mice. Furthermore, TREK-2 mRNA and protein expression levels were markedly upregulated in B35 cells by GABA_AR and GABA_BR agonists. In particular, muscimol, a GABA_AR agonist, significantly increased TREK-2 expression and activity, but the effect was reduced in the presence of the GABA_AR antagonist bicuculine or TREK-2 inhibitor norfluoxetine. In the whole-cell and single-channel patch configurations, muscimol increased TREK-2 activity, but the muscimol effect disappeared in the N-terminal deletion mutant. These results indicate that muscimol directly induces TREK-2 activation through the N-terminus and suggest that muscimol can reduce cellular excitability by activating the TREK-2 channel and by inducing Cl^- influx in GABAergic neurons.  相似文献   

    

Eunil Hahm  Ahla Jo  Eun Ji Kang  Sungje Bock  Xuan-Hung Pham  Hyejin Chang  Bong-Hyun Jun 《International journal of molecular sciences》2021,22(21)

To study the distance-dependent electromagnetic field effects related to the enhancement and quenching mechanism of surface-enhanced Raman scattering (SERS) or fluorescence, it is essential to precisely control the distance from the surface of the metal nanoparticle (NP) to the target molecule by using a dielectric layer (e.g., SiO₂, TiO₂, and Al₂O₃). However, precisely controlling the thickness of this dielectric layer is challenging. Herein, we present a facile approach to control the thickness of the silica shell on silver nanoparticle-assembled silica nanocomposites, SiO₂@Ag NPs, by controlling the number of reacting SiO₂@Ag NPs and the silica precursor. Uniform silica shells with thicknesses in the range 5–40 nm were successfully fabricated. The proposed method for creating a homogeneous, precise, and fine silica coating on nanocomposites can potentially contribute to a comprehensive understanding of the distance-dependent electromagnetic field effects and optical properties of metal NPs.  相似文献