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Necessity of Research for Safe Drug use in Pregnant Women (임신부에서 약물의 안전사용을 위한 연구의 필요성)

  • Han, Jung Yeol;Cho, Geum Joon;Oh, Jung Mi
    • Journal of The Korean Society of Maternal and Child Health
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    • v.21 no.3
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    • pp.159-165
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    • 2017
  • The thalidomide tragedy in the 1960s has resulted in a perpetuation of a certain perception amongst physicians and pregnant women that the use of medication during pregnancy is a potential teratogen. Consequently, physicians hesitate in prescribing medication to pregnant women. In addition, pregnant women often refuse medication despite therapeutic necessity because of this existing perception. Recently there have been frequent adverse pregnancy outcomes related to the recurrence of chronic diseases, such as hypertension and diabetes, following pregnancy in older women. And there are lots of unnecessary termination of pregnancy due to the of information of medication exposed to medication following over 50% of unintended pregnancy. In light of this, better dissemination of information regarding the safe usage of medication for pregnant women is required. This would not only be cost-effective in terms of medical expenditure, but also prove beneficial for the treatment of diseases. In addition, Korea needs to adapt to the increasing changes of the international information system regarding supporting the safe usage of medication during pregnancy. An example of this is shown by the recent changes to the labeling of medication by the United States Food and Drug Administration. The new labeling includes information on the risk of usage, rather than just an arbitrary alphabetic classification of B, C, D, or X. Furthermore, this information is limited in Korea because of the lack of research, which in turn is due to several limitations on ethics and methodology, as well as present regulations on the research of pregnant women. From this, we can learn that government support is critical for the establishment of research so that we can alter the perception that all medication is harmful to pregnant women.

Involvement of Orai1 in tunicamycin-induced endothelial dysfunction

  • Yang, Hui;Xue, Yumei;Kuang, Sujuan;Zhang, Mengzhen;Chen, Jinghui;Liu, Lin;Shan, Zhixin;Lin, Qiuxiong;Li, Xiaohong;Yang, Min;Zhou, Hui;Rao, Fang;Deng, Chunyu
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.2
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    • pp.95-102
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    • 2019
  • Endoplasmic reticulum (ER) stress is mediated by disturbance of $Ca^{2+}$ homeostasis. The store-operated calcium (SOC) channel is the primary $Ca^{2+}$ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on $Ca^{2+}$ influx in human umbilical vein endothelial cells (HUVECs) were observed with the fluorescent probe Fluo-4 AM. The effect of tunicamycin on the expression of the unfolded protein response (UPR)-related proteins BiP and CHOP was assayed by western blotting with or without inhibition of Orai1. Tunicamycin induced endothelial dysfunction by activating ER stress. Orai1 expression and the influx of extracellular $Ca^{2+}$ in HUVECs were both upregulated during ER stress. The SOC channel inhibitor SKF96365 reversed tunicamycin-induced endothelial cell dysfunction by inhibiting ER stress. Regulation of tunicamycin-induced ER stress by Orai1 indicates that modification of Orai1 activity may have therapeutic value for conditions with ER stress-induced endothelial dysfunction.

In Silico Analysis of Potential Antidiabetic Phytochemicals from Matricaria chamomilla L. against PTP1B and Aldose Reductase for Type 2 Diabetes Mellitus and its Complications

  • Hariftyani, Arisvia Sukma;Kurniawati, Lady Aqnes;Khaerunnisa, Siti;Veterini, Anna Surgean;Setiawati, Yuani;Awaluddin, Rizki
    • Natural Product Sciences
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    • v.27 no.2
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    • pp.99-114
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    • 2021
  • Type 2 diabetes mellitus (T2DM) and its complications are important noncommunicable diseases with high mortality rates. Protein tyrosine phosphatase 1B (PTP1B) and aldose reductase inhibitors are recently approached and advanced for T2DM and its complications therapy. Matricaria chamomilla L. is acknowledged as a worldwide medicinal herb that has many beneficial health effects as well as antidiabetic effects. Our research was designed to determine the most potential antidiabetic phytochemicals from M. chamomilla employing in silico study. 142 phytochemicals were obtained from the databases. The first screening employed iGEMdock and Swiss ADME, involving 93 phytochemicals. Finally, 30 best phytochemicals were docked. Molecular docking and visualization analysis were performed using Avogadro, AutoDock 4.2., and Biovia Discovery Studio 2016. Molecular docking results demonstrate that ligand-protein interaction's binding affinities were -5.16 to -7.54 kcal/mol and -5.30 to -12.10 kcal/mol for PTP1B and aldose reductase protein targets respectively. In silico results demonstrate that M. chamomilla has potential antidiabetic phytochemical compounds for T2DM and its complications. We recommended anthecotulide, quercetin, chlorogenic acid, luteolin, and catechin as antidiabetic agents due to their binding affinities against both PTP1B and aldose reductase protein. Those phytochemicals' significant efficacy and potential as antidiabetic must be investigated in further advanced research.

A Newly Synthesized Flavone from Luteolin Escapes from COMT-Catalyzed Methylation and Inhibits Lipopolysaccharide-Induced Inflammation in RAW264.7 Macrophages via JNK, p38 and NF-κB Signaling Pathways

  • Ye, Lin;Xin, Yang;Wu, Zhi-yuan;Sun, Hai-jian;Huang, De-jian;Sun, Zhi-qin
    • Journal of Microbiology and Biotechnology
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    • v.32 no.1
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    • pp.15-26
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    • 2022
  • Luteolin is a common dietary flavone possessing potent anti-inflammatory activities. However, when administrated in vivo, luteolin becomes methylated by catechol-O-methyltransferases (COMT) owing to the catechol ring in the chemical structure, which largely diminishes its anti-inflammatory effect. In this study, we made a modification on luteolin, named LUA, which was generated by the chemical reaction between luteolin and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Without a catechol ring in the chemical structure, this new flavone could escape from the COMT-catalyzed methylation, thus affording the potential to exert its functions in the original form when administrated in the organism. Moreover, an LPS-stimulated RAW cell model was applied to detect the anti-inflammatory properties. LUA showed much more superior inhibitory effect on LPS-induced production of NO than diosmetin (a major methylated form of luteolin) and significantly suppressed upregulation of iNOS and COX-2 in macrophages. LUA treatment dramatically reduced LPS-stimulated reactive oxygen species (ROS) and mRNA levels of pro-inflammatory mediators such as IL-1β, IL-6, IL-8 and IFN-β. Furthermore, LUA significantly reduced the phosphorylation of JNK and p38 without affecting that of ERK. LUA also inhibited the activation of NF-κB through suppression of p65 phosphorylation and nuclear translocation.

MST1R as a potential new target antigen of chimeric antigen receptor T cells to treat solid tumors

  • Wen An;Ju-Seop Kang;Sukjoong Oh;Ang Tu
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.3
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    • pp.241-256
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    • 2023
  • Although chimeric antigen receptor T cell (CAR-T) is a promising immunotherapy in hematological malignancies, there remain many obstacles to CART cell therapy for solid tumors. Identifying appropriate tumor-associated antigens (TAAs) is especially critical for success. Using a bioinformatics approach, we identified common potential TAAs for CAR-T cell immunotherapy in solid tumors. We used the GEO database as a training dataset to find differentially expressed genes (DEGs) and verified candidates using the TCGA database, obtaining seven common DEGs (HM13, SDC1, MST1R, HMMR, MIF, CD24, and PDIA4). Then, we used MERAV to analyze the expression of six genes in normal tissues to determine the ideal target genes. Finally, we analyzed tumor microenvironment factors. The results of major microenvironment factor analyses showed that MDSCs, CXCL1, CXCL12, CXCL5, CCL2, CCL5, TGF- β, CTLA-4, and IFN-γ were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF- β, CTLA-4, and IFN-γ. In lung adenocarcinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN-γ were significantly overexpressed in tumor tissues. The expression of MST1R was positively correlated with TGF- β, CTLA-4, and IFN-γ. In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF- β. Our results demonstrate that MST1R has the potential as a new target antigen for treating breast cancer, lung adenocarcinoma, and bladder cancer and may be used as a progression indicator for bladder cancer.

PSME4 determines mesenchymal stem cell fate towards cardiac commitment through YAP1 degradation

  • Mira Kim;Yong Sook Kim;Youngkeun Ahn;Gwang Hyeon Eom;Somy Yoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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    • pp.407-416
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    • 2023
  • The regeneration of myocardium following acute circulatory events remains a challenge, despite numerous efforts. Mesenchymal stem cells (MSCs) present a promising cell therapy option, but their differentiation into cardiomyocytes is a time-consuming process. Although it has been demonstrated that PSME4 degrades acetyl-YAP1, the role of PSME4 in the cardiac commitment of MSCs has not been fully elucidated. Here we reported the novel role of PSME4 in MSCs cardiac commitment. It was found that overnight treatment with apicidin in primary-cultured mouse MSCs led to rapid cardiac commitment, while MSCs from PSME4 knock-out mice did not undergo this process. Cardiac commitment was also observed using lentivirus-mediated PSME4 knockdown in immortalized human MSCs. Immunofluorescence and Western blot experiments revealed that YAP1 persisted in the nucleus of PSME4 knockdown cells even after apicidin treatment. To investigate the importance of YAP1 removal, MSCs were treated with shYAP1 and apicidin simultaneously. This combined treatment resulted in rapid YAP1 elimination and accelerated cardiac commitment. However, overexpression of acetylation-resistant YAP1 in apicidin-treated MSCs impeded cardiac commitment. In addition to apicidin, the universal effect of histone deacetylase (HDAC) inhibition on cardiac commitment was confirmed using tubastatin A and HDAC6 siRNA. Collectively, this study demonstrates that PSME4 is crucial for promoting the cardiac commitment of MSCs. HDAC inhibition acetylates YAP1 and facilitates its translocation to the nucleus, where it is removed by PSME4, promoting cardiac commitment. The failure of YAP1 to translocate or be eliminated from the nucleus results in the MSCs' inability to undergo cardiac commitment.

Testing and evaluation of the corrosion behavior of Aluminum/Alumina bulk composites fabricated via combined stir casting and APB process

  • Abdalkareem Jasim;Ghassan Fadhil Smaisim;Abduladheem Turki Jalil;Surendar Aravindhan;Abdullah Hasan Jabbar;Shaymaa Abed Hussein;Muneam Hussein Ali;Muataz S. Alhassan;Yasser Fakri Mustafa
    • Advances in materials Research
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    • v.12 no.4
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    • pp.263-271
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    • 2023
  • In this study, AA1060/Alumina composites were fabricated by combined stir casting and accumulative press bonding (APB). The APB process was repeated up to six press bonding steps at 300Ċ. As the novelty, potential dynamic polarization in 3.5Wt% NaCl solution was used to study the corrosion properties of these composites. The corrosion behavior of these samples was compared and studied with that of the annealed aluminum alloy 1060 and versus the number of APB steps. So, as a result of enhancing influence on the number of APB process, this experimental investigation showed a significant enhancement in the main electrochemical parameters and the inert character of the Alumina particles. Together with Reducing the active zones of the material surfaces could delay the corrosion process. Also, at higher number of steps, the corrosion resistance of composites improved. The sample produced after six number of steps had a low corrosion density in comparison with high corrosion density of annealed specimens. Also, the scanning electron microscopy (SEM), was used to study the corrosion surface of samples.

The Effect of the Combination of Ginseng, Tribulus Terrestris, and L-arginine on the Sexual Performance of Men with Erectile Dysfunction: a randomized, double-blind, parallel, and placebo-controlled clinical trial

  • Reza Tahvilian;Mohammad Amin Golesorkhi;Farajollah Parhoudeh;Fatemeh Heydarpour;Hossein Hosseini;Hojjat Baghshahi;Hossein Akbari;Mohammad Reza Memarzadeh;Mehdi Mehran;Hosna Bagheri
    • Journal of Pharmacopuncture
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    • v.27 no.2
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    • pp.82-90
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    • 2024
  • Objectives: Nitric oxide is the most important mediator of penile erection after the onset of sexual excitement. It activates cyclic guanosine monophosphate (cGMP), increasing penile blood flow. Most pharmaceutical medications prevent enzyme phosphodiesterase type 5 (PDE-5) from breaking down cGMP, thus keeping its level high. However, due to the adverse effects of pharmacological therapies, herbal drugs that improve sexual function have gained attention recently. This study aimed to investigate the combined effects of ginseng, Tribulus terrestris, and L-arginine amino acid on the sexual performance of individuals with erectile dysfunction (ED) using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Methods: Over three months, 98 men with erectile dysfunction were randomly assigned to receive either 500 mg of herbal supplements or placebo pills. Each herbal tablet contained 100 mg of protodioscin, 35 mg of ginsenosides, and 250 mg of L-arginine. Results: The results showed that the changes in the average scores of ILEF-5 within each group before and after the intervention indicated that all parameters related to the improvement of sexual function in patients with erectile dysfunction improved in the herbal treatment group (p < 0.001). The herbal group significantly improved IIEF-5 scores in nondiabetics (p < 0.05). However, there was no significant difference in the changes of IIEF-5 scores between the two intervention and control groups in diabetic patients. Conclusion: In conclusion, ginseng, Tribulus terrestris, and L-arginine have properties that increase energy and strengthen sexual function, making them suitable for patients with sexual disorders.

Phytotherapy in periodontics as an effective and sustainable supplemental treatment: a narrative review

  • Abeer Saad Gawish;Mohammed Sherif ElMofty;Safa Jambi;Doaa Felemban;Yassmeen SalahEldin Ragheb;Shadia Abdelhameed Elsayed
    • Journal of Periodontal and Implant Science
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    • v.54 no.4
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    • pp.209-223
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    • 2024
  • Purpose: Periodontal disease is a chronic condition caused by microbial infection and mediated by the host's immune response. Phytotherapy is a therapeutic approach that utilizes a renewable resource capable of supplying less expensive medicines for the world's growing population. This review aimed to present clinical evidence on the use of complementary medicinal herbs in the treatment of periodontal diseases. Methods: Different databases were searched using the terms "herbal" and "periodontitis." All included studies were examined with a focus on herbal indications, type, and prescription length. Dentists' therapeutic and prophylactic herbal prescribing habits were also assessed. Results: Various herbs such as turmeric, neem, aloe-vera, pomegranate, catechu, tulsi, cloves, lemon grass, green tea, tea tree oil, peppermint, garlic, pineapple, oak bark, babul, bakul, sage, coriander, moringa, amla, guava, and grape seed extract have been used in the treatment of periodontitis. These herbs have been reported to exhibit a range of therapeutic effects, including anti-inflammatory, antiplaque, antihalitosis, antiresorptive, antioxidant, antibacterial, antifungal, antiviral, and antimicrobial properties. These components can be utilized in various forms such as mouth rinse, gel, oil, toothpaste, aqueous extract, mouthwash, or tooth powder. Conclusions: Several readily available herbal formulations are now available on the market and have been shown to be effective as supplemental periodontal phytotherapy. However, these should be used under the supervision of a dental professional to ensure optimal benefits and effectiveness. Therefore, it is necessary to improve the understanding of suggested herbal prescription practices among dental professionals.

Determination of Heavy Metals and Residual Pepsticides in Oriental Medical Materials - Cultivated Oriental Medical Materials at Sangji University Oriental Medical Hospital - (한약재내 중금속 함량 및 잔류농약 분석 - 모 한방병원 한약재 중심으로 -)

  • Heo, Seong-Kyu;Kim, Dong-Gun;Baik, Tai-Hyun;Seo, Hyung-Sik;Park, Hee-Soo;Kim, Byoung-Woo;Kwon, Ki-Rok;Lee, Seung-Gi;Yoo, Jun-Sang;Sohn, Young-Joo;Sun, Seung-Ho;Cha, Bae-Cheon;Seo, Seung-Hak;Cha, Yun-Yeop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.1
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    • pp.226-230
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    • 2007
  • The purpose of this study was to analyze harmful heavy metals and residual pepsticides in 30 kinds of oriental medical materials. This study was carried out on 32 samples with 30 kinds of Oriental medical materials. The GC-ECD(Varian, CP-3800) was used to analyze residual pepsticides. ICP-OES(Varian, Vista-MPX) was used to analyze lead, arsenic, cadmium. Mercury was analyzed by amalgamation method. Arsenic was detected less than 3(mg/kg) in 21 samples and was not detected 11 samples. Lead was detected less than 5(mg/kg) in 25 samples and was not detected 7 samples. Mercury was detected less than 0.2(mg/kg) in 12 samples and was not detected 20 samples. Cadmium was detected more than 0.3(mg/kg) in 3 samples was detected less than 0.3(mg/kg) in 17 samples and was not detected 12 samples. A few residual pepsticides was detected, but all residual pepsticides was safe.