Archives of Pharmacal Research最新文献

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Stabilization of RNA G-quadruplexes in the SARS-CoV-2 genome inhibits viral infection via translational suppression SARS-CoV-2基因组中RNA g -四联体的稳定通过翻译抑制抑制病毒感染
IF 6.7 3区 医学
Archives of Pharmacal Research Pub Date : 2023-08-10 DOI: 10.1007/s12272-023-01458-x
Maria Razzaq, Ji Ho Han, Subramaniyam Ravichandran, Jaehyun Kim, Joon-Yong Bae, Man-Seong Park, Shrute Kannappan, Woo-Chang Chung, Jin-Hyun Ahn, Moon Jung Song, Kyeong Kyu Kim
{"title":"Stabilization of RNA G-quadruplexes in the SARS-CoV-2 genome inhibits viral infection via translational suppression","authors":"Maria Razzaq,&nbsp;Ji Ho Han,&nbsp;Subramaniyam Ravichandran,&nbsp;Jaehyun Kim,&nbsp;Joon-Yong Bae,&nbsp;Man-Seong Park,&nbsp;Shrute Kannappan,&nbsp;Woo-Chang Chung,&nbsp;Jin-Hyun Ahn,&nbsp;Moon Jung Song,&nbsp;Kyeong Kyu Kim","doi":"10.1007/s12272-023-01458-x","DOIUrl":"10.1007/s12272-023-01458-x","url":null,"abstract":"<div><p>The G-quadruplex (G4) formed in single-stranded DNAs or RNAs plays a key role in diverse biological processes and is considered as a potential antiviral target. In the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 25 putative G4-forming sequences are predicted; however, the effects of G4-binding ligands on SARS-CoV-2 replication have not been studied in the context of viral infection. In this study, we investigated whether G4-ligands suppressed SARS-CoV-2 replication and whether their antiviral activity involved stabilization of viral RNA G4s and suppression of viral gene expression. We found that pyridostatin (PDS) suppressed viral gene expression and genome replication as effectively as the RNA polymerase inhibitor remdesivir. Biophysical analyses revealed that the 25 predicted G4s in the SARS-CoV-2 genome formed a parallel G4 structure. In particular, G4-644 and G4-3467 located in the 5′ region of ORF1a, formed a G4 structure that could be effectively stabilized by PDS. We also showed that PDS significantly suppressed translation of the reporter genes containing these G4s. Taken together, our results demonstrate that stabilization of RNA G4s by PDS in the SARS-CoV-2 genome inhibits viral infection via translational suppression, highlighting the therapeutic potential of G4-ligands in SARS-CoV-2 infection.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"598 - 615"},"PeriodicalIF":6.7,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ubiquitin–proteasome system as a target for anticancer treatment—an update 泛素-蛋白酶体系统作为抗癌治疗靶点的最新进展
IF 6.7 3区 医学
Archives of Pharmacal Research Pub Date : 2023-08-05 DOI: 10.1007/s12272-023-01455-0
Yeon Jung Kim, Yeonjoo Lee, Hyungkyung Shin, SuA Hwang, Jinyoung Park, Eun Joo Song
{"title":"Ubiquitin–proteasome system as a target for anticancer treatment—an update","authors":"Yeon Jung Kim,&nbsp;Yeonjoo Lee,&nbsp;Hyungkyung Shin,&nbsp;SuA Hwang,&nbsp;Jinyoung Park,&nbsp;Eun Joo Song","doi":"10.1007/s12272-023-01455-0","DOIUrl":"10.1007/s12272-023-01455-0","url":null,"abstract":"<div><p>As the ubiquitin–proteasome system (UPS) regulates almost every biological process, the dysregulation or aberrant expression of the UPS components causes many pathological disorders, including cancers. To find a novel target for anticancer therapy, the UPS has been an active area of research since the FDA’s first approval of a proteasome inhibitor bortezomib in 2003 for treating multiple myeloma (MM). Here, we summarize newly described UPS components, including E3 ubiquitin ligases, deubiquitinases (DUBs), and immunoproteasome, whose malfunction leads to tumorigenesis and whose inhibitors have been investigated in clinical trials as anticancer therapy since 2020. We explain the mechanism and effects of several inhibitors in depth to better comprehend the advantages of targeting UPS components for cancer treatment. In addition, we describe attempts to overcome resistance and limited efficacy of some launched proteasome inhibitors, as well as an emerging PROTAC-based tool targeting UPS components for anticancer therapy. </p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"573 - 597"},"PeriodicalIF":6.7,"publicationDate":"2023-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01455-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Paeoniflorin increases the survival of Pseudomonas aeruginosa infected Caenorhabditis elegans at the immunosuppression stage by activating PMK-1, BAR-1, and EGL-1 signals 芍药苷通过激活PMK-1、BAR-1和EGL-1信号,提高了铜绿假单胞菌感染秀丽隐杆线虫免疫抑制期的存活率
IF 6.7 3区 医学
Archives of Pharmacal Research Pub Date : 2023-08-03 DOI: 10.1007/s12272-023-01459-w
Le Zhang, Yuxing Wang, Dayong Wang
{"title":"Paeoniflorin increases the survival of Pseudomonas aeruginosa infected Caenorhabditis elegans at the immunosuppression stage by activating PMK-1, BAR-1, and EGL-1 signals","authors":"Le Zhang,&nbsp;Yuxing Wang,&nbsp;Dayong Wang","doi":"10.1007/s12272-023-01459-w","DOIUrl":"10.1007/s12272-023-01459-w","url":null,"abstract":"<div><p>Paeoniflorin is the major active compound of total glycoside of paeony in <i>Paeonia lactiflora</i> Pall. Although several aspects of beneficial effects of paeoniflorin have been described, whether the paeoniflorin treatment is helpful for inhibiting the pathogen infection-induced immunosuppression remains largely unclear. Using the immunosuppression model in <i>Caenorhabditis elegans</i> induced by <i>Pseudomonas aeruginosa</i> infection, we here examined the beneficial effect of paeoniflorin treatment against the immunosuppression induced by bacterial pathogen infection. In this immunosuppression model, we observed that the survival rate of <i>P. aeruginosa</i> infected nematodes at the immunosuppression stage could be significantly increased by 25–100 mg/L paeoniflorin treatment. <i>P. aeruginosa</i> accumulation in intestinal lumen of nematodes at the immunosuppression stage was reduced by paeoniflorin treatment. Paeoniflorin could activate the expressions of antimicrobial genes (<i>lys-1</i> and <i>lys-8</i>) in nematodes at the immunosuppression stage. Moreover, at the immunosuppression stage, paeoniflorin treatment increased the expressions of <i>bar-1</i>, <i>pmk-1</i>, and <i>egl-1</i> required for the control of innate immunity against bacterial infection. Meanwhile, RNAi of <i>bar-1</i>, <i>pmk-1</i>, and <i>egl-1</i> inhibited the beneficial effect of paeoniflorin treatment in increasing the survival, reducing the <i>P. aeruginosa</i> accumulation in intestinal lumen, and activating the expressions of antimicrobial genes (<i>lys-1</i> and <i>lys-8</i>) in nematodes at the immunosuppression stage. Therefore, paeoniflorin treatment could effectively inhibit the immunosuppression induced by bacterial pathogen infection in the hosts.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"616 - 628"},"PeriodicalIF":6.7,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10405702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Ionically bridged dexamethasone sodium phosphate–zinc–PLGA nanocomplex in alginate microgel for the local treatment of ulcerative colitis 海藻酸盐微凝胶中离子桥接地塞米松磷酸钠-锌- plga纳米复合物局部治疗溃疡性结肠炎
IF 6.7 3区 医学
Archives of Pharmacal Research Pub Date : 2023-08-03 DOI: 10.1007/s12272-023-01456-z
Aruzhan Saparbayeva, Juho Lee, Shwe Phyu Hlaing, Jihyun Kim, Dongmin Kwak, Hyunwoo Kim, Eun Hee Lee, Seonghwan Hwang, Min-Soo Kim, Hyung Ryong Moon, Yunjin Jung, Jin-Wook Yoo
{"title":"Ionically bridged dexamethasone sodium phosphate–zinc–PLGA nanocomplex in alginate microgel for the local treatment of ulcerative colitis","authors":"Aruzhan Saparbayeva,&nbsp;Juho Lee,&nbsp;Shwe Phyu Hlaing,&nbsp;Jihyun Kim,&nbsp;Dongmin Kwak,&nbsp;Hyunwoo Kim,&nbsp;Eun Hee Lee,&nbsp;Seonghwan Hwang,&nbsp;Min-Soo Kim,&nbsp;Hyung Ryong Moon,&nbsp;Yunjin Jung,&nbsp;Jin-Wook Yoo","doi":"10.1007/s12272-023-01456-z","DOIUrl":"10.1007/s12272-023-01456-z","url":null,"abstract":"<div><p>Colon-targeted oral drug delivery systems comprising nanoparticles and microparticles have emerged as promising tools for the treatment of ulcerative colitis (UC) because they minimize side effects and maximize the local drug concentration. Dexamethasone sodium phosphate (DSP) is a potent anti-inflammatory glucocorticoid used for the treatment of UC. However, it remains a rather short-term treatment option owing to its side effects. In the present study, we developed the alginate gel encapsulating ionically bridged DSP-zinc-poly(lactic-co-glycolic acid) (PLGA) nanocomplex (DZP-NCs-in-microgel) for the oral local treatment of UC. The successful encapsulation of DSP-zinc-PLGA nanocomplex (DZP-NCs) in alginate microgel was confirmed by SEM imaging. The prepared gel released DZP-NCs in the stimulated intestinal fluid and dampened the release of DSP in the upper gastrointestinal tract. Furthermore, DZP-NCs-in-microgel alleviated colonic inflammation in a mouse model of dextran sodium sulfate-induced colitis by relieving clinical symptoms and histological marks. Our results suggest a novel approach for the oral colon-targeted delivery of dexamethasone sodium phosphate for the treatment of UC.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"646 - 658"},"PeriodicalIF":6.7,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01456-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Myriocin suppresses tumor growth by modulating macrophage polarization and function through the PI3K/Akt/mTOR pathway 肉豆蔻素通过PI3K/Akt/mTOR通路调节巨噬细胞极化和功能,抑制肿瘤生长
IF 6.7 3区 医学
Archives of Pharmacal Research Pub Date : 2023-07-19 DOI: 10.1007/s12272-023-01454-1
Hyeonha Jang, Uttam Ojha, Ji-Hak Jeong, Keun-Gyu Park, Shin Yup Lee, You Mie Lee
{"title":"Myriocin suppresses tumor growth by modulating macrophage polarization and function through the PI3K/Akt/mTOR pathway","authors":"Hyeonha Jang,&nbsp;Uttam Ojha,&nbsp;Ji-Hak Jeong,&nbsp;Keun-Gyu Park,&nbsp;Shin Yup Lee,&nbsp;You Mie Lee","doi":"10.1007/s12272-023-01454-1","DOIUrl":"10.1007/s12272-023-01454-1","url":null,"abstract":"<div><p>Macrophages within the tumor microenvironment (TME), referred to as tumor-associated macrophages (TAMs), are involved in various aspects of tumor progression including initiation, angiogenesis, metastasis, immunosuppression, and resistance to therapy. Myriocin, a natural compound isolated from <i>Mycelia sterilia</i>, is an immunosuppressant that inhibits tumor growth and angiogenesis. However, the mechanisms underlying the effects of myriocin on TAMs and TAM-mediated tumor growth have not yet been elucidated. In this study, we determined the effects of myriocin on TAMs and the underlying mechanism in vitro and in vivo. Myriocin significantly suppressed monocyte–macrophage differentiation and M2 polarization of macrophages but not M1 polarization. In addition, myriocin inhibited the expression of anti-inflammatory cytokines and secretion of proangiogenic factors, such as vascular endothelial growth factor, in M2 macrophages as well as M2-induced endothelial cell permeability. Myriocin also inhibited the PI3K/Akt/mTOR signaling pathway in M2 macrophages. Myriocin reduced the population of M2-like TAMs within the tumor tissue of a mouse allograft tumor model but not that of M1-like TAMs. Moreover, combined treatment with myriocin and cisplatin synergistically suppressed tumor growth and enhanced survival rate in mice by reducing the population of M2-like TAMs. Overall, these results suggest that myriocin inhibits tumor growth by remodeling the TME through suppression of differentiation and polarization of M2-like TAMs via the PI3K/Akt/mTOR signaling pathway.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"629 - 645"},"PeriodicalIF":6.7,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01454-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent advances on Pestalotiopsis genus: chemistry, biological activities, structure–activity relationship, and biosynthesis 拟盘多毛孢属植物的化学、生物活性、构效关系及生物合成研究进展
IF 6.7 3区 医学
Archives of Pharmacal Research Pub Date : 2023-06-30 DOI: 10.1007/s12272-023-01453-2
Peng Jiang, Xiujuan Fu, Hong Niu, Siwei Chen, Feifei Liu, Yu Luo, Dan Zhang, Hui Lei
{"title":"Recent advances on Pestalotiopsis genus: chemistry, biological activities, structure–activity relationship, and biosynthesis","authors":"Peng Jiang,&nbsp;Xiujuan Fu,&nbsp;Hong Niu,&nbsp;Siwei Chen,&nbsp;Feifei Liu,&nbsp;Yu Luo,&nbsp;Dan Zhang,&nbsp;Hui Lei","doi":"10.1007/s12272-023-01453-2","DOIUrl":"10.1007/s12272-023-01453-2","url":null,"abstract":"<div><p>Strains of the fungal genus <i>Pestalotiopsis</i> are reported as large promising sources of structurally varied biologically active metabolites. Many bioactive secondary metabolites with diverse structural features have been derived from <i>Pestalotiopsis</i>. Moreover, some of these compounds can potentially be developed into lead compounds. Herein, we have systematically reviewed the chemical constituents and bioactivities of the fungal genus <i>Pestalotiopsis</i>, covering a period ranging from January 2016 to December 2022. As many as 307 compounds, including terpenoids, coumarins, lactones, polyketides, and alkaloids, were isolated during this period. Furthermore, for the benefit of readers, the biosynthesis and potential medicinal value of these new compounds are also discussed in this review. Finally, the perspectives and directions for future research and the potential applications of the new compounds are summarized in various tables.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"449 - 499"},"PeriodicalIF":6.7,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01453-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9856754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Beyond DNA sensing: expanding the role of cGAS/STING in immunity and diseases 超越DNA传感:扩大cGAS/STING在免疫和疾病中的作用
IF 6.7 3区 医学
Archives of Pharmacal Research Pub Date : 2023-06-24 DOI: 10.1007/s12272-023-01452-3
Jin Kyung Seok, Minhyuk Kim, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee
{"title":"Beyond DNA sensing: expanding the role of cGAS/STING in immunity and diseases","authors":"Jin Kyung Seok,&nbsp;Minhyuk Kim,&nbsp;Han Chang Kang,&nbsp;Yong-Yeon Cho,&nbsp;Hye Suk Lee,&nbsp;Joo Young Lee","doi":"10.1007/s12272-023-01452-3","DOIUrl":"10.1007/s12272-023-01452-3","url":null,"abstract":"<div><p>Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a DNA sensor that elicits a robust type I interferon response by recognizing ubiquitous danger-associated molecules. The cGAS/stimulator of interferon genes (cGAS/STING) is activated by endogenous DNA, including DNA released from mitochondria and extranuclear chromatin, as well as exogenous DNA derived from pathogenic microorganisms. cGAS/STING is positioned as a key axis of autoimmunity, the inflammatory response, and cancer progression, suggesting that the cGAS/STING signaling pathway represents an efficient therapeutic target. Based on the accumulated evidence, we present insights into the prevention and treatment of cGAS/STING-related chronic immune and inflammatory diseases. This review presents the current state of clinical and nonclinical development of modulators targeting cGAS/STING, providing useful information on the design of therapeutic strategies.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"500 - 534"},"PeriodicalIF":6.7,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01452-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9855801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Paritaprevir ameliorates experimental acute lung injury in vitro and in vivo Paritaprevir在体外和体内改善实验性急性肺损伤
IF 6.7 3区 医学
Archives of Pharmacal Research Pub Date : 2023-06-12 DOI: 10.1007/s12272-023-01451-4
Rui Ren, Xin Wang, Zehui Xu, Wanglin Jiang
{"title":"Paritaprevir ameliorates experimental acute lung injury in vitro and in vivo","authors":"Rui Ren,&nbsp;Xin Wang,&nbsp;Zehui Xu,&nbsp;Wanglin Jiang","doi":"10.1007/s12272-023-01451-4","DOIUrl":"10.1007/s12272-023-01451-4","url":null,"abstract":"<div><p>Paritaprevir is a potent inhibitor of the NS3/4A protease used to treat chronic hepatitis C virus infection. However, its therapeutic effect on acute lung injury (ALI) remains to be elucidated. In this study, we investigated the effect of paritaprevir on a lipopolysaccharide (LPS)-induced two-hit rat ALI model. The anti-ALI mechanism of paritaprevir was also studied in human pulmonary microvascular endothelial (HM) cells following LPS-induced injury in <i>vitro</i>. Administration of 30 mg/kg paritaprevir for 3 days protected rats from LPS-induced ALI, as reflected by the changes in the lung coefficient (from 0.75 to 0.64) and lung pathology scores (from 5.17 to 5.20). Furthermore, the levels of the protective adhesion protein VE-cadherin and tight junction protein claudin-5 increased, and the cytoplasmic p-FOX-O1 and nuclear β-catenin and FOX-O1 levels decreased. Similar effects were observed in vitro with LPS-treated HM cells, including decreased nuclear β-catenin and FOX-O1 levels and higher VE-cadherin and claudin-5 levels. Moreover, β-catenin inhibition resulted in higher p-FOX-O1 levels in the cytoplasm. These results suggested that paritaprevir could alleviate experimental ALI via the β-catenin/p-Akt/ FOX-O1 signaling pathway.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"564 - 572"},"PeriodicalIF":6.7,"publicationDate":"2023-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01451-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Harnessing deep learning into hidden mutations of neurological disorders for therapeutic challenges 利用深度学习研究神经系统疾病的隐藏突变,以应对治疗挑战
IF 6.7 3区 医学
Archives of Pharmacal Research Pub Date : 2023-06-01 DOI: 10.1007/s12272-023-01450-5
Sumin Yang, Sung-Hyun Kim, Mingon Kang, Jae-Yeol Joo
{"title":"Harnessing deep learning into hidden mutations of neurological disorders for therapeutic challenges","authors":"Sumin Yang,&nbsp;Sung-Hyun Kim,&nbsp;Mingon Kang,&nbsp;Jae-Yeol Joo","doi":"10.1007/s12272-023-01450-5","DOIUrl":"10.1007/s12272-023-01450-5","url":null,"abstract":"<div><p>The relevant study of transcriptome-wide variations and neurological disorders in the evolved field of genomic data science is on the rise. Deep learning has been highlighted utilizing algorithms on massive amounts of data in a human-like manner, and is expected to predict the dependency or druggability of hidden mutations within the genome. Enormous mutational variants in coding and noncoding transcripts have been discovered along the genome by far, despite of the fine-tuned genetic proofreading machinery. These variants could be capable of inducing various pathological conditions, including neurological disorders, which require lifelong care. Several limitations and questions emerge, including the use of conventional processes via limited patient-driven sequence acquisitions and decoding-based inferences as well as how rare variants can be deduced as a population-specific etiology. These puzzles require harnessing of advanced systems for precise disease prediction, drug development and drug applications. In this review, we summarize the pathophysiological discoveries of pathogenic variants in both coding and noncoding transcripts in neurological disorders, and the current advantage of deep learning applications. In addition, we discuss the challenges encountered and how to outperform them with advancing interpretation.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"535 - 549"},"PeriodicalIF":6.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Recent advances in GPR35 pharmacology; 5-HIAA serotonin metabolite becomes a ligand GPR35的药理研究进展5-HIAA 5-羟色胺代谢物成为配体
IF 6.7 3区 医学
Archives of Pharmacal Research Pub Date : 2023-05-25 DOI: 10.1007/s12272-023-01449-y
Dong-Soon Im
{"title":"Recent advances in GPR35 pharmacology; 5-HIAA serotonin metabolite becomes a ligand","authors":"Dong-Soon Im","doi":"10.1007/s12272-023-01449-y","DOIUrl":"10.1007/s12272-023-01449-y","url":null,"abstract":"<div><p>GPR35, an orphan receptor, has been waiting for its ligand since its cloning in 1998. Many endogenous and exogenous molecules have been suggested to act as agonists of GPR35 including kynurenic acid, zaprinast, lysophosphatidic acid, and CXCL17. However, complex and controversial responses to ligands among species have become a huge hurdle in the development of therapeutics in addition to the orphan state. Recently, a serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), is reported to be a high potency ligand for GPR35 by investigating the increased expression of GPR35 in neutrophils. In addition, a transgenic knock-in mouse line is developed, in which GPR35 was replaced with a human ortholog, making it possible not only to overcome the different selectivity of agonists among species but also to conduct therapeutic experiments on human GPR35 in mouse models. In the present article, I review the recent advances and prospective therapeutic directions in GPR35 research. Especially, I’d like to draw attention of readers to the finding of 5-HIAA as a ligand of GPR35 and lead to apply the 5-HIAA and human GPR35 knock-in mice to their research fields in a variety of pathophysiological conditions.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"550 - 563"},"PeriodicalIF":6.7,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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