Journal of Pharmaceutical Analysis最新文献

{"title":"Integrating UHPLC-MS/MS quantitative analysis and exogenous purine supplementation to elucidate the antidepressant mechanism of Chaigui granules by regulating purine metabolism","authors":"Jiajun Chen ,&nbsp;Tian Li ,&nbsp;Dehua Huang ,&nbsp;Wenxia Gong ,&nbsp;Junsheng Tian ,&nbsp;Xiaoxia Gao ,&nbsp;Xuemei Qin ,&nbsp;Guanhua Du ,&nbsp;Yuzhi Zhou","doi":"10.1016/j.jpha.2023.08.008","DOIUrl":"10.1016/j.jpha.2023.08.008","url":null,"abstract":"<div><p>Chaigui granules (CG) are a compound composed of six herbal medicines with significant antidepressant effects. However, the antidepressant mechanism of CG remains unclear. In the present study, we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling. First, the regulatory effect of CG on purine metabolites in the prefrontal cortex (PFC) of chronic unpredictable mild stress (CUMS) rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) targeted quantitative analysis. Meanwhile, purinergic receptors (P2X7 receptor (P2X7R), A₁ receptor (A₁R) and A_2A receptor (A_2AR)) and signaling pathways (nod-like receptor protein 3 (NLRP3) inflammasome pathway and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway) associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay (ELISA). Besides, antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro. An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG. Additionally, purinergic receptors (P2X7R, A₁R and A_2AR) and related signaling pathways (NLRP3 inflammasome pathway and cAMP-PKA pathway) were also significantly regulated by CG. The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway, and the reduction of adenosine and inosine inhibited the A₁R-cAMP-PKA pathway, which was significantly ameliorated by CG. Overall, CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A₁R-cAMP-PKA pathway.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 12","pages":"Pages 1562-1576"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923001983/pdfft?md5=5d4ef125d131b2aea0ffd469c92a57db&pid=1-s2.0-S2095177923001983-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43159675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnenolone 16α-carbonitrile negatively regulates hippocampal cytochrome P450 enzymes and ameliorates phenytoin-induced hippocampal neurotoxicity","authors":"Shuai Zhang ,&nbsp;Tingting Wang ,&nbsp;Ye Feng ,&nbsp;Fei Li ,&nbsp;Aijuan Qu ,&nbsp;Xiuchen Guan ,&nbsp;Hui Wang ,&nbsp;Dan Xu","doi":"10.1016/j.jpha.2023.07.013","DOIUrl":"10.1016/j.jpha.2023.07.013","url":null,"abstract":"<div><p>The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme (CYP), which plays a crucial role in the metabolism of neurosteroids. The antiepileptic drug phenytoin (PHT) has been observed to induce neuronal side effects in patients, which could be attributed to its induction of CYP expression and testosterone (TES) metabolism in the hippocampus. While pregnane X receptor (PXR) is widely known for its regulatory function of CYPs in the liver, we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile (PCN), a PXR agonist, has differential effects on CYP expression in the liver and hippocampus. Specifically, the PCN treatment resulted in the induction of cytochrome P450, family 3, subfamily a, polypeptide 11 (CYP3A11), and CYP2B10 expression in the liver, while suppressing their expression in the hippocampus. Functionally, the PCN treatment protected mice from PHT-induced hippocampal nerve injury, which was accompanied by the inhibition of TES metabolism in the hippocampus. Mechanistically, we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent, rather than PXR independent, as demonstrated by genetic and pharmacological models. In conclusion, our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR. Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 12","pages":"Pages 1510-1525"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923001624/pdfft?md5=0b897eda3250422742df40c9f9642673&pid=1-s2.0-S2095177923001624-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44174162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “GB7 acetate, a galbulimima alkaloid from Galbulimima belgraveana, possesses anticancer effects in colorectal cancer cells” [J. Pharm. Anal. 12 (2022) 339–349]","authors":"Ziyin Li ,&nbsp;Lianzhi Mao ,&nbsp;Bin Yu ,&nbsp;Huahuan Liu ,&nbsp;Qiuyu Zhang ,&nbsp;Zhongbo Bian ,&nbsp;Xudong Zhang ,&nbsp;Wenzhen Liao ,&nbsp;Suxia Sun","doi":"10.1016/j.jpha.2023.12.014","DOIUrl":"10.1016/j.jpha.2023.12.014","url":null,"abstract":"","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 12","pages":"Pages 1580-1582"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923002976/pdfft?md5=2eb7e08c989617c99058286e64675bd9&pid=1-s2.0-S2095177923002976-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139070538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutaredoxin-1 alleviates acetaminophen-induced liver injury by decreasing its toxic metabolites","authors":"Ying Xu ,&nbsp;Yan Xia ,&nbsp;Qinhui Liu,&nbsp;Xiandan Jing,&nbsp;Qin Tang,&nbsp;Jinhang Zhang,&nbsp;Qingyi Jia,&nbsp;Zijing Zhang,&nbsp;Jiahui Li,&nbsp;Jiahao Chen,&nbsp;Yimin Xiong,&nbsp;Yanping Li,&nbsp;Jinhan He","doi":"10.1016/j.jpha.2023.08.004","DOIUrl":"10.1016/j.jpha.2023.08.004","url":null,"abstract":"<div><p>Excessive <em>N</em>-acetyl-<em>p</em>-benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP) overdose caused acute liver failure (ALF). <em>S-</em>glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity. Glutaredoxin-1 (Glrx1), a glutathione-specific thioltransferase, is a primary enzyme to catalyze deglutathionylation. The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP. The <em>Glrx1</em> knockout mice (<em>Glrx1</em>^{<em>−/−</em>}) and liver-specific overexpression of <em>Glrx1</em> (<em>AAV8-Glrx1</em>) mice were produced and underwent APAP-induced ALF. Pirfenidone (PFD), a potential inducer of Glrx1, was administrated preceding APAP to assess its protective effects. Our results revealed that the hepatic total protein <em>S-</em>glutathionylation (PSSG) increased and the Glrx1 level reduced in mice after APAP toxicity. <em>Glrx1</em>^−/− mice were more sensitive to APAP overdose, with higher oxidative stress and more toxic metabolites of APAP. This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the <em>S-</em>glutathionylation of cytochrome p450 3a11 (Cyp3a11), which likely increased the activity of Cyp3a11. Conversely, <em>AAV8-Glrx1</em> mice were defended against liver damage caused by APAP overdose by inhibiting the <em>S-</em>glutathionylation and activity of Cyp3a11, which reduced the toxic metabolites of APAP and oxidative stress. PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress. We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose. Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 12","pages":"Pages 1548-1561"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923001855/pdfft?md5=29c0995ccef2f685487e2e9ea8ae6430&pid=1-s2.0-S2095177923001855-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44845134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent trends of machine learning applied to multi-source data of medicinal plants","authors":"Yanying Zhang ,&nbsp;Yuanzhong Wang","doi":"10.1016/j.jpha.2023.07.012","DOIUrl":"10.1016/j.jpha.2023.07.012","url":null,"abstract":"<div><p>In traditional medicine and ethnomedicine, medicinal plants have long been recognized as the basis for materials in therapeutic applications worldwide. In particular, the remarkable curative effect of traditional Chinese medicine during corona virus disease 2019 (COVID-19) pandemic has attracted extensive attention globally. Medicinal plants have, therefore, become increasingly popular among the public. However, with increasing demand for and profit with medicinal plants, commercial fraudulent events such as adulteration or counterfeits sometimes occur, which poses a serious threat to the clinical outcomes and interests of consumers. With rapid advances in artificial intelligence, machine learning can be used to mine information on various medicinal plants to establish an ideal resource database. We herein present a review that mainly introduces common machine learning algorithms and discusses their application in multi-source data analysis of medicinal plants. The combination of machine learning algorithms and multi-source data analysis facilitates a comprehensive analysis and aids in the effective evaluation of the quality of medicinal plants. The findings of this review provide new possibilities for promoting the development and utilization of medicinal plants.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 12","pages":"Pages 1388-1407"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923001612/pdfft?md5=4cf8a0d917034e32fd8f94bc9798b0c7&pid=1-s2.0-S2095177923001612-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43110072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of microfluidic technology based on surface-enhanced Raman scattering in cancer biomarker detection: A review","authors":"Changhong Nie,&nbsp;Ibrahim Shaw,&nbsp;Chuanpin Chen","doi":"10.1016/j.jpha.2023.08.009","DOIUrl":"10.1016/j.jpha.2023.08.009","url":null,"abstract":"<div><p>With the continuous discovery and research of predictive cancer-related biomarkers, liquid biopsy shows great potential in cancer diagnosis. Surface-enhanced Raman scattering (SERS) and microfluidic technology have received much attention among the various cancer biomarker detection methods. The former has ultrahigh detection sensitivity and can provide a unique fingerprint. In contrast, the latter has the characteristics of miniaturization and integration, which can realize accurate control of the detection samples and high-throughput detection through design. Both have the potential for point-of-care testing (POCT), and their combination (lab-on-a-chip SERS (LoC-SERS)) shows good compatibility. In this paper, the basic situation of circulating proteins, circulating tumor cells, exosomes, circulating tumor DNA (ctDNA), and microRNA (miRNA) in the diagnosis of various cancers is reviewed, and the detection research of these biomarkers by the LoC-SERS platform in recent years is described in detail. At the same time, the challenges and future development of the platform are discussed at the end of the review. Summarizing the current technology is expected to provide a reference for scholars engaged in related work and interested in this field.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 12","pages":"Pages 1429-1451"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923002009/pdfft?md5=a1469761fcb4a6733e5690d5b6055730&pid=1-s2.0-S2095177923002009-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43875776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut dysbiosis aggravates cognitive deficits, amyloid pathology and lipid metabolism dysregulation in a transgenic mouse model of Alzheimer's disease","authors":"Chang Qu ,&nbsp;Qing-Qing Xu ,&nbsp;Wen Yang ,&nbsp;Mei Zhong ,&nbsp;Qiuju Yuan ,&nbsp;Yan-Fang Xian ,&nbsp;Zhi-Xiu Lin","doi":"10.1016/j.jpha.2023.07.014","DOIUrl":"10.1016/j.jpha.2023.07.014","url":null,"abstract":"<div><p>Gut dysbiosis, a well-known risk factor to triggers the progression of Alzheimer's disease (AD), is strongly associated with metabolic disturbance. Trimethylamine <em>N</em>-oxide (TMAO), produced in the dietary choline metabolism, has been found to accelerate neurodegeneration in AD pathology. In this study, the cognitive function and gut microbiota of TgCRND8 (Tg) mice of different ages were evaluated by Morris water maze task (MWMT) and 16S rRNA sequencing, respectively. Young pseudo germ-free (PGF) Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type (WT) mice were selected to determine the role of the gut microbiota in the process of neuropathology. Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions. Our results showed that gut dysbiosis, neuroinflammation response, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and cyclin-dependent kinase 5 (CDK5)/transcription 3 (STAT3) activation occurred in Tg mice age-dependently. Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice, with the activation of CDK5/STAT3 signaling in the brains. On the contrary, faecal microbiota transplantation from WT mice alleviated the cognitive deficits, attenuated neuroinflammation, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice. Moreover, excessive choline treatment was also shown to aggravate the cognitive deficits, Aβ deposition, neuroinflammation and CDK5/STAT3 pathway activation. These findings provide a novel insight into the interaction between gut dysbiosis and AD progression, clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 12","pages":"Pages 1526-1547"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923001740/pdfft?md5=f9584002be3af686bfca5fbc1cebed4a&pid=1-s2.0-S2095177923001740-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48575278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies","authors":"Shiyao Zhang ,&nbsp;Nur Farah Meor Azlan ,&nbsp;Sunday Solomon Josiah ,&nbsp;Jing Zhou ,&nbsp;Xiaoxia Zhou ,&nbsp;Lingjun Jie ,&nbsp;Yanhui Zhang ,&nbsp;Cuilian Dai ,&nbsp;Dong Liang ,&nbsp;Peifeng Li ,&nbsp;Zhengqiu Li ,&nbsp;Zhen Wang ,&nbsp;Yun Wang ,&nbsp;Ke Ding ,&nbsp;Yan Wang ,&nbsp;Jinwei Zhang","doi":"10.1016/j.jpha.2023.09.002","DOIUrl":"10.1016/j.jpha.2023.09.002","url":null,"abstract":"<div><p>The <em>solute carrier family 12</em> (<em>SLC12</em>) of cation-chloride cotransporters (CCCs) comprises potassium chloride cotransporters (KCCs, e.g. KCC1, KCC2, KCC3, and KCC4)-mediated Cl⁻ extrusion, and sodium potassium chloride cotransporters (N[K]CCs, NKCC1, NKCC2, and NCC)-mediated Cl⁻ loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues. In recent years, there have been considerable advances in our understanding of CCCs' control mechanisms in cell volume regulations, with many techniques developed in studying the functions and activities of CCCs. Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs. These techniques include the ammonium pulse technique, radioactive or nonradioactive rubidium ion uptake-assay, and thallium ion-uptake assay. CCCs' activity can also be indirectly observed by measuring γ-aminobutyric acid (GABA) activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes, radiotracer ³⁶Cl⁻, and fluorescent dyes. Other techniques include directly looking at kinase regulatory sites phosphorylation, flame photometry, ²²Na⁺ uptake assay, structural biology, molecular modeling, and high-throughput drug screening. This review summarizes the role of CCCs in genetic disorders and cell volume regulation, current methods applied in studying CCCs biology, and compounds developed that directly or indirectly target the CCCs for disease treatments.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 12","pages":"Pages 1471-1495"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923002150/pdfft?md5=562cd98246c9366ca1587007136016c0&pid=1-s2.0-S2095177923002150-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135889544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apatinib and gamabufotalin co-loaded lipid/prussian blue nanoparticles for synergistic therapy to gastric cancer with metastasis","authors":"Binlong Chen, Yanzhong Zhao, Zichang Lin, Jiahao Liang, Jialong Fan, Yanyan Huang, Leye He, Bin Liu","doi":"10.1016/j.jpha.2023.11.011","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.11.011","url":null,"abstract":"<p>Due to the non-targeted release and low solubility of anti-gastric cancer agent, apatinib (Apa), a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects, as well. In order to avoid these drawbacks, lipid-film-coated Prussian blue nanoparticles (PB NPs) with hyaluronan (HA) modification was used for Apa loading to improve its solubility and targeting ability. Furthermore, anti-tumor compound of gamabufotalin (CS-6) was selected as a partner of Apa with reducing dosage for combinational gastric therapy. Thus, HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor tissue. <em>In vitro</em> assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating VEGFR and MMP-9. <em>In vivo</em> assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects. In summary, we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer (GC) therapy.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"58 4","pages":""},"PeriodicalIF":8.8,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138515388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling","authors":"Hua Sui, Wanli Deng, Qiong Chai, Bing Han, Yuli Zhang, Zhenzhen Wei, Zan Li, Ting Wang, Jiling Feng, Man Yuan, Qingfeng Tang, Hongxi Xu","doi":"10.1016/j.jpha.2023.11.008","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.11.008","url":null,"abstract":"<p>The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer. Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in <em>Garcinia yunnanensis</em> (YTE-17), attributing these effects to the regulation of multiple signaling pathways. However, knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited. In this study, we conducted isobaric tags for relative and absolute quantification (iTRAQ) analysis on intestinal epithelial cells (IECs) exposed YTE-17, both in vitro and vivo, revealing a significant inhibition of the Wnt5a (Wnt family member 5a)/c-Jun N-terminal kinase (JNK) signaling pathway. Subsequently, we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment (TME), specifically focusing on macrophage-mediated T helper 17 (Th17) cell induction in a colitis-associated cancer (CAC) model with Wnt5a deletion. Additionally, we performed the single-cell RNA sequencing on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition, lineage, and functional status of immune mesenchymal cells during different stages of Colorectal Cancer (CRC) progression. Remarkably, our findings demonstrate a significant reduction in M2 macrophage polarization and Th17 phenotype upon treatment with YTE-17, leading to the restoration of regulatory T (Treg)/Th17 balance in azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Furthermore, we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages. Notably, our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo. Specifically, we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the tumor microenvironment, involving macrophages and T cells. In summary, our study undergoes the potential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment, thereby mitigating the risk of malignancies.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"32 10","pages":""},"PeriodicalIF":8.8,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138515331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}