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Articles
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Natural products in traditional Chinese medicine: molecular mechanisms and therapeutic targets of... 2024
https://ncsu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3db9MwELdQJyFe-BgIugEyEtrTrCa1Gye8jYlpCDFNou-WP6cg1lRN-9C_hX92d3a8dg8ICR5j2XES_3J39t39jpCP02CcK9E_yCvLRFUG1ghXsqo2oXJl4CYm0u4d5pDznAuDYZWD7E8yPUrroWUyfM3Jsm0nP0DZcY6OAsAobLNgC3QA6kjUI3Jw9vXb5dUu0qOKBa2xP8MBOYMuhnmZtkNeJqwiDuKjKrBq-J6GikT-DxTVnwzRqJAunpEuv0qMQ8HqB_sB-ZNIghiZLzLh43--9nPydLBd6Vnq94I88otD8vj74J0_JCfXiQd7e0rnu7Su_pSe0OsdQ_b2Jfl9pSPdB10mvtmetgu6XmnXppNJilW9fe9p9vx_ore5jC-0YbJy29_2VC8c3UsgoymsvaddoCuP9wmtgW_cpp4xd4p1gcEQDAikbrW5oc7_wtCULU2c1v0rMr_4Mj-_ZEOVCGaFFGtWGZBB3LrCGustr62FJTeSS18A0KSsvbEWS_H4WutCykbOhJk5XoIpGErJ3xAqxTTootESJJqwU6t9xaUuuTVl6YS3Y8IyItQykYCoHB33UyUEKUSQSggak88Im_u-SOEdG7rVjRoWU2le4d5YeG6RU80YB7ZekAVMbGvh_JjIDDr1ABpwq_Yv03_IGFUgLNADpBe-2_Rq2hQN2NxSzMbkdQLv_UOC6QZ7T8GP_nneY_IErkQ6oHpLRuvVxr8jI4T---GfvANYXUO2
Biomedicine & Pharmacotherapy, Vol. 170, p. 116039.
Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of ren... Read more
Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of renal tubular cells, fibroblast activation, immune cell infiltration, and renal cell apoptosis. RF can eventually lead to renal dysfunction or even renal failure. A large body of evidence suggests that natural products in traditional Chinese medicine (TCM) have great potential for treating RF. In this article, we first describe the recent advances in RF treatment by several natural products and clarify their mechanisms of action. They can ameliorate the RF disease phenotype, which includes apoptosis, endoplasmic reticulum stress, and EMT, by affecting relevant signaling pathways and molecular targets, thereby delaying or reversing fibrosis. We also present the roles of nanodrug delivery systems, which have been explored to address the drawback of low oral bioavailability of natural products. This may provide new ideas for using natural products for RF treatment. Finally, we provide new insights into the clinical prospects of herbal natural products. [Display omitted] •There is abundant evidence that natural products of Chinese medicines have reversal or delaying effects on renal fibrosis.•Natural products can play therapeutic roles in treating various causes of renal fibrosis through different signaling pathways.•Nano-delivery systems can help address the low bioavailability of natural products, making the treatment of renal fibrosis with Chinese medicine more promising. Read less
Journal Article | Full Text Online
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Cyclin-dependent protein serine/threonine kinase inhibitors as anticancer drugs 2019
https://ncsu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEB50vXjxja4vIogXt3bTtEl6XBYXRVDB9VzSJtUqVNnHYf-9k7ZxV1g8KPSSktAkM52ZTGa-ATgP8lRrau8HGc-8kNPci0NNPS7TnGuas7RKpF1w5kDf5cLYsMpG9tcyvZLWzRu_2U3_syj8J2rR0zlqKIl8KWS4CmuojkLZgrXe7d3N_Rx7N3SgBMyzA5rcmTrMC7fMonZTeWXBPKuqb0v101L7M2j00GATPtwKqvATW_RgMQ7fr7APK8ALh_P4z9VuwUZjspJe3W8bVky5AxePNeb1rEOG8xSucYdckMc5GvZsFx76M5t96blquxNSQUMUJRlXmYf-BLnJ-oQNeS9K1KmkKF-LtLBVgIjCp7TedpzoiOjR9GW8B8-D62H_xmuqOHgZi_jE091U80DRPI1VpNNMMW3QrJM6MoGIRS4Ul5orpZVgPM5kFOehEkYLlNXGBIYdAMHze666sRIocsIsyJThTCjKspRSHZqsDZeOaMlnjdKRuPC1t8SSOLEkxuNOgiRuQ-TomvzY_QTVyK_jzhwTJPgT2psVVZqPKXbCcybaPSKQbdivueN7HihQuxY08PCPXz2CdWzFtdvnGFqT0dScQMty1mnD6V_Qqwrm
Pharmacological Research, Vol. 139, pp. 471 - 488.
[Display omitted] [Display omitted] Cyclins and cyclin-dependent protein kinases (CDKs) are important proteins that are required for the regulation and expression of the large number of components ... Read more
[Display omitted] [Display omitted] Cyclins and cyclin-dependent protein kinases (CDKs) are important proteins that are required for the regulation and expression of the large number of components necessary for the passage through the cell cycle. The concentrations of the CDKs are generally constant, but their activities are controlled by the oscillation of the cyclin levels during each cell cycle. Additional CDK family members play significant roles in a wide range of activities including gene transcription, metabolism, and neuronal function. In response to mitogenic stimuli, cells in the G1-phase of the cell cycle produce D type cyclins that activate CDK4/6. These activated enzymes catalyze the monophosphorylation of the retinoblastoma protein. Subsequently, CDK2-cyclin E catalyzes the hyperphosphorylation of Rb that promotes the release and activation of the E2F transcription factor, which in turn lead to the biosynthesis of dozens of proteins required for cell cycle progression. Consequently, cells pass the G1-restriction point and are committed to complete cell division in the absence of mitogenic stimulation. CDK2-cyclin A, CDK1-cyclin A, and CDK1-cyclin B are required for S-, G2-, and M-phase progression. A crucial mechanism in controlling cell cycle progression is the precise timing of more than 32,000 phosphorylation and dephosphorylation reactions catalyzed by a network of protein kinases and phosphoprotein phosphatases as determined by mass spectrometry. Increased cyclin or CDK expression or decreased levels of endogenous CDK modulators/inhibitors such as INK4 or CIP/KIP have been observed in a wide variety of carcinomas, hematological malignancies, and sarcomas. The pathogenesis of neoplasms because of mutations in the CDKs are rare. Owing to their role in cell proliferation, CDKs represent natural targets for anticancer therapies. Palbociclib, ribociclib, and abemaciclib are FDA-approved CDK4/6 inhibitors used in the treatment of breast cancer. These drugs have IC50 values for CKD4/6 in the low nanomolar range. These inhibitors bind in the cleft between the N-terminal and C-terminal lobes of the CDKs and they inhibit ATP binding. Like ATP, these agents form hydrogen bonds with hinge residues that connect the small and large lobes of protein kinases. Like the adenine base of ATP, these antagonists interact with catalytic spine residues CS6, CS7, and CS8. These and other CDK antagonists are in clinical trials for the treatment of a wide variety of malignancies. As inhibitors of the cell cycle, it is not surprising that one of their most common toxicities is myelosuppression with decreased neutrophil production. Read less
Journal Article | Full Text Online
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Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update 2020
https://ncsu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3NS-wwEB9k9-LF9_xAV58SQbxoWdOkaettURdFkMWPc0nTBPvU7qLug_3v30zTugriQa8loU1mOvNLZuY3AHuhy4uCU3xQKBNIxV2QyoIHKsmdKrgTeV1I--4yB07aWhhKq2xsv7fptbVunvSb3exPyrJ_w4k9XaGHQgiSJCme27vojmTSge7g4vL8as69K1tSAhHQhKZ2xqd54ZYRazdP62gn5SV-7p8-xZ-i8UPDXzBuV1Cnn1DTg_d5-P2a-7AmvGh5Hn-42t-w1EBWNvDjlmHBViuwP_Kc17NDdjsv4Xo5ZPtsNGfDnq3C9Yiu-5-Jt5WNHRueDoKax_yfLdjLk358ZE--Q69lNWdEWbGHskLfysrqvsxL6gZ0zAYsRMTJphO6oFiDu-HZ7cl50DRyCIyI1GuAmA5xg02KJEULIRMXRkaHsXJRmGoTakRVqrAITJJIOU7BTZkaG-eRlrkQkRYbwPAI7_RRqmO0OtKERlslYs2FyTkvpDU9OGjllk08UUfWZrD9zUjKGUk581LuQdSKNvsggAw9yZfzdls9yPA_pOCKrux4ioMEdQFDNCt6sO4V5O070G6qUMbx5jffugWLtMk-WfwPdF6fp3YbOqRcO42y_wfyXAc8
Pharmacological Research, Vol. 152, p. 104609.
[Display omitted] Because genetic alterations including mutations, overexpression, translocations, and dysregulation of protein kinases are involved in the pathogenesis of many illnesses, this enzy... Read more
[Display omitted] Because genetic alterations including mutations, overexpression, translocations, and dysregulation of protein kinases are involved in the pathogenesis of many illnesses, this enzyme family is currently the subject of many drug discovery programs in the pharmaceutical industry. The US FDA approved four small molecule protein kinase antagonists in 2019; these include entrectinib, erdafitinib, pexidartinib, and fedratinib. Entrectinib binds to TRKA/B/C and ROS1 and is prescribed for the treatment of solid tumors with NTRK fusion proteins and for ROS1-postive non-small cell lung cancers. Erdafitinib inhibits fibroblast growth factor receptors 1–4 and is used in the treatment of urothelial bladder cancers. Pexidartinib is a CSF1R antagonist that is prescribed for the treatment of tenosynovial giant cell tumors. Fedratinib blocks JAK2 and is used in the treatment of myelofibrosis. Overall, the US FDA has approved 52 small molecule protein kinase inhibitors, nearly all of which are orally effective with the exceptions of temsirolimus (which is given intravenously) and netarsudil (an eye drop). Of the 52 approved drugs, eleven inhibit protein-serine/threonine protein kinases, two are directed against dual specificity protein kinases, eleven target non-receptor protein-tyrosine kinases, and 28 block receptor protein-tyrosine kinases. The data indicate that 46 of these drugs are used in the treatment of neoplastic diseases (eight against non-solid tumors such as leukemias and 41 against solid tumors including breast and lung cancers; some drugs are used against both tumor types). Eight drugs are employed in the treatment of non-malignancies: fedratinib, myelofibrosis; ruxolitinib, myelofibrosis and polycythemia vera; fostamatinib, chronic immune thrombocytopenia; baricitinib, rheumatoid arthritis; sirolimus, renal graft vs. host disease; nintedanib, idiopathic pulmonary fibrosis; netarsudil, glaucoma; and tofacitinib, rheumatoid arthritis, Crohn disease, and ulcerative colitis. Moreover, sirolimus and ibrutinib are used for the treatment of both neoplastic and non-neoplastic diseases. Entrectinib and larotrectinib are tissue-agnostic anti-cancer small molecule protein kinase inhibitors. These drugs are prescribed for the treatment of any solid cancer harboring NTRK1/2/3 fusion proteins regardless of the organ, tissue, anatomical location, or histology type. Of the 52 approved drugs, seventeen are used in the treatment of more than one disease. Imatinib, for example, is approved for the treatment of eight disparate disorders. The most common drug targets of the approved pharmaceuticals include BCR-Abl, B-Raf, vascular endothelial growth factor receptors (VEGFR), epidermal growth factor receptors (EGFR), and ALK. Most of the approved small molecule protein kinase antagonists (49) bind to the protein kinase domain and six of them bind covalently. In contrast, everolimus, temsirolimus, and sirolimus are larger molecules (MW ≈ 1000) that bind to FK506 binding protein-12 (FKBP-12) to generate a complex that inhibits the mammalian target of rapamycin (mTOR) protein kinase complex. This review presents the physicochemical properties of all of the FDA-approved small molecule protein kinase inhibitors. Twenty-two of the 52 drugs have molecular weights greater than 500, exceeding a Lipinski rule of five criterion. Excluding the macrolides (everolimus, sirolimus, temsirolimus), the average molecular weight of the approved drugs is 480 with a range of 306 (ruxolitinib) to 615 (trametinib). More than half of the antagonists (29) have lipophilic efficiency values of less than five while the recommended optima range from 5 to 10. One of the troublesome problems with both targeted and cytotoxic drugs in the treatment of malignant diseases is the near universal development of resistance to every therapeutic modality. Read less
Journal Article | Full Text Online
Books & Media
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PubMed
https://catalog.lib.ncsu.edu/catalog/NCSU304279
Online Resources HE 20.3627: | Government publication
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Academic Research Foundations: Quantitative
https://www.linkedin.com/checkpoint/enterprise/login/53565897?pathWildcard=53565897&application=learning&dApp=45717204&redirect=https%3A%2F%2Fwww%2Elinkedin%2Ecom%2Flearning%2Facademic-research-foundations-quantitative%3FdApp%3D45717204%26leis%3DLAA%26u%3D53565897
Explore the foundations of quantitative research, and learn how to tackle your own quantitative research study.
Explore the foundations of quantitative research, and learn how to tackle your own quantitative research study. Read less
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Create and Deliver Standout Technical Presentations
https://www.linkedin.com/checkpoint/enterprise/login/53565897?pathWildcard=53565897&application=learning&dApp=45717204&redirect=https%3A%2F%2Fwww%2Elinkedin%2Ecom%2Flearning%2Fcreate-and-deliver-standout-technical-presentations%3FdApp%3D45717204%26leis%3DLAA%26u%3D53565897
Create high-impact technical presentations with techniques used by professionals at NASA, Pfizer, and other leading organizations.
Create high-impact technical presentations with techniques used by professionals at NASA, Pfizer, and other leading organizations. Read less
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How to Train Your Brain For Happiness
https://www.linkedin.com/checkpoint/enterprise/login/53565897?pathWildcard=53565897&application=learning&dApp=45717204&redirect=https%3A%2F%2Fwww%2Elinkedin%2Ecom%2Flearning%2Fhow-to-train-your-brain-for-happiness%3FdApp%3D45717204%26leis%3DLAA%26u%3D53565897
Train your brain for happiness. Happiness professor Jay Kumar shares insights, exercises, and techniques from cutting-edge research in brain science and behavior.
Train your brain for happiness. Happiness professor Jay Kumar shares insights, exercises, and techniques from cutting-edge research in brain science and behavior. Read less
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Genetics and Genomics
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...f whole ecosystems. Jump to... Key Databases Human Genetics More Databases Need Help? Filter database results Show All Material properties Patents Pricing information Search by CAS number Self-d... Read more
...f whole ecosystems. Jump to... Key Databases Human Genetics More Databases Need Help? Filter database results Show All Material properties Patents Pricing information Search by CAS number Self-directed learning Theses and ... Read less
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Keeping Up With Veterinary Knowledge
https://www.lib.ncsu.edu/vetmed/research/keepingup
...ding Free Animal Health Resources Recursos en Español Keeping Up With Veterinary Knowledge The information resources and services that you use now may not be freely available once you leave acad... Read more
...ding Free Animal Health Resources Recursos en Español Keeping Up With Veterinary Knowledge The information resources and services that you use now may not be freely available once you leave academia. Here are some strategies for staying connected to the latest research. Information Resources PubMed - The National Library of Medicine's database of millions of citations includes millions of articles that are available for free through PubMed Central or the... Read less
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Does the library have technical reports or NTIS documents? How do I locate them?
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The library has a large collection of National Technical Information Service (NTIS) documents, usually in digital form on a CD or on microfilm, but it does not ha... Read more
The library has a large collection of National Technical Information Service (NTIS) documents, usually in digital form on a CD or on microfilm, but it does not have every document. Here are the steps to take to obtain these documents or technical reports:First check to see if the document is available online by searching the web (use Google or another broad search engine). This approach does not always turn up this type of document, but when available, this makes the search easy.If a general web search for a document doesn't work, search deeper by checking the publishing agency's site, or try the following portals:Department of Energy (DOE) / Office of Scientific & Technical Information (OSTI)WorldWideScience.orgScience.govDepartment of Defense (DoD) / Defense Technical Information CenterNASA Technical Reports ServerEPA National CatalogPubMed Search the Libraries' catalog by title or author to see if the document is readily available in the Libraries. Most of these are not cataloged, so not finding it doesn't mean the Libraries doesn't own it.If you haven't been able to locate the document in the Libraries or online, place a Tripsaver request for it. Click the Other tile, then use the Media / Microforms Request request form. We will then check to see if the document is in our collection in the Hunt Library bookBot. If it's not available, we will attempt to locate the document at another library. If we need to find your document elsewhere, it will take longer to complete your request. Read less