| 1. |
- Shen, Weixing, et al.
(författare)
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Protective effects of Wang-Bi tablet on bone destruction in collagen-induced arthritis by regulating osteoclast-osteoblast functions.
- 2019
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Ingår i: Journal of Ethnopharmacology. - : Elsevier BV. - 0378-8741 .- 1872-7573. ; 238
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Tidskriftsartikel (refereegranskat)abstract
- ETHNOPHARMACOLOGICAL RELEVANCE: Wang-bi tablet (WB) consists of 17 traditional Chinese medicines and has been used for treating rheumatoid arthritis (RA) in China for many years, however, its pharmacologic mechanism is not clear.AIM OF STUDY: The aim of this study was to investigate the therapeutic effect of WB on collagen-induced mouse arthritis and explored the underlying mechanism.MATERIALS AND METHODS: DBA/1 mice were used to establish a type II collagen-induced arthritis (CIA) model. From the day of arthritis onset, mice were treated daily by gavage with either total glucosides of paeony (TGP, 0.37 g/kg/d) or WB at a lower (1.11 g/kg/d, WBL) or higher dose of (3.33 g/kg/d, WBH) for 8 weeks. The severity of arthritis, levels of cytokines and the activation of signaling pathways were determined.RESULTS: Our results revealed that WB treatment effectively alleviated inflammatory symptoms and prevented bone erosions and joint destructions. It obviously decreased the serum concentration of pro-inflammatory cytokines TNF-α, IL-6 and IL-17α, while increased the concentration of anti-inflammatory cytokine IL-10. Interestingly, the proportion of splenic Treg cells were increased significantly. In vitro experiments showed that WB inhibited the differentiation of osteoclasts. Consistently, the mRNA levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CtsK), and the activation of NF-κB and JAK-STAT3 signaling pathways in the paws of CIA mice were inhibited by WB treatment. On the other hand, up-regulation of osteogenic genes Runx2, Osterix mRNA, and activation of Wnt/β-catenin signaling pathway along with a decreased receptor activator of nuclear factor κB ligand (RANKL) expression were found in WB treated mice.CONCLUSION: Our results suggest that the therapeutic effect of Wang-bi tablet could be attributed to its inhibitory activity on NF-κB and STAT3 signaling pathway-mediated osteoclast differentiation, and its enhancement on Wnt/β-catenin signaling pathway-mediated osteoblast functions.
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| 2. |
- Bergdahl, Johan, et al.
(författare)
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Evaluation of an algorithm ascertaining cases of osteonecrosis of the jaw in the Swedish National Patient Register
- 2013
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Ingår i: Clinical Epidemiology. - Macclesfield : Dove Medical Press Ltd.. - 1179-1349 .- 1179-1349. ; 5:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteonecrosis of the jaw (ONJ) is a medical condition associated with antiresorptive drugs, among others, used to treat osteoporosis and bone metastasis. Currently, there is no consensus regarding the definition of ONJ, and no ONJ-specific International Classification of Diseases-10 code exists. Therefore, register-based studies of this condition may be troublesome.Purpose: To evaluate an algorithm ascertaining ONJ cases in an attempt to facilitate future assessments of ONJ in clinical and epidemiological studies.Methods: By means of the Patient Register and the Prescribed Drug Register, we identified all postmenopausal female residents in Sweden from 2005 through 2009. To identify potential cases of ONJ, we employed an algorithm including the following conditions: periapical abscess with sinus, inflammatory conditions of jaws, alveolitis of jaws, idiopathic aseptic necrosis of bone, osteonecrosis due to drugs, osteonecrosis due to previous trauma, other secondary osteonecrosis, other osteonecrosis, and unspecified osteonecrosis. Women seen at departments of oral and maxillofacial surgery, with at least one of the conditions, were classified as potential cases of ONJ. Conditions in anatomic sites other than the jaw were excluded. Validation was performed through medical record review. Case confirmation was based on the ONJ definition by the American Association of Oral and Maxillofacial Surgeons. The algorithm was evaluated by positive predictive values (PPVs) stratified by diagnosis.Results: For the 87 potential cases identified through our algorithm, the medical records were obtained for 83. The overall PPV was 18% (95% confidence interval (CI) 10%–28%). The highest PPV was observed in osteonecrosis due to drugs (83%, 95% CI 36%–100%). Several diagnoses had a PPV of 0 or were not used at all (periapical abscess with sinus, alveolitis of jaws, idiopathic aseptic necrosis of bone, osteonecrosis due to previous trauma, other secondary osteonecrosis, other osteonecrosis, and unspecified osteonecrosis).Conclusion: It was possible to ascertain cases of ONJ from the Swedish registers using this algorithm; however, the PPV was low. Thus, further refinements of the algorithm are necessary. © 2013 Bergdahl et al, publisher and licensee Dove Medical Press Ltd.
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| 3. |
- Chen, Zhipeng, et al.
(författare)
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Design, Synthesis, and Structure-Activity Relationship of N-Aryl-N'-(thiophen-2-yl) thiourea Derivatives as Novel and Specific Human TLR1/2 Agonists for Potential Cancer Immunotherapy
- 2021
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Ingår i: Journal of Medicinal Chemistry. - Washington, DC : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:11, s. 7371-7389
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Tidskriftsartikel (refereegranskat)abstract
- The previous virtual screening of ten million compounds yielded two novel nonlipopeptide-like chemotypes as TLR2 agonists. Herein, we present the chemical optimization of our initial hit, 1-phenyl-3-(thiophen-2-yl) urea, which resulted in the identification of SMU-C80 (EC50 = 31.02 ± 1.01 nM) as a TLR2-specific agonist with a 370-fold improvement in bioactivity. Mechanistic studies revealed that SMU-C80, through TLR1/2, recruits the adaptor protein MyD88 and triggers the NF-κB pathway to release cytokines such as TNF-α and IL-1β from human, but not murine, cells. To the best of our knowledge, it is the first species-specific TLR1/2 agonist reported until now. Moreover, SMU-C80 increased the percentage of T, B, and NK cells ex vivo and activated the immune cells, which suppressed cancer cell growth in vitro. In summary, we obtained a highly efficient and specific human TLR1/2 agonist that acts through the MyD88 and NF-κB pathway, facilitating cytokine release and the simultaneous activation of immune cells that in turn affects the apoptosis of cancer cells. © 2021 American Chemical Society
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| 4. |
- Dang, Wen-Zhen, et al.
(författare)
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Therapeutic effects of artesunate on lupus-prone MRL/lpr mice are dependent on T follicular helper cell differentiation and activation of JAK2-STAT3 signaling pathway
- 2019
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Ingår i: Phytomedicine. - München : Elsevier. - 0944-7113 .- 1618-095X. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anti-malarial drug artesunate (ART), a semi-synthetic derivative of artemisnin, has immunosuppressive effects on several autoimmune diseases, including Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), and Colitis. However, molecular mechanisms of ART, especially on follicular helper T cells (Tfh), central players in SLE pathology, are far from clear.PURPOSE: The object for this work is to investigate the therapeutic effect of ART on lupus-prone MRL/lpr mice and its regulatory function on Tfh cells.STUDY DESIGN AND METHODS: MRL/lpr mice were used to explore therapeutic effects of ART on lupus-prone MRL/lpr mice and its regulatory functions on Tfh cells. Then, experiments of renal function were accomplished using the biochemical kits. Effects of ART on histopathology of kidneys, inflammatory factors and autoantibodies were examined using H&E staining, ELISA and real-time PCR. Flow cytometry and western blot analysis were used to examine effects of ART on Tfh differentiation and Jak2-Stat3 signaling pathway.RESULTS: Upon oral administration, ART significantly prolonged the survival of MRL/lpr mice, ameliorated the lupus nephritis symptoms, decreased the levels of anti-dsDNA antibodies deposited in the kidney, and the levels of pathogenic cytokines (IL-6, IFN-γ and IL-21). After ART treatment, T-cell compartment in the spleen of MRL/lpr mice was restored in terms of reduction in the number of Tfh cells and in the maintenance of the ratio of Tfr to follicular regulatory T cells (Tfh). In addition, ART has significantly inhibited the phosphorylation levels of Jak2 and Stat3 in the MRL/lpr mice.CONCLUSION: ART showed therapeutic effects on lupus-prone MRL/lpr mice by inhibiting the differentiation of Tfh cells as well as altering the activation status of Jak2-Stat3 signaling cascade. Copyright © 2019 Elsevier GmbH
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| 5. |
- Hansen, Kirstine M., et al.
(författare)
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Mo-clay for treatment of psoriasis
- 2016
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Ingår i: Planta Medica. - Stuttgart : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221.
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Konferensbidrag (refereegranskat)abstract
- Mo-clay was used by German doctors to treat injured soldiers' wounds during the First World War. Today, there are anecdotal cases of mo-clay being beneficial for patients suffering from psoriasis, a chronic, inflammatory disease. There are several histological features in the psoriatic skin, including acanthosis, hyperkeratosis, pararkeratosis and a loss of granular layer. Mo-clay is a unique marine deposit, an Eocene clayed diatomite. It was formed 54 million years ago from deposits of single-celled algae along with clay minerals and volcanic ash. The major elements are silicon, aluminium and iron. It is found in Denmark and Germany. As mo-clay had been used to treat wounds, it was tested for antibacterial activity. Mo-clay did not show any anti-bacterial activity against a battery of Gram-positive and -negative bacteria. Mo-clay showed stimulation of cell proliferation at concentrations 39 – 78 µg/ml in splenic mouse lymphocytes, and at 156 µg/ml in HaCat cells, whereas an inhibition of proliferation was observed at 313 µg/ml. Mo-clay was tested for anti-psoriatic activity in vivo using the mouse tail test [1]. This model can be used to investigate agents for effect on psoriasis, since the adult mouse tail has regions of both orthokeratosis and parakeratosis. Mo-clay induced orthokeratosis and showed a significant increase in epidermis thickness. The results suggest that mo-clay may have anti-psoriatic effects.
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| 6. |
- Hu, Fanjie, et al.
(författare)
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Imidazole Scaffold Based Compounds in the Development of Therapeutic Drugs
- 2021
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Ingår i: Current Topics in Medicinal Chemistry. - Oak Park, IL : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 21:28, s. 2514-2528
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Tidskriftsartikel (refereegranskat)abstract
- Imidazole has an important five-membered aromatic heterocyclic ring, which is available widely in natural products and synthetic molecules. The special structural characteristics of imidazole ring enable it to bind with a variety of enzymes and receptors through hydrogen bonds, coordination, ion-dipole and cation-π interactions, hydrophobic effects, and Van der Waals forces. These interactions promote several biological activities involving anti-tumor, anti-inflammatory, anti-microbial, and anti-viral properties. Herein, we review and discuss recent developments in using imidazole derivatives and their special pharmacological activities for the treatment of various diseases. © 2021 Bentham Science Publishers.
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| 7. |
- Liang, Yuqing, et al.
(författare)
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Design and pharmaceutical applications of proteolysis-targeting chimeric molecules
- 2020
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Ingår i: Biochemical pharmacology. - Philadelphia, PA : Elsevier. - 1873-2968 .- 0006-2952. ; 182
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Tidskriftsartikel (refereegranskat)abstract
- Proteolysis-targeting chimeras (PROTACs), the hetero-bifunctional compounds containing a specific ligand to bind the target protein, a suitable linker, and an E3 ubiquitin ligase substrate, are being developed for therapeutic applications. PROTACs hijack the catalytic activity of ubiquitin E3 ligases to mediate proteasome dependent degradation of selected protein of interest (POI), by bringing the ligase and POI into close spatial proximity and initiating the poly-ubiquitination process. Compared to the traditional small-molecule drugs, PROTACs reduce the problems of dosage, drug resistance, side effects and undruggable targets that could not be targeted pharmacologically. In this review, all the POIs, and peptide to small-molecule based PROTACs developed during the past two decades are summarized and directions for future development are discussed. © 2020 Elsevier Inc.
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| 8. |
- Liu, Junkai, et al.
(författare)
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AMDGT : Attention aware multi-modal fusion using a dual graph transformer for drug–disease associations prediction
- 2024
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Ingår i: Knowledge-Based Systems. - Amsterdam : Elsevier. - 0950-7051 .- 1872-7409. ; 284
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Tidskriftsartikel (refereegranskat)abstract
- Identification of new indications for existing drugs is crucial through the various stages of drug discovery. Computational methods are valuable in establishing meaningful associations between drugs and diseases. However, most methods predict the drug–disease associations based solely on similarity data, neglecting valuable biological and chemical information. These methods often use basic concatenation to integrate information from different modalities, limiting their ability to capture features from a comprehensive and in-depth perspective. Therefore, a novel multimodal framework called AMDGT was proposed to predict new drug associations based on dual-graph transformer modules. By combining similarity data and complex biochemical information, AMDGT understands the multimodal feature fusion of drugs and diseases effectively and comprehensively with an attention-aware modality interaction architecture. Extensive experimental results indicate that AMDGT surpasses state-of-the-art methods in real-world datasets. Moreover, case and molecular docking studies demonstrated that AMDGT is an effective tool for drug repositioning. Our code is available at GitHub: https://github.com/JK-Liu7/AMDGT. © 2023 The Author(s)
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| 9. |
- Pan, Rongbin, et al.
(författare)
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Gancao Nurish-Yin Decoction medicated serum inhibits growth and migration of ovarian cancer cells : Network pharmacology-based analysis and biological validation
- 2022
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Ingår i: Pharmacological Research - Modern Chinese Medicine. - Beijing : Elsevier. - 2667-1425. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is one of the leading causes of death in women. It is also an important factor for an increased worldwide gynecological death observed recently. Here, we have elucidated the effect and mechanisms of Gancao Nurish-Yin Decoction (GNYD) on the viability of ovarian cancer cells. Network pharmacology analysis was performed to explore the putative therapeutic targets of GNYD on the ovarian cancer cells. Experiments at the cellular and molecular levels using ovarian cancer cells were performed to further verify the effect of GNYD. According to the network pharmacology analysis, 282 genes related to the targets of GNYD were identified. Among them, 123 genes were found to be overlapping as the potential targets for treating ovarian cancer. Subsequent experiments proved that GNYD medicated serum has significantly inhibited the survival, growth and migration of the ovarian cancer cells. The number of apoptotic cells has increased after the treatment with GNYD medicated serum, and a higher proportion of cells were arrested at G2/M phase. Importantly, genes present in the AMPK-p53/p21 pathway were found to be significantly promoted. Thus, this study has not only demonstrated the potential therapeutic value of GNYD in inhibiting the survival, growth and migration of ovarian cancer cells in vitro, but also provide clues for further exploring the pharmacological and molecular mechanisms of Chinese medicine preparations acting on various types of cancer. © 2022 The Authors.
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