4,171 results match your criteria Acta Pharmacol. Sin.[Journal]


Zonisamide, an antiepileptic drug, alleviates diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress.

Acta Pharmacol Sin 2020 Jul 9. Epub 2020 Jul 9.

Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.

Endoplasmic reticulum stress (ER stress) plays a key role in the development of cardiac hypertrophy and diabetic cardiomyopathy (DCM). Zonisamide (ZNS) was originally developed as an antiepileptic drug. Studies have shown that ZNS suppresses ER stress-induced neuronal cell damage in the experimental models of Parkinson's disease. Read More

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http://dx.doi.org/10.1038/s41401-020-0461-zDOI Listing

Increased S1P induces S1PR2 internalization to blunt the sensitivity of colorectal cancer to 5-fluorouracil via promoting intracellular uracil generation.

Acta Pharmacol Sin 2020 Jul 9. Epub 2020 Jul 9.

Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.

Sphingosine-1-phosphate (S1P), the backbone of most sphingolipids, activating S1P receptors (S1PRs) and the downstream G protein signaling has been implicated in chemoresistance. In this study we investigated the role of S1PR2 internalization in 5-fluorouracil (5-FU) resistance in human colorectal cancer (CRC). Clinical data of randomly selected 60 CRC specimens showed the correlation between S1PR2 internalization and increased intracellular uracil (P < 0. Read More

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http://dx.doi.org/10.1038/s41401-020-0460-0DOI Listing

KLF4 initiates sustained YAP activation to promote renal fibrosis in mice after ischemia-reperfusion kidney injury.

Acta Pharmacol Sin 2020 Jul 9. Epub 2020 Jul 9.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

Acute renal injury (AKI) causes a long-term risk for progressing into chronic kidney disease (CKD) and interstitial fibrosis. Yes-associated protein (YAP), a key transcriptional cofactor in Hippo signaling pathway, shuttles between the cytoplasm and nucleus, which is required for the renal tubular epithelial cells repair in the acute phase of AKI. In this study we investigated the role of YAP during ischemia-reperfusion (IR)-induced AKI to CKD. Read More

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http://dx.doi.org/10.1038/s41401-020-0463-xDOI Listing

Publisher Correction: 'TRAIL-based gene delivery and therapeutic strategies' and 'Overview of recent advances in liposomal nanoparticle-based cancer immunotherapy'.

Acta Pharmacol Sin 2020 Jul 6. Epub 2020 Jul 6.

State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. Read More

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http://dx.doi.org/10.1038/s41401-020-0444-0DOI Listing

GJA1-20k attenuates Ang II-induced pathological cardiac hypertrophy by regulating gap junction formation and mitochondrial function.

Acta Pharmacol Sin 2020 Jul 3. Epub 2020 Jul 3.

Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.

Cardiac hypertrophy (CH) is characterized by an increase in cardiomyocyte size, and is the most common cause of cardiac-related sudden death. A decrease in gap junction (GJ) coupling and mitochondrial dysfunction are important features of CH, but the mechanisms of decreased coupling and energy impairment are poorly understood. It has been reported that GJA1-20k has a strong tropism for mitochondria and is required for the trafficking of connexin 43 (Cx43) to cell-cell borders. Read More

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http://dx.doi.org/10.1038/s41401-020-0459-6DOI Listing

Eleutheroside B, a selective late sodium current inhibitor, suppresses atrial fibrillation induced by sea anemone toxin II in rabbit hearts.

Acta Pharmacol Sin 2020 Jul 1. Epub 2020 Jul 1.

Cardiac Electrophysiological Research Laboratory, Medical College, Wuhan University of Science and Technology, Wuhan, 430065, China.

Eleutheroside B (EB) is the main active constituent derived from the Chinese herb Acanthopanax senticosus (AS) that has been reported to possess cardioprotective effects. In this study we investigated the effects of EB on cardiac electrophysiology and its suppression on atrial fibrillation (AF). Whole-cell recording was conducted in isolated rabbit atrial myocytes. Read More

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http://dx.doi.org/10.1038/s41401-020-0453-zDOI Listing

Ubiquitin-proteasome system-targeted therapy for uveal melanoma: what is the evidence?

Acta Pharmacol Sin 2020 Jun 29. Epub 2020 Jun 29.

Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

Uveal melanoma (UM) is a rare ocular tumor. The loss of BRCA1-associated protein 1 (BAP1) and the aberrant activation of G protein subunit alpha q (GNAQ)/G protein subunit alpha 11 (GNA11) contribute to the frequent metastasis of UM. Thus far, limited molecular-targeted therapies have been developed for the clinical treatment of UM. Read More

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http://dx.doi.org/10.1038/s41401-020-0441-3DOI Listing

Identification of critical molecular pathways involved in exosome-mediated improvement of cardiac function in a mouse model of muscular dystrophy.

Acta Pharmacol Sin 2020 Jun 29. Epub 2020 Jun 29.

Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.

Duchenne muscular dystrophy (DMD) is a progressive disease characterized by skeletal muscle atrophy, respiratory failure, and cardiomyopathy. Our previous studies have shown that transplantation with allogeneic myogenic progenitor-derived exosomes (MPC-Exo) can improve cardiac function in X-linked muscular dystrophy (Mdx) mice. In the present study we explored the molecular mechanisms underlying this beneficial effect. Read More

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http://dx.doi.org/10.1038/s41401-020-0446-yDOI Listing

Species differences in the CYP3A-catalyzed metabolism of TPN729, a novel PDE5 inhibitor.

Acta Pharmacol Sin 2020 Jun 24. Epub 2020 Jun 24.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

TPN729 is a novel phosphodiesterase 5 (PDE5) inhibitor used to treat erectile dysfunction in men. Our previous study shows that the plasma exposure of metabolite M3 (N-dealkylation of TPN729) in humans is much higher than that of TPN729. In this study, we compared its metabolism and pharmacokinetics in different species and explored the contribution of its main metabolite M3 to pharmacological effect. Read More

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http://dx.doi.org/10.1038/s41401-020-0447-xDOI Listing
June 2020
2.496 Impact Factor

Recombinant human ACE2: potential therapeutics of SARS-CoV-2 infection and its complication.

Acta Pharmacol Sin 2020 Jun 24. Epub 2020 Jun 24.

School of Pharmacy and State Key Laboratory for the Quality Research of Chinese Medicine, Macau University of Science and Technology, Macau, China.

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http://dx.doi.org/10.1038/s41401-020-0430-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313652PMC

A simple, quick, and efficient CRISPR/Cas9 genome editing method for human induced pluripotent stem cells.

Acta Pharmacol Sin 2020 Jun 18. Epub 2020 Jun 18.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.

Induced pluripotent stem cells (iPSCs) have become an essential research platform to study different human diseases once being discovered by Dr. Shinya Yamanaka in 2006. Another breakthrough in biomedical research is the application of CRISPR/Cas9 system for genome editing in mammalian cells. Read More

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http://dx.doi.org/10.1038/s41401-020-0452-0DOI Listing

Free fatty acid receptor 4 (FFA4) activation ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by increasing regulatory T cells in mice.

Acta Pharmacol Sin 2020 Jun 18. Epub 2020 Jun 18.

College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea.

High dose intake of docosahexaenoic acid showed beneficial effects on atopic dermatitis in patients and was found to increase regulatory T cells in mice, but its molecular target has not been identified. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor sensing polyunsaturated long-chain fatty acids including docosahexaenoic acid. In the present study, we examined whether FFA4 acted as a therapeutic target of docosahexaenoic acid for treating atopic dermatitis. Read More

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http://dx.doi.org/10.1038/s41401-020-0435-1DOI Listing

Identification of important genes and drug repurposing based on clinical-centered analysis across human cancers.

Acta Pharmacol Sin 2020 Jun 18. Epub 2020 Jun 18.

National Center for Liver Cancer, Second Military Medical University, Shanghai, 200438, China.

Identification of the functional impact of mutated and altered genes in cancer is critical for implementing precision oncology and drug repurposing. In recent years, the emergence of multiomics data from large, well-characterized patient cohorts has provided us with an unprecedented opportunity to address this problem. In this study, we investigated survival-associated genes across 26 cancer types and found that these genes tended to be hub genes and had higher K-core values in biological networks. Read More

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http://dx.doi.org/10.1038/s41401-020-0451-1DOI Listing

Overview of therapeutic drug research for COVID-19 in China.

Acta Pharmacol Sin 2020 Jun 17. Epub 2020 Jun 17.

Laboratory of Immunopharmacology, Shanghai Institute of MateriaMedica, Chinese Academy of Sciences, Shanghai, 201203, China.

Since the outbreak of novel coronavirus pneumonia (COVID-19) in December 2019, more than 2,500,000 people worldwide have been diagnosed with SARS-CoV-2 as of April 22. In response to this epidemic, China has issued seven trial versions of diagnosis and treatment protocol for COVID-19. According to the information that we have collected so far, this article provides an overview of potential therapeutic drugs and compounds with much attention, including favipiravir and hydroxychloroquine, as well as traditional Chinese medicine, which have been reported with good clinical treatment effects. Read More

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http://dx.doi.org/10.1038/s41401-020-0438-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298161PMC
June 2020
2.496 Impact Factor

Cancer nanomedicine meets immunotherapy: opportunities and challenges.

Acta Pharmacol Sin 2020 Jul 17;41(7):954-958. Epub 2020 Jun 17.

Institute for Experimental Molecular Imaging, Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.

Cancer nanomedicines have shown promise in combination immunotherapy, thus far mostly preclinically but also already in clinical trials. Combining nanomedicines with immunotherapy aims to reinforce the cancer-immunity cycle, via potentiating key steps in the immune reaction cascade, namely antigen release, antigen processing, antigen presentation, and immune cell-mediated killing. Combination nano-immunotherapy can be realized via three targeting strategies, i. Read More

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http://dx.doi.org/10.1038/s41401-020-0448-9DOI Listing

Short-chain fatty acids exert opposite effects on the expression and function of p-glycoprotein and breast cancer resistance protein in rat intestine.

Acta Pharmacol Sin 2020 Jun 17. Epub 2020 Jun 17.

Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are involved in intestinal barrier. Short-chain fatty acids (SCFAs) play important roles in maintaining intestinal barrier. In this study we explored how SCFAs affected the expression and function of intestinal P-gp and BCRP in rats. Read More

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http://dx.doi.org/10.1038/s41401-020-0402-xDOI Listing

ADP receptor P2y12 prevents excessive primitive hematopoiesis in zebrafish by inhibiting Gata1.

Acta Pharmacol Sin 2020 Jun 17. Epub 2020 Jun 17.

Key Laboratory of Stem Cell Biology, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, 200031, China.

In the past two decades, purinergic signaling has emerged as a key regulator of hematopoiesis in physiological and pathological conditions. ADP receptor P2y12 is a crucial component of this signaling, but whether it is involved in primitive hematopoiesis remains unknown. To elucidate the function of P2y12 and provide new insights for drug development, we established a zebrafish P2y12 mutant by CRISPR/Cas 9-based genetic modification system, and investigated whether P2y12 acted as an important regulator for primitive hematopoiesis. Read More

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http://dx.doi.org/10.1038/s41401-020-0431-5DOI Listing

Sirt1 inhibits renal tubular cell epithelial-mesenchymal transition through YY1 deacetylation in diabetic nephropathy.

Acta Pharmacol Sin 2020 Jun 17. Epub 2020 Jun 17.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China.

Silent information regulator 1 (Sirt1) is a deacetylase, which plays an important role in the occurrence and development of diabetic nephropathy (DN). Our previous study shows that Yin yang 1 (YY1), a widely expressed zinc finger DNA/RNA-binding transcription factor, is a novel regulator of renal fibrosis in diabetic nephropathy. Since the activity of YY1 is regulated via acetylation and deacetylation modification, this study aimed to explore whether Sirt1-induced deacetylation of YY1 mediated high glucose (HG)-induced renal tubular epithelial-mesenchymal transition (EMT) and renal fibrosis in vivo and in vitro. Read More

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http://dx.doi.org/10.1038/s41401-020-0450-2DOI Listing
June 2020
2.496 Impact Factor

L-Carnitine protects against tacrolimus-induced renal injury by attenuating programmed cell death via PI3K/AKT/PTEN signaling.

Acta Pharmacol Sin 2020 Jun 17. Epub 2020 Jun 17.

Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.

Reducing immunosuppressant-related complications using conventional drugs is an efficient therapeutic strategy. L-carnitine (LC) has been shown to protect against various types of renal injury. In this study, we investigated the renoprotective effects of LC in a rat model of chronic tacrolimus (TAC) nephropathy. Read More

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http://dx.doi.org/10.1038/s41401-020-0449-8DOI Listing
June 2020
2.496 Impact Factor

MDL-800, an allosteric activator of SIRT6, suppresses proliferation and enhances EGFR-TKIs therapy in non-small cell lung cancer.

Acta Pharmacol Sin 2020 Jun 15. Epub 2020 Jun 15.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Sirtuin 6 (SIRT6), a member of the sirtuin family, is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that is involved in various physiological and pathological processes. SIRT6 is generally downregulated and linked to tumorigenesis in non-small cell lung carcinoma (NSCLC), thus regarded as a promising therapeutic target of NSCLC. In this study, we investigated whether MDL-800, an allosteric activator of SIRT6, exerted antiproliferation effect against NSCLC cells in vitro and in vivo. Read More

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http://dx.doi.org/10.1038/s41401-020-0442-2DOI Listing
June 2020
2.496 Impact Factor

ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma.

Acta Pharmacol Sin 2020 Jun 15. Epub 2020 Jun 15.

Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, China.

Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. Read More

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http://dx.doi.org/10.1038/s41401-020-0439-xDOI Listing

β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling.

Acta Pharmacol Sin 2020 Jun 5. Epub 2020 Jun 5.

State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

β-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of β-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that β-sitosterol (150-450 μg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Read More

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http://dx.doi.org/10.1038/s41401-020-0403-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273125PMC

Intrinsic and acquired resistance to CDK4/6 inhibitors and potential overcoming strategies.

Acta Pharmacol Sin 2020 Jun 5. Epub 2020 Jun 5.

Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

Abnormal activation of the cyclin-dependent kinases (CDKs), which result in aberrant cell proliferation, is one of the inherent characteristics of tumor. Thus targeting the activity of CDKs represents a promising tumor therapeutic strategy. Currently, the specific inhibitors that target CDK4 and CDK6 have been approved for the treatment of estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER HER2) breast cancer in combination with endocrine therapy; other combination strategies are being tested in a number of clinical trials. Read More

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http://dx.doi.org/10.1038/s41401-020-0416-4DOI Listing

Puerarin ameliorated pressure overload-induced cardiac hypertrophy in ovariectomized rats through activation of the PPARα/PGC-1 pathway.

Acta Pharmacol Sin 2020 Jun 5. Epub 2020 Jun 5.

Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China.

Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Read More

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http://dx.doi.org/10.1038/s41401-020-0401-yDOI Listing

Icariside II attenuates cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction in rats via regulating the balance of MMP9/TIMP1.

Acta Pharmacol Sin 2020 Jun 2. Epub 2020 Jun 2.

Department of Pharmacology, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, China.

Cerebral ischemia/reperfusion (I/R) results in harmful consequences during ischemic stroke, especially the disruption of the blood-brain barrier (BBB), which leads to severe hemorrhagic transformation through aggravation of edema and brain hemorrhage. Our previous study demonstrated that icariside II (ICS II), which is derived from Herba Epimedii, attenuates cerebral I/R injury by inhibiting the GSK-3β-mediated activation of autophagy both in vitro and in vivo. However, the effect of ICS II on the BBB remains unclear. Read More

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http://dx.doi.org/10.1038/s41401-020-0409-3DOI Listing
June 2020
2.496 Impact Factor

Nanomedicine-based immunotherapy for central nervous system disorders.

Acta Pharmacol Sin 2020 Jul 28;41(7):936-953. Epub 2020 May 28.

Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences Henan University, Kaifeng, 475004, China.

Central nervous system (CNS) disorders represent a broad spectrum of brain ailments with short- and long-term disabilities, and nanomedicine-based approaches provide a new therapeutic approach to treating CNS disorders. A variety of potential drugs have been discovered to treat several neuronal disorders; however, their therapeutic success can be limited by the presence of the blood-brain barrier (BBB). Furthermore, unique immune functions within the CNS provide novel target mechanisms for the amelioration of CNS diseases. Read More

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http://dx.doi.org/10.1038/s41401-020-0429-zDOI Listing

CS1003, a novel human and mouse cross-reactive PD-1 monoclonal antibody for cancer therapy.

Acta Pharmacol Sin 2020 May 28. Epub 2020 May 28.

CStone Pharmaceuticals (Suzhou) Co., Ltd, Shanghai, 201203, China.

The programmed cell death protein 1 (PD-1) is an immune-checkpoint that negatively regulates the immune system and a key mechanism that tumors utilize to escape from immune surveillance. PD-1 antibodies can block the interaction of PD-1 with its ligands (PD-L1 and PD-L2), restore T cells activation, and elicit antitumor activity. In this paper, we reported a novel PD-1 monoclonal antibody (mAb) CS1003, which is a humanized IgG4 PD-1 mAb generated by conventional hybridoma technology, and currently being developed in multiple clinical trials as monotherapy or in combination with other anticancer agents. Read More

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http://dx.doi.org/10.1038/s41401-020-0422-6DOI Listing
May 2020
2.496 Impact Factor

Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells.

Acta Pharmacol Sin 2020 Jul 28;41(7):895-901. Epub 2020 May 28.

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, China.

Immunotherapy that activates the host immune system to reverse immunosuppression has emerged as a new generation of cancer treatment in both preclinical studies and clinical trials. Although immunotherapy has shown significant achievements in the treatment of various cancers, it faces challenges that limit its further evolution such as poor permeation and modest responsiveness. The development of nanoparticle drug delivery system has provided an opportunity to overcome these drawbacks and to achieve optimized immunotherapy. Read More

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http://dx.doi.org/10.1038/s41401-020-0423-5DOI Listing

Nanomedicine and cancer immunotherapy.

Acta Pharmacol Sin 2020 Jul 28;41(7):879-880. Epub 2020 May 28.

Department of Pharmaceutics, Ghent University, Ghent, Belgium.

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http://dx.doi.org/10.1038/s41401-020-0426-2DOI Listing

Baicalin prevents LPS-induced activation of TLR4/NF-κB p65 pathway and inflammation in mice via inhibiting the expression of CD14.

Acta Pharmacol Sin 2020 May 26. Epub 2020 May 26.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.

Previous studies have shown that baicalin, an active ingredient of the Chinese traditional medicine Huangqin, attenuates LPS-induced inflammation by inhibiting the activation of TLR4/NF-κBp65 pathway, but how it affects this pathway is unknown. It has been shown that CD14 binds directly to LPS and plays an important role in sensitizing the cells to minute quantities of LPS via chaperoning LPS molecules to the TLR4/MD-2 signaling complex. In the present study we investigated the role of CD14 in the anti-inflammatory effects of baicalin in vitro and in vivo. Read More

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http://dx.doi.org/10.1038/s41401-020-0411-9DOI Listing
May 2020
2.496 Impact Factor

Blockage of sphingosine-1-phosphate receptor 2 attenuates 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice.

Acta Pharmacol Sin 2020 May 26. Epub 2020 May 26.

College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea.

Sphingosine-1-phosphate (S1P) and its receptors have been implicated in functions of Langerhans cells and atopic dermatitis. In this study, we investigated the roles of S1P receptor type 2 (S1P) in a mouse model of atopic dermatitis, which was induced by topical application of 2,4-dinitrochlorobenzene (DNCB) on ventral skin on D0, followed by repeated DNCB challenge on both ears from D7 to D49. Wild-type mice with atopic dermatitis displayed severe inflammation and mast cell accumulation in ear tissues and elevated IgE levels in serum. Read More

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http://dx.doi.org/10.1038/s41401-020-0412-8DOI Listing

Gasdermin E-derived caspase-3 inhibitors effectively protect mice from acute hepatic failure.

Acta Pharmacol Sin 2020 May 26. Epub 2020 May 26.

State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism, China Pharmaceutical University, Nanjing, 210009, China.

Programmed cell death (PCD), including apoptosis, apoptotic necrosis, and pyroptosis, is involved in various organ dysfunction syndromes. Recent studies have revealed that a substrate of caspase-3, gasdermin E (GSDME), functions as an effector for pyroptosis; however, few inhibitors have been reported to prevent pyroptosis mediated by GSDME. Here, we developed a class of GSDME-derived inhibitors containing the core structure of DMPD or DMLD. Read More

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http://dx.doi.org/10.1038/s41401-020-0434-2DOI Listing

Application of targeted therapy strategies with nanomedicine delivery for atherosclerosis.

Acta Pharmacol Sin 2020 May 26. Epub 2020 May 26.

Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.

Atherosclerosis (AS) is the main pathological cause of coronary heart disease (CHD). Current clinical interventions including statin drugs can effectively reduce acute myocardial infarction and stroke to some extent, but residual risk remains high. The current clinical treatment regimens are relatively effective for early atherosclerotic plaques and can even reverse their progression. Read More

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http://dx.doi.org/10.1038/s41401-020-0436-0DOI Listing

Author Correction: Ophiopogonin D maintains Ca homeostasis in rat cardiomyocytes in vitro by upregulating CYP2J3/ EETs and suppressing ER stress.

Acta Pharmacol Sin 2020 May 26. Epub 2020 May 26.

Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. Read More

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http://dx.doi.org/10.1038/s41401-020-0428-0DOI Listing

Drinking water temperature affects cognitive function and progression of Alzheimer's disease in a mouse model.

Acta Pharmacol Sin 2020 May 25. Epub 2020 May 25.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.

Lifestyle factors may affect mental health and play a critical role in the development of neurodegenerative diseases including Alzheimer's disease (AD). However, whether the temperatures of daily beverages have any impact on cognitive function and AD development has never been studied. In this study, we investigated the effects of daily drinking water temperatures on cognitive function and AD development and progression in mice and the underlying mechanisms. Read More

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http://dx.doi.org/10.1038/s41401-020-0407-5DOI Listing

Avasimibe exerts anticancer effects on human glioblastoma cells via inducing cell apoptosis and cell cycle arrest.

Acta Pharmacol Sin 2020 May 25. Epub 2020 May 25.

The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China.

Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, but there is no effective drug available for GBM. Avasimibe is a potent inhibitor of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1), which was used to treat atherosclerosis. Experimental evidence and bioinformatics have shown that avasimibe has anticancer activity. Read More

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http://dx.doi.org/10.1038/s41401-020-0404-8DOI Listing

Sphingomyelin synthase 2 facilitates M2-like macrophage polarization and tumor progression in a mouse model of triple-negative breast cancer.

Acta Pharmacol Sin 2020 May 25. Epub 2020 May 25.

Department of Pharmacology and Biochemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China.

High infiltration of M2-polarized macrophages in the primary tumor indicates unfavorable prognosis and poor overall survival in the patients with triple-negative breast cancer (TNBC). Thus, reversing M2-polarized tumor-associated macrophages in the tumors has been considered as a potential therapeutic strategy for TNBC. Sphingomyelin synthase 2 (SMS2) is the key enzyme for sphingomyelin production, which plays an important role in plasma membrane integrity and function. Read More

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http://dx.doi.org/10.1038/s41401-020-0419-1DOI Listing

Comparing the immunogenicity of glycosidase-directed resiquimod prodrugs mediated by cancer cell metabolism.

Acta Pharmacol Sin 2020 Jul 25;41(7):995-1004. Epub 2020 May 25.

Department of Chemistry, Washington State University, Pullman, WA, 99164, USA.

We have recently developed an enzyme-directed immunostimulant (EDI) prodrug motif, which is metabolized to active immunostimulant by cancer cells and, following drug efflux, activates nearby immune cells, resulting in immunogenicity. In this study, we synthesized several EDI prodrugs featuring an imidazoquinoline immunostimulant resiquimod (a Toll-like receptor 7/8 agonist) covalently modified with glycosidase enzyme-directing groups selected from substrates of β-glucuronidase, α-mannosidase, or β-galactosidase. We compared the glycosidase-dependent immunogenicity elicited by each EDI in RAW-Blue macrophages following conversion to active immunostimulant by complementary glycosidase. Read More

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http://dx.doi.org/10.1038/s41401-020-0432-4DOI Listing
July 2020
2.496 Impact Factor

Nanomedicine-mediated alteration of the pharmacokinetic profile of small molecule cancer immunotherapeutics.

Acta Pharmacol Sin 2020 Jul 25;41(7):881-894. Epub 2020 May 25.

Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

The advent of immunotherapy is a game changer in cancer therapy with monoclonal antibody- and T cell-based therapeutics being the current flagships. Small molecule immunotherapeutics might offer advantages over the biological drugs in terms of complexity, tissue penetration, manufacturing cost, stability, and shelf life. However, small molecule drugs are prone to rapid systemic distribution, which might induce severe off-target side effects. Read More

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http://dx.doi.org/10.1038/s41401-020-0425-3DOI Listing

Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment.

Acta Pharmacol Sin 2020 Jul 18;41(7):970-985. Epub 2020 May 18.

Laboratory of Nano and Translational Medicine, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Cancer immunotherapy has received extensive attention due to its ability to activate the innate or adaptive immune systems of patients to combat tumors. Despite a few clinical successes, further endeavors are still needed to tackle unresolved issues, including limited response rates, development of resistance, and immune-related toxicities. Accumulating evidence has pinpointed the tumor microenvironment (TME) as one of the major obstacles in cancer immunotherapy due to its detrimental impacts on tumor-infiltrating immune cells. Read More

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http://dx.doi.org/10.1038/s41401-020-0424-4DOI Listing

MG53 protects against contrast-induced acute kidney injury by reducing cell membrane damage and apoptosis.

Acta Pharmacol Sin 2020 May 18. Epub 2020 May 18.

Department of Cardiology, Daping Hospital, Army Medical University, Chongqing, 400042, China.

Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. Read More

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http://dx.doi.org/10.1038/s41401-020-0420-8DOI Listing

Chromatin accessibility analysis reveals that TFAP2A promotes angiogenesis in acquired resistance to anlotinib in lung cancer cells.

Acta Pharmacol Sin 2020 May 15. Epub 2020 May 15.

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.

Anlotinib, a multitarget tyrosine kinase inhibitor, is effective as a third-line treatment against non-small cell lung cancer (NSCLC). However, acquired resistance occurs during its administration. To understand the molecular mechanisms of anlotinib resistance, we characterized chromatin accessibility in both the parental and anlotinib-resistant lung cancer cell line NCI-H1975 through ATAC-seq. Read More

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http://dx.doi.org/10.1038/s41401-020-0421-7DOI Listing

Dihydro-stilbene gigantol relieves CCl-induced hepatic oxidative stress and inflammation in mice via inhibiting C5b-9 formation in the liver.

Acta Pharmacol Sin 2020 May 13. Epub 2020 May 13.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

In general, anti-inflammatory treatment is considered for multiple liver diseases despite the etiology. But current drugs for alleviating liver inflammation have defects, making it necessary to develop more potent and safer drugs for liver injury. In this study, we screened a series of (dihydro-)stilbene or (dihydro-)phenanthrene derivatives extracted from Pholidota chinensis for their potential biological activities. Read More

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http://dx.doi.org/10.1038/s41401-020-0406-6DOI Listing

DCZ5248, a novel dual inhibitor of Hsp90 and autophagy, exerts antitumor activity against colon cancer.

Acta Pharmacol Sin 2020 May 13. Epub 2020 May 13.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Hsp90 is a potential therapeutic target for tumor, as it maintains the stability of a variety of proteins related to tumor development and progression. Autophagy is a self-degradation process to maintain cellular homeostasis and autophagy inhibitors can suppress tumor growth. In this study, we identified DCZ5248, a triazine derivative, was a dual inhibitor of both Hsp90 and late-autophagy with potent antitumor activity against colon cancer cells in vitro and in vivo. Read More

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http://dx.doi.org/10.1038/s41401-020-0398-2DOI Listing

HKB99, an allosteric inhibitor of phosphoglycerate mutase 1, suppresses invasive pseudopodia formation and upregulates plasminogen activator inhibitor-2 in erlotinib-resistant non-small cell lung cancer cells.

Acta Pharmacol Sin 2020 May 13. Epub 2020 May 13.

Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, remains a major challenge in the targeted therapy of non-small cell lung cancer (NSCLC). HKB99 is a novel allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1) that preferentially suppresses cell proliferation and induces more apoptosis in acquired erlotinib-resistant HCC827ER cells compared with its parental HCC827 cells. In this study we identified the molecular biomarkers for HKB99 response in erlotinib-resistant HCC827ER cells. Read More

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http://dx.doi.org/10.1038/s41401-020-0399-1DOI Listing

Osimertinib successfully combats EGFR-negative glioblastoma cells by inhibiting the MAPK pathway.

Acta Pharmacol Sin 2020 May 12. Epub 2020 May 12.

High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.

Glioblastoma (GBM) patients have extremely poor prognoses, and currently no effective treatment available including surgery, radiation, and chemotherapy. MAPK-interacting kinases (MNK1/2) as the downstream of the MAPK-signaling pathway regulate protein synthesis in normal and tumor cells. Research has shown that targeting MNKs may be an effective strategy to treat GBM. Read More

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http://dx.doi.org/10.1038/s41401-020-0418-2DOI Listing
May 2020
2.496 Impact Factor

Dipeptidyl peptidase 4 inhibitor sitagliptin protected against dextran sulfate sodium-induced experimental colitis by potentiating the action of GLP-2.

Acta Pharmacol Sin 2020 May 12. Epub 2020 May 12.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Dipeptidyl peptidase 4 (DPP4), a ubiquitously expressed protease that cleaves off the N-terminal dipeptide from proline and alanine on the penultimate position, has important roles in many physiological processes. In the present study, experimental colitis was induced in mice receiving 3% dextran sulfate sodium (DSS) in drinking water. We found that mice with DSS-induced colitis had significantly increased intestinal DPP activity and decreased serum DPP activity, suggesting a probable correlation of DPP4 with experimental colitis. Read More

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http://dx.doi.org/10.1038/s41401-020-0413-7DOI Listing

Nanoengineered targeting strategy for cancer immunotherapy.

Acta Pharmacol Sin 2020 Jul 12;41(7):902-910. Epub 2020 May 12.

Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.

Cancer immunotherapy is rapidly changing the paradigm of cancer care and treatment by evoking host immunity to kill cancer cells. As clinical approval of checkpoint inhibitors (e.g. Read More

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http://dx.doi.org/10.1038/s41401-020-0417-3DOI Listing

An optically active isochroman-2H-chromene conjugate potently suppresses neuronal oxidative injuries associated with the PI3K/Akt and MAPK signaling pathways.

Acta Pharmacol Sin 2020 May 11. Epub 2020 May 11.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Increasing evidence suggests that the use of potent neuroprotective agents featured with novel pharmacological mechanism would offer a promising strategy to delay or prevent the progression of neurodegeneration. Here, we provide the first demonstration that the chiral nonracemic isochroman-2H-chromene conjugate JE-133, a novel synthetic 1,3-disubstituted isochroman derivative, possesses superior neuroprotective effect against oxidative injuries. Pretreatment with JE-133 (1-10 μM) concentration-dependently prevented HO-induced cell death in SH-SY5Y neuroblastoma cells and rat primary cortical neurons. Read More

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http://dx.doi.org/10.1038/s41401-020-0391-9DOI Listing

Ex vivo pulsed dendritic cell vaccination against cancer.

Acta Pharmacol Sin 2020 Jul 4;41(7):959-969. Epub 2020 May 4.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.

As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo, hence becoming optimal cell population for vaccination purposes. DCs can be derived ex vivo in quantity and manipulated extensively to be endowed with adequate immune-stimulating capacity. After pulsing with cancer antigens in various ways, the matured DCs are administrated back into the patient. Read More

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http://dx.doi.org/10.1038/s41401-020-0415-5DOI Listing