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Plant-derived Exosomal MicroRNAs Inhibit Lung Inflammation Induced by Exosomes SARS-CoV-2 Nsp12.

Mol Ther 2021 May 10. Epub 2021 May 10.

Robley Rex Veterans Affairs Medical Center, Louisville, KY, 40206, USA; Department of Microbiology & Immunology, University of Louisville, KY, 40202, USA; James Graham Brown Cancer Center, University of Louisville, KY, 40202, USA, Department of ICU, The affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu 223300, China. Electronic address:

Lung inflammation is a hallmark of coronavirus disease 2019 (COVID-19). Here, we show that mice develop inflamed lung tissue after being administered exosomes released from the lung epithelial cells exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp12 and Nsp13 (exosomes). Mechanistically, we show that exosomes are taken up by lung macrophages, leading to activation of NF-κB and the subsequent induction of an array of inflammatory cytokines. Read More

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Identification of bioactive compounds from mulberry enhancing glucose-stimulated insulin secretion.

Bioorg Med Chem Lett 2021 May 10:128096. Epub 2021 May 10.

College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea. Electronic address:

Previously, we isolated six heterocyclic compounds (1-6) from the fruits of mulberry trees (Morus alba L.) and determined that loliolide affords rat pancreatic islet β-cell (INS-1) protection against streptozotocin‑induced cytotoxicity. In the present study, we further investigated the effect of the six heterocyclic compounds (1-6) on glucose-stimulated insulin secretion (GSIS) in INS-1 cells. Read More

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Versicolorin A enhances the genotoxicity of Aflatoxin B1 in human liver cells by inducing the transactivation of the Ah-Receptor.

Food Chem Toxicol 2021 May 10:112258. Epub 2021 May 10.

Toxalim (Research Centre in Food Toxicology), University of Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France. Electronic address:

Aflatoxins are a group of mycotoxins that have major adverse effects on human health. Aflatoxin B1 (AFB1) is the most important aflatoxin and a potent carcinogen once converted into a DNA-reactive form by cytochrome P450 enzymes (CYP450). AFB1 biosynthesis involves the formation of Versicolorin A (VerA) which shares structural similarities with AFB1 and can be found in contaminated commodities, often co-occurring with AFB1. Read More

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Tanshinone IIA induces TRAIL sensitization of glioblastoma through death receptors induction and STAT3 pathway inhibition.

Brain Res 2021 May 10:147515. Epub 2021 May 10.

Department of Neurosurgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, PR China. Electronic address:

Objective: This work was designed to explore whether the combination of Tanshinone IIA (T-IIA) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has a direct anti-cancer effect in glioblastoma (GBM) and the possible mechanisms.

Methods: GBM cells (U-87 and U-251 MG) were treated with T-IIA or/and TRAIL, or the expression of death receptors (DRs), DR4 and DR5, was suppressed in GBM cells. The activity of GBM cells was determined by MTT, and the apoptosis was assessed by Hoechst33342 staining and flow cytometry. Read More

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MEF2C silencing downregulates NF2 and E-cadherin and enhances Erastin-induced ferroptosis in meningioma.

Neuro Oncol 2021 May 13. Epub 2021 May 13.

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Ferroptosis, a programmed cell death characterized by lipid peroxidation, is implicated in various diseases including cancer. Although cell density-dependent E-cadherin and Merlin/Neurofibromin (NF2) loss can modulate ferroptosis, the role of ferroptosis and its potential link to NF2 status and E-cadherin expression in meningioma remain unknown.

Methods: Relationship between ferroptosis modulators expression and NF2 mutational status was examined in 35 meningiomas (10 NF2 loss and 25 NF2 wildtype). Read More

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Combined Platelet and Erythrocyte Salvage: Evaluation of a New Filtration-based Autotransfusion Device.

Anesthesiology 2021 May 13. Epub 2021 May 13.

Background: The SAME device (i-SEP, France) is an innovative filtration-based autotransfusion device able to salvage and wash both red blood cells and platelets. This study evaluated the device performances using human whole blood with the hypothesis that the device will be able to salvage platelets while achieving a erythrocyte yield of 80% and removal ratios of 90% for heparin and 80% for major plasma proteins without inducing signification activation of salvaged cells.

Methods: Thirty healthy human whole blood units (median volume, 478 ml) were diluted, heparinized, and processed by the device in two consecutive treatment cycles. Read More

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Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo.

J Cell Mol Med 2021 May 13. Epub 2021 May 13.

China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.

Lung cancer is the leading cause of cancer-related deaths. LIM domain kinase (LIMK) 1 is a member of serine/threonine kinase family and highly expressed in various cancers. Luteolin, a polyphenolic plant flavonoid, has been reported to suppress tumour proliferation through inducing apoptosis and autophagy via MAPK activation in glioma. Read More

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Cryptotanshinone, a novel PDK 4 inhibitor, suppresses bladder cancer cell invasiveness via the mTOR/β‑catenin/N‑cadherin axis.

Int J Oncol 2021 Jul 13;59(1). Epub 2021 May 13.

Division of Microbiology and Infectious Diseases, Shiga University of Medical Science, Setatsukinowa‑cho, Otsu, Shiga 520‑2192, Japan.

The phosphorylation of pyruvate dehydrogenase (PDH) by pyruvate dehydrogenase kinase (PDK) 4 inhibits its ability to induce a glycolytic shift. PDK4 expression is upregulated in various types of human cancer. Because PDK4 regulation is critical for metabolic changes in cancer cells, it is an attractive target for cancer therapy given its ability to shift glucose metabolism. Read More

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LY‑294002 enhances the chemosensitivity of liver cancer to oxaliplatin by blocking the PI3K/AKT/HIF‑1α pathway.

Mol Med Rep 2021 Jul 13;24(1). Epub 2021 May 13.

Medical School, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China.

Liver cancer remains one of the leading causes of cancer deaths worldwide. The therapeutic effect of oxaliplatin on liver cancer is often limited by acquired resistance of the cancer cells. Abnormal activation of the PI3K/AKT pathway plays an important role in the acquired resistance of oxaliplatin. Read More

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[Research progress on anti-tumor effect of Chinese dragon's blood].

Zhongguo Zhong Yao Za Zhi 2021 Apr;46(8):2037-2044

Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 100029, China.

As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Read More

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Neuroimmune interactions and osteoarthritis pain: focus on macrophages.

Pain Rep 2021 9;6(1):e892. Epub 2021 Mar 9.

Division of Rheumatology, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.

Bidirectional interactions between the immune system and the nervous system are increasingly appreciated as playing a pathogenic role in chronic pain. Unraveling the mechanisms by which inflammatory pain is mediated through communication between nerves and immune cells may lead to exciting new strategies for therapeutic intervention. In this narrative review, we focus on the role of macrophages in the pathogenesis of osteoarthritis (OA) pain. Read More

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Recombinant enterotoxin-1 (rBFT-1) promotes proliferation of colorectal cancer via CCL3-related molecular pathways.

Open Life Sci 2021 27;16(1):408-418. Epub 2021 Apr 27.

Surgical Department, General Hospital of Ningxia Medical University, Yinchuan, China.

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and stands among the leading causes of cancer-related deaths. Although deregulation of the microbiota in the gastrointestinal tract has been frequently described in CRC, very little is known about the precise molecular mechanisms by which bacteria and their toxins modulate the process of tumorigenesis and behavior of cancer cells. In this study, we produced recombinant enterotoxin-1 (rBFT1) and demonstrate that rBFT1 could promote cell proliferation in colorectal cancer cells and accelerate tumor growth . Read More

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CPNE7-Induced Autophagy Restores the Physiological Function of Mature Odontoblasts.

Front Cell Dev Biol 2021 26;9:655498. Epub 2021 Apr 26.

Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology and Developmental Biology, School of Dentistry, Seoul National University, Seoul, South Korea.

Dentin, which composes most of the tooth structure, is formed by odontoblasts, long-lived post-mitotic cells maintained throughout the entire life of the tooth. In mature odontoblasts, however, cellular activity is significantly weakened. Therefore, it is important to augment the cellular activity of mature odontoblasts to regenerate physiological dentin; however, no molecule regulating the cellular activity of mature odontoblasts has yet been identified. Read More

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Secretory Mevalonate Kinase Regulates Host Immune Response and Facilitates Phagocytosis.

Front Cell Infect Microbiol 2021 26;11:641985. Epub 2021 Apr 26.

Department of Molecular Biology, ICMR-Rajendra Memorial Research Institute of Medical Sciences, Patna, India.

secretes over 151 proteins during cultivation. Cellular functions of one such novel protein: mevalonate kinase is discussed here; signifying its importance in infection. Visceral Leishmaniasis is a persistent infection, caused by in Indian subcontinent. Read More

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Kirenol Inhibits B[a]P-Induced Oxidative Stress and Apoptosis in Endothelial Cells via Modulation of the Nrf2 Signaling Pathway.

Oxid Med Cell Longev 2021 23;2021:5585303. Epub 2021 Apr 23.

Department of Biochemistry, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600 077, India.

Atherosclerosis is a persistent inflammatory disorder specified by the dysfunction of the arteries, the world's leading cause of cardiovascular diseases. We sought to determine the effectiveness of KRL in B[a]P-induced oxidative stress and programmed cell death in endothelial cells. Western blotting, real-time PCR, DCFH2-DA, and TUNEL staining were performed to detect pPI3K, pAKT, Nrf2, HO-1, NQO-1, Bcl2, Bax, and caspase-3 on the HUVECs. Read More

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Possibility of inducing tumor cell senescence during therapy.

Oncol Lett 2021 Jul 27;22(1):496. Epub 2021 Apr 27.

School of Pharmaceutical Sciences and Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, P.R. China.

The treatment options for cancer include surgery, radiotherapy and chemotherapy. However, the traditional approach of high-dose chemotherapy brings tremendous toxic side effects to patients, as well as potentially causing drug resistance. Drug resistance affects cell proliferation, cell senescence and apoptosis. Read More

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Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Infection in a Humanized Mouse Model.

Front Immunol 2021 26;12:666290. Epub 2021 Apr 26.

Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute for Tuberculosis Research, 8th Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.

Background: Tuberculosis (TB) is still a global infectious disease that seriously threatens human beings. The only licensed TB vaccine Bacille Calmette-Guérin (BCG)'s protective efficacy varies significantly among populations and regions. It is very urgent to develop more effective vaccines. Read More

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PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease.

Front Immunol 2021 26;12:594376. Epub 2021 Apr 26.

Laboratory of Cellular Immunology and Pharmacology, National Institute for infectious Diseases "Lazzaro Spallanzani"-IRCCS, Rome, Italy.

Tuberculosis (TB), due to infection, is still the principal cause of death caused by a single infectious agent. The balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. Factors defining this variety are unclear and likely involve both mycobacterial and immunological components. Read More

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Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production.

Front Pharmacol 2021 26;12:646628. Epub 2021 Apr 26.

Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Galangin, a flavonoid isolated from the rhizome of (Hance), exerts anticancer activities against many cancer cells such as liver cancer, breast cancer, lung cancer and esophageal cancer. However, the effect, as well as the underlying molecular mechanism of galangin on gastric cancer remains to be elucidated. In the present study, galangin inhibited cell viability of MGC 803 cells but not normal gastric mucosal epithelial GES-1 cells. Read More

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Optimization of PhysicoChemical Parameters for Production of Cytotoxic Secondary Metabolites and Apoptosis Induction Activities in the Culture Extract of a Marine Algal-Derived Endophytic Fungus sp.

Front Pharmacol 2021 26;12:542891. Epub 2021 Apr 26.

Department of Biochemistry, Indian Institute of Science, Bangalore, India.

The endophytic fungal community in the marine ecosystem has been demonstrated to be relevant source of novel and pharmacologically active secondary metabolites. The current study focused on the evaluation of cytotoxic and apoptosis induction potential in the culture extracts of endophytic fungi associated with , a marine brown alga. The cytotoxicity of the four marine endophytes, sp. Read More

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DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer.

Nature 2021 May 12. Epub 2021 May 12.

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Ferroptosis, a form of regulated cell death that is induced by excessive lipid peroxidation, is a key tumour suppression mechanism. Glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) constitute two major ferroptosis defence systems. Here we show that treatment of cancer cells with GPX4 inhibitors results in acute depletion of N-carbamoyl-L-aspartate, a pyrimidine biosynthesis intermediate, with concomitant accumulation of uridine. Read More

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Cinnamaldehyde induces autophagy-mediated cell death through ER stress and epigenetic modification in gastric cancer cells.

Authors:
Tae Woo Kim

Acta Pharmacol Sin 2021 May 12. Epub 2021 May 12.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

Previous reports suggested that cinnamaldehyde (CA), the bioactive ingredient in Cinnamomum cassia, can suppress tumor growth, migratory, and invasive abilities. However, the role and molecular mechanisms of CA in GC are not completely understood. In the present study, we found that CA-induced ER stress and cell death via the PERK-CHOP axis and Ca release in GC cells. Read More

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The GAR/RGG motif defines a family of nuclear alarmins.

Cell Death Dis 2021 May 12;12(5):477. Epub 2021 May 12.

Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD4, 5 Science Drive 2, Singapore, 117545, Singapore.

The nucleus is the target of autoantibodies in many diseases, which suggests intrinsic nuclear adjuvants that confer its high autoimmunogenicity. Nucleolin (NCL) is one abundant nucleolar autoantigen in systemic lupus erythematosus (SLE) patients and, in lupus-prone mice, it elicits autoantibodies early. With purified NCL, we observed that it was a potent alarmin that activated monocytes, macrophages and dendritic cells and it was a ligand for TLR2 and TLR4. Read More

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Mesenchymal stromal exosome-functionalized scaffolds induce innate and adaptive immunomodulatory responses toward tissue repair.

Sci Adv 2021 May 12;7(20). Epub 2021 May 12.

Department of Biomedical Engineering, College of Engineering, Peking University, Haidian District, Beijing 100871, China.

Designing scaffolds capable of inducing and guiding appropriate immune responses holds promise for tissue repair/regeneration. Biofunctional scaffolds were here prepared by immobilizing mesenchymal stromal exosomes onto fibrous polyester materials and allowed cell-mediated delivery of membrane-bound vesicles. Quantitative cell-level analyses revealed that immune cells dominated the uptake of exosomes from scaffolds in vivo, with materials and exosomes acting as the recruiter and trainer for immune cells, respectively, to synergistically promote beneficial macrophage and regulatory T cell responses in skin wounds in mice. Read More

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Millifolide A, a dimeric ether of degraded sesquiterpene lactones, inhibited the proliferation of human lung cancer cell line A549.

Nat Prod Res 2021 May 13:1-3. Epub 2021 May 13.

Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan.

The inhibitory effect of three degraded sesquiterpene lactones, -seco-tanapartholide, arteludooicinolide A and millifolide A isolated from L., on anti-human lung cancer cells was examined using MTT and reporter gene assays. Millifolide A has significant inhibitory effects on the proliferation of human lung cancer cells probably through inducing cell apoptosis. Read More

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Axenic amastigotes of Leishmania species as a suitable model for in vitro studies.

Acta Trop 2021 May 9:105956. Epub 2021 May 9.

Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas, Rio de Janeiro, RJ, Brazil. Electronic address:

Leishmania spp. are etiological agents of infection diseases, which in some cases can be fatal. The main forms of their biological cycle, promastigotes and amastigotes, can be maintained in vitro. Read More

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Phragmunis A suppresses glioblastoma through the regulation of MCL1-FBXW7 by blocking ELK1-SRF complex-dependent transcription.

Neurochem Int 2021 May 9:105051. Epub 2021 May 9.

Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002# Sungang Road, Futian District, Shenzhen 518035, China. Electronic address:

Glioblastoma (GBM) is a highly aggressive brain tumour. During screening work, we found a new compound named phragmunis A (PGA), which is derived from the fruitbody of Trogia venenata, exhibits a potential cytotoxic effect on patient-derived recurrent GBM cells and temozolomide (TMZ)-resistant cell lines. The present study was designed to investigate the potential molecular mechanism of the anti-glioma effects of PGA in vitro and in vivo. Read More

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LncRNA NEAT1 Regulates Infantile Pneumonia by Sponging miR-146b.

Mol Biotechnol 2021 May 12. Epub 2021 May 12.

Department of Pediatrics, Shangdong Provincial Western Hospital, No. 4 Duanxing West Road, Huaiyin District, Jinan, 252022, Shandong Province, China.

This study designed to investigate the potential role of lncRNA NEAT1/miR-146b in infantile pneumonia. In this study, 58 children with pneumonia and 58 healthy children collected for routine examination from December 2016 to January 2019. The lncRNA NEAT1 and miR-146b expression levels were detected by qPCR in both groups. Read More

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Acceleration of Trichinella spiralis worm expulsion by leukotriene B4 receptor binding inhibition.

Parasite Immunol 2021 May 11:e12843. Epub 2021 May 11.

Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University, Yangsan, 50612, Republic of Korea.

Aims: Helminth infection typically induces a Th2 inflammatory response that is characterized by eosinophilia, high levels of IgE, and mast cells. LTB4 is generated from innate immune cells, such as neutrophils, macrophages, and mast cells, in response to a range of stimuli. It mainly acts on myeloid leukocytes, inducing the activation of integrins, adhesion to endothelium walls, and chemotaxis. Read More

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