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Adenine base editing and prime editing of chemically derived hepatic progenitors rescue genetic liver disease.

Cell Stem Cell 2021 Apr 26. Epub 2021 Apr 26.

Department of Surgery, Hanyang University College of Medicine, Seoul 04763, Republic of Korea; HY Indang Center of Regenerative Medicine and Stem Cell Research, Hanyang University, Seoul 04763, Republic of Korea; Department of HY-KIST Bio-convergence, Hanyang University, Seoul 04763, Republic of Korea. Electronic address:

DNA base editors and prime editing technology enable therapeutic in situ correction of disease-causing alleles. These techniques could have broad applications for ex vivo editing of cells prior to transplantation in a range of diseases, but it is critical that the target population is efficiently modified and engrafts into the host. Chemically derived hepatic progenitors (CdHs) are a multipotent population capable of robust engraftment and hepatocyte differentiation. Read More

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Aging modulates the effects of ischemic injury upon mesenchymal cells within the renal interstitium and microvasculature.

Stem Cells Transl Med 2021 May 5. Epub 2021 May 5.

Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.

The renal mesenchyme contains heterogeneous cells, including interstitial fibroblasts and pericytes, with key roles in wound healing. Although healing is impaired in aged kidneys, the effect of age and injury on the mesenchyme remains poorly understood. We characterized renal mesenchymal cell heterogeneity in young vs old animals and after ischemia-reperfusion-injury (IRI) using multiplex immunolabeling and single cell transcriptomics. Read More

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Multifunctional Graphdiyne-Cerium Oxide Nanozymes Facilitate MicroRNA Delivery and Attenuate Tumor Hypoxia for Highly Efficient Radiotherapy of Esophageal Cancer.

Adv Mater 2021 May 5:e2100556. Epub 2021 May 5.

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

Radioresistance is an important challenge for clinical treatments. The main causes of radioresistance include hypoxia in the tumor microenvironment, the antioxidant system within cancer cells, and the upregulation of DNA repair proteins. Here, a multiple radiosensitization strategy of high-Z-element-based radiation enhancement is designed, attenuating hypoxia and microRNA therapy. Read More

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Injectable hydrogel-mediated combination of hyperthermia ablation and photo-enhanced chemotherapy in the NIR-II window for tumor eradication.

Biomater Sci 2021 May;9(9):3516-3525

School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China.

Local administration of therapeutic agents with long-term retention capabilities efficiently avoids nonspecific distribution in normal organs with an increased drug concentration in pathological tissue. Herein, we developed an injectable and degradable alginate-calcium (Ca2+) hydrogel for the local administration of corn-like Au/Ag nanorods (NRs) and doxorubicin hydrochloride (DOX·HCl). The immobilized Au/Ag NRs with strong absorbance in the near-infrared II (NIR-II) window efficiently ablated the majority of tumor cells after 1064 nm laser irradiation and triggered the release of DOX to kill residual tumor cells. Read More

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Nano-assembly of ursolic acid with platinum prodrug overcomes multiple deactivation pathways in platinum-resistant ovarian cancer.

Biomater Sci 2021 May 5. Epub 2021 May 5.

Department of Pharmacy, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan 528300, P. R. China. and A School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.

As the most common cause of gynecological cancer-related deaths worldwide, ovarian cancer requires novel therapy strategies. Pt(ii)-Based antitumor drugs (e.g. Read More

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An efficient localized catalytic hairpin assembly-based DNA nanomachine for miRNA-21 imaging in living cells.

Analyst 2021 May;146(9):3041-3051

Research Center of Analytical Instrumentation, Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an, 710069, Shaanxi, P.R. China.

As an enzyme-free isothermal amplification strategy, catalytic hairpin assembly (CHA) is a very promising method for cell imaging. However, the practical application of CHA on intracellular miRNA imaging is limited by slow kinetics, insufficient amplification efficiency and strong interference in living cells. Herein, a localized catalytic hairpin assembly-based DNA nanomachine (LCHA nanomachine) was developed for the rapid, efficient and reliable fluorescence resonance energy transformation (FRET) imaging of miRNA-21 in living cells. Read More

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Efficacy of orthobiologic adjuvants to core decompression for hip preservation in avascular necrosis hip.

J Hip Preserv Surg 2020 Aug 22;7(3):423-438. Epub 2020 Nov 22.

Department of Orthopaedics, PGIMER, Chandigarh 160012, India.

Head preserving modalities in avascular necrosis (AVN) hip are variably effective in early stages, and further options that could prevent head distortion and osteoarthritis are needed. Core decompression (CD) is the most commonly used surgery in the early stages of osteonecrosis with variable rates of success. The present review aimed to determine the effectiveness of bone marrow aspirate concentrate (BMAC), platelet-rich plasma (PRP), bone morphogenetic proteins (BMP) or their combination with CD in early stages of AVN hip, prior to collapse of femoral head. Read More

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Comparison of amniotic membrane versus the induced membrane for bone regeneration in long bone segmental defects using calcium phosphate cement loaded with BMP-2.

Mater Sci Eng C Mater Biol Appl 2021 May 20;124:112032. Epub 2021 Mar 20.

Univ. Bordeaux, INSERM, BIOTIS, U1026, F-33000 Bordeaux, France; CHU Bordeaux, Service de chirurgie orale, F-33076 Bordeaux, France.

Thanks to its biological properties, the human amniotic membrane (HAM) combined with a bone substitute could be a single-step surgical alternative to the two-step Masquelet induced membrane (IM) technique for regeneration of critical bone defects. However, no study has directly compared these two membranes. We first designed a 3D-printed scaffold using calcium phosphate cement (CPC). Read More

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Manifestations of Age on Autophagy, Mitophagy and Lysosomes in Skeletal Muscle.

Cells 2021 Apr 29;10(5). Epub 2021 Apr 29.

Muscle Health Research Centre, York University, Toronto, ON M3J 1P3, Canada.

Sarcopenia is the loss of both muscle mass and function with age. Although the molecular underpinnings of sarcopenia are not fully understood, numerous pathways are implicated, including autophagy, in which defective cargo is selectively identified and degraded at the lysosome. The specific tagging and degradation of mitochondria is termed mitophagy, a process important for the maintenance of an organelle pool that functions efficiently in energy production and with relatively low reactive oxygen species production. Read More

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Characterization of Extracellular Vesicles Secreted in Lentiviral Producing HEK293SF Cell Cultures.

Viruses 2021 04 29;13(5). Epub 2021 Apr 29.

Department of Bioengineering, McGill University, Montreal, QC H3A 0E9, Canada.

Lentiviral vectors (LVs) are a powerful tool for gene and cell therapy and human embryonic kidney cells (HEK293) have been extensively used as a platform for production of these vectors. Like most cells and cellular tissues, HEK293 cells release extracellular vesicles (EVs). EVs released by cells share similar size, biophysical characteristics and even a biogenesis pathway with cell-produced enveloped viruses, making it a challenge to efficiently separate EVs from LVs. Read More

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Lipopolysaccharide-Induced Nitric Oxide and Prostaglandin E2 Production Is Inhibited by Tellimagrandin II in Mouse and Human Macrophages.

Life (Basel) 2021 Apr 30;11(5). Epub 2021 Apr 30.

Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

Sepsis develops from a serious microbial infection that causes the immune system to go into overdrive. The major microorganisms that induce sepsis are Gram-negative bacteria with lipopolysaccharide (LPS) in their cell walls. Nitric oxide (NO) and cyclooxygenase-2 (COX-2) are the key factors involved in the LPS-induced pro-inflammatory process. Read More

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Metabolite Biomarkers of Antimony Resistance.

Cells 2021 Apr 30;10(5). Epub 2021 Apr 30.

Programa de Estudio y Control de Enfermedades Tropicales, Facultad de Medicina, Universidad de Antioquia, Medellín 050010, Colombia.

parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associated with increased incidence, mortality, and healthcare costs. The antimonial drug is the main historically implemented drug for leishmaniasis. Read More

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Hydro-alcoholic extract of reduces fasting blood glucose and HbA1c% in diabetic patients, probably via competitive and allosteric interaction with alpha-glucosidase enzyme; a clinical trial and analysis.

J Complement Integr Med 2021 May 5. Epub 2021 May 5.

Department of Nursing, Khomein University of Medical Sciences, Khomein, Iran.

Objectives: 1-Deoxynojirimycin (1-DNJ), the main active component found in () is reported to be effective in controlling diabetes. We have evaluated the effect of hydro-alcoholic extract of leaves on the fasting blood glucose (FBS) and hemoglobin A1c% (HbA1c%) in diabetic patients. Furthermore, we compared the interaction of 1-DNJ and glucose molecules with the alpha-glucosidase enzyme, which has a critical role in the lysis of glucose-based polymers in human cells. Read More

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RNA cancer vaccines: developing mRNA nanovaccine with self-adjuvant property for cancer immunotherapy.

Hum Vaccin Immunother 2021 May 4:1-4. Epub 2021 May 4.

Department of Experiment Medicine, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Messenger RNA (mRNA)-based cancer vaccine has become a popular approach for developing personalized and effective antitumor immunotherapy. To achieve robust antitumor efficacy, mRNA-encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells for efficient antigen presentation; meanwhile, the vaccine would have adjuvant effect by stimulating innate immune response to boost the full activation of adaptive immunity. Recently, we reported a minimalist nanovaccine by formulating tumor antigen-encoding mRNA with a lipid-like material named C1, which could efficiently deliver mRNA into dendritic cells with simultaneous Toll-like receptor 4 (TLR4) stimulation, together induced T cell activation. Read More

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Well-Defined Nanostructured Biointerfaces: Strengthened Cellular Interaction for Circulating Tumor Cells Isolation.

Adv Healthc Mater 2021 May 4:e2002202. Epub 2021 May 4.

Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, Berlin, 14195, Germany.

The topographic features at the cell-material biointerface are critical for cellular sensing of the extracellular environment (ECM) and have gradually been recognized as key factors that regulate cell adhesion behavior. Herein, a well-defined nanostructured biointerface is fabricated via a new generation of mussel-inspired polymer coating to mimic the native ECM structures. Upon the bioinert background presence and biospecific ligands conjugation, the affinity of cancer cells to the resulting biofunctional surfaces, which integrate topographic features and biochemical cues, is greatly strengthened. Read More

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Programmable RNA editing with compact CRISPR-Cas13 systems from uncultivated microbes.

Nat Methods 2021 May 3. Epub 2021 May 3.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Competitive coevolution between microbes and viruses has led to the diversification of CRISPR-Cas defense systems against infectious agents. By analyzing metagenomic terabase datasets, we identified two compact families (775 to 803 amino acids (aa)) of CRISPR-Cas ribonucleases from hypersaline samples, named Cas13X and Cas13Y. We engineered Cas13X. Read More

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DNA-inspired nanomaterials for enhanced endosomal escape.

Proc Natl Acad Sci U S A 2021 05;118(19)

Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269

To realize RNA interference (RNAi) therapeutics, it is necessary to deliver therapeutic RNAs (such as small interfering RNA or siRNA) into cell cytoplasm. A major challenge of RNAi therapeutics is the endosomal entrapment of the delivered siRNA. In this study, we developed a family of delivery vehicles called Janus base nanopieces (NPs). Read More

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Inhibition of Jumonji histone demethylases selectively suppresses HER2+ breast leptomeningeal carcinomatosis growth via inhibition of GM-CSF expression.

Cancer Res 2021 May 3. Epub 2021 May 3.

Neurosurgery, City of Hope Medical Center

HER2+ breast leptomeningeal carcinomatosis (HER2+ LC) occurs when tumor cells spread to cerebrospinal fluid-containing leptomeninges surrounding the brain and spinal cord, a complication with a dire prognosis. HER2+ LC remains incurable with few treatment options. Currently, much effort is devoted towards development of therapies that target mutations. Read More

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A novel non-viral delivery method that enables efficient engineering of primary human T cells for ex vivo cell therapy applications.

Cytotherapy 2021 Apr 30. Epub 2021 Apr 30.

Avectas Ltd, Maynooth, Ireland. Electronic address:

Background Aims: Next-generation immune cell therapy products will require complex modifications using engineering technologies that can maintain high levels of cell functionality. Non-viral engineering methods have the potential to address limitations associated with viral vectors. However, while electroporation is the most widely used non-viral modality, concerns about its effects on cell functionality have led to the exploration of alternative approaches. Read More

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Lipid nanocapsules co-encapsulating paclitaxel and salinomycin for eradicating breast cancer and cancer stem cells.

Colloids Surf B Biointerfaces 2021 Apr 19;204:111775. Epub 2021 Apr 19.

Department of Biomedical Engineering, Indian Institute of Technology, Hyderabad, India. Electronic address:

Cancer stem cells (CSCs) comprise a diminutive population of the tumor but pose major obstacles in cancer treatment, often their presence being correlated with poor prognosis, therapeutic resistance and relapse. Nanocarriers of combined drugs regimes demonstrate improved pharmacokinetics and decreased systemic toxicity by targeting the bulk tumor cells along with CSCs, holding the key to future successful chemotherapy. Herein, we developed lipid nanocapsules (LNCs) with co-encapsulated paclitaxel (PTX) and salinomycin (SAL) to eliminate breast cancer cells (MCF-7; non-bCSCs) and cancer stem cells (bCSCs) respectively. Read More

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Computer simulations of lipid regulation by molecular semi-grand canonical ensembles.

Biophys J 2021 Apr 30. Epub 2021 Apr 30.

Van 't Hoff Institute for Molecular Sciences and Informatics Institute, University of Amsterdam, Amsterdam 1098 XH, The Netherlands; Max Planck Institute for Polymer Research, Ackermannweg 10, Mainz 55128, Germany.

The plasma membrane is the interface between cells and exterior media. While its existence has been known for a long time, organization of its constituent lipids remain a challenge. Recently, we have proposed that lipid populations may be controlled by chemical potentials of different lipid species, resulting in semi-grand canonical thermodynamic ensembles. Read More

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MMFGRN: a multi-source multi-model fusion method for gene regulatory network reconstruction.

Brief Bioinform 2021 May 3. Epub 2021 May 3.

College of Intelligence and Computing, Tianjin University, Tianjin, China.

Lots of biological processes are controlled by gene regulatory networks (GRNs), such as growth and differentiation of cells, occurrence and development of the diseases. Therefore, it is important to persistently concentrate on the research of GRN. The determination of the gene-gene relationships from gene expression data is a complex issue. Read More

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Making Aggregation-Induced Emission Luminogen More Valuable by Gold: Enhancing Anticancer Efficacy by Suppressing Thioredoxin Reductase Activity.

ACS Nano 2021 May 3. Epub 2021 May 3.

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China.

Gold complexes have been recognized as potential anticancer agents against various kinds of diseases due to their inherent suppressions of antioxidant thioredoxin reductase (TrxR) activity. Herein, a powerful aggregation-induced emission luminogen (AIEgen), TBP-Au, was designed and synthesized by integrating an anticancer Au(I) moiety with an AIE-active photosensitizer (TBP), in which both the production and consumption routes of reactive oxygen species (ROS) were elaborately considered simultaneously to boost the anticancer efficacy. It has been demonstrated that TBP-Au could realize superior two-photon fluorescence imaging in tumor tissues with high resolution and deep penetration as well as long-term imaging in live animals due to its AIE property. Read More

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Patient-Specific induced Pluripotent Stem Cell-Derived Hepatocyte-Like Cells as a Model to Study Autosomal Recessive Hypercholesterolemia.

Stem Cells Dev 2021 May 2. Epub 2021 May 2.

Associatie KU Leuven, 418666, Department of Development and Regeneration, Stem Cell Biology and Embryology, Interdepartmental Stem Cell Institute, Leuven, Belgium;

Autosomal recessive hypercholesterolemia (ARH) is a rare monogenic disorder caused by pathogenic variants in the low-density lipoprotein receptor (LDLR) adaptor protein-1 (LDLRAP1) gene, encoding for the LDLRAP1 protein, which impairs internalization of hepatic LDLR. There are variable responses of ARH patients to treatment and the pathophysiological mechanism(s) for this variability remains unclear. This is in part caused by absence of reliable cellular models to evaluate the effect of LDLRAP1 mutations on LDLRAP1 protein function and its role in LDLR internalization. Read More

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Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis.

Bioact Mater 2021 Nov 13;6(11):3879-3891. Epub 2021 Apr 13.

Academy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Tianjin University, 92 Weijin Road, Nankai District, Tianjin, 300072, China.

The conventional immunoadjuvants in vaccine have weak effect on stimulating antigen presentation and activating anti-tumor immunity. Unexpectedly, we discovered that non-pathogenic Sendai virus (SeV) could activate antigen-presenting cells (APCs) represented by dendritic cells (DCs). Here, we designed an injectable SeV-based hydrogel vaccine (SHV) to execute multi-channel recruitment and stimulation of DCs for boosting the specific immune response against tumors. Read More

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November 2021

Identification of an IRGP Signature to Predict Prognosis and Immunotherapeutic Efficiency in Bladder Cancer.

Front Mol Biosci 2021 15;8:607090. Epub 2021 Apr 15.

Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Identify immune-related gene pairs (IRGPs) signature related to the prognosis and immunotherapeutic efficiency for bladder cancer (BLCA) patients.

Materials And Methods: One RNA-seq dataset (The Cancer Genome Atlas Program) and two microarray datasets (GSE13507 and GSE31684) were included in this study. We defined these cohorts as training set to construct IRGPs and one immunotherapy microarray dataset as validation set. Read More

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Morphological characterization of the human corneal epithelium by confocal laser scanning microscopy.

Quant Imaging Med Surg 2021 May;11(5):1737-1750

Department of Ophthalmology, Rostock University Medical Center, Rostock, Germany.

Background: Regarding the growing interest and importance of understanding the cellular changes of the cornea in diseases, a quantitative cellular characterization of the epithelium is becoming increasingly important. Towards this, the latest research offers considerable improvements in imaging of the cornea by confocal laser scanning microscopy (CLSM). This study presents a pipeline to generate normative morphological data of epithelial cell layers of healthy human corneas. Read More

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Improvement of Targeted Chemotherapy of HER2-positive Ovarian Malignant Cell Line by Z-Idarubicin Conjugate: An in vitro Study.

Iran J Pathol 2021 20;16(2):109-118. Epub 2020 Dec 20.

Hyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background & Objective: Overexpression of human epidermal growth factor receptor 2 (HER2) causes cell transformation and development of various types of malignancies. Idarubicin is an effective anti-neoplastic drug but its specific delivery to the targeted cells is still a great challenge. Affibody as a cost-effective peptide molecule with low molecular weight has a high affinity for HER2 receptors. Read More

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December 2020

Adapting T Cell Receptor Ligand Discrimination Capability LAT.

Front Immunol 2021 16;12:673196. Epub 2021 Apr 16.

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States.

Self- and non-self ligand discrimination is a core principle underlying T cell-mediated immunity. Mature αβ T cells can respond to a foreign peptide ligand presented by major histocompatibility complex molecules (pMHCs) on antigen presenting cells, on a background of continuously sensed self-pMHCs. How αβ T cells can properly balance high sensitivity and high specificity to foreign pMHCs, while surrounded by a sea of self-peptide ligands is not well understood. Read More

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