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A glypican-1-targeted antibody-drug conjugate exhibits potent tumor growth inhibition in glypican-1-positive pancreatic cancer and esophageal squamous cell carcinoma.

Neoplasia 2021 Jul 28;23(9):939-950. Epub 2021 Jul 28.

Department of Clinical Immunology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan; Institute for Biomedical Sciences Molecular Pathophysiology, Iwate Medical University, Yahaba, Iwate, Japan; Division of Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Iwate, Japan. Electronic address:

An antibody-drug conjugate (ADC) is a promising therapeutic modality because selective and effective delivery of an anti-cancer drug is achieved by drug-conjugated antibody-targeting cancer antigen. Glypican 1 (GPC1) is highly expressed in malignant tumors, including pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC). Herein, we describe the usefulness of GPC1-targeting ADC. Read More

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Subtyping of head and neck squamous cell cancers based on immune signatures.

Int Immunopharmacol 2021 Jul 28;99:108007. Epub 2021 Jul 28.

Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Big Data Research Institute, China Pharmaceutical University, Nanjing 211198, China. Electronic address:

Although head and neck squamous cell cancer (HNSCC) is one of the cancer types in which immune checkpoint inhibitors (ICIs) has achieved a certain success, only a subset of HNSCC patients respond to ICIs. Thus, identification of HNSCC subtypes responsive to ICIs is crucial. Using hierarchical clustering, we identified three subtypes of HNSCC, termed Immunity-H, Immunity-M, and Immunity-L, based on the enrichment scores of 28 immune cells generated by the single-sample gene-set enrichment analysis of transcriptome data. Read More

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Near infrared photoimmunotherapy for cancers: A translational perspective.

EBioMedicine 2021 Jul 28;70:103501. Epub 2021 Jul 28.

Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

Near-infrared photoimmunotherapy (NIR-PIT) is a newly-developed, highly-selective cancer treatment, which utilizes a monoclonal antibody conjugated to a photoabsorbing dye, IRDye700DX (IR700). The antibody conjugate is injected into the patient and accumulates in the tumour. Within 24 h of injection the tumour is exposed to NIR light which activates the conjugate and causes rapid, selective cancer cell death. Read More

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Controllable synthesis and self-template phase transition of hydrous TiO colloidal spheres for photo/electrochemical applications.

Adv Colloid Interface Sci 2021 Jul 21;295:102493. Epub 2021 Jul 21.

MOE Key Laboratory of Resources and Environmental Systems Optimization, College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, China. Electronic address:

Hydrous TiO colloidal spheres (HTCS) derived from the direct precipitation of titanium alkoxides have attracted continuous interests since 1982. Entering the 21st century, rapid progress in the development of structure-directing agents (SDAs) have enabled reproducible and size-controllable synthesis of highly uniform HTCS with diameters in the nano- to micro-meter range. The availability of various HTCS provides versatile self-templating platforms for the targeted synthesis of nanoporous TiO and titanate spheres with tunable composition, crystallographic phases, and internal structures for a variety of advanced photo/electrochemical applications. Read More

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Local and systemic gene expression levels of IL-10, IL-17 and TGF-β in active ocular toxoplasmosis in humans.

Cytokine 2021 Jul 28;146:155643. Epub 2021 Jul 28.

Department of Parasitology and Mycology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: To compare mRNA expression of interleukin 10 (IL-10), interleukin 17 (IL-17) and Transforming Growth Factor-β (TGF-β) in aqueous humor (AH) and peripheral blood mononuclear cells (PBMCs) in human ocular toxoplasmosis (OT) and controls.

Method: RNA isolation, cDNA synthesis and real-time polymerase chain reaction were performed on AH sediments and PBMCs of 16 patients with active OT and 21 controls at the Khatam-al-Anbia Eye Hospital, Iran. For comparison, Mann Whitney U test was used at a discrimination level of p < 0. Read More

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NAC antagonizes arsenic-induced neurotoxicity through TMEM179 by inhibiting oxidative stress in Oli-neu cells.

Ecotoxicol Environ Saf 2021 Jul 28;223:112554. Epub 2021 Jul 28.

Department of Occupational Health, Army Medical University, 400038, Chongqing, People's Republic of China. Electronic address:

Arsenic is one of the most common environmental pollutants. Neurotoxicity induced by arsenic has become a major public health concern. However, the effects of arsenic-induced neurotoxicity in the brain and the underlying molecular mechanisms are not well understood. Read More

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Direct Reprogramming Induces Vascular Regeneration Post Muscle Ischemic Injury.

Mol Ther 2021 Jul 28. Epub 2021 Jul 28.

Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 10029; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 10029; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 10029. Electronic address:

Reprogramming non-cardiomyocytes (non-CMs) into cardiomyocyte (CM)-like cells is a promising strategy for cardiac regeneration in conditions such as ischemic heart disease. Here, we used a modified mRNA (modRNA) gene delivery platform to deliver a cocktail of four cardiac-reprogramming genes (Gata4 (G), Mef2c (M), Tbx5 (T) and Hand2 (H)) together with three reprogramming-helper genes (Dominant Negative (DN)-TGFβ, DN-Wnt8a and Acid ceramidase (AC)), termed 7G-modRNA, to induce CM-like cells. We showed that 7G-modRNA reprogrammed 57% of CM-like cells in vitro. Read More

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Biomechanical Consequences of Compromised Elastic Fiber Integrity and Matrix Cross-Linking on Abdominal Aortic Aneurysmal Enlargement.

Acta Biomater 2021 Jul 28. Epub 2021 Jul 28.

Department of Biomedical Engineering, Yale University, New Haven, CT; Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT. Electronic address:

Abdominal aortic aneurysms (AAAs) are characterized histopathologically by compromised elastic fiber integrity, lost smooth muscle cells or their function, and remodeled collagen. We used a recently introduced mouse model of AAAs that combines enzymatic degradation of elastic fibers and blocking of lysyl oxidase, and thus matrix cross-linking, to study progressive dilatation of the infrarenal abdominal aorta, including development of intraluminal thrombus. We quantified changes in biomaterial properties and biomechanical functionality within the aneurysmal segment as a function of time of enlargement and degree of thrombosis. Read More

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Oxidized GAPDH transfers S-glutathionylation to a nuclear protein Sirtuin-1 leading to apoptosis.

Free Radic Biol Med 2021 Jul 28. Epub 2021 Jul 28.

Vascular Biology Section, Boston University School of Medicine, Boston, MA, USA.

Aims: S-glutathionylation is a reversible oxidative modification of protein cysteines that plays a critical role in redox signaling. Glutaredoxin-1 (Glrx), a glutathione-specific thioltransferase, removes protein S-glutathionylation. Glrx, though a cytosolic protein, can activate a nuclear protein Sirtuin-1 (SirT1) by removing its S-glutathionylation. Read More

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Isorhapontigenin (ISO) inhibits EMT through FOXO3A/METTL14/VIMENTIN pathway in bladder cancer cells.

Cancer Lett 2021 Jul 28. Epub 2021 Jul 28.

Department of Environmental Medicine, New York University Grossman School of Medicine, 341 East 25th Street, New York, NY, 10010, USA. Electronic address:

Epithelial mesenchymal transition (EMT) is highly correlated with metastasis during cancer development. Although previous studies have revealed that ISO is able to inhibit cancer cell invasion and stem-cell properties, little is known about the effects of ISO on EMT markers. The present study explores the potential regulation of ISO on EMT, leading to the inhibition of migration and invasion of bladder cancer cells. Read More

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Sialic acid-conjugate modified doxorubicin nanoplatform for treating neutrophil-related inflammation.

J Control Release 2021 Jul 28. Epub 2021 Jul 28.

College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China. Electronic address:

Neutrophils, the most abundant leukocytes in human peripheral blood, are important effector cells that mediate the inflammatory response. During neutrophil dysfunction, excessive activation and uncontrolled infiltration are the core processes in the progression of inflammation-related diseases, including severe coronavirus disease-19 (COVID-19), sepsis, etc. Herein, we used sialic acid-modified liposomal doxorubicin (DOX-SAL) to selectively target inflammatory neutrophils in the peripheral blood and deliver DOX intracellularly, inducing neutrophil apoptosis, blocking neutrophil migration, and inhibiting the inflammatory response. Read More

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T cells protect against hepatitis A virus infection and limit infection-induced liver injury.

J Hepatol 2021 Jul 28. Epub 2021 Jul 28.

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:

Background & Aims: Hepatitis A virus (HAV) is a common cause of enterically-transmitted viral hepatitis. In non-immune individuals, infection results in typically transient but occasionally fulminant and fatal inflammatory liver injury. Virus-specific T cell frequencies peak when liver damage is at its zenith, leading to the prevalent notion that T cells exacerbate liver disease, as suspected for other hepatotropic virus infections. Read More

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Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review.

Cancer Commun (Lond) 2021 Jul 31. Epub 2021 Jul 31.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P. R. China.

Pancreatic cancer is a highly malignant digestive system tumor with a poor prognosis. Most pancreatic cancer patients are diagnosed at an advanced stage or even metastasis due to its highly aggressive characteristics and lack of typical early symptoms. Thus, an early diagnosis of pancreatic cancer is crucial for improving its prognosis. Read More

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Modifying effects of menthol against benzo(a)pyrene-induced forestomach carcinogenesis in female Swiss mice.

Environ Toxicol 2021 Jul 31. Epub 2021 Jul 31.

Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, Brazil.

Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon widespread in the environment and closely associated to tobacco use, which is an important risk factor for highly incident stomach cancer. Menthol, a monoterpene extracted from Mentha genus species, has multiple biological properties, including anti-inflammatory and gastroprotective properties, but its effects on carcinogenesis are still to be fully understood. Thus, we evaluated the modifying effects of Ment against BaP-induced forestomach carcinogenesis. Read More

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Morphological and histochemical features of the digestive tract of Leiarius marmoratus (Gill, 1870).

J Fish Biol 2021 Jul 31. Epub 2021 Jul 31.

Faculty of Sciences, Department of Biological Sciences, São Paulo State University (UNESP), Bauru, SP, Brazil.

Leiarius marmoratus, a freshwater catfish from Pimelodidae family, shows great biological and commercial relevance, due its geographic distribution and adaptation to fish-farm. The knowledge of the morphological characteristics of the digestive tract is fundamental to the understanding of fish physiology and nutrition, helping in the planning of diets to provide better management and success in fish farming. Thus, this work described the morphology and histochemistry of the digestive tract of Leiarius marmoratus adults. Read More

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Dephosphorylation of annexin A2 by protein phosphatase 1 regulates endothelial cell barrier.

IUBMB Life 2021 Jul 30. Epub 2021 Jul 30.

Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Annexin A2 (ANXA2) is a multifunctional protein expressed in nearly all human tissues and cell types, playing a role in various signaling pathways. It is subjected to phosphorylation, but no specific protein phosphatase has been identified in its posttranslational regulation yet. Using pull down assay followed by LC-MS/MS analysis we found that ANXA2 interacts with TIMAP (TGF-beta-inhibited membrane-associated protein) in pulmonary artery endothelial cells. Read More

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UltraPlex Hapten-Based Multiplexed Fluorescent Immunohistochemistry.

Methods Mol Biol 2021 ;2350:267-287

Cell IDx, San Diego, CA, USA.

The UltraPlex method for multiplexed two-dimensional fluorescent immunohistochemistry is described, in which hapten tags conjugated to primary antibodies facilitate multiplexed imaging of four or more antigens per tissue section at once. Anti-hapten secondary antibodies labeled with fluorophores provide amplified signal for detection, which is accomplished using a standard fluorescent microscope or digital slide scanner. The protocol is rapid and straightforward and utilizes conventionally prepared tissue samples. Read More

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January 2021

Boron rich nanotube drug carrier system is suited for boron neutron capture therapy.

Sci Rep 2021 Jul 30;11(1):15520. Epub 2021 Jul 30.

Department of Chemistry, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada.

Boron neutron capture therapy (BNCT) is a two-step therapeutic process that utilizes Boron-10 in combination with low energy neutrons to effectively eliminate targeted cells. This therapy is primarily used for difficult to treat head and neck carcinomas; recent advances have expanded this method to cover a broader range of carcinomas. However, it still remains an unconventional therapy where one of the barriers for widespread adoption is the adequate delivery of Boron-10 to target cells. Read More

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Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells.

Sci Rep 2021 Jul 30;11(1):15510. Epub 2021 Jul 30.

Department of Renal Medicine, UCL Medical School, Royal Free Campus, 2nd floor, Rowland Hill Street, London, NW3 2PF, UK.

Ischemia is a major cause of kidney damage. Proximal tubular epithelial cells (PTECs) are highly susceptible to ischemic insults that frequently cause acute kidney injury (AKI), a potentially life-threatening condition with high mortality. Accumulating evidence has identified altered mitochondrial function as a central pathologic feature of AKI. Read More

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PolyG-DS: An ultrasensitive polyguanine tract-profiling method to detect clonal expansions and trace cell lineage.

Proc Natl Acad Sci U S A 2021 Aug;118(31)

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195;

Polyguanine tracts (PolyGs) are short guanine homopolymer repeats that are prone to accumulating mutations when cells divide. This feature makes them especially suitable for cell lineage tracing, which has been exploited to detect and characterize precancerous and cancerous somatic evolution. PolyG genotyping, however, is challenging because of the inherent biochemical difficulties in amplifying and sequencing repetitive regions. Read More

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The tails of PKA.

Mol Pharmacol 2021 Jul 30. Epub 2021 Jul 30.

Nutrition, University of Oslo, Norway.

The catalytic subunit of PKA is regulated by two tails that each wrap around the N- and C-lobes of the kinase core. While the Ct-Tail is classified as an intrinsically disordered region (IDR), the Nt-Tail is dominated by a strong helix that is flanked by short IDRs. In contrast to the Ct-Tail, which is a conserved and highly regulated feature of all AGC kinases, the Nt-Tail has evolved more recently and is not even conserved in non-mammalian PKAs. Read More

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Epigenetic Analysis of the Chromatin Landscape Identifies a Repertoire of Murine Eosinophil-Specific PU.1-Bound Enhancers.

J Immunol 2021 Jul 30. Epub 2021 Jul 30.

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH;

Eosinophils develop in the bone marrow from hematopoietic progenitors into mature cells capable of a plethora of immunomodulatory roles via the choreographed process of eosinophilopoiesis. However, the gene regulatory elements and transcription factors (TFs) orchestrating this process remain largely unknown. The potency and resulting diversity fundamental to an eosinophil's complex immunomodulatory functions and tissue specialization likely result from dynamic epigenetic regulation of the eosinophil genome, a dynamic eosinophil regulome. Read More

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Macrophage regulation of angiogenesis in health and disease.

Semin Cell Dev Biol 2021 Jul 27. Epub 2021 Jul 27.

Department of Biology & Biochemistry, Faculty of Science, University of Bath, Claverton Down, Bath BA2 7AY, UK. Electronic address:

Macrophages are primarily known as phagocytic innate immune cells, but are, in fact, highly dynamic multi-taskers that interact with many different tissue types and have regulatory roles in development, homeostasis, tissue repair, and disease. In all of these scenarios angiogenesis is pivotal and macrophages appear to play a key role in guiding both blood vessel sprouting and remodelling wherever that occurs. Recent studies have explored these processes in a diverse range of models utilising the complementary strengths of rodent, fish and tissue culture studies to unravel the mechanisms underlying these interactions and regulatory functions. Read More

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A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery.

J Nanobiotechnology 2021 Jul 30;19(1):227. Epub 2021 Jul 30.

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

The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Read More

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The ESCRT-0 subcomplex component Hrs/Hgs is a master regulator of myogenesis via modulation of signaling and degradation pathways.

BMC Biol 2021 Jul 30;19(1):153. Epub 2021 Jul 30.

Institut NeuroMyoGène, CNRS UMR5310, INSERM U1217, Faculté de Médecine Rockefeller, Université Claude Bernard Lyon, 8 avenue Rockefeller, 69373, 09, Lyon, Cedex, France.

Background: Myogenesis is a highly regulated process ending with the formation of myotubes, the precursors of skeletal muscle fibers. Differentiation of myoblasts into myotubes is controlled by myogenic regulatory factors (MRFs) that act as terminal effectors of signaling cascades involved in the temporal and spatial regulation of muscle development. Such signaling cascades converge and are controlled at the level of intracellular trafficking, but the mechanisms by which myogenesis is regulated by the endosomal machinery and trafficking is largely unexplored. Read More

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Self-assembled micelles of the (lipo) glycopeptides, teicoplanin, as taxane nanocarriers.

Nanotechnology 2021 Jul 30. Epub 2021 Jul 30.

Centro de Excelencia en Productos y Procesos Cordoba, Pabellon Ceprocor. Santa Maria de Punilla, Cordoba, 5004, ARGENTINA.

The use of nanoparticles is one of the strategies currently studied to minimize the toxicity and lack of tissue specificity of many cancer drugs used in chemotherapy. In this research the physicochemical and biological behavior of a novel self-assembled nanostructure of the antibiotic Teicoplanin (Teico) was characterized as a nanocarrier system for solubilizing highly hydrophobic drugs like Paclitaxel (Ptx) in aqueous media. The Teico micelles were loaded with Ptx in DMSO or PEG-400. Read More

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Polymeric nanoparticle mediated inhibition of miR-21 with enhanced miR-124 expression for combinatorial glioblastoma therapy.

Biomaterials 2021 Jul 20;276:121036. Epub 2021 Jul 20.

Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China; Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China; Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia. Electronic address:

Glioblastoma (GBM) is the most common and fatal form of malignant brain tumor. Despite intensive effort, there is still no effective GBM treatment. Therefore, novel and more effective GBM therapeutic approaches are highly desired. Read More

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N, N, dimethyl-hexadecylamine modulates Arabidopsis root growth through modifying the balance between stem cell niche and jasmonic acid-dependent gene expression.

Gene Expr Patterns 2021 Jul 27:119201. Epub 2021 Jul 27.

Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo. Edificio B3, Ciudad Universitaria, Morelia, Michoacán, Mexico. Electronic address:

N, N, dimethyl-hexadecylamine (DMHDA) is released as part of blends emitted by plant probiotic bacteria and affects root architecture, defense and nutrition of plants. Here, we investigated the changes in gene expression of transcription factors responsible of maintenance of the root stem cell niche and jasmonic acid signaling in Arabidopsis seedlings in response to this volatile. Concentrations of DMHDA that repress primary root growth were found to alter cell size and division augmenting cell tissue layers in the meristem and causing root widening. Read More

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PCNA inhibition enhances the cytotoxicity of β-lapachone in NQO1-Positive cancer cells by augmentation of oxidative stress-induced DNA damage.

Cancer Lett 2021 Jul 27. Epub 2021 Jul 27.

Department of Radiation Oncology, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. Electronic address:

β-Lapachone is a classic quinone-containing antitumor NQO1-bioactivatable drug that directly kills NQO1-overexpressing cancer cells. However, the clinical applications of β-lapachone are primarily limited by its high toxicity and modest lethality. To overcome this side effect and expand the therapeutic utility of β-lapachone, we demonstrate the effects of a novel combination therapy including β-lapachone and the proliferating cell nuclear antigen (PCNA) inhibitor T2 amino alcohol (T2AA) on various NQO1 cancer cells. Read More

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Nitric oxide protects against ferroptosis by aborting the lipid peroxidation chain reaction.

Nitric Oxide 2021 Jul 27. Epub 2021 Jul 27.

Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.

Ferroptosis is a type of iron-dependent necrotic cell death, which is typically triggered by the depletion of intracellular glutathione (GSH), which is associated with increased lipid peroxidation. Nitric oxide (NO) is a highly reactive gaseous radical mediator with anti-oxidation properties that terminates lipid peroxidation reactions. In the current study, we report the anti-ferroptotic action of NOC18, an NO donor that spontaneously releases NO, in cells under various ferroptototic conditions in vitro. Read More

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