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Current status of novel pyridine fused derivatives as anticancer agents: An insight into future perspectives and structure activity relationship (SAR).

Curr Top Med Chem 2021 Sep 16. Epub 2021 Sep 16.

Department of Chemistry, School of Chemical and Life sciences, Jamia Hamdard, New Delhi-110062. India.

Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the cells leading to tumors that invade the adjacent normal tissues. After cardiovascular diseases, it is the second most prevalent disease accounting for one in every six deaths worldwide. This alarming rate thus, demands an urgent need to investigate more effective drugs to combat the said disease. Read More

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September 2021

Overexpression of Matricellular Mechanical Proteins Demands Functional Immune Signature and Mitigates Non-Small Cell Lung Cancer Progression.

Front Immunol 2021 16;12:714230. Epub 2021 Aug 16.

Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.

Non-small cell lung carcinoma (NSCLC) is a complex cancer biome composed of malignant cells embedded in a sophisticated tumor microenvironment (TME) combined with different initiating cell types, including immune cells and cancer-associated fibroblasts (CAFs), and extracellular matrix (ECM) proteins. However, little is known about these tumors' immune-matricellular relationship as functional and mechanical barriers. This study investigated 120 patients with NSCLC to describe the immune-matricellular phenotypes of their TME and their relationship with malignant cells. Read More

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Three novel piperidones exhibit tumor-selective cytotoxicity on leukemia cells via protein degradation and stress-mediated mechanisms.

Pharmacol Rep 2021 Aug 26. Epub 2021 Aug 26.

Department of Biological Sciences and Border Biomedical Research Center, The University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968-0519, USA.

Background: Cancer is an ongoing worldwide health problem. Although chemotherapy remains the mainstay therapy for cancer, it is not always effective and has detrimental side effects. Here, we present piperidone compounds P3, P4, and P5 that selectively target cancer cells via protein- and stress-mediated mechanisms. Read More

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Detection of granzyme B in CD3-positive cells infiltrated in lesional skin of a dog with erythema multiforme associated with zonisamide.

J Vet Med Sci 2021 Aug 25. Epub 2021 Aug 25.

Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University.

In human erythema multiforme (EM), cytotoxic T lymphocytes (CTLs) play an essential role in the pathogenesis. In canine EM, immunohistochemical staining with anti-CD8 antibody using frozen sections has shown the involvement of CTLs; however, CTL infiltration has never been quantitatively analyzed. We herein quantitatively analyzed CTL infiltration by immunohistochemical staining with granzyme B and CD3 antibodies using paraffin sections of a dog with EM associated with zonisamide. Read More

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Antibacterial and cytotoxic potency of thermophilic Streptomyces werraensis MI-S.24-3 isolated from an Egyptian extreme environment.

Arch Microbiol 2021 Jul 14. Epub 2021 Jul 14.

Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo, 255000, China.

The need for novel and active antibiotics specially from actinomycetes is essential due to new and drug-resistant pathogens. In this study, 87 actinomycetes were isolated, and 18 strains among them characterized as thermophilic actinomycetes. Further fractionation and preliminary antibacterial activities indicated that one strain, coded as MI-S. Read More

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Design, Syntheses, and Bioevaluations of Some Novel -Acryloylbenzohydrazides as Chemostimulants and Cytotoxic Agents.

Medicines (Basel) 2021 Jun 3;8(6). Epub 2021 Jun 3.

Drug Discovery and Development Research Cluster, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.

A series of novel -acryloylhydrazides and a related series of compounds were prepared as potential chemostimulants. In general, these compounds are cytotoxic to human HCT 116 colon cancer cells, as well as human MCF-7 and MDA-MB-231 breast cancer cell lines. A representative compound -(3,4-dimethoxyphenylcarbonyl)--acryloylhydrazine sensitized HCT 116 cells to the potent antineoplastic agent 3,5-bis(benzylidene)-4-piperidone , and also to 5-fluorouracil. Read More

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Behavioral and ultrastructural effects of novaluron on Aedes aegypti larvae.

Infect Genet Evol 2021 09 21;93:104974. Epub 2021 Jun 21.

Department of General Biology, Federal University of Viçosa, 36570-000 Viçosa, MG, Brazil. Electronic address:

Chitin synthesis inhibitors (CSI) are supposed to inhibit formation of chitin microfibrils in newly synthesized cuticle during molting process. Conversely, there has been comparatively few data on morphological effects of CSI on non-target insect organs. In this work, the effects of the CSI novaluron on behavior and midgut of A. Read More

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September 2021

Binding and neutralization of C. difficile toxins A and B by purified clinoptilolite-tuff.

PLoS One 2021 27;16(5):e0252211. Epub 2021 May 27.

GLOCK Health, Science and Research G.m.b.H., Deutsch-Wagram, Austria.

Clostridioides difficile (C. difficile) infection is a major public health problem worldwide. The current treatment of C. Read More

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Thiazolidinedione "Magic Bullets" Simultaneously Targeting PPARγ and HDACs: Design, Synthesis, and Investigations of their and Antitumor Effects.

J Med Chem 2021 05 18;64(10):6949-6971. Epub 2021 May 18.

Department of Pharmaceutical Chemistry, Bharati Vidyapeeth's College of Pharmacy, CBD Belapur, Navi Mumbai- 400614, India.

Monotargeting anticancer agents suffer from resistance and target nonspecificity concerns, which can be tackled with a multitargeting approach. The combined treatment with HDAC inhibitors and PPARγ agonists has displayed potential antitumor effects. Based on these observations, this work involves design and synthesis of molecules that can simultaneously target PPARγ and HDAC. Read More

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Impact of cytotoxic T-lymphocyte-associated protein 4 codon 17 variant and expression on vitiligo risk.

J Clin Lab Anal 2021 Jun 1;35(6):e23777. Epub 2021 May 1.

Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA.

Background: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the essential brakes expressed on T cells that prevent T-cell hyperactivation-associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c. Read More

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Methamphetamine facilitates pulmonary and splenic tissue injury and reduces T cell infiltration in C57BL/6 mice after antigenic challenge.

Sci Rep 2021 Apr 15;11(1):8207. Epub 2021 Apr 15.

Department of Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Room DG-48, P.O. Box 100424, Gainesville, FL, 32610, USA.

Methamphetamine (METH) is a strong addictive central nervous system stimulant. METH abuse can alter biological processes and immune functions necessary for host defense. The acquisition and transmission of HIV, hepatitis, and other communicable diseases are possible serious infectious consequences of METH use. Read More

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Effect of amphotericin B-deoxycholate (Fungizone) on the mitochondria of Wistar rats' renal proximal tubules cells.

J Appl Toxicol 2021 Oct 19;41(10):1620-1633. Epub 2021 Mar 19.

Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY, USA.

Amphotericin B-deoxycholate (Fungizone [FZ]) is a widely used potent antimycotic drug in spite of its nephrotoxic effect via different mechanisms. The effect of FZ on renal cell bioenergetics is not clear. The current study evaluated the effect of FZ on the bioenergetics of albino rats' isolated renal proximal tubule cells (PTCs). Read More

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October 2021

Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma.

Cells 2021 02 5;10(2). Epub 2021 Feb 5.

School of Pharmacy, Experimental Medicine Section, University of Camerino, 62032 Camerino, Italy.

Glioblastoma is the most aggressive cancer among primary brain tumours. As with other cancers, the incidence of glioblastoma is increasing; despite modern therapies, the overall mean survival of patients post-diagnosis averages around 16 months, a figure that has not changed in many years. Cannabigerol (CBG) has only recently been reported to prevent the progression of certain carcinomas and has not yet been studied in glioblastoma. Read More

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February 2021

Assessment of the Antileishmanial Potential of Leaf Extract.

ACS Omega 2021 Jan 11;6(3):2318-2327. Epub 2021 Jan 11.

Infection and Immunity Lab (414), Department of Biotechnology, Jamia Millia Islamia (A Central University), New Delhi 110025, India.

has a wide array of biologically active and therapeutically important class of compounds. important drug targets, sterol 24-c methyltransferase (SMT), trypanothione reductase (TR), pteridine reductase (PTR1), and nucleoside hydrolase (NH), were modelled, and molecular docking was performed against the abundant phytochemicals of its leaf extract. Molecular docking results provided the significant prima facie evidence of the leaf extract to have antileishmanial potential. Read More

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January 2021

Continuous Exposure to Low Doses of Ultrafine Black Carbon Reduces the Vitality of Immortalized Lung-Derived Cells and Activates Senescence.

J Toxicol 2020 7;2020:5702024. Epub 2020 Dec 7.

Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968-0519, USA.

Combustion-derived nanomaterials are noxious ultrafine (<100 nm) aerosol by-products of human activity. They pose threats to pulmonary health due to their small size, allowing them to penetrate alveoli causing detrimental responses downstream. Information regarding the cellular activity that connects nanocarbon particle exposure to poor pulmonary health remains lacking. Read More

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December 2020

Roles of oxidative stress, apoptosis, and inflammation in metal-induced dysfunction of beta pancreatic cells isolated from CD1 mice.

Saudi J Biol Sci 2021 Jan 4;28(1):651-663. Epub 2020 Nov 4.

General Education Department, Dar Al-Hekma University, Jeddah Saudi Arabia.

The diabetogenic effects of metals including lead (Pb), mercury (Hg), cadmium (Cd), and molybdenum (Mo) have been reported with poorly identified underlying mechanisms. The current study assessed the effect of metals on the roles of oxidative stress, apoptosis, and inflammation in beta pancreatic cells isolated from CD-1 mice, via different biochemical assays. Data showed that the tested metals were cytotoxic to the isolated cells with impaired glucose stimulated insulin secretion (GSIS). Read More

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January 2021

Cytotoxic Effects of Water-Soluble Extracts of Coarse and Fine Atmospheric Particulate Matter on Mast Cell Lines.

Biol Pharm Bull 2021 ;44(1):57-62

School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University.

Fine particulate matter (PM) pollution causes serious health disorders, because PM becomes deposited in the tracheobronchial and alveoli regions. In the extrathoracic region, there are more deposits of coarse particulate matter than fine particulates. As adverse health issues caused by coarse particulates have not been well investigated, this study examined the cytotoxicity of water-soluble extracts of both fine (0. Read More

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Synthesis, Molecular Docking and Preliminary Antileukemic Activity of 4-Methoxybenzyl Derivatives Bearing Imidazo[2,1-b][1,3,4]thiadiazole.

Chem Biodivers 2021 Feb 7;18(2):e2000800. Epub 2021 Jan 7.

Department of Pharmaceutical Chemistry, KLE College of Pharmacy (A Constituent Unit of KAHER-Belagavi), Bengaluru, 560010, Karnataka, India.

In this study, we synthesized 22 compounds in a series with various substitution on imidazo[2,1-b][1,3,4]thiadiazole. The potential cytotoxic activity of these compounds investigated in leukemia cell lines by Differential Nuclear Staining (DNS). Our results identified two compounds, 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate and 6-(4-chlorophenyl)-2-(4-methoxybenzyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde, exhibited the most cytotoxic effect against murine leukemia cells (L1210), human T-lymphocyte cells (CEM) and human cervix carcinoma cells (HeLa) with IC values ranging between 0. Read More

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February 2021

Ni-Cu Nanoparticles and Their Feasibility for Magnetic Hyperthermia.

Nanomaterials (Basel) 2020 Oct 9;10(10). Epub 2020 Oct 9.

Department of Physics, the University of Texas at El Paso (UTEP), El Paso, TX 79968, USA.

Ni-Cu nanoparticles have been synthesized by reducing Ni and Cu from metal precursors using a sol-gel route followed by annealing at 300 °C for 1, 2, 3, 6, 8, and 10 h for controlled self-regulating magnetic hyperthermia applications. Particle morphology and crystal structure revealed spherical nanoparticles with a cubic structure and an average size of 50, 60, 53, 87, and 87 nm for as-made and annealed samples at 300 °C for 1, 3, 6, and 10 h, respectively. Moreover, hysteresis loops indicated ferromagnetic behavior with saturation magnetization (Ms) ranging from 13-20 emu/g at 300 K. Read More

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October 2020

Pharmacodynamic biomarkers in metronomic chemotherapy: multiplex cytokine measurements in gastrointestinal cancer patients.

Clin Exp Med 2021 Feb 13;21(1):149-159. Epub 2020 Oct 13.

Border Biomedical Research Center, University of Texas at El Paso (UTEP), El Paso, TX, USA.

Metronomic chemotherapy has shown promising antitumor activity in a number of malignancies. We previously reported a phase II clinical trial of metronomic UFT (a 5-fluorouracil prodrug; 100 mg/twice per day p.o. Read More

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February 2021

Effects of environmental metals on mitochondrial bioenergetics of the CD-1 mice pancreatic beta-cells.

Toxicol In Vitro 2021 Feb 8;70:105015. Epub 2020 Oct 8.

General Education Department, Dar Al-Hekma University, Jeddah, Saudi Arabia.

Environmental metals are believed to have diabetogenic effects without any clear underlying mechanisms. The study investigated the effects of metals, lead (Pb), mercury (Hg), cadmium (Cd), and molybdenum (Mo), on the bioenergetics of isolated pancreatic β-cells from CD-1 mice via different functional and structural techniques. The tested metals caused significant decrease in ATP production in concentration and exposure duration-dependent pattern; Cd was the most potent cytotoxic metal. Read More

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February 2021

Connecting Immune Cell Infiltration to the Multitasking Microglia Response and TNF Receptor 2 Induction in the Multiple Sclerosis Brain.

Front Cell Neurosci 2020 7;14:190. Epub 2020 Jul 7.

Department of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.

Signaling from central nervous system (CNS)-infiltrating lymphocytes and macrophages is critical to activate microglia and cause tissue damage in multiple sclerosis (MS). We combined laser microdissection with high-throughput real time RT-PCR to investigate separately the CNS exogenous and endogenous inflammatory components in postmortem brain tissue of progressive MS cases. A previous analysis of immune infiltrates isolated from the white matter (WM) and the meninges revealed predominant expression of genes involved in antiviral and cytotoxic immunity, including IFNγ and TNF. Read More

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Discovery of novel N-substituted thiazolidinediones (TZDs) as HDAC8 inhibitors: in-silico studies, synthesis, and biological evaluation.

Bioorg Chem 2020 07 15;100:103934. Epub 2020 May 15.

Department of Pharmaceutical Chemistry, Bharati Vidyapeeth's College of Pharmacy, Navi Mumbai, India. Electronic address:

Epigenetics plays a fundamental role in cancer progression, and developing agents that regulate epigenetics is crucial for cancer management. Among Class I and Class II HDACs, HDAC8 is one of the essential epigenetic players in cancer progression. Therefore, we designed, synthesized, purified, and structurally characterized novel compounds containing N-substituted TZD (P1-P25). Read More

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Interactions of graphene oxide and graphene nanoplatelets with the in vitro Caco-2/HT29 model of intestinal barrier.

Sci Rep 2020 02 17;10(1):2793. Epub 2020 Feb 17.

Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain.

Carbon-based nanomaterials are being increasingly used, demanding strong information to support their safety in terms of human health. As ingestion is one of the most important exposure routes in humans, we have determined their potential risk by using an in vitro model simulating the human intestinal barrier and evaluated the effects of both graphene oxide (GO) and graphene nanoplatelets (GNPs). A coculture of differentiated Caco-2/HT29 cells presenting inherent intestinal epithelium characteristics (i. Read More

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February 2020

Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from on Inflammatory Response in Mouse Macrophages.

Molecules 2019 Dec 18;25(1). Epub 2019 Dec 18.

Dr Panjwani Center For Molecular Medicine and Drug Research, University of Karachi, Karachi 75270, Pakistan.

(1) Introduction: Reactive oxygen species (ROS) and nitric oxide (NO) are key signaling molecules that play important roles in the progression of inflammatory disorders. The objective of this study was to explore the use of myrtucommuacetalone-1 (MCA-1), as a novel compound of natural origin and a potential anti-inflammatory agent. (2) Methodology: The anti-inflammatory potential of MCA-1, which was isolated from Linn, was determined by assaying superoxide, hydrogen peroxide, and nitric oxide production in macrophages. Read More

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December 2019

The heavy metals lead and cadmium are cytotoxic to human bone osteoblasts via induction of redox stress.

PLoS One 2019 22;14(11):e0225341. Epub 2019 Nov 22.

School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom.

The heavy metals (HMs) lead and cadmium are persistent environmental pollutants capable of inducing ill-health in exposed individuals. One of the primary sites of accumulation and potential damage from HMs is bone, and we therefore examined the acute effects of lead and cadmium on human bone osteoblasts in vitro over a concentration range of 0.1 μM to 1mM, and for 3, 6, 12, 24, and 48 hour exposures. Read More

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Pyriproxyfen, a juvenile hormone analog, damages midgut cells and interferes with behaviors of larvae.

PeerJ 2019 4;7:e7489. Epub 2019 Sep 4.

Departamento de Biologia Geral, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.

Juvenile hormone analogs (JHA) are known to interfere with growth and biosynthesis of insects with potential for insecticide action. However, there has been comparatively few data on morphological effects of JHA on insect organs. To determine pyriproxyfen effects on larvae, we conducted toxicity, behavioral bioassays and assessed ultrastructural effects of pyriproxyfen on midgut cells. Read More

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September 2019

Prognostic Value of Combined Analysis of CTLA-4 and PLR in Esophageal Squamous Cell Carcinoma (ESCC) Patients.

Dis Markers 2019 14;2019:1601072. Epub 2019 Aug 14.

Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan, 750004 Ningxia, China.

Objective: The purpose of this study was to evaluate the prognostic role of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) expression level and the platelet lymphocyte ratio (PLR) level in esophageal squamous cell carcinoma (ESCC) patients.

Methods: 84 ESCC patients who received surgical treatment in our hospital were enrolled in the study. The correlation of each biomarker's level with ESCC patients' clinicopathological characteristics and overall survival (OS) was assessed. Read More

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February 2020

Innate lymphoid cells and cancer at border surfaces with the environment.

Semin Immunol 2019 02 28;41:101278. Epub 2019 Aug 28.

Laboratory of Innate Immunity, Department of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch Strasse 2, 10117 Berlin, Germany; Mucosal and Developmental Immunology, Deutsches Rheuma-Forschungszentrum, Charitéplatz 1, 10117 Berlin, Germany. Electronic address:

Innate lymphoid cells (ILC) are a recently identified group of innate lymphocytes. ILC are subdivided into cytotoxic ILC (i.e. Read More

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February 2019