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Emerg Med Australas 2021 May 4. Epub 2021 May 4.

Department of Critical Care, The University of Melbourne, Melbourne, Victoria, Australia.

Objectives: Paracetamol overdose is common and can lead to fulminant hepatic failure. In cases that are not improving with standard medical therapy with N-acetylcysteine, some patients may require liver transplant. The Australia and New Zealand (ANZ) referral criteria for transfer to a liver unit have not been extensively studied for its predictive value. Read More

Bioorg Chem 2021 Apr 14;112:104913. Epub 2021 Apr 14.

Ankara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey. Electronic address:

Discovery of novel anticancer drugs which have low toxicity and high activity is very significant area in anticancer drug research and development. One of the important targets for cancer treatment research is topoisomerase enzymes. In order to make a contribution to this field, we have designed and synthesized some 5(or 6)-nitro-2-(substitutedphenyl)benzoxazole (1a-1r) and 2-(substitutedphenyl)oxazolo[4,5-b]pyridine (2a-2i) derivatives as novel candidate antitumor agents targeting human DNA topoisomerase enzymes (hTopo I and hTopo IIα). Read More

Biomed Pharmacother 2021 May 1;139:111670. Epub 2021 May 1.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt. Electronic address:

Cisplatin (Cis) is an effective cancer therapy commonly employed in many therapeutic regimens. However, treatment regimens that contain either a high dose or cumulative doses of Cis could trigger liver damage. A unique study demonstrated that captopril (Cap) protects against Cis-induced liver toxicity, but only some liver function enzymes and some antioxidant enzymes were investigated in that study. Read More

Aquat Toxicol 2021 Apr 18;236:105840. Epub 2021 Apr 18.

College of Biological, Chemical Science and Engineering, Jiaxing University, Jiaxing 314001, P.R. China.

In this study, effects of polystyrene microplastics (MPS) on Euglena gracilis were investigated via examination on its photosynthesis and motility, two typical properties of the protozoan. No adverse effects were observed after 4-d exposure except for decrease in motility at two high MPS concentrations (5 and 25 mg/L). After 8-d duration, MPS at 1 mg/L had no obvious effects on E. Read More

Ecotoxicol Environ Saf 2021 May 1;218:112284. Epub 2021 May 1.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Copper poses huge environmental and public health concerns due to its widespread and persistent use in the past several decades. Although it is well established that at higher levels copper causes nephrotoxicity, the exact mechanisms of its toxicity is not fully understood. Therefore, this experimental study for the first time investigates the potential molecular mechanisms including transcriptomics, metabolomics, serum biochemical, histopathological, cell apoptosis and autophagy in copper-induced renal toxicity in pigs. Read More

Neurotoxicol Teratol 2021 May 1:106993. Epub 2021 May 1.

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.

With the increasing use of ketamine as an off-label treatment for depression and the recent FDA approval of (S)-ketamine for treatment-resistant depression, there is an increased need to understand the long-term safety profile of chronic ketamine administration. Of particular concern is the neurotoxicity previously observed in rat models following acute exposure to high doses of ketamine, broadly referred to as 'Olney's lesions'. This type of toxicity presents as abnormal neuronal cellular vacuolization, followed by neuronal death and has been associated with ketamine's inhibition of the N-methyl-d-aspartate receptor (NMDAR). Read More

Food Chem Toxicol 2021 May 1:112249. Epub 2021 May 1.

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, 300071, China. Electronic address:

Heterocyclic amines (HCAs) are a group of mutagenic compounds produced during thermal processing of protein-rich foods. One of the most abundant HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) has potential carcinogenic and mutagenic effects on human organs, especially the colon. This study aimed to explore the toxic effects of PhIP on amino acid metabolism in the colon of Wistar rats using RNA-seq and LC-MS/MS. Read More

Neurochem Int 2021 May 1:105050. Epub 2021 May 1.

Institut für Inflammation und Neurodegeneration (Neurobiochemie), Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany. Electronic address:

Neurons spurn hydrogen-rich fatty acids for energizing oxidative ATP synthesis, contrary to other cells. This feature has been mainly attributed to a lower yield of ATP per reduced oxygen, as compared to glucose, and the use of fatty acids as hydrogen donor is accompanied by severe β-oxidation-associated ROS generation. Neurons are especially susceptible to detrimental activities of ROS due to their poor antioxidative equipment. Read More

Neurochem Int 2021 May 1:105049. Epub 2021 May 1.

Department of Biological Sciences, Wichita State University, 1845 Fairmount, Wichita, KS, 67260, USA. Electronic address:

Glioblastoma multiforme (GBM) is a severe form of brain cancer with an average five-year survival rate of 6.7%. Current treatment strategies include surgical resection of the tumor area and lining the lesion site with therapeutics, which offer only a moderate impact on increasing survival rates. Read More

Acta Trop 2021 May 1:105945. Epub 2021 May 1.

Department of Biological Sciences, University of Medical Sciences, Ondo, Ondo State, Nigeria. Electronic address:

Schistosomiasis continues to pose significant public health problems in many developing countries. Mass drug administration (MDA) is the most adopted control option but there is increasing evidence for the development of praziquantel-resistant Schistosoma strains. This shortcoming has necessitated the search for other effective methods for the control of schistosomiasis. Read More

Environ Toxicol Chem 2021 May 4. Epub 2021 May 4.

NiPERA, Durham, NC, 27713.

A review of nickel (Ni) toxicity to aquatic organisms was conducted to determine the primary water quality factors that affect Ni toxicity, and to provide information for the development and testing of a biotic ligand model (BLM) for Ni. Acute and chronic data for 66 aquatic species were compiled for this review. This review found that dissolved organic carbon (DOC) and hardness act as toxicity modifying factors (TMFs) because they reduced Ni toxicity to fish and aquatic invertebrates and these effects were consistent in acute and chronic exposures. Read More

PLoS One 2021 4;16(5):e0250649. Epub 2021 May 4.

Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, United States of America.

Treatment for the lethal primary adult brain tumor glioblastoma (GBM) includes the chemotherapy temozolomide (TMZ), but TMZ resistance is common and correlates with promoter methylation of the DNA repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT). To improve treatment of GBMs, including those resistant to TMZ, we explored the potential of targeting dopamine receptor signaling. We found that dopamine receptor 3 (DRD3) is expressed in GBM and is also a previously unexplored target for therapy. Read More

PLoS One 2021 4;16(5):e0250408. Epub 2021 May 4.

Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.

Gyps species have been previously shown to be highly sensitive to the toxic effects of diclofenac, when present in their food sources as drug residues following use as a veterinary medicine. Vultures exposed to diclofenac soon become depressed and die with signs of severe visceral gout and renal damage on necropsy. The molecular mechanism behind toxicity and renal excretion of uric acid is still poorly understood. Read More

J Clin Oncol 2021 May 4:JCO2002822. Epub 2021 May 4.

Northwestern University, Chicago, IL.

Purpose: Effective therapies are needed for the treatment of patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) with brain metastases. A trastuzumab radioisotope has been shown to localize in brain metastases of patients with HER2-positive MBC, and intracranial xenograft models have demonstrated a dose-dependent response to trastuzumab.

Methods: In the phase II PATRICIA study (ClinicalTrials. Read More

J Clin Oncol 2021 May 4:JCO2003143. Epub 2021 May 4.

Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.

Purpose: Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex).

Methods: Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years. Read More

Biomacromolecules 2021 May 4. Epub 2021 May 4.

Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India.

Inhibition of hen egg white lysozyme (HEWL) and Aβ42 fibrillation have been established as the main models for the treatment of systemic lysozyme amyloidosis and Alzheimer's disease (AD), respectively. Several antiamyloidogenic nanomaterials have been developed over the period; however, their intracellular mechanism of action is still not well understood. In this context, plant-based, gold-conjugated, injectable, hydrophilic cellulose nanoonions (CNOs), viz. Read More

ACS Infect Dis 2021 May 4. Epub 2021 May 4.

Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, 101 Stephenson Parkway, Norman, Oklahoma 73019, United States.

The rise of life-threatening carbapenem-resistant (CRE) infections has become a critical medical threat. Some of the most dangerous CRE bacteria can produce enzymes that degrade a wide range of antibiotics, including carbapenems and β-lactams. Infections by CRE have a high mortality rate, and survivors can have severe morbidity from treatment with toxic last-resort antibiotics. Read More

J Clin Pharmacol 2021 May 4. Epub 2021 May 4.

Samuel J. and Joan B. Williamson Institute for Pharmacometrics, Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, 11201, USA.

Clinical studies in preterm neonates are rarely performed due to ethical concerns and difficulties associated with trials and recruitment. Consequently, dose selection in this population is primarily empirical. Scaling neonatal doses from adult doses does not account for developmental changes and may not accurately predict drug kinetics. Read More

Neurotox Res 2021 May 4. Epub 2021 May 4.

Laboratory of Clinical and Experimental Toxicology, and Poison Control Centre and National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri 10, 27100, Pavia, Italy.

Considering the consequences on human health, in general population and workplace, associated with the use of new psychoactive substances and their continuous placing on the market, novel in vitro models for neurotoxicology research, applying human-derived CNS cells, may provide a means to understand the mechanistic basis of molecular and cellular alterations in brain. Cytotoxic effects of MAM-2201, a potent-naphthoyl indole derivative-synthetic cannabinoid, have been evaluated applying a panel of human cell-based models of neurons and astrocytes, testing different concentrations (1-30 µM) and exposure times (3-24-48 h). MAM-2201 induced toxicity in primary neuron-like cells (hNLCs), obtained from transdifferentiation of mesenchymal stem cells derived from human umbilical cord. Read More

Environ Sci Pollut Res Int 2021 May 4. Epub 2021 May 4.

Department of Medical Services and Techniques, Vocational School of Health Services, Giresun University, Giresun, Turkey.

Gastric Cancer 2021 May 4. Epub 2021 May 4.

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Hai-Dian District, Fu-Cheng Road 52, Beijing, 100142, China.

Purpose: RC48 contains the novel humanized anti-HER2 antibody hertuzumab conjugated to MMAE via a cleavable linker. A phase I study was initiated to evaluate the toxicity, MTD, PK, and antitumor activity of RC48 in patients with HER2-overexpressing locally advanced or metastatic solid carcinomas, particularly gastric cancer.

Patients And Methods: This was a 2-part phase I study. Read More

J Genet Eng Biotechnol 2021 May 4;19(1):62. Epub 2021 May 4.

Department of Biotechnology, Yeungnam University, Gyeongsan, South Korea.

Background: Lupeol, a triterpene bioactive compound isolated from Indian traditional plant Crateva adansonii acted as promising and alternative anti-inflammatory agent to treatments of diseases related to inflammation. The inflammatory process in the body serves an important function in the control and repair of injury. However, it is self-perpetuating in number of disease conditions, which must be prevented and treated. Read More

Amino Acids 2021 May 4. Epub 2021 May 4.

Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China.

The nervous system disorders caused by doxorubicin (DOX) are among the severe adverse effects that dramatically reduce the quality of life of cancer survivors. Astragali Radix (AR), a popular herbal drug and dietary supplement, is believed to help treat brain diseases by reducing oxidative stress and maintaining metabolic homeostasis. Here we show the protective effects of AR against DOX-induced oxidative damage in rat brain via regulating amino acid homeostasis. Read More

Bull Environ Contam Toxicol 2021 May 4. Epub 2021 May 4.

School of Public Health/Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, 550025, Guiyang, China.

This study was designed to investigate the molecular mechanism of mercury (Hg) toxicity in the newborns by mRNA sequencing (mRNA-seq). A questionnaire survey, routine blood parameters of pregnant women, and umbilical cord blood (UCB) of newborns were collected. The median (25th percentile, 75th percentile) of total Hg (THg) concentrations in UCB of newborns was 3. Read More

Acta Crystallogr A Found Adv 2021 May 23;77(Pt 3):217-221. Epub 2021 Mar 23.

Structure and Dynamics of Energy Materials, Helmholtz-Zentrum Berlin für Materialien und Energie, Hahn-Meitner-Platz 1, 14109 Berlin, Germany.

Heterovalent ternary nitrides are considered one of the promising classes of materials for photovoltaics, combining attractive physical properties with low toxicity and element abundance. One of the front-runner systems under consideration is ZnSnN. Although it is nominally a ternary compound, no clear crystallographic evidence for cation ordering has been observed so far. Read More

N Z Vet J 2021 May 4:1-6. Epub 2021 May 4.

Department of Animal Medicine and Surgery, School of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain.

To compare survival in dogs with recurrent or metastatic insulinomas that were treated with palliative therapy, alone or in combination with toceranib phosphate and to assess tolerability of the combined therapy in dogs. Dogs diagnosed with insulinoma were retrospectively identified in the records of the Veterinary Teaching Hospital Complutense (Madrid, Spain). Diagnosis of insulinoma was based on clinical signs of hypoglycaemia, concentrations in serum of glucose <3. Read More

Nanotoxicology 2021 May 4:1-14. Epub 2021 May 4.

National Institute of Advanced Science and Technology (AIST), Tsukuba, Japan.

The present study compared the effects of two commonly-used dispersants, bovine serum albumin (BSA) and polyethylene glycol (PEG), on the biodistribution and toxicity of oxidized super-growth single-wall carbon nanotubes (oxSG) injected intravenously into mice over 3 months. About 1-2% of the injected dose (ID) of oxSG dispersed in BSA (oxSG-BSA) was present in the lungs at all time points. By contrast, about 15% of the ID of oxSG dispersed in PEG (oxSG-PEG) was present in the lungs at 1 day (D1), with accumulation decreasing to about 5% of the ID at 90 days (D90). Read More

J Liposome Res 2021 May 4:1-9. Epub 2021 May 4.

Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan.

The markedly low oral bioavailability of domperidone (anti-emetic drug) is associated with rapid first-pass metabolism in the intestine and liver. To counteract such affects, there is a need to devise a strategy to enhance absorption and subsequently bioavailability. Thus, the current study was aimed at synthesizing phytosomes consisting of phosphatidylcholine and piperine (a P-glycoprotein inhibitor). Read More

MAbs 2021 Jan-Dec;13(1):1917484

Immunology Department, Hospital Universitario De La Princesa, IIS-IP, Madrid, Spain.

Lymph node (LN) is a key tissue in the pathophysiology of mature blood cancers, especially for chronic lymphocytic leukemia (CLL). Within the multiple de-regulated pathways affecting CLL homeostasis, the CC-chemokine receptor 7 (CCR7) grants homing of CLL cells into the LN where protective environments foster tumor progression. To cover the lack of specific therapies targeting the CCR7-dependence of CLL to enter into the LN, and aiming to displace the disease from LN, we generated CAP-100, an antibody that specifically binds to hCCR7 and neutralizes its ligand-binding site and signaling. Read More

J Drug Target 2021 May 4:1-15. Epub 2021 May 4.

Key Laboratory of Chemical Biology, Department of Pharmaceutics, School of Pharmaceutical Sciences, Ministry of Education, Shandong University, Jinan, China.

Since the discovery of cell-penetrating peptides (CPP) in the 1980s, they have played a unique role in various fields owing to their excellent and unique cell membrane penetration function. In particular, in the treatment of tumours, CPPS have been used to deliver several types of 'cargos' to cancer cells. To address the insufficient targeting ability, non-selectivity, and blood instability, activatable cell-penetrating peptides, which can achieve targeted drug delivery in tumour treatment, enhance curative effects, and reduce toxicity have been developed. Read More