Toxics

INTRODUCTION: The TGF-β signaling pathway is a complex network that plays a crucial role in regulating essential biological functions and is implicated in the onset and progression of multiple diseases. This review highlights the recent advancements in developing inhibitors targeting the TGF-β signaling pathway and their potential therapeutic applications in various diseases. AREA COVERED: The review discusses patents on active molecules related to the TGF-β signaling pathway, focusing on three strategies: TGF-β activity inhibition, blocking TGF-β receptor binding, and disruption of the signaling pathway using small molecule inhibitors...

Single-stranded oligonucleotides (SSOs) are a rapidly expanding class of therapeutics that comprises antisense oligonucleotides, microRNAs, and aptamers, with ten clinically approved molecules. Chemical modifications such as the phosphorothioate backbone and the 2'- O -methyl ribose can improve the stability and pharmacokinetic properties of therapeutic SSOs, but they can also lead to toxicity in vitro and in vivo through nonspecific interactions with cellular proteins, gene expression changes, disturbed RNA processing, and changes in nuclear structures and protein distribution...

Under laboratory conditions, the toxicological effects of pesticides tend to be less variable and realistic than under field conditions, limiting their usefulness in environmental risk assessment. In the current study, the earthworm Eisenia fetida was selected as a bioindicator for assessing glyphosate toxic effects in two different trials to solve this dilemma. In Trial 1, the worms were exposed for 7 and 14 days to concentrations of a commercial glyphosate formulation (1 to 500 mg a.i. kg-1 ) currently used in the field...

Acanthamoeba spp. emerged as a clinically important pathogen related to amoebic keratitis. It is among the main causes of corneal transplantation and vision loss in ophthalmology. The treatment protocols have a low cure rate, high toxicity, and need for drug combination. Transition metal compounds have shown promising antiprotozoal effects. This study evaluates the amoebicidal activity of copper(II) coordination compounds in combination with chlorhexidine and the cytotoxicity to topical ocular application. These copper(II) coordination compounds were screened against Acanthamoeba castellanii trophozoites (ATCC 50492)...

Pyrolysis, a thermal decomposition without oxygen, is a promising technology for transportable liquids from whole fractions of lignocellulosic biomass. However, due to the hydrophilic products of pyrolysis, the liquid oils have undesirable physicochemical characteristics, thus requiring an additional upgrading process. Biological upgrading methods could address the drawbacks of pyrolysis by utilizing various hydrophilic compounds as carbon sources under mild conditions with low carbon footprints. Versatile chemicals, such as lipids, ethanol, and organic acids, could be produced through microbial assimilation of anhydrous sugars, organic acids, aldehydes, and phenolics in the hydrophilic fractions...

PURPOSE: An optimal radiotherapy field for superficial esophageal carcinoma is yet to be established. We evaluated the long-term outcomes and recurrence patterns of involved-field radiotherapy (IFRT) in older patients with superficial thoracic esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Fifty-four patients (49 men and 5 women; mean age, 77 [range: 66-90] years) who underwent IFRT for superficial thoracic ESCC between January 2003 and January 2019 were retrospectively reviewed...

Aspergillus section Flavi (Flavi) is a diverse group of fungal species whose common members include A. flavus and A. parasiticus. These are well-known for the production of aflatoxin (AF) B and G and other toxic metabolites, like cyclopiazonic acid (CPA). They are saprophytic soil dwellers and also become crop opportunistic epiphytes. The consequence is contamination of the crop with mycotoxins, such as carcinogenic AF. We investigated the Flavi community structure of maize and that of their surrounding soil, including their mycotoxigenicity...

Ultrasonic manufacturing has emerged as a promising eco-friendly approach to synthesize lipid-based nanocarriers for targeted drug delivery. This study presents the novel ultrasonic preparation of lipid nanocarriers loaded with Scutellaria barbata extract, repurposed for anticancer and antibacterial use. High-frequency ultrasonic waves enabled the precise self-assembly of DSPE-PEG, Span 40, and cholesterol to form nanocarriers encapsulating the therapeutic extract without the use of toxic solvents, exemplifying green nanotechnology...

Iron contributes to tumor initiation and progression; however, excessive intracellular free Fe2+ can be toxic to cancer cells. Our findings confirmed that multiple myeloma (MM) cells exhibited elevated intracellular iron levels and increased ferritin, a key protein for iron storage, compared with normal cells. Interestingly, Bortezomib (BTZ) was found to trigger ferritin degradation, increase free intracellular Fe2+ , and promote ferroptosis in MM cells. Subsequent mechanistic investigation revealed that BTZ effectively increased NCOA4 levels by preventing proteasomal degradation in MM cells...

Wastewater treatment recycling is critical to ensure safe water supply or to overcome water shortage. Herein, we developed metallic Co integration onto MnO nanorods (MON) resulting in a phase-separated synergetic catalyst by creating more Mn(III) via the Jahn-Teller effect and oxygen vacancies and improving the redox capability of Co nanoparticles mediated by a thin carbon layer. Additionally, the N-doped surface carbon network on MON contributes to polar sites, facilitating the enrichment of contaminants around reactive sites, thereby shortening the migration of reactive oxidative species (ROS) toward contaminants...

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos...

Extensive research has been conducted over the years on the bacterial degradation of dioxins and their related compounds including carbazole, because these chemicals are highly toxic and has been widely distributed in the environment. There is a pressing need to explore and develop more bacterial strains with unique catabolic features to effectively remediate dioxin-polluted sites. Carbazole has a chemical structure similar to dioxins, and the degradation pathways of these two chemicals are highly homologous...

The aim is to investigate the possible pulmonary protective effect of vanillic acid (VA) in liposome-TPGS nanoparticles, to overcome VA's poor bioavailability. VA was successfully extracted. Liposomes were prepared using thin film hydration. Central composite design was adopted for optimisation of liposomes to get the maximum entrapment efficiency (EE%) and the minimum mean diameter, where the liposomes were further modified with TPGS, and tested for PDI, zeta-potential, and in-vitro drug release. In-vivo study on mice with LPS-acute pulmonary toxicity was tested...

The oral toxicity of recombinant human lactoferrin (rhLF, Helaina rhLF, Effera™) produced in Komagataella phaffii was investigated in adult Sprague Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3-6 rats/sex/dose. The vehicle control group received sodium citrate buffer, and the test groups received daily doses of 200, 1000, and 2000 mg of rhLF in sodium citrate buffer per kg body weight. Bovine LF at 2000 mg/kg body weight per day was used as a comparative control...

Patients with brain cancers including medulloblastoma lack treatments that are effective long-term and without side effects. In this study, a multifunctional fluoropolymer-engineered iron oxide nanoparticle gene-therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum...

Silver/polymeric vesicle composite nanoparticles with good antibacterial properties were fabricated in this study. Silver nanoparticles (AgNPs) were prepared in situ on cross-linked vesicle membranes through the reduction of silver nitrate (AgNO3 ) using polyvinylpyrrolidone (PVP) via coordination bonding between the Ag+ ions and the nitrogen atoms on the vesicles. X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-vis), and transmission electron microscopy (TEM) analyses confirmed the formation of AgNPs on the vesicles...

Alzheimer's disease (AD) is a complex neurodegenerative disorder that affects learning, memory, and cognition. Current treatments targeting amyloid-β (Aβ) and tau have shown limited effectiveness, necessitating further research on the aggregation and toxicity mechanisms. One of these mechanisms involves the liquid-liquid phase separation (LLPS) of tau, contributing to the formation of pathogenic tau aggregates, although their conformational details remain elusive. Another mechanism is ferroptosis, a type of iron-dependent lipid peroxidation-mediated cell death, which has been implicated in AD...

The recent international scenario highlights the importance to protect human health and environmental quality from toxic compounds. In this context, organophosphorous (OP) Nerve Agents (NAs) have received particular attention, due to their use in terrorist attacks. Classical instrumental detection techniques are sensitive and selective, but they cannot be used in real field due to the high cost, specialized personnel requested and huge size. For these reasons, the development of practical, easy and fast detection methods (smart methods) is the future of this field...

Organoid cell culture systems can recapitulate the complexity observed in tissues, making them useful in studying host-pathogen interactions, evaluating drug efficacy and toxicity, and tissue bioengineering. However, applying these models for the described reasons may be limited because of the three-dimensional (3D) nature of these models. For example, using 3D enteroid culture systems to study digestive diseases is challenging due to the inaccessibility of the intestinal lumen and its secreted substances. Indeed, stimulation of 3D organoids with pathogens requires either luminal microinjection, mechanical disruption of the 3D structure, or generation of apical-out enteroids...

Tolcapone is an orally active catechol-O-methyltransferase (COMT) inhibitor used as adjuvant therapy in Parkinson's disease. However, it has a highly hepatotoxic profile, as recognized by the U.S. Food and Drug Administration. As a possible solution, nanoscience brought us several tools in the development of new functional nanomaterials with tunable physicochemical properties, which can be part of a solution to solve several drawbacks, including drug's short half-life and toxicity. This work aims to use PEGylated poly(lactic- co -glycolic acid) (PLGA) nanoparticles as a stable carrier with lower hydrodynamic size and polydispersity to encapsulate tolcapone in order to overcome its therapeutic drawbacks...