Surface modification of hollow gold nanoparticles conducted by incorporating cancer cell membrane and AS1411 aptamer, aiming to achieve a dual-targeted therapy for colorectal cancer.

Due to its inherent membrane structure, a nanostructure enveloped by an active cell membrane possesses distinctive characteristics such as prolonged presence in the bloodstream, precise identification capabilities, and evasion of immune responses. This research involved the production of biomimetic nanoparticles, specifically hollow gold nanoparticles (HGNPs) loaded with methotrexate (MTX), which were further coated with cancer cell membrane. These nanoparticles were then adorned with AS1411 aptamer to serve as a targeting agent (Apt-CCM-HG@MTX). The nanoplatform demonstrated precise targeting towards cancer cells due to its dual-targeting characteristic (AS1411 aptamer and C26 cancer cell membrane), exhibiting uniformity in distribution. It also displayed a desirable response to photothermal stimulation, controlled release of drugs, and exceptional properties for fluorescence imaging. The system was composed of spherical HGNPs measuring 51.33 ± 5.70 nm in diameter, which were effectively loaded with MTX using a physical absorption method. The encapsulation efficiency achieved was recorded at 79.54 %, while the loading efficiency reached 38.21 %. The targeted formulation demonstrated a noteworthy mortality of approximately 45 % in the nucleolin positive cell line, C26, as determined by in vitro cytotoxicity assays. As a result of the functionalization process applied to the homologous binding adhesion molecules found in cancer cell membranes and targeting ability of AS1411 aptamer, Apt-CCM-HG@MTX demonstrated a substantial enhancement in targeting tumors and facilitating cellular uptake during in vivo experiments. Furthermore, under NIR radiation the photothermal effect exhibited by Apt-CCM-HG@MTX in the tumor area was notably robust due to the distinctive attributes of HGNPs. The conclusions obtained from this study have the potential to assist in adopting a bioinspired strategy that will significantly improve the effective management of MTX and therapy for individuals with colorectal cancer.

Robust tag-free aptasensor for monitoring of tobramycin: Architecting of rolling circle amplification and fluorescence synergism.

With the unpredictable risks on human health and ecological safety, tobramycin (TOB) as an extensively applied antibiotic has embraced global concern. Herein, a label-free fluorescent aptasensor was developed that opened up an innovative sensing strategy for monitoring trace TOB levels. Based on the rolling circle amplification (RCA) process, a giant DNA building was established by the catalytic action of T4 DNA ligase and Phi 29 DNA polymerase with the cooperation of the specific aptamer as a primer skeleton. By having the role of signal amplifier template, the RCA product with the G-quadruplex sequence duplications was decorated by a high number of the thioflavin T (ThT) fluorescent dyes. The aptasensor with good selectivity toward TOB achieved a detection limit as low as 150 pM. Thanks to its accurate target quantification, ease of operation, economic manufacture, as well as high potency for real-time and point-of-care testing, the represented aptasensor is superb for clinical application and food safety control.

The protective effect of natural or chemical compounds against arsenic-induced neurotoxicity: Cellular and molecular mechanisms.

Arsenic is a notorious metalloid that exists in the earth's crust and is considered toxic for humans and the environment. Both cancerous and non-cancerous complications are possible after arsenic exposure. Target organs include the liver, lungs, kidney, heart, and brain. Arsenic-induced neurotoxicity, the main focus of our study, can occur in central and peripheral nervous systems. Symptoms can develop in a few hours, weeks, or years depending on the quantity of arsenic and the duration of exposure. In this review, we aimed to gather all the compounds, natural and chemical, that have been studied as protective agents in cellular, animal, and human reports. Oxidative stress, apoptosis, and inflammation are frequently described as destructive mechanisms in heavy metal toxicity. Moreover, reduced activity of acetylcholinesterase, the altered release of monoamine neurotransmitters, down-regulation of N-methyl-D-aspartate receptors, and decreased brain-derived neurotrophic factor are important underlying mechanisms of arsenic-induced neurotoxicity. As for neuroprotection, though some compounds have yet limited data, there are others, such as curcumin, resveratrol, taurine, or melatonin which have been studied more deeply and might be closer to a reliable protective agent. We collected the available information on all protective agents and the mechanisms by which they fight against arsenic-induced neurotoxicity.

Minocycline as a Neuroprotective Agent in Arsenic-Induced Neurotoxicity in PC12 Cells.

Arsenic is a naturally occurring metalloid that exists in water, soil, food, and air. Humans can be exposed to arsenic through occupational, medical, or nutritional routes. Both acute and chronic forms of toxicity with severe outcomes are likely following arsenic exposure. Neurotoxicity is one of the serious manifestations of arsenic toxicity. In our study, the effect of minocycline, a widely used antimicrobial agent with antioxidant aspects and the ability to cross the blood-brain barrier, was evaluated against arsenic-induced neurotoxicity. PC12 cell line was used as the cellular model of this study. Cells were pre-treated with minocycline (50 nM-1 µM) for 2 h, and then incubated for 24 h after adding sodium arsenite (10 µM). The MTT assay and fluorimetry were performed to study cytotoxicity and reactive oxygen species generation, respectively. Finally, Western blotting was done to determine the levels of caspase-8, Bax, Bcl-2, and caspase-3. Once exposed to arsenic, the cell viability was significantly reduced, the intracellular oxidative balance was significantly disrupted, and the levels of proteins caspase-8, Bax/Bcl-2, and caspase-3 were significantly increased. Minocycline not only attenuated arsenic-induced cytotoxicity and reduced oxidative stress, but also led to lower levels of caspase-8, Bax/Bcl-2, and caspase-3 proteins compared with the arsenic-treated cells. Minocycline can significantly protect cells against arsenic-induced neurotoxicity by antioxidant and anti-apoptosis properties via both intrinsic and extrinsic caspase-dependent apoptotic pathways; therefore, at this point, it's worth considering it as a promising agent for the treatment of arsenic toxicity.

Minocycline Protects PC12 Cells Against Cadmium-Induced Neurotoxicity by Modulating Apoptosis.

Cadmium (Cd) is a well-known heavy metal and a neurotoxic agent. Minocycline (Mino) is an anti-microbial agent with a lipophilic structure that crosses the blood-brain barrier and enters the cerebral tissue. In recent studies, Mino has been introduced as an antioxidant and anti-apoptotic chemical compound, and therefore, it was examined as a protective candidate against Cd-induced neurotoxicity. In this study, PC12 cells were exposed to Cd alone, or after being pre-treated with Mino. Initially, the cell viability and oxidative stress were analyzed using the MTT assay and fluorimetry, respectively. Then, Cd-induced apoptosis and Mino anti-apoptotic effect were evaluated in both intrinsic and extrinsic pathways using western blot analysis. Exposing PC12 cells to Cd for 24 h decreased cell viability and increased production of reactive oxygen species in comparison with the control group. Cd (35 µM) also elevated the level of caspase-8, Bax/Bcl-2, and caspase-3 proteins in the cells. Mino pre-treatment for 2 h (100 nM) increased the number of viable cells and decreased the production of reactive oxygen species, and the level of all apoptotic markers in comparison to Cd-treated cells. Considering all the evidence, it appears that Mino holds promising antioxidant and anti-apoptotic activity and can protect cells against Cd-induced oxidative stress and prevent apoptotic cell death.

Cilastatin as a protective agent against drug-induced nephrotoxicity: a literature review.

INTRODUCTION: Cilastatin, a dehydropeptidase I inhibitor, has been used alongside imipenem, a broad spectrum antibiotic, in order to reduce its renal metabolism, consequently increasing its urinary recovery and effectiveness for many years. However, this measure could be useful in preventing imipenem-induced renal damage and decreasing the number of nephrotoxicity reports with imipenem. In this review, the authors gathered all available studies focusing on cilastatin use as a nephroprotective agent, beside well-known nephrotoxic medications like vancomycin, cisplatin, cyclosporine, or tacrolimus. AREAS COVERED: PubMed, Scopus, Google Scholar, and Medline databases were searched using key words like 'cilastatin,' 'nephroprotective,' 'nephroprotection,' 'vancomycin,' 'nephrotoxicity,' 'cisplatin,' 'cyclosporine,' 'tacrolimus,' and 'prevention' with varying combinations. All relevant animal and human studies up to the date of publication were included. EXPERT OPINION: It seems that cilastatin could potentially be effective against drug-induced nephrotoxicity via mechanisms such as reducing reactive oxygen species (ROS) production, apoptosis, P-glycoprotein suppression, and morphological changes of renal cells. Nearly all the in vitro, in vivo and human studies have supported this hypothesis. Though since cilastatin protective effect has not extensively been researched in humans, its efficacy and widespread use with other nephrotoxic agents is yet to be defined in large well-designed human studies.

Flaxseed for Health and Disease: Review of Clinical Trials.

BACKGROUND: Flaxseed (Linum usitatissimum) is an oil-based seed that contains high amounts of alpha-linolenic acid, linoleic acid, lignans, fiber and many other bioactive components which is suggested for a healthier life. Nowadays, flaxseed is known as a remarkable functional food with different health benefits for humans and protects against cardiovascular disease, diabetes, dyslipidemia, obesity and altogether metabolic syndrome. METHODS: To review the bioactive components of flaxseed and their potential health effects, PubMed and Scopus were searched from commencement to July 2019. Keywords including: "flaxseed", "Linum usitatissimum", "metabolic syndrome", "obesity", "inflammation", "insulin resistance", "diabetes", "hyperlipidemia" and "menopause" were searched in the databases with varying combinations. CONCLUSION: Consumption of flaxseed in different forms has valuable effects and protects against cardiovascular disease, hypertension, diabetes, dyslipidemia, inflammation and some other complications. Flaxseed can serve as a promising candidate for the management of metabolic syndrome to control blood lipid levels, fasting blood sugar, insulin resistance, body weight, waist circumference, body mass and blood pressure.