As microplastics (MPs) dispersed into the environment, people might be exposed to MPs. Most pollutants either pass through or concentrate in the kidney. Therefore, nephrotoxicity tests are needed to ...verify the toxic potential of MPs. Here we used human embryonic kidney 293 (HEK293) cells to determine the association between nephrotoxicity and round-shape polystyrene MPs (PSMPs) (3.54 ± 0.39 μm) under realistic environmental exposure concentrations. Results revealed that PSMPs can adhere to the cell membrane and get entirely engulfed by HEK293 cells. PSMPs can induce cytotoxicity by oxidative stress via inhibition of the antioxidant haem oxygenase-1. Depolarisation of the mitochondrial membrane potential and formation of autophagosomes confirmed that apoptosis and autophagy can be simultaneously induced by PSMPs. The inflammatory factor was only activated (33 cytokines) by noncytotoxic concentration of PSMPs (3 ng/mL); however, the cytotoxic concentration (300 ng/mL) of PSMPs induced autophagy, which might further reduce NLRP3 expression, thus contributing to dampening inflammation (35 cytokines) in HEK293 cells. PSMPs (300 ng/mL) can impair kidney barrier integrity and increase the probability of developing acute kidney injury through the depletion of the zonula occludens-2 proteins and α1-antitrypsin. Altogether, our results demonstrated that environmental exposure to PSMPs may lead to an increased risk of renal disease.
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•PSMPs can adhere to the cell membrane and be entirely engulfed by HEK293 cells.•PSMPs can induce cytotoxicity by ROS through the inhibition of antioxidant enzyme.•Apoptosis and autophagy can be simultaneously induced in HEK293 cells by PSMPs.•PSMP-induced autophagy can diminish inflammatory responses via NLRP-3 inhibition.•PSMPs can impair kidney barrier integrity and increase the risk of kidney injury.
Central and peripheral nerve injuries can lead to permanent paralysis and organ dysfunction. In recent years, many cell and exosome implantation techniques have been developed in an attempt to ...restore function after nerve injury with promising but generally unsatisfactory clinical results. Clinical outcome may be enhanced by bio-scaffolds specifically fabricated to provide the appropriate three-dimensional (3D) conduit, growth-permissive substrate, and trophic factor support required for cell survival and regeneration. In rodents, these scaffolds have been shown to promote axonal regrowth and restore limb motor function following experimental spinal cord or sciatic nerve injury. Combining the appropriate cell/exosome and scaffold type may thus achieve tissue repair and regeneration with safety and efficacy sufficient for routine clinical application. In this review, we describe the efficacies of bio-scaffolds composed of various natural polysaccharides (alginate, chitin, chitosan, and hyaluronic acid), protein polymers (gelatin, collagen, silk fibroin, fibrin, and keratin), and self-assembling peptides for repair of nerve injury. In addition, we review the capacities of these constructs for supporting in vitro cell-adhesion, mechano-transduction, proliferation, and differentiation as well as the in vivo properties critical for a successful clinical outcome, including controlled degradation and re-absorption. Finally, we describe recent advances in 3D bio-printing for nerve regeneration.
Epidermal growth factor receptor (EGFR) is upregulated in prostate cancer (PCa). However, suppression of EGFR did not improve the patient outcome, possibly due to the activation of PI3K/Akt signaling ...in PCa. Compounds able to suppress both PI3K/Akt and EGFR signaling may be effective for treating advanced PCa.
We examined if caffeic acid phenethyl ester (CAPE) simultaneously suppresses the EGFR and Akt signaling, migration and tumor growth in PCa cells.
Wound healing assay, transwell migration assay and xenograft mice model were used to determine the effects of CAPE on migration and proliferation of PCa cells. Western blot, immunoprecipitation, and immunohistochemistry staining were performed to determine the effects of CAPE on EGFR and Akt signaling.
CAPE treatment decreased the gene expression of HRAS, RAF1, AKT2, GSK3A, and EGF and the protein expression of phospho-EGFR (Y845, Y1069, Y1148, Y1173), phospho-FAK, Akt, and ERK1/2 in PCa cells. CAPE treatment inhibited the EGF-induced migration of PCa cells. Combined treatment of CAPE with EGFR inhibitor gefitinib showed additive inhibition on migration and proliferation of PCa cells. Injection of CAPE (15 mg/kg/3 days) for 14 days suppressed the tumor growth of prostate xenografts in nude mice as well as suppressed the levels of Ki67, phospho-EGFR Y845, MMP-9, phospho-Akt S473, phospho-Akt T308, Ras, and Raf-1 in prostate xenografts.
Our study suggested that CAPE can simultaneously suppress the EGFR and Akt signaling in PCa cells and is a potential therapeutic agent for advanced PCa.
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Bone has multiple functions in animals, such as supporting the body for mobility. The zebrafish skeleton is composed of craniofacial and axial skeletons. It shares a physiological curvature and ...consists of a similar number of vertebrae as humans. Bone degeneration and malformations have been widely studied in zebrafish as human disease models. High‐resolution imaging and different bone properties such as density and volume can be obtained using micro‐computed tomography (micro‐CT). This study aimed to understand the possible changes in the structure and bone mineral density (BMD) of the vertebrae and craniofacial skeleton with age (4, 12 and 24 months post fertilisation mpf) in zebrafish. Our data showed that the BMD in the vertebrae and specific craniofacial skeleton (mandibular arch, ceratohyal and ethmoid plate) of 12 and 24 mpf fish were higher than that of the 4 mpf fish. In addition, we found the age‐dependent increase in BMD was not ubiquitously observed in facial bones, and such differences were not correlated with bone type. In summary, such additional information on the craniofacial skeleton could help in understanding bone development throughout the lifespan of zebrafish.
Micro‐CT images and craniofacial BMD of zebrafish head. The study finds that the age‐dependent increase in BMD was not ubiquitously observed in facial bones, and such differences were not correlated with bone type.
We investigated the effects of antibiotics, drugs, and metals on lung and intestinal microbiomes after sub-chronic exposure of low-level air pollution in ageing rats. Male 1.5-year-old Fischer 344 ...ageing rats were exposed to low-level traffic-related air pollution via whole-body exposure system for 3 months with/without high-efficiency particulate air (HEPA) filtration (gaseous vs. particulate matter with aerodynamic diameter of ≤2.5 µm (PM2.5) pollution). Lung functions, antibiotics, drugs, and metals in lungs were examined and linked to lung and fecal microbiome analyses by high-throughput sequencing analysis of 16 s ribosomal (r)DNA. Rats were exposed to 8.7 μg/m3 PM2.5, 10.1 ppb NO2, 1.6 ppb SO2, and 23.9 ppb O3 in average during the study period. Air pollution exposure decreased forced vital capacity (FVC), peak expiratory flow (PEF), forced expiratory volume in 20 ms (FEV20), and FEF at 25∼75% of FVC (FEF25–75). Air pollution exposure increased antibiotics and drugs (benzotriazole, methamphetamine, methyl-1 H-benzotriazole, ketamine, ampicillin, ciprofloxacin, pentoxifylline, erythromycin, clarithromycin, ceftriaxone, penicillin G, and penicillin V) and altered metals (V, Cr, Cu, Zn, and Ba) levels in lungs. Fusobacteria and Verrucomicrobia at phylum level were increased in lung microbiome by air pollution, whereas increased alpha diversity, Bacteroidetes and Proteobacteria and decreased Firmicutes at phylum level were occurred in intestinal microbiome. Lung function decline was correlated with increasing antibiotics, drugs, and metals in lungs as well as lung and intestinal microbiome dysbiosis. The antibiotics, drugs, and Cr, Co, Ca, and Cu levels in lung were correlated with lung and intestinal microbiome dysbiosis. The lung microbiome was correlated with intestinal microbiome at several phylum and family levels after air pollution exposure. Our results revealed that antibiotics, drugs, and metals in the lung caused lung and intestinal microbiome dysbiosis in ageing rats exposed to air pollution, which may lead to lung function decline.
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•Air pollution decreased lung function in ageing rats.•Air pollution exposure led to antibiotics and metals deposition in lungs.•Air pollution caused significant imbalance in lung and intestinal microbiome.•Antibiotics and metals were correlated with lung and intestinal microbiome dysbiosis.•Lung function decline was linked to microbiome dysbiosis by antibiotics and metals.
•Chitosan/fucoidan nanoparticles (CS/F NPs) are potential carriers for gentamicin (GM) delivery.•The release of GM from CS/F NPs is biphasic, attaining a value of 99% release.•The GM-loaded CS/F NPs ...exhibited more effective antibacterial activity than free GM.•The CS/F NPs facilitated antibacterial capability before GM were completely released.•By intratracheal administration, GM-loaded CS/F NP presented a superior AUC/MIC ratio.
Gentamicin (GM), one of the most commonly used aminoglycoside antibiotics, has been used for treating pneumonia; however, the applicability of GM is limited by its bioavailability and toxic side effects. This study used chitosan (CS)/fucoidan (F) nanoparticles (NPs) to develop a nanoformulation for pulmonary delivery of GM, presenting a biphasic release feature. The NPs exhibited a zero-order release of GM for the first 10h, followed by a sustained release of up to 72h, attaining a value of 99%. The GM-loaded CS/F NPs provide multiple antimicrobial capabilities against Klebsiella pneumoniae, including the CS and biphasic release of GM. Compared with the intravenous administration of free GM (0.5mg/kg), the intratracheal administration of GM-loaded CS/F NP (0.27mg/kg) presented a superior area under the concentration–time curve/minimum inhibitory concentration ratio, indicating the simultaneous improvement of antimicrobial efficacy and elimination of systemic toxicity. These results suggested that CS/F NPs are potential carriers in pulmonary delivery of GM for pneumonia treatment.
Black tea is one of the world's most popular beverages, and its health-promoting effects have been intensively investigated. The antiobesity and hypolipidemic effects of black tea have attracted ...increasing interest, but the mechanisms underlying these phenomena remain unclear. In the present study, the black tea major component theaflavins were assessed for their hepatic lipid-lowering potential when administered in fatty acid overload conditions both in cell culture and in an animal experimental model. We found that theaflavins significantly reduced lipid accumulation, suppressed fatty acid synthesis, and stimulated fatty acid oxidation. Furthermore, theaflavins also inhibited acetyl-coenzyme A carboxylase activities by stimulating AMP-activated protein kinase (AMPK) through the LKB1 and reactive oxygen species pathways. These observations support the idea that AMPK is a critical component of decreased hepatic lipid accumulation by theaflavin treatments. Our results show that theaflavins are bioavailable both in vitro and in vivo and may be active in the prevention of fatty liver and obesity.
Effects of air pollution on neurotoxicity and behavioral alterations have been reported. The objective of this study was to investigate the pathophysiology caused by particulate matter (PM) in the ...brain. We examined the effects of traffic-related particulate matter with an aerodynamic diameter of < 1 μm (PM
), high-efficiency particulate air (HEPA)-filtered air, and clean air on the brain structure, behavioral changes, brainwaves, and bioreactivity of the brain (cortex, cerebellum, and hippocampus), olfactory bulb, and serum after 3 and 6 months of whole-body exposure in 6-month-old Sprague Dawley rats.
The rats were exposed to 16.3 ± 8.2 (4.7~ 68.8) μg/m
of PM
during the study period. An MRI analysis showed that whole-brain and hippocampal volumes increased with 3 and 6 months of PM
exposure. A short-term memory deficiency occurred with 3 months of exposure to PM
as determined by a novel object recognition (NOR) task, but there were no significant changes in motor functions. There were no changes in frequency bands or multiscale entropy of brainwaves. Exposure to 3 months of PM
increased 8-isoporstance in the cortex, cerebellum, and hippocampus as well as hippocampal inflammation (interleukin (IL)-6), but not in the olfactory bulb. Systemic CCL11 (at 3 and 6 months) and IL-4 (at 6 months) increased after PM
exposure. Light chain 3 (LC3) expression increased in the hippocampus after 6 months of exposure. Spongiosis and neuronal shrinkage were observed in the cortex, cerebellum, and hippocampus (neuronal shrinkage) after exposure to air pollution. Additionally, microabscesses were observed in the cortex after 6 months of PM
exposure.
Our study first observed cerebral edema and brain impairment in adult rats after chronic exposure to traffic-related air pollution.
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