Nanoplastic Exposure at Environmental Concentrations Disrupts Hepatic Lipid Metabolism through Oxidative Stress Induction and Endoplasmic Reticulum Homeostasis Perturbation.

In this study, we investigated the mechanism underlying the perturbation of hepatic lipid metabolism in response to micro/nanoplastic (MP/NP) exposure at environmentally relevant concentrations. Polystyrene (PS) MPs/NPs with different sizes (0.1, 0.5, and 5.0 µm) were studied for their effects on the homeostasis and function of Nile tilapia (Oreochromis niloticus) liver. Results showed that PS MPs/NPs were readily internalized and accumulated in various internal organs/tissues, especially in fish liver and muscle. Smaller-sized NPs caused more severe toxicity than larger MPs, including hepatic steatosis, inflammatory response, and disturbed liver function. Mechanistically, PS NPs with a particle size of 100 nm perturbed protein homeostasis in the endoplasmic reticulum (ER) by inhibiting the expression of chaperone proteins and genes involved in ER-associated degradation. This led to the activation of the PERK-eIF2α pathway, which caused dysfunction of hepatic lipid metabolism. Induction of oxidative stress and activation of the Nrf2/Keap1 pathway were also involved in the PS NP-induced hepatic lipid accumulation. These findings highlight the potential adverse effects of environmental MPs/NPs on aquatic organisms, raising concerns about their ecotoxicity and food safety.

Melatonin influences proliferation and differentiation of rat dental papilla cells in vitro and dentine formation in vivo by altering mitochondrial activity.

Melatonin mediates a variety of biological processes ranging from the control of circadian rhythms to immune regulation. Melatonin also influences bone formation and osteointegration of dental implants. However, the effects of melatonin on dentine formation have not been examined. This study investigated the effects of melatonin on the proliferation and differentiation of rat dental papilla cells (rDPCs) in vitro and dentine formation in vivo. We found that melatonin (0, 10(-12) , 10(-10) ,10(-8)  m) induced a dose-dependent reduction in rDPCs proliferation, increased alkaline phosphatase (ALP) activity, the expression of dentine sialoprotein (DSP), and mineralized matrix formation in vitro. In vivo melatonin (50 mg/kg, BW, i.p.) inhibited dentine formation. Melatonin (10(-8 ) m) suppressed the activity of complex I and IV in the basal medium (OS-) and enhanced the activity of complex I and complex IV in osteogenic medium (OS+). These results demonstrate that melatonin suppresses the proliferation and promotes differentiation of rDPCs, the mechanisms of which may be related to activity of mitochondrial complex I and complex IV.

Electrostatic attraction of cationic pollutants by microplastics reduces their joint cytotoxicity.

Microplastic (MP) pollution causes global concerns regarding the consequential impacts on human health. In particular, MPs may act as vectors for various contaminants to induce adverse effects in human. In this work, the joint cytotoxicity of two different MPs co-exposed with diverse ionic pollutants was investigated in two cell lines from human digestive system: human gastric epithelium (GES-1) and colorectal mucosa (FHC) cell lines. The results indicated that the cytotoxicity of cationic pollutants was alleviated by MPs more significantly than that of anionic pollutants in both culture medium and river water. The electrostatic attraction between the negatively charged MPs and cations was a key factor in determining the ultimate joint toxicity. Our findings indicate that the joint cytotoxicity of MP-pollutant mixtures may be proactively reduced by modulating the surface charge of MPs.

Bone cement leaking into iliac vein during artificial femoral head replacement: A case report.

RATIONALE: Leakage of bone cement from femoral medullary cavity is a rare complication after hip arthroplasty, and there is no report on the leaked bone cement entering into iliac vessels. PATIENT CONCERNS: An 89-year-old woman presented with a fracture in the right femoral neck. She had well-fixed right femoral head replacement after careful preoperative examinations, and no adverse reactions appeared. She was able to get off bed to walk at the 2nd day after surgery. DIAGNOSES: Postoperative radiograph showed leakage of bone cement into the joint through femoral medullary cavity entering into iliac vessels, but the patient complained no discomforts. She received a treatment with low-molecular weight heparin and rivaroxaban. OUTCOMES: The patient was able to walk with normal gait, without swelling in both lower extremities and discomfort in the hip. There was no other complication concerning intravascular foreign bodies. LESSONS: This case calls into the phenomenon of leakage of injected bone cement in femoral head replacement regardless of complete and nonfractured femur, which may be into the lower limb and pelvic veins, given that, dangerous consequences will not occur.

Predicting Nano-Bio Interactions by Integrating Nanoparticle Libraries and Quantitative Nanostructure Activity Relationship Modeling.

The discovery of biocompatible or bioactive nanoparticles for medicinal applications is an expensive and time-consuming process that may be significantly facilitated by incorporating more rational approaches combining both experimental and computational methods. However, it is currently hindered by two limitations: (1) the lack of high-quality comprehensive data for computational modeling and (2) the lack of an effective modeling method for the complex nanomaterial structures. In this study, we tackled both issues by first synthesizing a large library of nanoparticles and obtained comprehensive data on their characterizations and bioactivities. Meanwhile, we virtually simulated each individual nanoparticle in this library by calculating their nanostructural characteristics and built models that correlate their nanostructure diversity to the corresponding biological activities. The resulting models were then used to predict and design nanoparticles with desired bioactivities. The experimental testing results of the designed nanoparticles were consistent with the model predictions. These findings demonstrate that rational design approaches combining high-quality nanoparticle libraries, big experimental data sets, and intelligent computational models can significantly reduce the efforts and costs of nanomaterial discovery.

[Experimental study on micro-dystrophin gene transfection into C57/BL10 mice's myoblast].

OBJECTIVE: To investigate the expression of micro-dystrophin gene in myoblast cultured in vitro, to explore the possibility of combining myoblast transplantation with gene transfer for Duchenne muscular dystrophy therapy. METHODS: Competent Escherichia coli JM109 was prepared, which transformed with plasmid pSL139, and positive clones were picked to cultivate. Plasmid was extracted with Alkaline lysis method and cutter with both Pvu I and Cla I enzyme. Agarose gel electrophoresis was employed to take pictures. Ten healthy 5-7 days old male C57/BL10 mice were selected, weighing 4-5 g, the primary and subcultured myoblasts were cultured with multi-step enzymatic digestion and differential adhesion method, and Desmin immunofluorescent method was used to identify. The 3rd generation myoblasts that were transfected with plasmid pSL139 mediated by liposome served as the experimental group, untransfected cells served as the control group. After 48 hours of transfection, the expressions of micro-dystrophin mRNA and protein in myoblasts were detected with RT-PCR and cell immunofluorescent methods, and the transfection efficiency was calculated. RESULTS: After pSL139 plasmids being digested and for 40 minutes agarose gel of electrophoresis, 3.75 kb fragment of target gene and vector were observed. The cells were almost uniform, and triangular or diamond shape after 24-48 hours of culture; the cells turned to fusion manner and could be passaged after 4-6 days. Desmin immunofluorescent result showed that green fluorescence was seen in cytoplasm of most 2nd myoblasts, and the purity of the myoblasts was above 90%. At 48 hours after transfection of myoblasts with plasmid pSL139, RT-PCR results showed that about 300 bp fragment was seen in the experimental group and the control group, and the brightness was higher in experimental group. Immunofluorescent staining displayed that green fluorescence was seen in the cytoplasm of the myoblasts in the experimental group and no green fluorescence in the control group; the expression efficiency of positive cells for micro-dystrophin was 45%-55% in experimental group. CONCLUSION: Micro-dystrophin gene can highly express at the levels of mRNA and protein respectively in myoblasts transfected with plasmid pSL139 mediated by liposome.

Reducing nanotube cytotoxicity using a nano-combinatorial library approach.

Carbon nanotubes (CNTs) have a great potential for applications in medicine. However, their biocompatibility and toxicity cause a great concern. Due to the large surface area of CNTs, chemical modification can dramatically alter their physiochemical properties and hence biological activity. Using a combinatorial chemistry approach, we report the synthesis of an 80-member surface-modified nanotube library. Based upon screening of this library with respect to protein-binding capacity, cytotoxicity, and immune response, we were able to select highly biocompatible nanotubes with reduced protein-binding cytotoxicity and immune response.