Revisiting Microplastics in Landfill Leachate: Unnoticed Tiny Microplastics and Their Fate in Treatment Works.

Due to the environmental risks caused by microplastics, understanding the sources and characteristics of microplastics and cutting off their routes into the environment are crucial. However, so far, studies on microplastics in the landfill leachate system (a major pathway of microplastics into the environment) are still limited, especially for tiny particles <50 µm that might have higher risks to the environment. This study investigated the microplastics in landfill leachate and in leachate treatment works, with a size detection limit down to 10 µm. The results showed that the microplastics particle and mass concentrations in the untreated leachate were 235.4 ± 17.1 item/L and 11.4 ± 0.8 µg/L, respectively, with tiny particles (<50 µm) accounting for over 50%. Overall, 27 polymeric materials were detected in leachate samples, with polyethylene and polypropylene being the most abundant in the untreated leachate. The neutral buoyancy of microplastics (average density: 0.94 g/cm3), together with irregular shapes, suggested they may be difficult to be removed by sedimentation. Further exploring the fate of microplastics in leachate treatment works showed that the membrane treatment effectively reduced microplastics loading to 0.14% for particle and 0.01% for mass, but the average particle density rose. The differences in polymeric materials distribution at different sampling locations and the presence of membrane-related polymer in membrane treatment effluent suggested tiny microplastics could be generated and released from membrane systems. Moreover, this study discovered that the sludge dewatering liquor could contain a high amount of microplastics, and the estimated particle loading was about 3.6 times higher than that in dewatered sludge. This suggested a new approach to microplastics mitigation through separating microplastics from the sludge dewatering liquor before its recirculation.

Arsenite-loaded nanoparticles inhibit the invasion and metastasis of a hepatocellular carcinoma: in vitro and in vivo study.

Postoperative recurrence and metastasis are the major problems for the current treatment of hepatocellular carcinomas (HCC) in the clinic, including hepatectomy and liver transplantation. Here, we report that arsentic-loaded nanoparticles (ALNPs) are able to reduce the invasion of HCC cells in vitro, and, more importantly, can strongly suppress the invasion and metastasis of HCC in vivo without adverse side effects. Compared to free drug arsenic trioxide , ALNPs can deliver the drug into cancer cells more efficiently, destroy the structure of microtubules and reduce the aggregation of microfilaments in cell membranes more significantly. Furthermore, our results also reveal that tumor cells in murine blood were reduced remarkably after intravenous injection of ALNPs, indicating that this nano-drug may efficiently kill circulating tumor cells in vivo. In conclusion, our nano-drug ALNPs have great potential for the suppression of metastasis of HCC, which may open up a new avenue for the effective treatment of HCC without metastasis and recurrence.

GABPA predicts prognosis and inhibits metastasis of hepatocellular carcinoma.

BACKGROUND: Increasing evidence indicates that abnormal expression of GABPA is associated with tumor development and progression. However, the function and clinicopathological significance of GABPA in hepatocellular carcinoma (HCC) remain obscure. METHODS: The mRNA and protein expression of GABPA in HCC clinical specimens and cell lines was examined by real-time PCR and western blotting, respectively. Follow-up data were used to uncover the relationship between GABPA expression and the prognosis of HCC patients. HCC cell lines stably overexpressing or silencing GABPA were established to explore the function of GABPA in HCC cell migration and invasion by Transwell and wound healing assays in vitro and in a xenograft model in vivo. Restoration of function analysis was used to examine the underlying molecular mechanisms. RESULTS: GABPA was downregulated at the protein and mRNA levels in HCC tissues compared with adjacent normal tissues. Decreased GABPA expression was correlated with alpha-fetoprotein levels (P = 0.001), tumor grade (P = 0.017), and distant metastasis (P = 0.021). Kaplan-Meier survival analysis showed that patients with lower GABPA expression had significantly shorter survival times than those with higher GABPA (P = 0.031). In vivo and in vitro assays demonstrated that GABPA negatively regulated HCC cell migration and invasion, and the effect of GABPA on HCC cell migration was mediated at least partly by the regulation of E-cadherin. CONCLUSIONS: Collectively, our data indicate that GABPA inhibits HCC cell migration by modulating E-cadherin and could serve as a novel biomarker for HCC prognosis. GABPA may act as a tumor suppressor during HCC progression and metastasis, and is a potential therapeutic target in HCC.

Albumin-based nanoparticles loaded with hydrophobic gadolinium chelates as T1-T2 dual-mode contrast agents for accurate liver tumor imaging.

Magnetic resonance contrast agents with T1-T2 dual mode contrast capability have attracted considerable interest because they offer complementary and synergistic diagnostic information, leading to high imaging sensitivity and accurate diagnosis. Here, we reported a facile strategy to construct albumin based nanoparticles loaded with hydrophobic gadolinium chelates by hydrophobic interaction for magnetic resonance imaging (MRI). We synthesized a glycyrrhetinic acid-containing Gd-DOTA derivative (GGD) and loaded GGD molecules into BSA nanoparticles to form GGD-BSA nanoparticles (GGD-BSA NPs). The large size and porous structure endow GGD-BSA NPs with geometrical confinement, which restricts the tumbling of GGD and the diffusion of surrounding water molecules. As a result, GGD-BSA NPs exhibit ultrahigh T1 and T2 relaxivities, which are approximately 8-fold higher than those of gadolinium-based clinical contrast agents at 0.5 T. Besides, due to the intrinsic properties of their components, GGD-BSA NPs show good biocompatibility in vitro and in vivo, which warrants their great potential in clinical translation. Furthermore, GGD-BSA NPs show remarkable sensitivity in noninvasive detection of liver tumors by self-confirmed T1-T2 dual-mode contrast-enhanced MRI. All of these merits make GGD-BSA NPs a potential candidate for fruitful biomedical and preclinical applications.

High expression of Rap2A is associated with poor prognosis of patients with hepatocellular carcinoma.

Rap2A is overexpressed in a multitude of human cancers and plays an important role in cytoskeleton rearrangement, arteriogenesis and cell migration. However, its role and function in hepatocellular carcinoma (HCC) has not yet been explored. Here, we aimed to investigate the expression of Rap2A in HCC and the relationship between Rap2A and clinicopathologic features of patients. Western blot and quantitative real-time PCR (qRT-PCR) showed that Rap2A was remarkably upregulated in HCC tissues compared to adjacent normal liver tissues. Immunohistochemistry (IHC) showed that Rap2A was mainly localized in the cytoplasm rather than nuclei in HCC tissues. Overexpression of Rap2A was significantly correlated with tumor size (P=0.019), metastasis (P=0.002), pathological differentiation (P=0.028) and vascular invasion (P=0.017) in HCC. Kaplan-Meier analysis demonstrated that HCC patients with high Rap2A expression had shorter overall survival time than those with low Rap2A expression (P=0.011). Furthermore, High level of Rap2A was a risk factor for HCC patients according to Cox's proportional hazard regression (P=0.026). In summary, our results suggest that high expression of Rap2A is involved in HCC progression and might be a novel prognostic indicator for patients.

Arsenite-loaded nanoparticles inhibit PARP-1 to overcome multidrug resistance in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the highest incidences in cancers; however, traditional chemotherapy often suffers from low efficiency caused by drug resistance. Herein, we report an arsenite-loaded dual-drug (doxorubicin and arsenic trioxide, i.e., DOX and ATO) nanomedicine system (FeAsOx@SiO2-DOX, Combo NP) with significant drug synergy and pH-triggered drug release for effective treatment of DOX resistant HCC cells (HuH-7/ADM). This nano-formulation Combo NP exhibits the synergistic effect of DNA damage by DOX along with DNA repair interference by ATO, which results in unprecedented killing efficiency on DOX resistant cancer cells. More importantly, we explored the possible mechanism is that the activity of PARP-1 is inhibited by ATO during the treatment of Combo NP, which finally induces apoptosis of HuH-7/ADM cells by poly (ADP-ribosyl) ation suppression and DNA lesions accumulation. This study provides a smart drug delivery strategy to develop a novel synergistic combination therapy for effectively overcome drug- resistant cancer cells.

The NKD1/Rac1 feedback loop regulates the invasion and migration ability of hepatocarcinoma cells.

Hepatocellular carcinoma (HCC) is complicated by aggressive migration and invasion, which contribute to the increased mortality of HCC patients. The NKD1 protein is abnormally expressed in many neoplasms and plays an important role in tumor progression. However, the regulation and underlying molecular mechanisms of NKD1 in HCC cell invasion and migration remain poorly understood. In the present study, ectopic expression of NKD1 in HCC cells attenuated migration and invasion in vitro and in vivo by down-regulating Rac1 expression level and activity, which affected the HCC cell cytoskeleton and E-cadherin expression. Mechanistic studies showed that NKD1 interacted with Rac1 in the cytoplasm and promoted its degradation by the ubiquitin-proteasome pathway. Over-expression of Rac1 enhanced the transcription of the NKD1 gene and protein expression conversely owing to its negative regulation of EZH2. Analysis of clinical samples showed that abnormal expression of NKD1 and Rac1 was associated with the poor prognosis of HCC patients. In summary, our data indicate a new role for NKD1 as a regulator of HCC cell invasion and migration via a feedback loop involving Rac1.

The Interplay Between miR-148a and DNMT1 Might be Exploited for Pancreatic Cancer Therapy.

We discovered the expression level of miR-148a significantly decreased in pancreatic cancer tissues whereas that of DNMT1 increased. In ASPC-1 cancer cells, the overexpression of miR-148a led to a decreased level of DNMT1 and reduced the proliferation and metastasis of ASPC-1 cells. Moreover, the increased expression of miR-148a arrested the UTR methylation of p27, giving rise to an increased level of p27. Interestingly, it was shown that the DNMT1 inhibition enhanced the expression of miR-148a. In vivo studies demonstrated that the tumorigenesis of ASPC-1 was significantly arrested by either the overexpression of miR-148a or the inhibition of DNMT1.