Reactive oxidative species (ROS)-based nanomedicine for BBB crossing and glioma treatment: current status and future directions

Glioma is the most common primary intracranial tumor in adults with poor prognosis. Current clinical treatment for glioma includes surgical resection along with chemoradiotherapy. However, the therapeutic efficacy is still unsatisfactory. The invasive nature of the glioma makes it impossible to completely resect it. The presence of blood-brain barrier (BBB) blocks chemotherapeutic drugs access to brain parenchyma for glioma treatment. Besides, tumor heterogeneity and hypoxic tumor microenvironment remarkably limit the efficacy of radiotherapy. With rapid advances of nanotechnology, the emergence of a new treatment approach, namely, reactive oxygen species (ROS)-based nanotherapy, provides an effective approach for eliminating glioma via generating large amounts of ROS in glioma cells. In addition, the emerging nanotechnology also provides BBB-crossing strategies, which allows effective ROS-based nanotherapy of glioma. In this review, we summarized ROS-based nanomedicine and their application in glioma treatment, including photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), radiation therapy, etc. Moreover, the current challenges and future prospects of ROS-based nanomedicine are also elucidated with the intention to accelerate its clinical translation

A Robust Shape Reconstruction Method for Facial Feature Point Detection

Facial feature point detection has been receiving great research advances in recent years. Numerous methods have been developed and applied in practical face analysis systems. However, it is still a quite challenging task because of the large variability in expression and gestures and the existence of occlusions in real-world photo shoot. In this paper, we present a robust sparse reconstruction method for the face alignment problems. Instead of a direct regression between the feature space and the shape space, the concept of shape increment reconstruction is introduced. Moreover, a set of coupled overcomplete dictionaries termed the shape increment dictionary and the local appearance dictionary are learned in a regressive manner to select robust features and fit shape increments. Additionally, to make the learned model more generalized, we select the best matched parameter set through extensive validation tests. Experimental results on three public datasets demonstrate that the proposed method achieves a better robustness over the state-of-the-art methods

Circular RNA circPOLR2A promotes clear cell renal cell carcinoma progression by facilitating the UBE3C-induced ubiquitination of PEBP1 and, thereby, activating the ERK signaling pathway

Abstract Background Increasing evidence has demonstrated that circular RNAs (circRNAs) are implicated in cancer progression. However, the aberrant expression and biological functions of circRNAs in clear cell renal cell carcinoma (cRCC) remain largely elusive. Method Differentially expressed circRNAs in cRCC were filtered via bioinformatics analysis. Aberrant circPOLR2A expression was validated in cRCC tissues and cell lines via qRT-PCR. Sanger sequencing was used to identify the backsplicing site of circPOLR2A. In vitro and in vivo functional experiments were performed to evaluate the role of circPOLR2A in cRCC malignancy. RNA pull-down, mass spectrometry, RIP, FISH and immunofluorescence assays were used to identify and validate the circPOLR2A-interacting proteins. Ubiquitination modification and interaction between proteins were detected via Co-IP and western blotting. The m6A modification in circPOLR2A was validated by the meRIP assay. Results Bioinformatics analysis revealed that circPOLR2A was highly expressed in cRCC tissues and metastatic cRCC tissues. CircPOLR2A expression was associated with tumor size and TNM stage in cRCC patients. In vitro and in vivo functional assays revealed that circPOLR2A accelerated cRCC cell proliferation, migration, invasion and angiogenesis, while inhibiting apoptosis. Further mechanistic research suggested that circPOLR2A could interact with UBE3C and PEBP1 proteins, and that UBE3C could act as a specific ubiquitin E3 ligase for the PEBP1 protein. The UBE3C/circPOLR2A/PEBP1 protein-RNA ternary complex enhanced the UBE3C-mediated ubiquitination and degradation of the PEBP1 protein which could inactivate the ERK signaling pathway. Rescue experiments revealed that the PEBP1 protein was the functional downstream target of circPOLR2A. Furthermore, m6A modification in circPOLR2A was confirmed, and the m6A reader YTHDF2 could regulate circPOLR2A expression. Conclusion Our study demonstrated that circPOLR2A modulated the UBE3C-mediated ubiquitination and degradation of the PEBP1 protein, and further activated the ERK pathway during cRCC progression and metastasis. The m6A reader, YTHDF2, regulated circPOLR2A expression in cRCC. Hence, circPOLR2A could be a potential target for the diagnosis and treatment of cRCC

Platelet-derived extracellular vesicles are associated with kidney injury in patients with urosepsis

Background: There is increasing evidence that platelet-derived extracellular vesicles (PEVs) may be involved in the mechanisms of inflammatory storm and organ damage in sepsis. However, there are no available studies on PEVs and renal injury in patients with urosepsis. Methods: We analyzed the concentration and ratio of PEVs in plasma by flow cytometry and measured plasma IL-1β/IL-6/TNF-α/NGAL levels by ELISA. Correlation analysis was also used to examine the concentration of PEVs in relation to levels of inflammatory factors and indicators of kidney damage, as well as the severity of the disease. Finally, the receiver operating characteristic curves were produced for PEVs concentrations as a diagnosis of S-AKI/AKI. Results: We found significantly higher levels of IL-1β/IL-6/TNF-α/NGAL in patients with urogenital sepsis. Furthermore, the concentrations of PEVs in plasma were significantly elevated in patients with urosepsis, especially in patients with Gram-negative bacterial infections, which were significantly and positively correlated with IL-1β/IL-6/TNF-α/NGAL levels. The area under the curve for PEVs diagnosing S-AKI and AKI was 0.746 [0.484, 1.000] and 0.943 [0.874, 1.000] respectively. Conclusion: Overall, the present study suggested that PEVs may mediate the release of inflammatory mediators in patients with urosepsis and participate in the mechanism of acute kidney injury, as well as having potential as diagnostic indicators of S-AKI and AKI and as early warning indicators of the severity of patients with urosepsis

Bioaccumulation and human health risks of OCPs and PCBs in freshwater products of Northeast China

The levels and spatial distribution of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in freshwater products from Northeast China were investigated by gas chromatography coupled to isotope dilution high-resolution mass spectrometry. All samples were on-spot sampled from main production regions of freshwater products in Northeast China, and these samples were used to systematically assess the potential health risks of OCPs and PCBs associated with consumption of these fishery products. Dichlorodiphenyltrichloroethanes (DDTs), hexa-chlorocyclohexane (HCHs), hexachlorobenzene (HCB) and PCBs were the major pollutants with 100% detection rates, and their levels ranged from 0.086 to 58, 0.038-3.3, 0.093-4.5 and 0.032-1.4 ng g(-1) wet weight, respectively. The estimated dietary intakes of these contaminants were all below their corresponding acceptable daily intakes. Significant regional differences in the levels of OCPs and PCBs (P <= 0.001) were found in samples from Liaoning and Inner Mongolia. The results showed that the concentrations of targeted contaminants in aquatic products had species-specific characteristics, and the levels of targeted pollutants in Oncorhynchus mykiss and Eriocheir sienesis were significantly higher than those in other aquatic product species. Advisories on ten species of aquatic products suggested that consumption of Eriocheir sinensis, Oncorhynchus mykiss and Cyprinus carpio at a rate exceeding 15 meals per month would pose a cancer risk. A health risk assessment indicated that exposure to these pollutants through freshwater products consumption would cause a non-ignorable potential carcinogenic risk to humans. (C) 2018 Elsevier Ltd. All rights reserved

Table4_The predictive value of prognostic nutritional index on early complications after robot-assisted radical cystectomy.docx

ObjectiveThe purpose of the study was to evaluate the predictive value of prognostic nutritional index (PNI) on early complications (within 30-day) after robot-assisted radical cystectomy (RARC) and urinary diversion.Patients and methodsPatients underwent RARC and urinary diversion between November 2018 and December 2021 in our centre were screened in this retrospective study. Baseline characteristics and perioperative data were recorded. Early complications after surgery were classified according to Clavien-Dindo system. Univariate and multivariate logistic analysis were performed to decide the potential factors associated with post-RARC complications. The receiver operating characteristic (ROC) curve was conducted to determine the predictive value of PNI on early overall and major complications after RARC.ResultsOverall 139 men and 13 women with a median age of 69 years and mean BMI of 24.4 kg/m2 were included in this study. As for urinary diversion, most patients (n = 111, 73%) received cutaneous ureterostomy, 36 patients (23.7%) underwent orthotopic neobladder and 5 patients (3.3%) received ileal conduit. The incidence of postoperative complication rate was 44.7%, which included 82.2% minor complications and 17.8% major complications. Further univariate and multivariate logistic analyses demonstrated that hypertension (OR = 2.96, 95% CI: 1.24–7.07, P = 0.015), PNI (OR = 0.73, 95% CI: 0.62–0.86, P ConclusionPNI can be an early alert for RARC patients thus aiding in closer monitoring and postoperative management.</p