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N6-methyladenosine (m 6 A) RNA methylation has been considered the most prevalent, abundant, and conserved internal transcriptional modification throughout the eukaryotic mRNAs. Typically, m 6 A RNA methylation is catalyzed by the RNA methyltransferases (writers), is removed by its demethylases (erasers), and interacts with m 6 A-binding proteins (readers). Accumulating evidence shows that abnormal changes in the m 6 A levels of these regulators are increasingly associated with human tumorigenesis and drug resistance. However, the molecular mechanisms underlying m 6 A RNA methylation in tumor occurrence and development have not been comprehensively clarified. We reviewed the recent findings on biological regulation of m 6 A RNA methylation and summarized its potential therapeutic strategies in various human cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Hu, Jin, Yang, Ding, Zhang, Li and Pan.)

α-Enolase 1 (ENO1) is a critical glycolytic enzyme whose aberrant expression drives the pathogenesis of various cancers. ENO1 has been indicated as having additional roles beyond its conventional metabolic activity, but the underlying mechanisms and biological consequences remain elusive. Here, we show that ENO1 suppresses iron regulatory protein 1 (IRP1) expression to regulate iron homeostasis and survival of hepatocellular carcinoma (HCC) cells. Mechanistically, we demonstrate that ENO1, as an RNA-binding protein, recruits CNOT6 to accelerate the messenger RNA decay of IRP1 in cancer cells, leading to inhibition of mitoferrin-1 (Mfrn1) expression and subsequent repression of mitochondrial iron-induced ferroptosis. Moreover, through in vitro and in vivo experiments and clinical sample analysis, we identified IRP1 and Mfrn1 as tumor suppressors by inducing ferroptosis in HCC cells. Taken together, this study establishes an important role for the ENO1-IRP1-Mfrn1 pathway in the pathogenesis of HCC and reveals a previously unknown connection between this pathway and ferroptosis, suggesting a potential innovative cancer therapy., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Xanthatin is a plant-derived bioactive sesquiterpene lactone from the Xanthium strumarium L., and it has been used as a traditional Chinese medicine. Recently, many studies have reported that xanthatin has anticancer activity. However, a comprehensive understanding of the mechanism underlying the antitumor effects of xanthatin is still lacking., Objective: To systematically and comprehensively identify the underlying mechanisms of xanthatin on cancer cells, quantitative proteomic techniques were performed., Methods: Xanthatin induced HT-29 colon cancer cells death was detected by lactate dehydrogenase (LDH) release cell death assay. Differentially abundant proteins in two groups (xanthatin treatment groups and control groups) of human HT-29 colon cancer cells were identified using tandem mass tag (TMT) quantitative proteomic techniques. All the significant differentially abundant proteins were generally characterized by performing hierarchical clustering, Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We chose Western blot analysis to validate the candidate proteins in the proteomics results., Results: A total of 5637 proteins were identified, of which 397 significantly differentially abundant proteins in the groups were quantified. Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, we found that p53-related signaling played an important role in xanthatin-treated HT-29 colon cancer cells. p53- upregulated modulator of apoptosis (Puma), Sestrin-2 and p14ARF, which were selected from among p53-related signaling proteins, were further validated, and the results were consistent with the tandem mass tag quantitative proteomic results., Conclusion: We first investigated the molecular mechanism underlying the effects of xanthatin treatment on HT-29 colon cancer cells using tandem mass tag quantitative proteomic methods and provided a global comprehensive understanding of the antitumor effects of xanthatin. However, it is necessary to further confirm the function of the differentially abundant proteins and the potentially associated signaling pathways., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Understanding how the living human brain functions requires sophisticated in vivo neuroimaging technologies to characterise the complexity of neuroanatomy, neural function, and brain metabolism. Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of human brain function have historically been limited in their capacity to measure dynamic neural activity. Simultaneous [18 F]-FDG-PET and functional magnetic resonance imaging (fMRI) with FDG infusion protocols enable examination of dynamic changes in cerebral glucose metabolism simultaneously with dynamic changes in blood oxygenation. The Monash vis-fPET-fMRI dataset is a simultaneously acquired FDG-fPET/BOLD-fMRI dataset acquired from n = 10 healthy adults (18-49 yrs) whilst they viewed a flickering checkerboard task. The dataset contains both raw (unprocessed) images and source data organized according to the BIDS specification. The source data includes PET listmode, normalization, sinogram and physiology data. Here, the technical feasibility of using opensource frameworks to reconstruct the PET listmode data is demonstrated. The dataset has significant re-use value for the development of new processing pipelines, signal optimisation methods, and to formulate new hypotheses concerning the relationship between neuronal glucose uptake and cerebral haemodynamics., (© 2021. The Author(s).)

Background: The strong inter-individual pharmacokinetic variability and the narrow therapeutic window of tacrolimus (TAC) have hampered the clinical application. Gene polymorphisms play an important role in TAC pharmacokinetics. Here, we investigate the influence of genotypes of IL-10, CYP3A5, CYP2C8, and ABCB1 on dose-adjusted trough blood concentrations (the C 0 /D ratio) of TAC to reveal unclear genetic factors that may affect TAC dose requirements for renal transplant recipients., Methods: Genetic polymorphisms of IL-10, CYP3A5, CYP2C8, and ABCB1 in 188 renal transplant recipients were determined using Kompetitive Allele Specific PCR (KASP). Statistical analysis was applied to examine the effect of genetic variation on the TAC C 0 /D at 5, 10, 15, and 30 days after transplantation., Results: Recipients carrying the IL-10 -819C > T TT genotype showed a significantly higher TAC C 0 /D than those with the TC/CC genotype (p < 0.05). Additionally, the TAC C 0 /D values of recipients with the capacity for low IL-10 activity (-819 TT) engrafted with CYP3A5 non-expressers were higher compared to the intermediate/high activity of IL-10 -819C > T TC or CC carrying CYP3A5 expressers, and the difference was statistically significant at different time points (p < 0.05)., Conclusions: Genetic polymorphisms of IL-10 -819C > T and CYP3A5 6986A > G influence the TAC C 0 /D, which may contribute to variation in TAC dose requirements during the early post-transplantation period. Detecting IL-10 -819C > T and CYP3A5 6986A > G polymorphisms may allow determination of individualized tacrolimus dosage regimens for renal transplant recipients during the early post-transplantation period., (© 2021. Maj Institute of Pharmacology Polish Academy of Sciences.)

Drug resistance, including adriamycin (ADR)-based therapeutic resistance, is a crucial cause of chemotherapy failure in breast cancer treatment. Acquired chemoresistance has been identified to be closely associated with the overexpression of P-glycoprotein (P-gp/ABCB1). Long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) can be involved in carcinogenesis; however, its roles in ABCB1-mediated ADR resistance are poorly understood. In this study, we identified a panel of differentially expressed lncRNAs, mRNAs, and microRNAs (miRNAs) in MCF-7 and MCF-7/ADR cell lines through RNA sequencing (RNA-seq) technologies. GAS5 level was downregulated whereas ABCB1 level was upregulated in the resistant breast cancer tissues and cells. Overexpression of GAS5 significantly enhanced the ADR sensitivity and apoptosis, and it inhibited the efflux function and expression of ABCB1 in vitro, while knockdown of GAS5 had the opposite effects. Further mechanism-related investigations indicated that GAS5 acted as an endogenous "sponge" by competing for miR-221-3p binding to regulate its target dickkopf 2 (DKK2), and then it inhibited the activation of the Wnt/β-catenin pathway. Functionally, GAS5 enhanced the anti-tumor effect of ADR in vivo. Collectively, our findings reveal that GAS5 exerted regulatory function in ADR resistance possibly through the miR-221-3p/DKK2 axis, providing a novel approach to develop promising therapeutic strategy for overcoming chemoresistance in breast cancer patients., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mastering the "arcana of neuroimaging analysis", the obscure knowledge required to apply an appropriate combination of software tools and parameters to analyse a given neuroimaging dataset, is a time consuming process. Therefore, it is not typically feasible to invest the additional effort required generalise workflow implementations to accommodate for the various acquisition parameters, data storage conventions and computing environments in use at different research sites, limiting the reusability of published workflows. We present a novel software framework, Abstraction of Repository-Centric ANAlysis (Arcana), which enables the development of complex, "end-to-end" workflows that are adaptable to new analyses and portable to a wide range of computing infrastructures. Analysis templates for specific image types (e.g. MRI contrast) are implemented as Python classes, which define a range of potential derivatives and analysis methods. Arcana retrieves data from imaging repositories, which can be BIDS datasets, XNAT instances or plain directories, and stores selected derivatives and associated provenance back into a repository for reuse by subsequent analyses. Workflows are constructed using Nipype and can be executed on local workstations or in high performance computing environments. Generic analysis methods can be consolidated within common base classes to facilitate code-reuse and collaborative development, which can be specialised for study-specific requirements via class inheritance. Arcana provides a framework in which to develop unified neuroimaging workflows that can be reused across a wide range of research studies and sites.

Introduction: To investigate the relationship between malnutrition and the severity of radiation pneumonitis (RP) in patients with lung cancer with normal baseline pulmonary function and lungs' V20 < 35% treated by intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy., Materials and Methods: A total of 150 patients with lung cancer who received definitive IMRT (≥ 60 Gy) and concurrent chemotherapy were enrolled. In the condition of normal baseline pulmonary function and strict constraints of the irradiation dose to normal lung tissues, we recorded Eastern Cooperative Oncology Group score; concurrent chemotherapy; clinical stage; the level of albumin (ALB), hemoglobin, and C-reactive protein; Subjective Global Assessment (SGA) scores; radiation esophagitis grade; V20 of lungs; and mean lung dose. These factors were correlated with RP using univariate and multivariate regression analyses., Results: Of 150 patients, 12 patients (8.0%) developed Grade 3 to 5 RP, 37 (24.6%) patients developed grade 3 to 5 esophageal toxicity. In univariate analysis, ALB level (P = .002), radiation esophagitis (P < .001), and SGA score (P < .001) were significantly associated with RP. Multivariate analysis revealed that SGA (P < .001) was the independent predictor of RP., Conclusions: SGA could be a predictor for RP in patients with lung cancer treated with definitive IMRT and concurrent chemotherapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: The effect of local therapy (LT) for oligoprogressive epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) has not been well established. Forty-six patients with stage IIIB/IV EGFR-mutated NSCLC were treated by LT and continuing tyrosine kinase inhibitors (TKIs) for oligoprogression. The median overall survival (OS) and progression-free survival (PFS) after LT were 13.0 and 7.0 months, respectively. EGFR mutation type, sites of LT, and time from first progressive disease (PD) to LT were prognostic of OS after LT., Purpose: Patients with advanced stage EGFR-mutated NSCLC treated with EGFR TKIs could experience oligoprogression. This study investigated the benefits of LT and continuation of TKIs for oligoprogression retrospectively., Materials and Methods: Forty-six patients with stage IIIB/IV EGFR-mutated NSCLC on TKIs were treated by LT and continuation of TKIs for oligoprogressive disease. The impact of clinicopathologic variables on survival was explored using Cox regression., Results: With a median follow-up of 32 months, the 2-year OS was 65.2%, and the estimated OS was 35.0 months. The median OS after LT (LT-OS) was 13.0 months. The median PFS after LT (LT-PFS) was 7.0 months. Univariate analysis showed that stage at initial diagnosis, EGFR mutation type, site of LT, metastatic status at initial TKIs, and time from first PD to LT correlated with LT-OS significantly. Multivariate analysis suggested that EGFR mutation type (P = .001), sites of LT (P = .000), and time from first PD to LT (P = .034) were prognostic of LT-OS. Univariate analysis showed that metastatic status at initial TKIs and time from first PD to LT correlated with LT-PFS significantly. Multivariate analysis suggested that only time from first PD to LT (P = .000) was prognostic of LT-PFS., Conclusion: This study revealed that LTs are feasible and effective for EGFR-mutated NSCLC with oligoprogression. EGFR mutation type, sites of LT, and time from first PD to LT were prognostic factors for LT-OS. Time from first PD to LT was a prognostic factor for LT-PFS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Parallel Magnetic Resonance Imaging (pMRI) is one of the most important technical advances in current MRI technology. Although many reconstruction methods have been proposed for pMRI, the reconstructed images still suffer visible artifacts especially when high acceleration is used. To improve the reconstruction quality of pMRI, this paper proposes a new reconstruction method. Instead of achieving perfect reconstruction under ideal assumptions, the proposed method uses weighted H(infinity) optimization to minimize the total reconstruction error, including that raised by the noise and uncertainty in sensitivity map. The experimental studies on in vivo data sets demonstrate that the proposed method outperforms significantly the existing methods at high acceleration.

In dynamic Magnetic Resonance Imaging (MRI), due to the limitation of imaging speed, it is commonly required to reconstruct the images from a reduced fourier encoded K-space sequence. This paper presents two temporal model based methods to estimate the un-acquired K-space data, called Adaptive K-space Updating (AKU) methods. The AKU reconstruction algorithms are directly applicable to the truncated K-space sequence generated by the well known Fourier Keyhole (FK) encoding scheme. The experimental study on the real MRI data shows that the proposed AKU methods can produce images with much lower reconstruction error than conventional FK method.