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Zinc oxide nanoparticles (ZnONPs), characterized by their nanoscale dimensions and unique properties, have emerged as promising materials in various applications. From electronics to biomedicine, their versatility and biocompatibility makes them valuable assets to address multifaceted challenges. This study aimed to comparatively analyze chemically synthesized ZnONPs (CS-ZnONPs) and Illicium verum-mediated ZnONPs (IV-ZnONPs) in terms of characteristics and biological activities. Characterization of both types of synthesized ZnONPs were done by using various techniques namely XRD, UV-vis spectroscopy, FTIR, TEM, and EDX. TEM and XRD results revealed the variability in size and shape of IV-ZnONPs (∼13.75 nm; triangular) and CS-ZnONPs (∼38.9 nm; flower-shaped). FTIR spectra showed the presence of different phytochemicals present in I. verum extract involved in the capping of IV-ZnONPs. Both types of ZnONPs were found to be biocompatible in nature. Furthermore, variations in their biological properties were observed using different in vitro assays, such as FRAP (242.3 ± 18.9 and 101.5 ± 9.5 μM TEAC), CUPRAC (249.8 ± 8.9 and 149.5 ± 8.2 μM TEAC), ABTS (I36.2 ± 0.5 and 28.2 ± 0.8 μM TEAC), and ORAC cell-free assays (19.9 ± 0.6 and 11.9 ± 0.9 μM TEAC) for anti-oxidant investigations of IV-ZnONPs and CS-ZnONPs, respectively. Percentage Inhibition of Vespelysine-like AGEs and pentosidine-like AGEs for anti-aging analysis were reported. In addition to these, the anti-cancerous potential of both types of ZnONPs was also studied based on MTT assay, ROS/NOS production, mitochondria membrane potential, activity of caspase 3/7 measurements, and expression of caspase-3 gene in mammalian HepG2 cell lines. Our findings revealed that both types of ZnONPs were found to be more active through electron-transfer anti-oxidant mechanism. Likewise, the findings of anti-aging analyses revealed significant difference of inhibitory potential between CS-ZnONPs and IV-ZnONPs. As far as anti-cancerous potential is concerned, both IV-ZnONPs and CS-ZnONPs were found to have promising potential against HepG2 cells. However, CS-ZnONPs were observed to have a slight edge over IV-ZnONPs. Nonetheless, the overall results indicated that ZnONPs synthesized through the green route exhibit outstanding biological potential, positioning them as promising candidates for future biomedical applications, particularly in the realm of cancer therapeutics. [ABSTRACT FROM AUTHOR]

Topical corticosteroids (TCSs) are classified into four potencies: mild, moderate, potent and very potent. Confusion arises from the wide range of products available, none of which have the potency level printed on the tubes or packaging. An online survey of patients and carers of people with eczema showed that only 17% of 984 respondents knew how many potencies there are. In a second survey, 315 respondents provided 1520 assignments of the potency of commonly used TCSs: 55.5% were correct, 21% were underestimates and 23.5% overestimates. Some errors were extreme: 12 (8%) of those using a very potent TCS considered it mild while 9 (27%) using a mild TCS considered it potent or very potent. Other themes expressed in free-text comments included inadequate and conflicting advice about using TCSs and lack of warnings about long-term adverse effects, particularly topical steroid withdrawal. Ninety-five per cent of respondents wanted TCSs to be clearly labelled with potency. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer in the stomach and oesophagus is deadly when discovered at a late stage. There are no good biomarkers for its detection or for making a prognostic prediction. In this study, we evaluate the analysis of cell-free DNA as a prognostic cancer biomarker. Cell-free DNA is DNA released from any tissue to a body fluid. When there is a tumour in the body, some of the cell-free DNA will come from that tumour, and it can be detected in a blood sample. We show that the detection of cell-free DNA from the cancer correlates to a worse prognosis than when no tumour DNA is detected. We also show that the method of analysis is important. Either a tissue biopsy must be included as a validation of the genetic variants detected or analysis of the blood cells or another blood sample after tumour resection needs to be analysed to improve detection. In this longitudinal study, cell-free tumour DNA (a liquid biopsy) from plasma was explored as a prognostic biomarker for gastro-oesophageal cancer. Both tumour-informed and tumour-agnostic approaches for plasma variant filtering were evaluated in 47 participants. This was possible through sequencing of DNA from tissue biopsies from all participants and cell-free DNA from plasma sampled before and after surgery (n = 42), as well as DNA from white blood cells (n = 21) using a custom gene panel with and without unique molecular identifiers (UMIs). A subset of the plasma samples (n = 12) was also assayed with targeted droplet digital PCR (ddPCR). In 17/31 (55%) diagnostic plasma samples, tissue-verified cancer-associated variants could be detected by the gene panel. In the tumour-agnostic approach, 26 participants (59%) had cancer-associated variants, and UMIs were necessary to filter the true variants from the technical artefacts. Additionally, clonal haematopoietic variants could be excluded using the matched white blood cells or follow-up plasma samples. ddPCR detected its targets in 10/12 (83%) and provided an ultra-sensitive method for follow-up. Detectable cancer-associated variants in plasma correlated to a shorter overall survival and shorter time to progression, with a significant correlation for the tumour-informed approaches. In summary, liquid biopsy gene panel sequencing using a tumour-agnostic approach can be applied to all patients regardless of the presence of a tissue biopsy, although this requires UMIs and the exclusion of clonal haematopoietic variants. However, if sequencing data from tumour biopsies are available, a tumour-informed approach improves the value of cell-free tumour DNA as a negative prognostic biomarker in gastro-oesophageal cancer patients. [ABSTRACT FROM AUTHOR]

A recent article in the I BJD i [1] drew attention to the worrying gap between patients' and health professionals' opinions about the safety of topical corticosteroids (TCs). In some SmPCs, potency is described in relation to other TCs, rather than stating the potency of the TC itself. [Extracted from the article]

Classification of pediatric T‐cell acute lymphoblastic leukemia (T‐ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T‐ALL patients were characterized by genome‐wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P < 0.001) and mitotic age (P < 0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2‐1, and novel genes in T‐ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP− subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL‐TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP−), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T‐ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies. In this study, an integrated methylomic, transcriptomic, and genomic analysis was performed to investigate the biology behind prognostically relevant DNA methylation (CIMP) subgroups in pediatric T‐cell acute lymphoblastic leukemia. We identified differentially expressed genes in the CIMP subgroups including known oncogenic drivers as well as novel genes in T‐ALL biology. Altogether, our findings suggest different routes for leukemogenic transformation in the T‐ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. [ABSTRACT FROM AUTHOR]

Background We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. Methods We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided. Results The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (P difference =.001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model. Conclusion Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung. [ABSTRACT FROM AUTHOR]

Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer and is associated with poor prognosis if metastasized. Up to one third of patients with local disease at diagnosis will develop metastasis after nephrectomy, and there is a need for new molecular markers to identify patients with high risk of tumor progression. In the present study, we performed genome-wide promoter DNA methylation analysis at diagnosis to identify DNA methylation profiles associated with risk for progress.Method: Diagnostic tissue samples from 115 ccRCC patients were analysed by Illumina HumanMethylation450K arrays and methylation status of 155,931 promoter associated CpGs were related to genetic aberrations, gene expression and clinicopathological parameters.Results: The ccRCC samples separated into two clusters (cluster A/B) based on genome-wide promoter methylation status. The samples in these clusters differed in tumor diameter (p < 0.001), TNM stage (p < 0.001), morphological grade (p < 0.001), and patients outcome (5 year cancer specific survival (pCSS5yr) p < 0.001 and cumulative incidence of progress (pCIP5yr) p < 0.001. An integrated genomic and epigenomic analysis in the ccRCCs, revealed significant correlations between the total number of genetic aberrations and total number of hypermethylated CpGs (R = 0.435, p < 0.001), and predicted mitotic age (R = 0.407, p < 0.001). We identified a promoter methylation classifier (PMC) panel consisting of 172 differently methylated CpGs accompanying progress of disease. Classifying non-metastatic patients using the PMC panel showed that PMC high tumors had a worse prognosis compared with the PMC low tumors (pCIP5yr 38% vs. 8%, p = 0.001), which was confirmed in non-metastatic ccRCCs in the publically available TCGA-KIRC dataset (pCIP5yr 39% vs. 16%, p < 0.001).Conclusion: DNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction in non-metastatic patients at diagnosis. [ABSTRACT FROM AUTHOR]

Despite increasing availability of therapeutic agents, Sézary syndrome (SS) remains associated with a generally poor prognosis. Typically, patients endure multi-line treatment, frequently with disappointingly short durations of clinical benefit. Time to next treatment (TTNT) measures the interval from the date of commencement of one therapy to the date of initiation of the next line of therapy, and provides a simple and reliable surrogate for duration of clinical benefit outside of clinical trials [ 1 ]. In this multi-centre collaborative study, we review the clinical outcomes of patients with SS/ mycosis fungoides (MF) with B1-2 blood involvement, and compare the treatment efficacy of the currently available systemic therapies using TTNT. In this retrospective analysis, eligible patients were identified from University Hospital Birmingham, Birmingham, Peter MacCallum Cancer Centre, Melbourne, and Hôpital Saint Louis, Paris. Strict eligibility required biopsy-proven MF/SS, with B1-2 blood involvement, newly diagnosed during 1/1/2012 to 31/12/2020. Studied treatment groups include monotherapy and combination therapies of interferon, methotrexate, ECP, HDAC inhibitors, retinoids, monoclonal antibodies, biologicals, chemotherapy, allogeneic stem cell transplant, and best supportive care. The primary endpoint was TTNT, with the aim to compare the efficacy of these systemic therapies. 178 patients were eligible. 77 (43%) were female, median age was 66 (17–94) years. At diagnosis, 35 (20%) patients had Stage IIIB, 131 (74%) Stage IVA and 12 (7%) Stage IVB MF/SS. Large cell transformation was present in 35 (20%) patients at time of diagnosis. A total of 802 treatment lines were delivered, of which 711 were systemic therapies and were included for analysis. Of the 178 patients, 168 received systemic therapy first-line: the most commonly delivered first-line systemic treatments were ECP-containing regimens in 42 (25%) patients (ECP-monotherapy, 17, ECP-based combination therapy, 25), retinoid monotherapy in 34 (19%), interferon monotherapy in 25 (14%) and methotrexate monotherapy in 25 (14%) patients. TTNT and overall survival data will be presented. As a surrogate for duration of clinical benefit, TTNT is a useful endpoint to retrospectively compare the treatment efficacy of currently available systemic therapies for SS/MF with B1-2 blood involvement. Long-term disease control with durable clinical benefit remains the ultimate goal for patients with SS/MF with blood involvement. [ABSTRACT FROM AUTHOR]

Background: Few biological markers are associated with survival after relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In pediatric T-cell ALL, we have identified promoter-associated methylation alterations that correlate with prognosis. Here, the prognostic relevance of CpG island methylation phenotype (CIMP) classification was investigated in pediatric BCP-ALL patients. Methods: Six hundred and one BCP-ALL samples from Nordic pediatric patients (age 1–18) were CIMP classified at initial diagnosis and analyzed in relation to clinical data. Results: Among the 137 patients that later relapsed, patients with a CIMP− profile (n = 42) at initial diagnosis had an inferior overall survival (pOS5years 33%) compared to CIMP+ patients (n = 95, pOS5years 65%) (p = 0.001), which remained significant in a Cox proportional hazards model including previously defined risk factors. Conclusion: CIMP classification is a strong candidate for improved risk stratification of relapsed BCP-ALL. [ABSTRACT FROM AUTHOR]

Epigenetic alterations during aging have been proposed to contribute to decline in physical and cognitive functions, and accelerated epigenetic aging has been associated with disease and all-cause mortality later in life. In this study, we estimated epigenetic age dynamics in groups with different memory trajectories (maintained high performance, average decline, and accelerated decline) over a 15-year period. Epigenetic (DNA-methylation [DNAm]) age was assessed, and delta age (DNAm age − chronological age) was calculated in blood samples at baseline (age: 55–65 years) and 15 years later in 52 age- and gender-matched individuals from the Betula study in Sweden. A lower delta DNAm age was observed for those with maintained memory functions compared with those with average ( p = 0.035) or accelerated decline ( p = 0.037). Moreover, separate analyses revealed that DNAm age at follow-up, but not chronologic age, was a significant predictor of dementia ( p = 0.019). Our findings suggest that young epigenetic age contributes to maintained memory in aging. [ABSTRACT FROM AUTHOR]