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circDYRK1A was found to be poorly expressed in GC tissues. RUNX3 was validated to bind to the circDYRK1A promoter, and circDYRK1A functioned as a miR-889-3p sponge to up-regulate FBXO4 expression. Moreover, RUNX3-upregulated circDYRK1A reduced levels of glutamine, glutamic acid, and α-KG, and protein levels of GLS and GDH, and further diminished malignant phenotypes in vitro. this website Furthermore, in vivo experimentation substantiated that circDYRK1A inhibited the tumorigenicity and augmented the apoptosis in GC.
In conclusion, these findings highlighted the significance and mechanism of RUNX3-mediated circDYRK1A in suppressing glutamine metabolism in GC via the miR-889-3p/FBXO4 axis.
In conclusion, these findings highlighted the significance and mechanism of RUNX3-mediated circDYRK1A in suppressing glutamine metabolism in GC via the miR-889-3p/FBXO4 axis.
DNA methylation alterations have emerged as hallmarks of cancer and have been proposed as screening, prognostic, and predictive biomarkers. Traditional approaches for methylation analysis have relied on bisulfite conversion of DNA, which can damage DNA and is not suitable for targeted gene analysis in low-input samples. Here, we have adapted methyl-CpG-binding domain protein 2 (MBD2)-based DNA enrichment for use on a semi-automated exclusion-based sample preparation (ESP) platform for robust and scalable enrichment of methylated DNA from low-input samples, called SEEMLIS.
We show that combining methylation-sensitive enzyme digestion with ESP-based MBD2 enrichment allows for single gene analysis with high sensitivity for GSTP1 in highly impure, heterogenous samples. We also show that ESP-based MBD2 enrichment coupled with targeted pre-amplification allows for analysis of multiple genes with sensitivities approaching the single cell level in pure samples for GSTP1 and RASSF1 and sensitivity down to 14 cellsCs from patients with prostate cancer as a real-world example of a low-input analyte of clinical importance. In summary, this novel assay provides a platform for determining methylation signatures in rare cell populations with broad implications for research as well as clinical applications.
The surgical Apgar score (SAS) predicts postoperative complications (POCs) following gastrointestinal surgery. Recently, the SAS was reported to be a predictor of not only POCs but also prognosis. However, the impact of the SAS on oncological outcomes in patients with colorectal cancer (CRC) has not been fully examined. The present study therefore explored the oncological significance of the SAS in patients with CRC, using a propensity score matching (PSM) method.
We retrospectively analyzed 639 patients who underwent radical surgery for CRC. The SAS was calculated based on three intraoperative parameters estimated blood loss, lowest mean arterial pressure, and lowest heart rate. All patients were classified into 2 groups based on the SAS (≤6 and >6). The association of the SAS with the recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) was analyzed.
After PSM, each group included 156 patients. Univariate analyses revealed that a lower SAS (≤6) was significantly associated with a worse OS and CSS. A multivariate analysis revealed that the age ≥75 years old, ASA-Physical Status ≥3, SAS ≤6, histologically undifferentiated tumor type, and an advanced pStage were independent factors for the OS, and open surgery, a SAS ≤6, histologically undifferentiated tumor type and advanced pStage were independent factors for the CSS.
A lower SAS (≤6) was an independent prognostic factor for not only the OS but also the CSS in patients with CRC, suggesting that the SAS might be a useful biomarker predicting oncological outcomes in patients with CRC.
A lower SAS (≤6) was an independent prognostic factor for not only the OS but also the CSS in patients with CRC, suggesting that the SAS might be a useful biomarker predicting oncological outcomes in patients with CRC.
Adaptive laboratory evolution (ALE) is an effective approach to study the evolution behavior of bacterial cultures and to select for strains with desired metabolic features. In this study, we explored the possibility of evolving Thermotoga sp. strain RQ7 for cellulose-degrading abilities.
Wild type RQ7 strain was subject to a series of transfers over six and half years with cellulose filter paper as the main and eventually the sole carbon source. Each transfer was accompanied with the addition of 50μg of Caldicellulosiruptor saccharolyticus DSM 8903 genomic DNA. A total of 331 transfers were completed. No cellulose degradation was observed with the RQ7 cultures. Thirty three (33) isolates from six time points were sampled and sequenced. Nineteen (19) of the 33 isolates were unique, and the rest were duplicated clones. None of the isolates acquired C. saccharolyticus DNA, but all accumulated small-scale mutations throughout their genomes. Sequence analyses revealed 35 mutations that were preserved throughohe study. Many of the affected genes participate in phosphate metabolism, substrate transport, stress response, sensory transduction, and gene regulation.
Gemcitabine (GEM) is the first-line chemotherapeutic drug used to treat pancreatic ductal adenocarcinoma carcinoma (PDAC), but chemoresistance is often encountered clinically. Nrf2, an oxidative stress responsive transcription factor, is an important contributor to chemoresistance and poor prognosis of PDAC. BruceinD (BD), a naturally occurring quassinoid, has been reported to exert anti-tumor effect in several cancers including PDAC. In this study, we aimed to investigate the efficacy of BD and the role of Nrf2 axes on the chemosensitivity of GEM and elucidate the underlying molecular mechanisms.
Analyses of clinical samples of PDAC and GEPIA database were first conducted to identify the expression of Nrf2 in PDAC. We then established cell lines with stable deletion of Nrf2 through transfecting lentivirus into PDAC cells. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to determine the expression of Nrf2 in these cell lines. The effects of BD and Nrf2 axes on PDAC cell proliferatated on both orthotopic xenograft and genetically engineered KPC mouse models.
BD was able to enhance the chemosensitivity of GEM in PDAC through inhibition of the Nrf2 pathway. Our experimental findings indicate that BD, a potent Nrf2 inhibitor, holds promise for further development into a novel adjuvant therapy for PDAC.
BD was able to enhance the chemosensitivity of GEM in PDAC through inhibition of the Nrf2 pathway. Our experimental findings indicate that BD, a potent Nrf2 inhibitor, holds promise for further development into a novel adjuvant therapy for PDAC.
The bryophytes are a plant group that is smaller than and not as well known as the vascular plants. They are less used and are almost completely neglected in ethnobotanical studies. Traditional nativity scenes depicting the birth of Christ are commonly decorated with both vascular plants and bryophytes. The aim of this study was to document the diversity of decorative bryophytes sold during the Advent season at farmers' markets in Croatia (Southeastern Europe, Balkan Peninsula).
Twenty-eight farmers' markets in the two largest Croatian cities (Zagreb in the continental part and Split in the Mediterranean part) were studied in the search for local vendors selling bryophytes during the pre-Christmas season. The bryophytes collected were identified and analysed with respect to families, growth type, life forms and threat status.
Among 275 collected specimens, 43 moss and four liverwort species were identified. The mean number of species per vendor was 3.5. The most frequent species were Hypnum cupressiformthe decorative use of bryophytes in Christmas festivities in Europe and globally.
The present study provided a first perspective on the use of bryophytes in traditional nativity scenes in Croatia and Southeastern Europe, contributing to scarce ethnobotanical documentation of the decorative use of bryophytes in Christmas festivities in Europe and globally.
Computerized clinical decision support systems (CDSSs) are a promising knowledge translation tool, but often fail to meaningfully influence the outcomes they target. Low CDSS provider uptake is a potential contributor to this problem but has not been systematically studied. The objective of this systematic review and meta-regression was to determine reported CDSS uptake and identify which CDSS features may influence uptake.
Medline, Embase, CINAHL, and the Cochrane Database of Controlled Trials were searched from January 2000 to August 2020. Randomized, non-randomized, and quasi-experimental trials reporting CDSS uptake in any patient population or setting were included. The main outcome extracted was CDSS uptake, reported as a raw proportion, and representing the number of times the CDSS was used or accessed over the total number of times it could have been interacted with. We also extracted context, content, system, and implementation features that might influence uptake, for each CDSS. Overall weightedthe impact of addressing these features as part of the CDSS implementation strategy. Uptake reporting must also become standard in future studies reporting CDSS intervention effects.
Pre-registered on PROSPERO, CRD42018092337.
Pre-registered on PROSPERO, CRD42018092337.
Many low and middle- income countries (LMICs) are repositioning community health worker (CHW) programmes to provide a more comprehensive range of promotive and preventive services and referrals to the formal health service. However, insufficient supervision, fragmented programmes, and the low literacy levels of CHWs often result in the under-performanceof the programmes. We evaluate the impact of a roving nurse mentor working with CHW teams proving supportive supervision in a semi-rural area of South Africa.
We conducted a longitudinal process evaluation, using in-depth interviews, focus groups and observations prior to the intervention, during the intervention, and 6 months post-intervention to assess how the effects of the intervention were generated and sustained. Our participants were CHWs, their supervisors, clients and facility staff membersand community representatives.
The nurse mentor operated in an environment of resource shortages, conflicts between CHWs and facility staff, and an active CHW opment of the CHWs and enhance the capacity of junior supervisors. However, the long-term sustainability of the effects of intervention is dependent on CHWs' formal employment by the Department of Health.
A roving nurse mentor overseeing several CHW teams within a district healthcare system is a feasible option, particularly in a context where there is a shortage of qualified supervisors to support CHWs activities. A roving nurse mentor can contribute to the knowledge and skills development of the CHWs and enhance the capacity of junior supervisors. However, the long-term sustainability of the effects of intervention is dependent on CHWs' formal employment by the Department of Health.
The wooden bowl is an important symbol of the Tibetan cultures, yet, in China, little has been documented regarding the raw materials used to make these items as well as their cultural significance in Tibet. This study explores the ethnobotanical uses of plants used to make wooden bowls to understand their sustainability, cultural significance, and current status of related traditional knowledge in Gyirong Town, which is one of the most famous places for wooden bowl making.
Between 2019 and 2021, key informant interviews, semi-structured interviews, and participatory observations were used to conduct ethnobotanical field surveys in Gyirong Valley. The field work was performed with the assistance of local guides. In this study, we utilized a use-report (UR) to reflect the number of mentions of a species by locals.
Our results show that 16 different plants are used during the wooden bowl making process, of which nine are used as raw materials, three for dyeing, and four for varnishing. Although communities rely heavily on these plants, good management and collection methods were observed.
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