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Gliomas, originating from glial cells, are prevalent and aggressive brain tumors with high recurrence rates and poor prognosis. Despite advancements in surgical, radiation, and chemotherapeutic treatments, the survival rates remain low. Current standard therapies, such as Temozolomide, have limitations due to cytotoxicity, restricted effectiveness, and severe side effects. So, the development of safer anti-glioma agents is the need of the hour. Bioactive compounds of plant origin, either natural or synthetic, have potential implications due to them actively attacking different targets with a wide range of bioactivities, including anti-glioma activities. In this review, for the first time, there is an overall overview of 51 small molecules of plant origin and seven of their synthetic derivatives, represented as anti-glioma agents in the past decades. The goal of the present review is to provide a summary to comprehend the anti-glioma effects of these compounds in addition to providing a reference for preclinical research into novel anti-glioma agents for future clinical application.- Book : 26(5)
- Pub. Date : 2025
- Page : pp.1942-1942
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AbstractDeveloping robust methods for amplifying and analysing highly-polymorphic nuclear genetic markers from environmental samples could assist in the reliable and scalable long-term monitoring of elusive, threatened or invasive species that are otherwise challenging to observe. In this study, we used zebrafish in controlled aquaria to apply forensic science approaches and demonstrate that microhaplotypes, which are short segments of nuclear DNA (100–300bp) containing two or more single nucleotide polymorphisms (SNPs), can be amplified from trace DNA in water samples to accurately estimate population genetic diversity and species abundance. We successfully amplified a panel of 17 microhaplotypes that comprised 69 SNPs which could reliably estimate population-level allele frequencies and genetic diversity estimates from water DNA. The panel of microhaplotypes amplified from water samples from replicate tanks strongly matched allele frequency estimates from corresponding tissue samples, and could also be used for estimating number of contributors from multi-individual samples. Our research demonstrates the effectiveness and potential of amplifying microhaplotype panels from eDNA as a non-invasive and scalable tool for population genetic studies of aquatic species.- Book : ()
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2025
BackgroundA20, also known as TNF-α-induced protein 3 (TNFAIP3), is a crucial negative regulator of inflammation and immune responses. Emerging evidence suggests that A20 is involved in the regulation of glucose metabolism and plays a significant role in bone metabolic diseases by inhibiting nuclear factor (NF)-κB activation. However, the potential relationship between serum A20 level and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM) has not been explored. This study aims to investigate the association between serum A20 level with BMD and bone turnover markers (BTMs) in patients with T2DM.MethodA total of 189 patients with T2DM and 183 non-diabetic individuals were included in the study based on the inclusion and exclusion criteria. Participants were categorized into normal BMD and low BMD groups. Baseline clinical histories were collected through face-to-face questionnaires. Participants underwent measurements of blood biochemistry and anthropometric, hand grip strength records and short physical performance battery (SPPB) assessment. Serum A20 level was quantified by enzyme-linked immunosorbent assay kit. Areal BMD was measured using dual-energy x-ray absorptiometry (DXA). A T-score of less than -1.0 at the lumbar spine 1-4, femoral neck and/or total hip was classified as low BMD.ResultsSerum A20 level was lower in patients with T2DM compared to controls [41.30 (29.91, 61.87) vs 76.01 (54.90, 109.64) pg/mL, P<0.001]. Bivariate correlation analysis revealed that A20 level was not associated with SPPB but negatively correlated with waist-to-hip ratio (WHR). Pearson correlation analysis showed A20 level was positively correlated with lumbar spine 1-4 BMD in male diabetic patients (r=0.253, P=0.032). Multivariate regression analysis showed a positive association between serum A20 level and lumbar spine 1-4 BMD (Beta=0.047; 95% CI: 0.007-0.086; P=0.024) after multivariate adjustment. Logistic regression analysis showed that lower serum A20 level predicted low BMD in male patients with T2DM (OR: 0.22; 95% CI: 0.09-0.59; P=0.002).ConclusionsType 2 diabetic patients exhibited lower serum A20 level compared to non-diabetic individuals. In male patients with T2DM, serum A20 level showed a significant positive correlation with lumbar spine 1-4 BMD and could serve as an independent negative predictor for low BMD.- Book : ()
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ABSTRACTGlioblastoma (GBM) is a highly aggressive and recurrent brain cancer characterized by diffuse metastasis at the tumor margins. Radiation therapy is a standard component of current treatment and offers potential for improved patient outcomes. While radiation therapy targets GBM cells in the tumor margins, it may also significantly damage adjacent non-cancerous tissues, leading to reduced quality of life and potentially creating a tumor-supportive microenvironment. The perivascular niche (PVN) in the tumor margins is believed to play a significant role in regulating the glioblastoma stem cell subpopulation as well as serving as a site for cancer recurrence and migration. Understanding the impact of radiation on the PVN can better inform radiation schemes and improve our understanding of GBM recurrence, but is difficultin vivo. Here we adapt a previously developed three-dimensional hydrogel model of the brain perivascular niche to investigate the impact of radiation dosage and delivery rate on perivascular niche propertiesin vitro. Effects of radiation on vessel architecture can be measured in this hydrogel-based model, suggesting an approach that can provide insight into the effects of radiation on a shorter time scale relative toin vivoexperiments.IMPACT STATEMENTGlioblastoma (GBM) is a highly aggressive and recurrent brain cancer characterized by diffuse metastasis at the tumor margins. The perivascular niche (PVN) in the tumor margins plays a significant role in GBM progression and is a target for radiation therapy. We report a method to use three-dimensional hydrogel models of the brain perivascular niche to benchmark the impact of radiation dosage and delivery rate on perivascular niche propertiesin vitro. This approach provides new insight into the effects of radiation on a shorter time scale relative toin vivoexperiments.- Book : ()
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2025
ABSTRACTThe Rev Response Element (RRE) forms an oligomeric complex with the viral protein Rev to facilitate the nuclear export of intron-retaining viral RNAs during the late phase of HIV-1 infection. However, our structural understanding of this crucial virological process remains limited. In this study, we determined several crystal structures of an intact RRE stem-loop II in two distinct conformations, performed negative-staining electron microscopy and molecular dynamics simulations, and revealed that this three-way junction RNA exhibits remarkable structural plasticity. Throughin vitroRev-binding andin vivoRev-activity assays using various stem-loop II mutants designed to favor one of the conformers, we demonstrated that the structural plasticity of stem-loop II modulates Rev binding and oligomerization. Our findings illuminate emerging perspectives on RRE dynamics-based regulation of HIV-1 RNA nuclear export and provide a framework for developing anti-HIV drugs that target specific RRE conformations.- Book : ()
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ObjectiveJuvenile SLE (jSLE) is an autoimmune disease characterised by the presence of high levels of autoantibodies, predominantly targeting nuclear antigens, resulting in a breakdown of self-tolerance. However, its pathogenesis is multifactorial and poorly understood. The aim of this study was to evaluate the potential of nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) as biomarkers for jSLE.MethodsIn this study, serum NF-κB and PPAR-γ levels were determined by immunoassay in 42 patients with jSLE. In addition, 19 juvenile systemic sclerosis (jSSc) and 25 age-matched healthy children were selected as patient control and healthy control, respectively.ResultsSerum NF-κB levels in patients with jSLE demonstrated a positive trend towards elevation compared with the controls with no significant difference (p=0.030). In addition, serum NF-κB levels in patients with jSSc were significantly higher than that of the healthy controls (p=0.005). Serum PPAR-γ levels were tend to be lower in both patients with jSLE and jSSc compared with the controls, with no significant difference. Specifically, NF-κB levels were significantly higher in patients with jSLE with cumulative damage (PedSDI≥1) compared with those without, at p=0.044. Logistic regression showed that PPAR-γ levels lower than 2.42 ng/mL were associated with the development of jSLE (OR 7.59) and lower than 2.16 ng/mL for jSSc (OR 10.90). The combined high levels of NF-κB with low PPAR-γ increased the risk of developing jSSc by 21.33-fold.ConclusionsThe observed trend of elevated NF-κB levels and decreased PPAR-γ levels in our study suggests their potential as biomarkers associated with increased proinflammatory signalling in jSLE and jSSc. However, our findings must be regarded as hypothesis-generating and confirmed in larger datasets. Moreover, their roles in monitoring the course of a disease and guiding therapeutic strategies in juvenile systemic autoimmune diseases need to be clearly investigated. Further extension of these findings may lead to better management and improvement in the outcomes of such patients.- Book : 12(1)
- Pub. Date : 2025
- Page : pp.e001263-e001263
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