Recent articles and news blogs have been written about nuclear waste management, specifically focusing on the alleged hazards of iodine-129. Here, we objectively review the specific details of iodine-129 as a radiation hazard. In contrast with the alarmist tone of these recent papers and news items, we conclude that iodine-129 is not nearly as concerning as has been projected. Rather, it appears to be a classic case of “much ado about nothing”.

Gastrointestinal malignancies, which arise from multiple etiological factors, are a global health burden due to their high incidence and mortality rates. Nearly all gastrointestinal cancers present genomic and epigenomic alterations that play a critical role in initiating and driving tumor progression. N6-methyladenosine (m6A) methylation, a key epigenetic modification in eukaryotic messenger RNA (mRNA), is pivotal for regulating various cellular biological processes and influences both the progression and prognosis of diverse diseases. In gastrointestinal cancers, m6A methylation is closely associated with tumor proliferation, invasion, metastasis, and radiosensitivity. This review aims to uncover the translational regulatory mechanisms mediated by m6A methylation in gastrointestinal cancers and to clarify its role in radiotherapy, as well as to identify potential molecular targets for improving the efficacy of radiotherapy in treating gastrointestinal tumors.

ObjectiveMicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression and remain stable in biological fluids, even under harsh conditions. Their stability and responsiveness to environmental stressors make them strong candidates for radiation biodosimetry. This study aimed to (1) establish a robust in vivo pipeline for miRNAome profiling and (2) identify plasma-based miRNA biomarkers of ionizing radiation at low and high doses.MethodsBALB/c mice were exposed to sham, 100 mGy, or 2 Gy of X-rays. Plasma was collected 6 h post-irradiation. Total RNA was extracted, and next-generation sequencing was used to profile the plasma miRNAome. Differentially expressed miRNAs were identified relative to sham controls, and selected candidates were validated using RT-qPCR.ResultsA total of 630 unique miRNAs were detected. High-dose exposure (2 Gy) significantly upregulated 14 and downregulated 5 miRNAs. Seven miRNAs were significantly induced at 100 mGy, including miR-126a-5p and miR-133a-3p, which were exclusive to low-dose exposure. Five miRNAs were shared between both doses, indicating dose-independent responses. RT-qPCR confirmed expression trends.ConclusionThis study identified distinct and shared circulating miRNA signatures for low- and high-dose radiation exposure. These findings support the potential of miRNAs as minimally invasive, dose-stratified biomarkers for radiation biodosimetry.

BackgroundRadiation therapy for brain tumors often leads to radiation-induced brain injury, which is closely linked to microglial hyperactivation and neuroinflammation. Lycium barbarum polysaccharide (LBP), the primary active component of Lycium barbarum, may provide neuroprotection by suppressing microglial overactivation and reducing neuroinflammation.MethodsBV2 microglial cells were pretreated with LBP for 12 hours (h), exposed to 10 Gy X-ray irradiation, and then post-treated with LBP for another 12 h. We assessed microglial polarization and measured levels of nitric oxide (NO), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and key proteins in the IKKβ/IκBα/NF-κB pathway.ResultsLBP treatment shifted microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype and significantly decreased the release of NO, IL-1β, and TNF-α following irradiation.ConclusionOur findings demonstrate that LBP mitigates radiation-induced microglial inflammation by inhibiting the IKKβ/IκBα/NF-κB pathway, suggesting its potential as a radioprotective agent against radiotherapy-induced neuroinflammation.

ObjectivesResistance to platinum-based chemotherapy in bladder cancer is closely associated with activation of the Fanconi anemia (FA) DNA interstrand crosslink repair pathway. Identifying pharmacological inhibitors of FA signaling may improve therapeutic response. We investigated the effects of the natural compound toosendanin (TSN) on FA pathway regulation in this study.MethodsBladder cancer cell lines (T24, RT4, J82) were pretreated with TSN and exposed to ultraviolet C (UVC). FANCI/FANCD2 monoubiquitination, FANCD2 nuclear foci, FA core gene expression, and JAK/STAT1 signaling were quantified. A T24 xenograft model was used to validate FA pathway inhibition in vivo. Statistical analyses were performed using one-way ANOVA followed by Tukey’s post-hoc test (mean ± SD; n = 3 independent replicates; Shapiro–Wilk test for normality).ResultsTSN reduced UVC-induced 58% FANCI (P = 0.004, n = 3) and 77% FANCD2 monoubiquitination (P = 0.004, n = 3) in bladder cancer cells, and decreased FANCD2 foci-positive nuclei by 27% (P = 0.015, n = 3). Co-immunoprecipitation assays further revealed that TSN disrupted 56% interaction between the FANCI-FANCD2 complex and the key scaffold protein SLX4 (FANCP) (P = 0.002, n = 6). TSN down-regulated FA core genes (FANCA, FANCC, FANCF, FANCM) by 30 to 65% (all P < 0.05, n = 3) as well as decreased STAT1 phosphorylation by 45% (P = 0.013, n = 3) and the binding capacity of STAT1 on these FA genes’ promoter by 33% to 47% (all P < 0.05, n = 3). In xenograft tumors, TSN also reduced 70% FANCI (P = 0.007, n = 3) and 45% FANCD2 monoubiquitination (P = 0.011, n = 3) as well as expression of FANCA, FANCC, FANCF, FANCM by 26% to 38% (all P < 0.05, n = 3). TSN selectively sensitized bladder cancer cells to UVC-induced cytotoxicity (IC50 decreased 35%, P = 0.026, n = 3), without affecting the viability of human urothelial cell SV-HUC-1 cells or lung adenocarcinoma A549 cells (both P > 0.05, n = 3).ConclusionTSN inhibits FA DNA repair signaling in bladder cancer by suppressing JAK/STAT1-mediated FA core gene transcription, supporting its potential as a combinatorial agent to overcome cisplatin resistance.

ObjectivesCisplatin, a frontline chemotherapeutic agent for bladder cancer (BC), induces DNA interstrand crosslinks that are primarily repaired through the Fanconi anemia (FA) pathway. Hyperactivation of this repair mechanism contributes to cisplatin resistance, underscoring the need for FA-targeted sensitizers. This study investigated the effect of ginsenoside Rh2 on FA signaling and cisplatin sensitivity in bladder cancer cells.MethodsBladder cancer cell lines (T24, 5637, and RT4) were treated with cisplatin, with or without Rh2 pretreatment. FANCI/FANCD2 (ID2) complex monoubiquitination, FANCD2 foci formation, and interactions with downstream repair proteins (FANCP, FANCQ, PCNA) were examined. FANCL expression was analyzed at the transcriptional level, and rescue experiments were performed by FANCL overexpression. NF-κB signaling involvement was assessed using pharmacological agonists. A T24 xenograft model was used to validate in vivo efficacy.ResultsCisplatin induced ID2 complex monoubiquitination, confirming FA pathway activation. Rh2 pretreatment abolished this modification and reduced FANCD2 foci formation, leading to persistent interstrand crosslinks without affecting intrastrand repair. Rh2 disrupted FANCD2- FANCP/FANCQ/PCNA interactions and selectively suppressed FANCL transcription. Overexpression of FANCL restored ID2 monoubiquitination despite Rh2 exposure. NF-κB agonists reversed Rh2-induced FANCL downregulation and FA inhibition. In vivo, Rh2 combined with cisplatin significantly reduced tumor growth in T24 xenografts, whereas NF-κB stimulation counteracted this effect.ConclusionGinsenoside Rh2 suppresses NF-κB signaling to transcriptionally downregulate FANCL, thereby impairing FA pathway-mediated DNA repair and enhancing cisplatin cytotoxicity in bladder cancer. These findings highlight Rh2 as a potential combinatorial agent to overcome platinum resistance.

BackgroundRadiation-induced lymphopenia (RIL), particularly severe RIL (G3+), significantly impacts cancer outcomes. This retrospective study aimed to determine the role of irradiation dose to the thymus on RIL in breast cancer (BC) patients who received adjuvant radiotherapy (RT).MethodsBC patients who received adjuvant RT in 2019 and had available complete blood count data were included. RIL was defined according to CTCAE v5.0 criteria. Logistic regression identified thymic dosimetric and clinical parameters linked to G3+ RIL, ROC analysis determined optimal protective thresholds, and Delong test compared model performance.ResultsThe data of a total of 93 consecutive patients were retrospectively retrieved, with 37.6% (35/93) experienced G3+ RIL. Logistic regression analysis identified thymic dosimetric factors (mean dose, V5, V10), baseline ALC, RT technique and IMNI were associated with G3+ RIL. ROC analysis showed that a combined model of baseline clinical and thymic dosimetry parameters had the highest AUC (0.869). The optimal cutoffs for avoiding G3+ RIL were baseline ALC 1.5 109/L, thymus V5 52.76%, thymus V10 9.08%, MTD 6.12 Gy, respectively.ConclusionsThymic radiation dose correlated with severe lymphopenia in breast cancer radiotherapy. Prospective trials are needed to validate these dose constraints for clinical use.

ObjectiveThe Eerdun Wurile Basic Formula (EWB) of Mongolian medicine has been widely used for the prevention and treatment of ischemic stroke, but its mechanism of action remains unclear. In this study, we combined transcriptomics, metabolomics, and in vivo experiments to explore the therapeutic mechanism of EWB in ischemic stroke, providing a scientific basis for clinical treatment.MethodsSD rats were divided into six groups: Sham operation group, MCAO/R group, MCAO/R + Nimodipine group, MCAO/R + EWB low-dose group (EWB-L group), MCAO/R + EWB medium-dose group (EWB-M group), and MCAO/R + EWB high-dose group (EWB-H group). The efficacy was evaluated using the Zea-Longa five-point neurological deficit score, rat survival rate, open field test, and Morris water maze test, along with hematoxylin and eosin (H&E) and TUNEL staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Transcriptomics and metabolomics analyses were conducted to identify key genes and metabolites, and qRT-PCR and western blot (WB) were used to verify key targets and elucidate the mechanism.ResultsCompared with the sham operation group, the model group exhibited significant neurological deficits in rats (P < 0.01). Compared with the model group, EWB significantly reduced the Zea-Longa five-point neurological deficit score (P < .05, P < .001), improved rat survival rate (P < .01, P <.001), increased activity distance (P < .01) and activity time (P < .01, P < .001), showing a significant therapeutic effect on spontaneous behavior and learning and memory impairments in rats. ELISA results demonstrated that EWB significantly reduced the expression levels of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α (P < .01), leading to a marked reduction in neuroinflammation. Combined transcriptomics and metabolomics analyses identified SLC17A6, SLC6A11, SLC6A9, ADORA1, and GNG7 as key molecular targets of EWB. These targets modulate downstream pathways, including synaptic vesicle cycling, tyrosine metabolism, and glycerophospholipid metabolism, through inflammatory mediators. Furthermore, qRT-PCR and western blot analyses confirmed that EWB mitigates inflammation and inhibits relevant metabolic pathways by regulating the gene and protein expression of these core targets.ConclusionIn summary, this study revealed that EWB reduces neuroinflammation and protects against ischemic stroke by modulating SLC17A6, SLC6A11, SLC6A9, ADORA1, GNG7, and the NF-κB signaling pathway, as well as regulating metabolites such as adenosine monophosphate and succinic acid.

ObjectiveThis study aimed to investigate the expression of FGF-19 in human umbilical cord mesenchymal stem cells (hUC-MSCs) after high-glucose culture. Furthermore, its regulatory effect on glucose metabolism in induced insulin-resistant hepatocytes (IIRHCs) and the underlying mechanism were investigated.MethodsghUC-MSCs were obtained via acclimation culture of hUC-MSCs with 2 g/L glucose medium. Immunofluorescence and ELISA were used to detect FGF-19 expression in ghUC-MSCs. GOD-POD, RT-qPCR and Western blot techniques were used to determine the effects of ghUC-MSCs and FGF-19 on glucose uptake and insulin sensitivity in IIRHCs.ResultsThe ghUC-MSCs efficiently expressed FGF-19 and promoted glucose uptake in IIRHCs. However, the FGF-19 receptor inhibitor (FGFR4-IN) significantly reduced ghUC-MSCs-induced glucose uptake in IIRHCs. Notably, FGF-19 and ghUC-MSCs did not influence the effect of insulin on glucose uptake in IIRHCs. Besides, ghUC-MSCs did not significantly increase the phosphorylation level of insulin receptors. Furthermore, ghUC-MSCs and ghUC-MSCs plus FGFR4-IN significantly increased the expression of Glucose Transporter 1 (GLUT1) in IIRHCs. Additionally, ghUC-MSCs significantly increased AKT/ERK phosphorylation in IIRHCs, but this effect was negated by FGFR4-IN1.ConclusionghUC-MSCs can efficiently express FGF-19. ghUC-MSCs and FGF-19 can regulate hepatocyte glucose metabolism. However, this regulatory effect is not dependent on the insulin signaling pathway.

BackgroundIn light of the growing problem of antibiotic resistance, it is imperative to investigate new sources, and plants offer a promising supply of bioactive chemicals. Because of its numerous uses in industry, health, and nutrition as well as its antibacterial qualities, Cannabis sativa (C.sativa) has garnered a lot of study interest. This study sought to determine whether ethanolic extracts from C.sativa leaves have antibacterial properties against six human pathogenic microorganisms.MethodologyThe antibacterial activity of C.sativa ethanolic extract was tested against six bacteria according to design of experiments made by Agar diffusion method accompanied by response surface method (RSM) of Minitab 17 software. The different combinations set were, concentration: 5.0, 7.5, and 10.0, pH: 5.0, 6.5, 8.0 and temperature: 35°C, 37.5°C, 40°C. By using RSM, maximum antibacterial activity has been checked for ethanolic extract of C.sativa against six bacteria by choosing three independent variables, temperature, pH, and concentration. In in-Silico studies, homology, threading approach, structure prediction, ligands designing and docking studies was performed against the antimicrobial target sequences for Beta-Lactamase, GABA Receptor, Lipoteichoic Acid, N-Acetylglucosamine (NAG), Peptidoglycan and Topoisomerase-IV through FASTA format from UniProt for structure prediction.ResultsThe results indicated that the three concentrations were effective against tested bacteria. Moreover, effect of pH caused a significant variation in zone of inhibition. The graphs presented in this study indicate the highest zone of inhibition for plant extract; have been achieved at concentration of 10.0, pH 5.1 and temperature 37.5°C. It shows that by keeping the pH low, antibacterial activity will increase. Through the multiple regression analysis on the experimental data, the fitted regression model for the response variable and the test variable x1, x2, x3 are correlated by the second order polymeric equation.ConclusionIt has been concluded that C.sativa can be considered as an effective drug in curing diseases caused by bacteria. Using the optimized values of temperature and pH analyzed in this experiment.