Open Life Sciences最新文献

Metastasis remains a major challenge to improve the survival of patients with hepatocellular carcinoma (HCC). Artesunate is an antimalarial drug that also has anti-cancer properties. Additionally, O-GlcNAcylation has been implicated in cancer progression. In this study, we investigated whether artesunate regulated HCC cell migration and invasion and explored its impact on protein O-GlcNAcylation. Cellular functions, including viability, migration, and invasion, were evaluated using the cell counting kit-8, scratch assay, and Transwell analysis. Molecular docking and biolayer interferometry were employed to assess the binding interaction between artesunate and OGA. Furthermore, the O-GlcNAcylation of ZEB1 was examined using immunoprecipitation, cycloheximide chase assay, and immunoblotting. Our results demonstrated that artesunate significantly inhibited HCC cell viability, migration, and invasion. OGA expression was increased in HCC cells after artesunate treatment. Artesunate directly bound to OGA, and OGA knockdown reversed the inhibition of malignant behaviors induced by artesunate. Additionally, OGA suppressed the O-GlcNAcylation of ZEB1 at the Ser670 site, decreasing protein stability. Knockdown of ZEB1 inhibited HCC cellular behaviors. In conclusion, artesunate inhibits HCC cell migration and invasion by binding to OGA, which removes the O-GlcNAcylation of ZEB1 at the Ser670 site. These findings provide a new action mechanism for artesunate to treat HCC.

In a cross-sectional analysis of 14,973 adults from North China, thyroid nodules (TNs) were detected via high-resolution ultrasonography in 8,104 participants (54.1%), with a higher prevalence among women. The mean age of those with TNs was significantly higher (51.39 ± 15.41 vs 41.83 ± 12.43 years, p < 0.001). Univariate analyses indicated that female sex (OR ≈ 2.0), older age (OR ≈ 1.03 per year), elevated low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and higher BMI were significantly linked to TNs. In contrast, total cholesterol and uric acid did not reach significance in the final model. A nomogram incorporating these risk factors demonstrated moderate predictive performance (AUC = 0.84 in the training set; 0.78 in the validation set). While the study's large sample size is a strength, its cross-sectional design limits conclusions about causality, and potential overfitting cannot be excluded. Future research should include thyroid hormone measurements, external validation of the nomogram, and longitudinal follow-up to clarify the role of metabolic factors. These findings highlight the importance of age, sex, and metabolic profiles - particularly dyslipidemia and obesity - in screening for TNs during routine health examinations.

Powdery mildew (Erysiphe necator Schw.) fungal disease in vineyards is becoming an increasingly important concern due to climate change and the emergence of resistant populations after heavy spraying. Recently, new disease control methods based on phenological development, disease development, and meteorological data have been established in Türkiye. These models can provide sufficient protection with minimal fungicide use and minimize residue problems due to excessive fungicide use. In this study, the activities of the UC Davis risk index model, decision support strategy (DSS) models, and classical model, based on plant phenological development stages suggested by the Turkish Ministry of Agriculture and Forestry, were used to protect against powdery mildew. Three alternative control strategies were investigated for 2 years using two grape varieties. In addition, the amount of pesticide residue in the final product by the spraying models was also evaluated. The UC Davis risk index model was applicable in places with similar climatic conditions, such as Bursa Province, and showed better results than other spraying programs. Although the classical model proposed by the Ministry of Agriculture and Forestry is generally less effective than the UC Davis risk index model, once less spraying achieved high effectiveness rates each season. The UC Davis risk index model considerably lowered the disease incidence rate in clusters below the 5% limit. The DSS model provided poorer protection than the other two models evaluated in this study. Among the fungicides with active ingredients, thiophanate-methyl, kresoxim-methyl, and penconazole, only thiophanate-methyl exceeded the 0.1 ppm (mg/kg) limit specified in the European Union Pesticide Maximum Residue Limits and Turkish Food Codex Pesticide Maximum Residue Limits for both grape varieties. Alternating fungicides with different active ingredients instead of a single fungicide at regular intervals throughout the season can reduce residue problems of grapes and the risk of pathogen resistance to fungicides.

This article conducts a meta-analysis to evaluate the safety and efficacy of PD-1/PD-L1 inhibitors in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). A total of 63 papers were initially retrieved, and eight clinical studies were collected. The estimated effect of ORR was [OR = 0.40, 95% CI 0.29-0.51; p = 0.08], the estimated effect of complete response rate was [OR = 0.21, 95% CI 0.14-0.31; p < 0.001], while the estimated effect of 1-year progression-free survival was [OR = 0.33, 95% CI 0.22-0.47; p = 0.01]. The estimated effect of 1-year OS was [OR = 0.67, 95% CI 0.55-0.77; p = 0.05]. In addition, the estimated effect of grade 3 adverse events was [OR = 0.33, 95% CI 0.22-0.46; p = 0.01]. Overall, PD-1/PD-L1 inhibitors demonstrated suboptimal therapeutic efficacy in the selected trials for R/R DLBCL. However, combining PD-1/PD-L1 inhibitors with CAR-T showed potential for improved treatment outcomes. Additionally, PD-1/PD-L1 inhibitors were found to be safe and well-tolerated in patients with R/R DLBCL.

The advancement of genetic techniques in food production offers significant potential for improving crop quality, yield, and sustainability. However, these innovations present a complex set of dilemmas concerning nutritional quality, food authenticity, socioeconomic implications, regulatory challenges, and human health. This article explores contemporary genetic methods such as marker-assisted selection, genome editing (CRISPR-Cas9), and tissue culture, highlighting their applications and limitations. Additionally, transgenic approaches and biofortification strategies are examined for their role in enhancing nutritional value. It examines the trade-offs between organoleptic properties and nutritional integrity, revealing a concerning trend toward prioritizing sensory attributes over health benefits. Furthermore, the potential health implications of genetic manipulation, including links to autoimmune and hormonal disorders, are critically analyzed with a focus on allergenicity concerns and long-term safety assessments. The discussion underscores the urgent need for sustainable practices in food genetics that align with environmental goals and public health priorities. Finally, a call to action is made for collaborative dialogue among scientists, policymakers, and consumers to prioritize health, sustainability, and transparency in food production, ensuring that agricultural advancements benefit all stakeholders while preserving the ecological balance for future generations.

RNF144 family proteins, including RNF144A and RNF144B, members of the RING-between-RING domain-containing ubiquitin E3 ligase family, serve as critical regulators of protein ubiquitination. Despite increasing research attention in recent years, particularly regarding their distinct functional roles in pathophysiological processes, a comprehensive synthesis of existing findings remains absent. To address this knowledge gap, we conducted a systematic literature search in PubMed using the following query terms: "RNF144," "RNF144A," "RNF144B," "PIR2," "IBRDC2," and "P53RFP." This review systematically examines current evidence regarding the molecular mechanisms and pathophysiological significance of RNF144A/B across various disease systems. Through critical analysis of structural characteristics, substrate interactions, and signaling pathways, we aim to clarify their dual roles in cellular homeostasis and disease pathogenesis. This synthesis not only consolidates current understanding but also identifies key knowledge gaps requiring further investigation, particularly regarding isoform-specific functions and therapeutic targeting potential.

Polydatin is a stilbene that has been demonstrated to regulate lipid, cholesterol, and glucose metabolism in humans. However, its potential role in cholesterol gallstone formation remains uncertain. C57BL/6 mice were fed a lithogenic diet (LD) and administered polydatin via intragastric administration. At the end of the 8-week study period, the animals were euthanized in order to collect bile/serum samples and gallbladder/liver tissues for subsequent analysis. In vitro studies were conducted in which human intrahepatic biliary epithelial cells (HIBECs) were exposed to lipopolysaccharide (LPS) for a period of 24 h. Subsequently, the culture supernatant and cells were harvested for further analysis. The results demonstrated that polydatin markedly reduced cholesterol gallstone formation, attenuated pathological alterations in the gallbladder and liver tissues, and improved lipid profiles in serum and bile samples. Moreover, polydatin exhibited anti-inflammatory properties, regulated cholesterol metabolism-related genes, and activated the PPAR-γ signaling pathway in mice fed an LD diet. In HIBECs, polydatin treatment prevented LPS-induced inflammatory cytokine release, dysregulation of cholesterol metabolism-related genes, and inactivation of the PPAR-γ pathway. This study is the first to demonstrate that polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via the PPAR-γ signaling pathway.

The aim of this study is to investigate the role of electroacupuncture in alleviating sciatic nerve injury. A rat model for sciatic nerve crush injury was established using clamping forceps, and then electroacupuncture at the "Zusanli" (ST36) and Huantiao" (GB30) acupoints was performed. The values of sciatic functional index (SFI), paw withdrawal latency (PWL), and paw withdrawal threshold (PWT) were evaluated. The mRNA expression of neurotrophic factors in nerve tissues was examined by RT-qPCR analysis. Morphometric analyses of transverse sections at the sciatic nerve distal to injury were performed 8 weeks post-injury. Immunofluorescence staining of sciatic nerve and western blotting were performed to measure the expression of myelin protein zero (MPZ) and autophagy markers. The experimental results displayed that the motor and sensory functions of sciatic nerve crush injury rats were restricted by pressure application. Electroacupuncture ameliorated sciatic nerve injury by increasing SFI, PWT, and PWL values in model rats during the recovery period. Electroacupuncture upregulated the mRNA expression of neurotrophic factors (brain-derived neurotrophic factor and nerve growth factor), increased the diameter of fibers and axon, and increased the thickness of myelin sheath after electroacupuncture. Electroacupuncture reduced MPZ and p62 expression while increasing LC3B and beclin-1 expression. In conclusion, electroacupuncture alleviates sciatic nerve injury by promoting nerve regeneration and autophagy.

In some cases, higher IgG4 levels are accompanied by increased circulating IgE, higher eosinophil counts, and various autoantibodies. Among these cases, IgG4-related disease (IgG4-RD) is one of the most frequently diagnosed conditions. This study reported two particularly complex and rare cases of hypereosinophilic syndrome (HES) associated with elevated IgG4 and T-cell clonality. The first case involved T-cell clonality complicated by HES and IgG4-RD, presenting with clinical features resembling eosinophilic granulomatosis with polyangiitis (EGPA). Laboratory findings showed a serum IgG4 concentration of 8.74 g/L, an IgG4/IgG ratio of 40.58%, and positive results for P-anti-neutrophil cytoplasmic antibodies (ANCA) and myeloperoxidase-ANCA. Renal biopsy findings were consistent with IgG4-related interstitial nephritis. However, routine hematological testing revealed a markedly elevated eosinophil count of 14.75 × 10⁹/L and eosinophilic infiltration in both lymph nodes and kidney tissue. Furthermore, monoclonal rearrangements of the T-cell receptor gamma and delta genes were identified. The second patient was ultimately diagnosed with HES with elevated IgG4 and T-cell clonality, with an elevated IgG4 concentration of 2.458 g/L and an eosinophil count of 14.75 × 10⁹/L. In conclusion, in cases presenting with elevated IgG4 levels and hypereosinophilia, further pathological and genetic evaluations may be essential to guide appropriate and timely treatment, improving patient prognosis.

The consumption of chia seeds has surged in recent years, primarily due to their beneficial chemical composition and health effects. Sprouting chia seeds can enhance the content of essential nutrients, including antioxidants and vitamins. The study investigates the impact of sprouting on the bioactive compounds and antioxidant activity of chia seeds under both favorable and stressful conditions. Chia seeds were sprouted in tap water, distilled water, and varying concentrations of seawater. The parameters analyzed included antioxidant activity, the reducing capacity of antioxidants, total polyphenol content, flavonoid content, and phenolic profile. Results indicated that sprouting significantly influences antioxidant activity in seeds sprouted in tap and distilled water, with a decrease observed only in the 2,2'-azinobis(3-ethyl-2,3-dihydrobenzothiazol-6-sulfonate) method for distilled water. Additionally, sprouting in both water types led to a statistically significant increase (p < 0.05) in reducing capacity and total polyphenol content. Under high salinity conditions, sprouting in 100% seawater resulted in a significant increase (p < 0.05) in antioxidant activity, reducing capacity, and total polyphenol content. These findings suggest that sprouting chia seeds, particularly under saline conditions, could enhance their nutritional profile, presenting potential applications in the food and nutrition industry and indicating possibilities for ecological cultivation.