Ipconazole Disrupts Mitochondrial Homeostasis and Alters GABAergic Neuronal Development in Zebrafish

Ipconazole, a demethylation inhibitor of fungal ergosterol biosynthesis, is widely used in modern agriculture for foliar and seed treatment, and is authorized for use in livestock feed. Waste from ipconazole treatment enters rivers and groundwater through disposal and rain, posing potential toxicity to humans and other organisms. Its metabolites remain stable under standard hydrolysis conditions; however, their neurodevelopmental toxicity is unknown. We investigated the potential neurodevelopmental toxicity of ipconazole pesticides in zebrafish (Danio rerio). Our behavioral monitoring demonstrated that the locomotive activity of ipconazole-exposed zebrafish larvae was reduced during early development, even when morphological abnormalities were undetected. Molecular profiling demonstrated that the mitochondrial-specific antioxidants, superoxide dismutases 1 and 2, and the genes essential for mitochondrial genome maintenance and functions were specifically reduced in ipconazole-treated (0.02 μg/mL) embryos, suggesting underlying ipconazole-driven oxidative stress. Consistently, ipconazole treatment substantially reduced hsp70 expression and increased ERK1/2 phosphorylation in a dose-dependent manner. Interrupted gad1b expression confirmed that GABAergic inhibitory neurons were dysregulated at 0.02 μg/mL ipconazole, whereas glutamatergic excitatory and dopaminergic neurons remained unaffected, resulting in an uncoordinated neural network. Additionally, ipconazole-treated (2 μg/mL) embryos exhibited caspase-independent cell death. This suggests that ipconazole has the potential to alter neurodevelopment by dysregulating mitochondrial homeostasis.     

Assessment of Renal Function in Head and Neck Cancer Patients Treated with Cisplatin: Different Biomarkers and Acute Kidney Injury Classifications

Cisplatin is associated with dose-limiting nephrotoxicity, and the timely detection of acute kidney injury (AKI) can affect morbimortality. Therefore, this study aimed to investigate the tools for monitoring renal function in AKI. This was a retrospective, cohort study. Cisplatin-treated patients with head and neck cancer were included. Nephrotoxicity was assessed using serum creatinine, estimated creatinine clearance, serum electrolytic alterations, and plasma kidney injury molecule-1 (KIM-1). The toxicity severity was classified according to Common Terminology Criteria for Adverse Events (CTCAE), and AKI was classified by Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN). A total of 81 participants were included, of whom only 32 did not have AKI. Almost 90% of participants had a decreased estimated glomerular filtration rate five (D5) days after chemotherapy. The AKI estimate differs between AKIN and RIFLE; more participants were diagnosed by the RIFLE at D5, 19.5% versus 2.4% by AKIN, and fifteen had a discordance between these classifications. All laboratory markers showed significant changes on D5. KIM-1 appeared a possible biomarker when considering CTCAE or AKIN classifications (p < 0.05 on D5), but not when RIFLE classification was used (p = 0.0780). Further studies may seek to understand the profiles of different biomarkers together.     

Safety Evaluation and Anti-Inflammatory Efficacy of Lacticaseibacillus paracasei PS23

Lacticaseibacillus paracasei strain PS23 (PS23) exhibits some probiotic properties. In this study, a genomic analysis of PS23 revealed no genes related to virulence or antibiotic resistance. Moreover, ornithine decarboxylase activity was not detected in vitro. In addition, PS23 was sensitive to the tested antibiotics. Genotoxicity tests for PS23 including the Ames test and chromosomal aberrations in vitro using Chinese hamster ovary cells and micronuclei in immature erythrocytes of ICR mice were all negative. Moreover, following a 28-day study involving repeated oral dose toxicity tests (40, 400, and 4000 mg/kg equal 1.28 × 10¹⁰, 1.28 × 10¹¹, and 1.28 × 10¹² CFU/kg body weight, respectively) using an ICR mouse model, no adverse effects were observed from any doses. In addition, supplementation with live or heat-killed PS23 ameliorates DSS-induced colonic inflammation in mice. Our findings suggest that PS23 is safe and has anti-inflammatory effects and may therefore have therapeutic implications.     

发光费氏弧菌对常用色素的生物毒性评价

在探寻出色素与费氏弧菌发光抑制率存在相关性的基础上,初步建立起评价色素生物毒性的方法,并将其应用于果汁中色素产生的综合毒性的检验。结果:色素溶液质量浓度与发光抑制率呈正相关,相关系数在0.8760～0.9873之间,EC50范围在0.72～2.86mg/L之间;果汁中色素质量浓度与发光抑制率同样呈正相关,相关系数在0.9136～0.9951之间,EC50值在1.02～2.96mg/L之间。柠檬黄毒性较小,苋菜红毒性较大。果汁对人工合成色素的生物毒性具有一定影响。色素在果汁中对费氏弧菌发光抑制率随浓度增加而上升的幅度明显大于在水溶液中。本研究为食品急性生物毒性监测的研究提供初步参考。      

进口乳制品中双氰胺对人类健康的风险概述

综述了进口乳制品中双氰胺对人类健康的风险。介绍了双氰胺的理化性质、应用情况、毒理作用、检测方法以及进入乳制品中可能的暴露途径,并提出风险管理措施的建议。      

牡蛎内脏多糖抗氧化活性及对四氯化碳所致小鼠急性肝损伤的影响作用

目的:研究牡蛎内脏多糖（CGOP）的体外抗氧化活性及对CCl₄所致小鼠肝损伤的影响作用。方法:通过测定DPPH自由基、羟基自由基、ABTS自由基清除效果及FRAP还原能力研究CGOP的体外抗氧化能力;通过测定各组小鼠血清中谷丙转氨酶（ALT）、谷草转氨酶（AST）含量及肝组织匀浆中超氧化物歧化酶（SOD）、丙二醛（MDA）含量,观察小鼠肝组织切片形态学变化,判断CGOP对小鼠急性肝损伤的影响。结果:CGOP具有较好的清除DPPH自由基、ABTS自由基、羟基自由基效果及FRAP还原能力,并能显著降低小鼠的ALT、AST及MDA含量（p<0.05）,显著升高小鼠的SOD含量（p<0.01）,减轻CCl₄对肝细胞的病理损伤。结论:CGOP具有保护CCl₄急性肝损伤的作用,为更充分利用牡蛎资源提供了基础数据。      

Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics

Acute kidney injury (AKI) is an increasingly common problem afflicting all ages, occurring in over 20% of non-critically ill hospitalized patients and >30% of children and >50% of adults in critical care units. AKI is associated with serious short-term and long-term consequences, and current therapeutic options are unsatisfactory. Large gaps remain in our understanding of human AKI pathobiology, which have hindered the discovery of novel diagnostics and therapeutics. Although animal models of AKI have been extensively studied, these differ significantly from human AKI in terms of molecular and cellular responses. In addition, animal models suffer from interspecies differences, high costs and ethical considerations. Static two-dimensional cell culture models of AKI also have limited utility since they have focused almost exclusively on hypoxic or cytotoxic injury to proximal tubules alone. An optimal AKI model would encompass several of the diverse specific cell types in the kidney that could be targets of injury. Second, it would resemble the human physiological milieu as closely as possible. Third, it would yield sensitive and measurable readouts that are directly applicable to the human condition. In this regard, the past two decades have seen a dramatic shift towards newer personalized human-based models to study human AKI. In this review, we provide recent developments using human stem cells, organoids, and in silico approaches to advance personalized AKI diagnostics and therapeutics.     

脑卒中血浆脂肪酸及其代谢产物的UPLC-MS分析

脑卒中是一类高致残率、高死亡率的脑血管疾病,分为缺血性脑卒中和出血性脑卒中2种亚型,二者具有相似的临床症状,但治疗策略完全不同.目前,主要依赖医学影像学技术进行诊断,但存在耗时、费用高、难以区分2种脑卒中亚型等缺点,进而影响疾病治疗和预后.本研究收集了59例健康志愿者、60例急性脑缺血和36例脑出血患者的血浆样本,运用...     

Assessing the Morphological and Behavioral Toxicity of Catechol Using Larval Zebrafish

Catechol is a ubiquitous chemical used in the manufacturing of fragrances, pharmaceuticals and flavorants. Environmental exposure occurs in a variety of ways through industrial processes, during pyrolysis and in effluent, yet despite its prevalence, there is limited information regarding its toxicity. While the genotoxicity and gastric carcinogenicity of catechol have been described in depth, toxicological studies have potentially overlooked a number of other effects relevant to humans. Here, we have made use of a general and behavioral larval zebrafish toxicity assay to describe previously unknown catechol-based toxicological phenomena. Behavioral testing revealed catechol-induced hypoactivity at concentrations an order of magnitude lower than observable endpoints. Catechol exposure also resulted in punctate melanocytes with concomitant decreases in the expression of pigment production and regulation markers mitfa, mc1r and tyr. Because catechol is converted into a number of toxic metabolites by tyrosinase, an enzyme found almost exclusively in melanocytes, an evaluation of the effects of catechol on these cells is critical to evaluating the safety of this chemical. This work provides insights into the toxic nature of catechol and highlights the benefits of the zebrafish larval testing platform in being able to dissect multiple aspects of toxicity with one model.     

黄花菜的保健功效及化学成分研究进展

黄花菜具有较高的营养价值,在中国传统中是药食两用的蔬菜。文中对近年来黄花菜的保健功效和化学成分的研究进行了综述,其保健功效主要包括抗氧化与抗癌、改善睡眠、杀虫、镇静、消炎、抗黄疸、抗抑郁等作用;化学成分主要为萜类、内酰胺类、蒽醌类、多酚类、精油、甾体皂苷、生物碱等;最后对其毒性进行了简要阐述。