Mercuric chloride induced brain toxicity in mice: The protective effects of puerarin-loaded PLGA nanoparticles

Mercury is a toxic, environmentally heavy metal that can cause severe damage to all organs, including the nervous system. The functions of puerarin include antioxidant, anti-inflammatory, nerve cell repair, regulation of autophagy, and so forth. But because of the limited oral absorption of puerarin, it affects the protective effect on brain tissue. The nano-encapsulation of Pue can improve its limitation. Therefore, this study investigated the protective effect of Pue drug-loaded PLGA nanoparticles (Pue-PLGA-nps) on brain injury induced by mercuric chloride (HgCl₂) in mice. The mice were divided into normal saline (NS) group, HgCl₂ (4 mg/kg) group, Pue-PLGA-nps (50 mg/kg) group, HgCl₂ + Pue (4 mg/kg + 30 mg/kg) group, and HgCl₂ + Pue-PLGA-nps (4 mg/kg + 50 mg/kg) group. After 28 days of treatment, the mice were observed for behavioral changes, antioxidant capacity, autophagy and inflammatory response, and mercury levels in the brain, blood, and urine were measured. The results showed that HgCl₂ toxicity caused learning and memory dysfunction in mice, increased mercury content in brain and blood, and increased serum levels of interleukin (IL-6), IL-1β, and tumor necrosis factor-α in the mice. HgCl₂ exposure decreased the activity of T-AOC, superoxide dismutase, and glutathione peroxidase, and increased the expression of malondialdehyde in the brain of mice. Moreover, the expression levels of TRIM32, toll-like receptor 4 (TLR4), and LC3 proteins were upregulated. Both Pue and Pue-PLGA-nps interventions mitigated the changes caused by HgCl₂ exposure, and Pue-PLGA-nps further enhanced this effect. Our results suggest that Pue-PLGA-nps can ameliorate HgCl₂-induced brain injury and reduce Hg accumulation, which is associated with inhibition of oxidative stress, inflammatory response, and TLR4/TRIM32/LC3 signaling pathway.     

Sample size considerations for stepped wedge designs with subclusters

The stepped wedge cluster randomized trial (SW-CRT) is an increasingly popular design for evaluating health service delivery or policy interventions. An essential consideration of this design is the need to account for both within-period and between-period correlations in sample size calculations. Especially when embedded in health care delivery systems, many SW-CRTs may have subclusters nested in clusters, within which outcomes are collected longitudinally. However, existing sample size methods that account for between-period correlations have not allowed for multiple levels of clustering. We present computationally efficient sample size procedures that properly differentiate within-period and between-period intracluster correlation coefficients in SW-CRTs in the presence of subclusters. We introduce an extended block exchangeable correlation matrix to characterize the complex dependencies of outcomes within clusters. For Gaussian outcomes, we derive a closed-form sample size expression that depends on the correlation structure only through two eigenvalues of the extended block exchangeable correlation structure. For non-Gaussian outcomes, we present a generic sample size algorithm based on linearization and elucidate simplifications under canonical link functions. For example, we show that the approximate sample size formula under a logistic linear mixed model depends on three eigenvalues of the extended block exchangeable correlation matrix. We provide an extension to accommodate unequal cluster sizes and validate the proposed methods via simulations. Finally, we illustrate our methods in two real SW-CRTs with subclusters.     

不同强度及时间窗骨骼肌缺血后处理对兔心肌的保护作用

目的:通过比较不同强度及时间窗骨骼肌缺血后处理对兔缺血/再灌注心肌的保护效能,试图寻找最佳强度和时间窗的骨骼肌缺血后处理方案。方法:健康新西兰大白兔42只(雄性)随机分为7组(n=6):①假手术组(Sham)、②缺血对照组(CON)、③标准骨骼肌后处理组(SP)、④延迟6min骨骼肌后处理组(6M-DSP)、⑤延迟1 min骨骼肌后处理组(1M-DSP)、⑥骨骼肌后处理加强组(SSP)、⑦骨骼肌后处理减弱组(WSP)。以开胸结扎冠状动脉左室支固定部位方法制作缺血/再灌注模型,以游离并夹闭双侧腹股沟髂外动脉固定位置方法造成骨骼肌缺血,再灌注末以TTC法确定心肌梗死范围,并分别于心肌缺血前、后及再灌注1 h、2 h,以生化法测定血清肌酸激酶(CK)及乳酸脱氢酶(LDH)水平。结果:和CON组相比,1M-DSP组心肌梗死重量比及面积比分别下降了42.32%及42.68%、SP组分别下降了49.97%及43.78%、SSP组分别下降了48.36%及48.86%,(P均<0.05),但三组之间相比,心梗范围未见明显差异;而6M-DSP、WSP组与CON组相比未见心肌保护作用;肌酸激酶(CK)的水平和梗死范围变化趋势一致。结论:兔在心肌缺血/再灌注之前完成骨骼肌5 min缺血/1 min再灌注1次循环的缺血后处理,可以起到明显的心肌保护作用。     

Protective Effect of Isorhynchophylline Against β-Amyloid-Induced Neurotoxicity in PC12 Cells

Beta-amyloid peptide (Aβ), a major protein component of senile plaques, has been considered as a critical cause in the pathogenesis of Alzheimer’s disease (AD). Modulation of the Aβ-induced neurotoxicity has emerged as a possible therapeutic approach to ameliorate the onset and progression of AD. The present study aimed to evaluate the protective effect of isorhynchophylline, an oxindole alkaloid isolated from a Chinese herb Uncaria rhynchophylla, on Aβ-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that pretreatment with isorhynchophylline significantly elevated cell viability, decreased the levels of intracellular reactive oxygen species and malondialdehyde, increased the level of glutathione, and stabilized mitochondrial membrane potential in Aβ_25-35-treated PC12 cells. In addition, isorhynchophylline significantly suppressed the formation of DNA fragmentation and the activity of caspase-3 and moderated the ratio of Bcl-2/Bax. These results indicate that isorhynchophylline exerts a neuroprotective effect against Aβ_25-35-induced neurotoxicity in PC12 cells, at least in part, via inhibiting oxidative stress and suppressing the mitochondrial pathway of cellular apoptosis.     

Novel loci for field resistance to black-streaked dwarf and stripe viruses identified in a set of reciprocal introgression lines of rice (Oryza sativa L.)

Rice black-streaked dwarf virus (RBSDV) and stripe virus (RSV) are the two chronic viral diseases causing great damage to rice (Oryza sativa L.) production in China, and both are transmitted by the small brown planthopper (SBPH, Laodelphax striatellus Fallén). Quantitative trait loci (QTL) affecting field resistance to these two viral diseases were identified using QTL mapping software in a set of reciprocal introgression lines derived from the cross between Lemont and Teqing. A panel of 119 landraces was used for marker confirmation and allele mining. A total of 17 quantitative resistance loci (QRL) for the infection incidences of RBSDV and RSV were discovered and belong to 16 regions on all chromosomes except chromosome 12. Among them, 12 QRL were confirmed by association mapping, and many novel alleles at these loci were mined from the set of landraces. Only one region was found to be responsible for the genetic overlap between the field resistance against RBSDV and RSV, which was reported to be associated with SBPH resistance. The favorable alleles at the above novel and/or overlapping loci should be effective for marker-assisted selection breeding for resistance against the two diseases and the insect. Different strategies of varietal development and effective deployment against the two viral diseases are also discussed.     

Research Progress on the Toxic Antagonism of Selenium Against Mycotoxins

Biological Trace Element Research - Aflatoxin B1 (AFB1) can cause hepatotoxicity, genotoxicity, and immunosuppressive effects for a variety of organisms. Selenium (Se), as an essential nutrient...     

Enhancement of l-arginine production by increasing ammonium uptake in an AmtR-deficient Corynebacterium crenatum mutant

Journal of Industrial Microbiology & Biotechnology - l-Arginine is an important amino acid with extensive application in the food and pharmaceutical industries. The efficiency of nitrogen...