Ketogenic Diets Alter the Gut Microbiome, Resulting in Decreased Susceptibility to and Cognitive Impairment in Rats with Pilocarpine-Induced Status Epilepticus.

A ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that exerts antiepileptic effects by attenuating spontaneous recurrent seizures, ameliorating learning and memory impairments, and modulating the gut microbiota composition. However, the role of the gut microbiome in the antiepileptic effects of a KD on temporal lobe epilepsy (TLE) induced by lithium-pilocarpine in adult rats is still unknown. Our study provides evidence demonstrating that a KD effectively mitigates seizure behavior and reduces acute-phase epileptic brain activity and that KD treatment alleviates hippocampal neuronal damage and improves cognitive impairment induced by TLE. We also observed that the beneficial effects of a KD are compromised when the gut microbiota is disrupted through antibiotic administration. Analysis of gut microbiota components via 16S rRNA gene sequencing in fecal samples collected from TLE rats fed either a KD or a normal diet. The Chao1 and ACE indices showed decreased species variety in KD-fed rats compared to TLE rats fed a normal diet. A KD increased the levels of Actinobacteriota, Verrucomicrobiota and Proteobacteria and decreased the level of Bacteroidetes. Interestingly, the abundances of Actinobacteriota and Verrucomicrobiota were positively correlated with learning and memory ability, and the abundance of Proteobacteria was positively correlated with seizure susceptibility. In conclusion, our study revealed the significant antiepileptic and neuroprotective effects of a KD on pilocarpine-induced epilepsy in rats, primarily mediated through the modulation of the gut microbiota. However, whether the gut microbiota mediates the antiseizure effects of a KD still needs to be better elucidated.

Elevated Expression of ADAP2 is Associated With Aggressive Behavior of Human Clear-Cell Renal Cell Carcinoma and Poor Patient Survival.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. ADAP2 is a GTPase-activating protein was upregulated in clear cell renal cell carcinoma. The role of ADAP2 in ccRCC progression is unknown. METHODS: ADAP2 expression in ccRCC cell lines and tissues was examined via real-time PCR, Western blot and IHC. MTS, colony formation and transwell assay to explore the role of ADAP2 in ccRCC. ADAP2 in growth and metastasis of ccRCC were evaluated in vivo through ccRCC xenograft tumor growth, lung metastatic mice model. The prognostic role of ADAP2 was evaluated by survival analysis. RESULTS: ADAP2 mRNA was expressed at significantly higher levels in 23 pairs of ccRCC tissues than in normal kidney tissues (P < 0.01). Immunohistochemical analysis of 298 ccRCC tissues revealed elevated ADAP2 expression as an independent unfavorable prognostic factor for the overall survival (P = 0.0042) and progression-free survival (P = 0.0232) of patients. The KaplanMeier survival curve showed that patients with a higher expression of ADAP2 showed a significantly lower overall survival rate and disease-free survival rate. Moreover, high expression of ADAP2 at the mRNA level was associated with a worse prognosis for overall survival (P = 0.0083) in The Cancer Genome Atlas (TCGA) cohort. In vivo and in vitro functional study showed that overexpression of ADAP2 promotes ccRCC cell proliferation and metastasis ability, whereas knockdown of ADAP2 inhibited cell proliferation, colony formation, migration and invasion. CONCLUSION: ADAP2 is a novel prognostic marker and could promotes tumor progression in ccRCC.

A Study on the Time-Effect and Dose-Effect Relationships of Polysaccharide from Opuntia dillenii against Cadmium-Induced Liver Injury in Mice.

The purpose of this study was to evaluate the protective effect of Opuntia dillenii (Ker-Gaw) Haw. polysaccharide (ODP) against cadmium-induced liver injury. Cadmium chloride (CdCl2) was used to construct a mice evaluation model, and the indicators chosen included general signs, liver index, biochemical indicators, blood indicators, and pathological changes. A dose of 200 mg/kg ODP was applied to the mice exposed to cadmium for different lengths of time (7, 14, 21, 28, and 35 days). The results showed that CdCl2 intervention led to slow weight growth (reduced by 13−20%); liver enlargement; significantly increased aspartate aminotransferase (AST, 45.6−52.0%), alanine aminotransferase (ALT, 26.6−31.3%), and alkaline phosphatase (ALP, 38.2−43.1%) levels; and significantly decreased hemoglobin (HGB, 13.1−15.2%), mean corpuscular hemoglobin (MCH, 16.5−19.3%), and mean corpuscular hemoglobin concentrations (MCHC, 8.0−12.7%) (p < 0.01). In addition, it led to pathological features such as liver cell swelling, nuclear exposure, central venous congestion, apoptosis, and inflammatory cell infiltration. The onset of ODP anti-cadmium-induced liver injury occurred within 7 days after administration, and the efficacy reached the highest level after continuous administration for 14 days, a trend that could continue until 35 days. Different doses (50, 100, 200, 400, and 600 mg/kg) of ODP have a certain degree of protective effect on cadmium-induced liver injury, showing a good dose−effect relationship. After 28 days of administration of a 200 mg/kg dose, all pathological indicators were close to normal values. These findings indicated that ODP had positive activity against cadmium-induced liver injury and excellent potential for use as a health food or therapeutic drug.

Development of chromosome-arm-specific microsatellite markers in Triticum aestivum (Poaceae) using NGS technology.

PREMISE OF THE STUDY: The aim of this study was to assess the feasibility of developing chromosome-arm-specific microsatellite markers in wheat on a large scale based on chromosome survey sequences obtained with next-generation sequencing (NGS) technology. METHODS AND RESULTS: The Illumina Hi Seq2000 sequencing platform was used to sequence DNA of isolated wheat chromosome-arm 7DL. The data were assembled and microsatellite loci were identified computationally. In total, 16315 microsatellites were identified from 161061 assembled contigs. Thirty-three markers were randomly selected for validation across 20 diverse wheat cultivars. Two nulli-tetrasomic stocks were also screened to validate the specificity of the newly developed markers. CONCLUSIONS: This is the first study on identification of chromosome-arm-specific microsatellite markers using NGS technology. These new chromosome-arm-specific markers will facilitate saturation of the 7DL genetic map, and their availability will support genetic mapping and positional cloning in wheat.