Diagnosis and functional prediction of microbial markers in tumor tissues of sporadic colorectal cancer patients associated with the MLH1 protein phenotype

ObjectiveMost patients with sporadic colorectal cancer (SCRC) develop microsatellite instability because of defects in mismatch repair (MMR). Moreover, the gut microbiome plays a vital role in the pathogenesis of SCRC. In this study, we assessed the microbial composition and diversity of SCRC tumors with varying MutL protein homolog 1 (MLH1) status, and the effects of functional genes related to bacterial markers and clinical diagnostic prediction.MethodsThe tumor microbial diversity and composition were profiled using high-throughput sequencing of the 16S ribosomal RNA (rRNA) gene V4 region. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) software and BugBase tool were used to predict the functional roles of the microbiome. We aimed to construct a high-accuracy model to detect and evaluate the area under the receiver operating characteristic curve with candidate biomarkers.ResultsThe study included 23 patients with negative/defective MLH1 (DM group) and 22 patients with positive/intact MLH1 (IM group). Estimation of alpha diversity indices showed that the Shannon index (p = 0.049) was significantly higher in the DM group than in the controls, while the Simpson index (p = 0.025) was significantly lower. At the genus level, we observed a significant difference in beta diversity in the DM group versus the IM group. Moreover, the abundance of Lachnoclostridium spp. and Coprococcus spp. was significantly more enriched in the DM group than in the IM group (q < 0.01 vs. q < 0.001). When predicting metagenomes, there were 18 Kyoto Encyclopedia of Genes and Genomes pathways and one BugBase function difference in both groups (all q < 0.05). On the basis of the model of diagnostic prediction, we built a simplified optimal model through stepwise selection, consisting of the top two bacterial candidate markers (area under the curve = 0.93).ConclusionIn conclusion, the genera Lachnoclostridium and Coprococcus as key species may be crucial biomarkers for non-invasive diagnostic prediction of DM in patients with SCRC in the future

Fabrication and properties of zirconia/hydroxyapatite composite scaffold based on digital light processing

Zirconia and hydroxyapatite(HA) are two typical implant materials, which have the advantages of excellent mechanical strength and good biological activity respectively. It was found that composite material had good biocompatibility and mechanical strength compared to the single material. In this paper, the porous scaffolds of ZrO2/HA composite were formed by digital light processing (DLP) technology and their performance were evaluated. Cell experiments showed that the addition of HA had a positive effect on cell proliferation and differentiation. Mechanical tests showed that the composite scaffold with 10 wt% HA had the best compressive capacity due to the pinning and bridging effect of a small amount of HA grains. When scaffolds were immersed in the simulated body fluid (SBF), the compressive strengths of the composite scaffolds decreased within the first 14 days and gradually increased after 14 days. The reason for this phenomenon was the degradation of calcium phosphate components and the deposition of apatite. By the 28th day, the compressive strengths of all the composite scaffolds increased to over 20 MPa, close to that of the zirconia scaffolds during the same period (25 MPa). The compressive strengths of all scaffolds met the requirement of cancellous bone during the entire soaking period, and the composite scaffolds have potential application value in bone repair

The research of immune mechanism with intestinal microflora to microsatellite instability in sporadic colorectal cancer

The research of immune mechanism</p

Diagnosis and functional prediction of microbial marker in tumor tissues of sporadic colorectal cancer patients associated with MLH1 protein phenotype

 Analysis of tumor-associated microbiota in sporadic colorectal cancer patients with different MLH1 status </p

Subthalamic nucleus deep brain stimulation alleviates oxidative stress via mitophagy in Parkinson’s disease

Abstract Subthalamic nucleus deep brain stimulation (STN-DBS) has the potential to delay Parkinson’s disease (PD) progression. Whether oxidative stress participates in the neuroprotective effects of DBS and related signaling pathways remains unknown. To address this, we applied STN-DBS to mice and monkey models of PD and collected brain tissue to evaluate mitophagy, oxidative stress, and related pathway. To confirm findings in animal experiments, a cohort of PD patients was recruited and oxidative stress was evaluated in cerebrospinal fluid. When PD mice received STN stimulation, the mTOR pathway was suppressed, accompanied by elevated LC3 II expression, increased mitophagosomes, and a decrease in p62 expression. The increase in mitophagy and balance of mitochondrial fission/fusion dynamics in the substantia nigra caused a marked enhancement of the antioxidant enzymes superoxide dismutase and glutathione levels. Subsequently, fewer mitochondrial apoptogenic factors were released to the cytoplasm, which resulted in a suppression of caspase activation and reservation of dopaminergic neurons. While interfaced with an mTOR activator, oxidative stress was no longer regulated by STN-DBS, with no neuroprotective effect. Similar results to those found in the rodent experiments were obtained in monkeys treated with chronic STN stimulation. Moreover, antioxidant enzymes in PD patients were increased after the operation, however, there was no relation between changes in antioxidant enzymes and motor impairment. Collectively, our study found that STN-DBS was able to increase mitophagy via an mTOR-dependent pathway, and oxidative stress was suppressed due to removal of damaged mitochondria, which was attributed to the dopaminergic neuroprotection of STN-DBS in PD

Pathological pallidal beta activity in Parkinson’s disease is sustained during sleep and associated with sleep disturbance

Abstract Parkinson’s disease (PD) is associated with excessive beta activity in the basal ganglia. Brain sensing implants aim to leverage this biomarker for demand-dependent adaptive stimulation. Sleep disturbance is among the most common non-motor symptoms in PD, but its relationship with beta activity is unknown. To investigate the clinical potential of beta activity as a biomarker for sleep quality in PD, we recorded pallidal local field potentials during polysomnography in PD patients off dopaminergic medication and compared the results to dystonia patients. PD patients exhibited sustained and elevated beta activity across wakefulness, rapid eye movement (REM), and non-REM sleep, which was correlated with sleep disturbance. Simulation of adaptive stimulation revealed that sleep-related beta activity changes remain unaccounted for by current algorithms, with potential negative outcomes in sleep quality and overall quality of life for patients