Objective Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare acquired immune-mediated neuropathy. Although microbial infection is potentially a contributing factor, a causative link between CIDP and microbial infection remains unclear. There is also no definitive biomarker for CIDP diagnostics and therapies. The present study aimed to characterize the serum metabolic profile and gut microbiome structure in CIDP. Methods Targeted metabolomics profiling of serum, using liquid chromatography-mass spectrometry, and metagenomics sequencing of stool samples from a cohort of CIDP and non-CIDP subjects were performed to evaluate serum metabolic profiles and gut microbiome structure in CIDP subjects relative to healthy controls. Results Metabolome data revealed that the bile acids profile was perturbed in CIDP with bile acids and arachidonic acid enriched significantly in CIDP versus non-CIDP controls. Metagenome data revealed that opportunistic pathogens, such as Klebsiella pneumonia and Megamonas funiformis, and genes involved in bacterial infection were notably more abundant in CIDP subjects, while gut microbes related to biotransformation of secondary bile acids were abnormal in CIDP versus non-CIDP subjects. Correlation analysis revealed that changes in secondary bile acids were associated with altered gut microbes, including Bacteroides ovatus, Bacteroides caccae, and Ruminococcus gnavus. Conclusion Bile acids and arachidonic acid metabolism were disturbed in CIDP subjects and might be affected by the dysbiosis of gut microbial flora. These findings suggest that the combination of bile acids and arachidonic acid could be used as a CIDP biomarker and that modulation of gut microbiota might impact the clinical course of CIDP.

Aim: The levels of urine metabolites, rheumatoid factor (RF) and inflammatory factors are altered in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. However, the level of them has not been quantitatively evaluated yet, as well as the correlation between the urine metabolites, RF and inflammatory factors. This research aims to investigate the urine metabolites and inflammatory factors from patients with OA and early rheumatoid arthritis (e-RA) to explore the relationship between the urine metabolites and RF or inflammatory factors. Methods: A total of 455 individuals were included in this study. Urine specimen was collected from 190 healthy volunteers, 26 osteoarthritis patients and 239 RA patients in which 37 subjects were diagnosed as early stage RA (e-RA). Metabolites in urine were extracted and analyzed with liquid chromatography-mass spectrometry (LC-MS) technique. Urine RF and inflammatory factors were measured with MSD V-Plex Proinflammatory Panel 1 Human Kit. Results: RF and nine of the inflammatory factors were significantly elevated in e-RA compared with OA and controls. Nine kinds of metabolites levels were found to positively correlated with urine RF level, two of which including 2-Methylnaphthalene (r= 0.636, p= 0.00195) and 3,4-Dihydroxy-L-phenylalanine (r= 0.524, p= 0.0149) were significantly elevated in e-RA group. Conclusion: Urine from e-RA patients exhibited different levels of metabolites, rheumatoid factor (RF) and inflammatory factors from patients without RA and OA. Nine metabolites showed significant positive correlation with RF level. Among these nine metabolites, 2-Methylnaphthalene (r= 0.636, p= 0.00195) and 3,4-Dihydroxy-L-phenylalanine (r= 0.524, p= 0.0149) elevated at early stage of RA, which could serve as a marker for arthritis screening and early diagnostic.

The human gene microcephalin (MCPH1) plays a key role in DNA damage-induced cellular responses and chromosome condensation. Recent clinical studies proposed MCPH1 as a tumor suppressor gene in lung cancer, pancreatic cancer, and breast cancer, yet its roles remain poorly understood in other types of tumors. Pan-cancer analyses of MCPH1 are urgently required to help us understand the potential molecular functions of MCPH1 in other types of tumors. Here, we used several bioinformatic database and tools, including TCGA, GEO, ONCOMINE, and Human Protein Atlas to investigate the role of MCPH1 in 33 tumor types. We found that the expression of MCPH1 in tumor cases and normal cases were significantly different, and the higher expression of MCPH1 generally predicted poor overall survival for tumor patients, such as acute myeloid leukemia, liver hepatocellular carcinoma, and pancreatic adenocarcinoma. Meanwhile, lower expression of the MCPH1 gene was related to poor OS prognosis for KIRC and gastric cancer. Moreover, the expression level of MCPH1 was highly associated with the immune microenvironment. Our result provides some fresh light into the oncogenic roles of MCPH1 in various human cancers and revealed that MCPH1 may be a potential diagnostic and prognostic marker in LAML, PAAD, and gastric cancer.

Background Intervertebral disc degenerative disease(IVDD)is one of the main causes of low back pain, causing serious economic burden to the society. The changes of microenvironment in the degenerative intervertebral disc cause oxidative stress injury and excessive apoptosis of intervertebral disc endogenous stem cells, which weakens their ability to repair intervertebral disc. 0.01-1µM melatonin has been shown to reduce excessive apoptosis of nucleus pulposus mesenchymal stem cells (NPMSCs) caused by oxidative stress injury. The purpose of this study is to explore the possible mechanism of the protective effect of melatonin on oxidative stress injury of NPMSC induced by hydrogen peroxide(H2O2). Methods The cell counting kit-8 (CCK-8) assay was used to evaluate the cytotoxicity of hydrogen peroxide and protective effects of melatonin. ROS content was detected by 2´7´-dichlorofluorescin diacetate (DCFH-DA). Mitochondrial membrane potential (MMP) was detected by the Tetraethylbenzimidazolylcarbocyanine iodide (JC-1) assay. A TUNEL cell apoptosis detection kit and Annexin V/PI double staining was conducted to determine apoptosis rate. Additionally, apoptosis-associated proteins and PI3K/Akt signaling pathway related proteins were evaluated by immunofluorescence, immunoblotting and PCR. (ECM) were evaluated by RT-PCR and immunofluorescence. In vivo, X-ray, MRI and histological analysis were used to evaluate the protective effect of melatonin in vivo. Results melatonin had obvious protective effect on NPMSCs treated with 0–10 µM for 24 hours. In addition, melatonin also had obvious protective effects on mitochondrial dysfunction, decrease of membrane potential and cell senescence induced by hydrogen peroxide. More importantly, melatonin could significantly reduce the apoptosis of nucleus pulposus mesenchymal stem cells induced by hydrogen peroxide, such as regulating the expression of apoptosis-related proteins and decreasing the rate of apoptosis. After treatment with melatonin, the PI3K/Akt pathway was significantly activated in nucleus pulposus mesenchymal stem cells, while the protective effect was significantly weakened after PI3K-IN-1 treatment. In vivo, the results of X-ray, MRI and histological analysis showed that therapy with melatonin could partially reduce the degree of intervertebral disc degeneration. Conclusion our research demonstrated that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of nucleus pulposus mesenchymal stem cells induced by oxidative stress via PI3K/Akt pathway, which provides a novel idea for the therapy of intervertebral disc degeneration.

No abstract