Abstract Background Understanding the complex relationships between bacteria and metabolites in ecological systems are extremely important in studies of different microbiomes. Longitudinal multi-omics study is adopted to investigate interactions between bacteria and metabolites, by directly associating their longitudinal profiles. Since a bacteria/metabolite may involve in many different biological processes, the longitudinal profile is an average of different interactions. Therefore, direct association could only uncover the strongest interactions. Results Here we present a computational approach that can rebuild short- and long-term bacteria-metabolite interactions from longitudinal multi-omics datasets. For this task, we re-analyse data (both microbial sequencing and metabolomic analysis) from an in vitro model of Clostridioides difficile infection and faecal microbiota transplant, a disease state and mode of therapy in which perturbed microbiome-metabolome interactions (and their reversal) are well-established to be pertinent. By analysing such a dataset, we generated both a short-term and a long-term interaction network, which predicted many new interactions. Four new interactions were randomly selected to be validated. In batch culture experiments, we validated two of them: (1) Ruminococcus gnavus and Ruminococcus luti could generate 3-ketocholanic acid (2) Blautia obeum could consume succinate. Conclusions The deconvolution of the raw longitudinal signal into short- and long-term trends can help users to gain a deeper understanding of their data. This tool will be useful for high-throughput screening of microbe/metabolite/host interactions from a longitudinal multi-omics setting.
Purpose: Pituitary adenylate cyclase-activating polypeptide (PACAP) has shown potent neuroprotective effects in central nervous system and retina disorders. However, whether PACAP can attenuate retinal neurodegeneration induced by acute ocular hypertension (AOH) and the underlying mechanisms remain unknown. In this study, we aimed to investigate the effects of PACAP on the survival and function of retinal ganglion cells (RGCs), apoptosis, and inflammation in a mouse model of AOH injury. Methods: PACAP was injected into the vitreous body immediately after inducing AOH injury. Hematoxylin and eosin staining and optical coherence tomography were used to evaluate the loss of retina tissue. Pattern electroretinogram was used to evaluate the function of RGCs. TUNEL assay was used to detect apoptosis. Immunofluorescence and western blot were employed to evaluate protein expression levels. Results: PACAP treatment significantly reduced the losses of whole retina and inner retina thicknesses, Tuj1-positive RGCs, and the amplitudes of pattern electroretinograms induced by AOH injury. Additionally, PACAP treatment remarkably reduced the number of TUNEL-positive cells and inhibited the upregulation of Bim, Bax, and cleaved caspase-3 and downregulation of Bcl-xL after AOH injury. Moreover, PACAP markedly inhibited retinal reactive gliosis and vascular inflammation, as demonstrated by the downregulation of GFAP, Iba1, CD68, and CD45 in PACAP-treated mice. Furthermore, upregulated expression of NF-κB and phosphorylated NF-κB induced by AOH injury was attenuated by PACAP treatment. Conclusions: PACAP could prevent the loss of retinal tissue and improve the survival and function of RGCs. The neuroprotective effect of PACAP is probably associated with its potent anti-apoptotic and anti-inflammatory effects.
Purpose: To explore whether oxidative stress and premature senescence occur in the anterior segment of acute primary angle-closure (APAC) eyes after increased intraocular pressure. Methods: The eye samples of 21 APAC patients, 22 age-related cataract patients, and 10 healthy donors were included. Aqueous humor (AqH), iris, and anterior lens capsule samples were collected. The levels of oxidative stress markers and senescence-associated secretory phenotype (SASP)–related cytokines in AqH were estimated using relevant reagent kits and multiplex bead immunoassay technique. The intensity of relevant markers in anterior segment tissues was examined by immunofluorescence- and senescence-associated β-galactosidase (SA-β-gal) staining. Results: Oxidative stress marker levels elevated significantly in the AqH of APAC eyes. Reactive oxygen species (ROS) and 8-hydroxydeoxyguanosine levels were positively correlated with preoperative peak intraocular pressure and age, whereas reduced glutathione/oxidized glutathione (GSH/GSSH) ratio was negatively correlated with both parameters. The levels of several SASP-related cytokines were markedly increased. ROS and malondialdehyde levels were positively correlated with the levels of some SASP-related cytokines, whereas superoxide dismutase level and GSH/GSSH ratio showed an opposite trend. The number of cells positive for oxidative mitochondrial DNA damage and apoptosis-related markers increased in the iris and anterior lens capsule of the APAC group. Senescence-associated markers (p16, p21, and p53) and SA-β-gal activity were increased in the iris of the APAC group. Conclusions: Oxidative stress and premature senescence occurred in the anterior segment of APAC patients, suggesting that they may be involved in the development of pathological changes in the anterior segment of APAC eyes.
Hypermethylation of CpG islands in adenomatous polyposis coli (APC) gene has been detected in a variety of human tumors, which is involved in the pathogenesis of these tumors. In previous research, we detected APC promoter methylation in 47% lung tumor tissues. This study was to analyze the effect of APC promoter methylation on the gene transcription in 3 lung cancer cell lines.The methylation status of APC promoter 1A in lung adenocarcinoma cell line SPCA1, small cell lung cancer cell line NCI-H446, and big cell lung cancer cell line NCI-H460 was detected by methylation-specific polymerase chain reaction (MSP) and microarray methylated cord blood DNA served as positive control, and unmethylated cord blood DNA served as negative control. The expression of APC was examined by real-time quantitative polymerase chain reaction (PCR) with Sybr-Green I staining. After treatment of 1, 5, 10, 15 micromol/L DNA methyltransferase inhibitor 5-aza-2-deoxycytidine (5-aza-dC), the expression of APC in NCI-H460 cells was detected by real-time PCR.APC promoter 1A was methylated in NCI-H460 cells, and unmethylated in NCI-H446 and SPC-A1 cells. Hypermethylation was detected in all 5 CpG islands (687, 707, 714, 719, 726) of APC promoter 1A in NCI-H460 cells. The expression of APC in NCI-H460 cells was decreased by 26.04% of that in NCI-H446 cells and by 32.36% of that in SPCA1 cells. After treatment of 1, 5, 10, 15 micromol/L 5-aza-dC, the expression of APC promoter 1A in NCI-H460 cells was enhanced by 4.59, 5.78, 9.58, 5.98 folds, respectively.APC gene is hypermethylated in HCI-H460 cells, and its transcription coud be activated by 5-aza-dC.
BACKGROUND The demand for plasma and plasma products has increased in China, which has a short supply. Compared with whole blood donors, plasma donors and their donation behavior have received less attention. This study aimed to investigate the demographic characteristics and lifestyle habits of Chinese plasma donors. MATERIAL AND METHODS During 2018-2019, information on plasma donors was collected from blood product companies using a 25-item questionnaire, including sex, age, height, weight, blood group, donation frequency, occupation, smoking and drinking, and sleeping and dietary habits. RESULTS Among 15 497 plasma donors, 70.5% were women and 78.5% were aged 46-55 years. Among 4847 plasma donors, the average height of men was 169.5±6.2 cm and the average height of women was 157.0±4.6 cm. In addition, the average weight of men was 67.0±10.4 kg and the average weight of women was 60.0±8.3 kg. The prevalence of obesity (body mass index ≥30.0 kg/m²) of all donors was 14.8%; 14.7% of men were obese, and 15% of women were obese. Among all plasma donors, 88.8% were farmers and 60% were frequent donors with a donation history of at least 5 years. Among all donors, 84.0% did not smoke, 67.3% did not drink, and 95.1% reported good sleep quality. All respondents reported healthy dietary habits. CONCLUSIONS Healthy lifestyle habits considerably affect the health of plasma donors and the quality of source plasma. Chinese plasma donors in this study demonstrated imbalances in terms of characteristics, which became more marked with age.
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