Aldehyde Dehydrogenase Isoform 1 Predicts a Poor Prognosis of Acute Cerebral Infarction.

To investigate the prognostic potential of serum aldehyde dehydrogenase isoform 1 (ALDH1) level in acute cerebral infarction, and the molecular mechanism in mediating neurological deficits, a total of 120 acute cerebral infarction cases within 72 h of onset were retrospectively analyzed. Serum ALDH1 level in them was detected by qRT-PCR. Receiver operating characteristic (ROC) and Kaplan-Meier curves were depicted for assessing the diagnostic and prognostic potentials of ALDH1 in acute cerebral infarction, respectively. An in vivo acute cerebral infarction model in rats was established by performing MCAO, followed by evaluation of neurological deficits using mNSS and detection of relative levels of ALDH1, Smad2, Smad4, and p21 in rat brain tissues. Pearson's correlation test was carried out to verify the correlation between ALDH1 and mNSS and relative levels of Smad2, Smad4, and p21. Serum ALDH1 level increased in acute cerebral infarction patients. A high level of ALDH1 predicted a poor prognosis of acute cerebral infarction patients. In addition, ALDH1 was sensitive and specific in distinguishing acute cerebral infarction cases, presenting a certain diagnostic potential. mNSS was remarkably higher in acute cerebral infarction rats than that of controls. Compared with sham operation group, relative levels of ALDH1, Smad2, and Smad4 were higher in brain tissues of modeling rats, whilst p21 level was lower. ALDH1 level in brain tissues of modeling rats was positively correlated to mNSS, and mRNA levels of Smad2 and Smad4, but negatively correlated to p21 level. Serum ALDH1 level is a promising prognostic and diagnostic factor of acute cerebral infarction, which is correlated to 90-day mortality. Increased level of ALDH1 in the brain of cerebral infarction rats is closely linked to neurological function, which is associated with the small mothers against decapentaplegic (Smad) signaling and p21.

In search of causal pathways in diabetes: a study using proteomics and genotyping data from a cross-sectional study.

AIMS/HYPOTHESIS: The pathogenesis of type 2 diabetes is not fully understood. We investigated whether circulating levels of preselected proteins were associated with the outcome 'diabetes' and whether these associations were causal. METHODS: In 2467 individuals of the population-based, cross-sectional EpiHealth study (45-75 years, 50% women), 249 plasma proteins were analysed by the proximity extension assay technique. DNA was genotyped using the Illumina HumanCoreExome-12 v1.0 BeadChip. Diabetes was defined as taking glucose-lowering treatment or having a fasting plasma glucose of ≥7.0 mmol/l. The associations between proteins and diabetes were assessed using logistic regression. To investigate causal relationships between proteins and diabetes, a bidirectional two-sample Mendelian randomisation was performed based on large, genome-wide association studies belonging to the DIAGRAM and MAGIC consortia, and a genome-wide association study in the EpiHealth study. RESULTS: Twenty-six proteins were positively associated with diabetes, including cathepsin D, retinal dehydrogenase 1, α-L-iduronidase, hydroxyacid oxidase 1 and galectin-4 (top five findings). Three proteins, lipoprotein lipase, IGF-binding protein 2 and paraoxonase 3 (PON-3), were inversely associated with diabetes. Fourteen of the proteins are novel discoveries. The Mendelian randomisation study did not disclose any significant causal effects between the proteins and diabetes in either direction that were consistent with the relationships found between the protein levels and diabetes. CONCLUSIONS/INTERPRETATION: The 29 proteins associated with diabetes are involved in several physiological pathways, but given the power of the study no causal link was identified for those proteins tested in Mendelian randomisation. Therefore, the identified proteins are likely to be biomarkers for type 2 diabetes, rather than representing causal pathways.

The prognostic roles of circulating ALDH1+ tumor cell in the patients with non-small cell lung cancer.

Circulating tumor cells can provide important diagnostic and prognostic information of the patients with non-small cell lung cancer (NSCLC). Aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, has been used in various tumors, including NSCLC. In the present study, we isolated the circulating ALDH1+ tumor cells from the NSCLC patients using ALDH1 as a potential marker. Higher percentage of ALDH1+ tumor cells was identified in blood samples from the NSCLC patients compared with normal controls. ALDH1+ cells were correlated with the poor prognosis of these patients by using Kaplan-Meier analysis. In the last, the tumorigenic properties of ALDH1+ tumor cells were determined in vitro and in vivo by using sphere assay and xenograft tumor mouse models. Our in vitro and in vivo experiments demonstrated that ALDH1 could drive the stemness of circulating NSCLC cells. Circulating ALDH1+ cells could be used as a prognostic marker for NSCLC.

Low serum Kallistatin level was associated with poor neurological outcome of out-of-hospital cardiac arrest survivors: Proteomics study.

AIM OF THE STUDY: To identify proteins of which depletion are associated with the poor 6-month neurological outcome of out-of-hospital cardiac arrest survivors. METHODS: Seven healthy volunteers and 34 out-of-hospital cardiac arrest survivors admitted to the intensive care unit (ICU) and underwent targeted-temperature management were enrolled. According to the 6-month cerebral performance category (CPC) scale, patients were divided into the good (CPC 1-2) and poor (CPC 3-5) outcome groups. Blood samples were obtained at 0, 24, and 72 h after admission to the ICU. RESULTS: With proteomic approaches, we found 23 proteins that showed group-differences between the sera pooled from 7 study groups: healthy volunteers, the good outcome groups (0, 24, and 72 h), and the poor outcome groups (0, 24, and 72 h). We selected 7 candidate proteins of which intensities were different between the good and poor outcome groups (>2-fold change) and excluded 5 proteins related to haemolysis or remaining high abundant proteins. To confirm the 2 identified proteins: retinal dehydrogenase 1 and Kallistatin, we performed enzyme-linked immunosorbent assay with individual serum. Finally, old age (odds ratio = 1.055; 95% confidence interval, 1.002-1.112; p = 0.043) and low serum kallistatin level at 0 h (odds ratio = 0.784; 95% confidence interval, 0.618-0.995; p = 0.046) were independently associated with the poor 6-month neurological outcome. CONCLUSION: The depletion of serum kallistatin at admission to the ICU was associated with the poor neurological outcome of out-of-hospital cardiac arrest survivors.

Glutamine promotes intestinal SIgA secretion through intestinal microbiota and IL-13.

SCOPE: Glutamine supplementation enhances secretory IgA (SIgA) production in the intestine, but the mechanism is largely unknown. We examined this issue using a mouse model. METHODS AND RESULTS: In mouse model, glutamine supplementation increased both SIgA abundance in intestinal luminal contents and IgA(+) plasma cell numbers in the mouse ileum, and decreased bacterial loads in mouse mesenteric lymph nodes. Glutamine supplementation increased mouse ileal expression of cytokines associated with T cell-dependent and T cell-independent pathways of SIgA induction, including IL-5, IL-6, IL-13, transforming growth factor (TGF-ß), a proliferation-inducing ligand (APRIL), B cell-activating factor (BAFF), vasoactive intestinal peptide (VIP) receptor, and retinal dehydrogenases. Injecting an IL-13 antibody during glutamine supplementation reduced J-chain expression in the mouse ileum. Glutamine supplementation increased bacterial invasion into the mouse ileal wall, while disrupting the mouse intestinal microbiota abrogated the influence of glutamine supplementation on SIgA secretion. CONCLUSION: Glutamine supplementation appears to enhance SIgA secretion in the mouse intestine through the intestinal microbiota and subsequently through T cell-dependent and T cell-independent pathways.

Influence of singlet oxygen inhalation on the state of blood pro- and antioxidant systems and energy metabolism.

Activity of lactate dehydrogenase in direct and reverse reactions, activity of aldehyde dehydrogenase, blood lactate and glucose levels, pro- and antioxidant balance in the blood were analyzed in rats after inhalations of singlet oxygen for 10 days. The course of inhalations improves antioxidant reserve of the blood and activity of blood oxidoreductases in healthy animals, thus strengthening the adaptive potential of the body.

Characterising the mucosal and systemic immune responses to experimental human hookworm infection.

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-ß) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.