Lactic Acid Metabolism And Transporter Related Three Genes Predict The Prognosis of Patients With Clear Cell Renal Cell Carcinoma

Background: Lactic acid was previously considered a waste product of glycolysis, and has now become a key metabolite for cancer development, maintenance and metastasis. So far, numerous studies have confirmed that tumor lactic acid levels are associated with increased metastasis, tumor recurrence and poor prognosis. However, the prognostic value of lactic acid metabolism and transporter related genes in patients with clear cell renal cell carcinoma has not been explored.Results: We selected lactic acid metabolism and transporter related twenty-one genes for LASSO cox regression analysis in the E-MTAB-1980 cohort, and finally screened three genes (PNKD, SLC16A8, SLC5A8) to construct a clinical prognostic model for patients with clear cell renal cell carcinoma. Based on the prognostic model we constructed, the over survival (hazard ratio = 4.117, 95% CI: 1.810 - 9.362, p < 0.0001) of patients in the high-risk group and the low-risk group in the training set E-MTAB-1980 cohort had significant differences, and similar results (hazard ratio = 1.909, 95% CI: 1.414 - 2.579 p < 0.0001) were also observed in the validation set TGCA cohort. Subsequently, survival prediction was carried out based on the survival prognosis model we constructed. In the E-MTAB-1980 cohort, the area under ROC curve (AUC) of 1-, 3- and 5- years was 0.71, 0.72, and 0.77, respectively. The AUC of 1-, 3- and 5- years in TCGA cohort was 0.65, 0.65, and 0.63, respectively. Using CIBERSORT algorithm to analyze the differences in immune cell infiltration in different risk groups, we found that dendritic cells and CD4+ memory cells in the high-risk group were significantly lower than those in the low-risk group, while Treg cells were higher than in the low-risk group. Finally, through gene enrichment analysis, we found that the signal pathway that is strongly related to the prognostic model is the cell cycle. Conclusions: We constructed a prognostic model using lactic acid metabolism and transporter related genes, which can accurately predict the prognosis of patients. The poor prognosis of the high-risk group may be related to the regulation of cell cycle by lactic acid metabolism.

Admission Serum Bicarbonate Predicts Adverse Clinical Outcomes in Hospitalized Cirrhotic Patients

A low serum bicarbonate (SB) level is predictive of adverse outcomes in kidney injury, infection, and aging. Because the liver plays an important role in acid-base homeostasis and lactic acid metabolism, we speculated that such a relationship would exist for patients with cirrhosis. To assess the prognostic value of admission SB on adverse hospital outcomes, clinical characteristics were extracted and analyzed from a large electronic health record system. Patients were categorized based on admission SB (mEq/L) into 7 groups based on the reference range (22–25) into mildly (18–21), moderately (14–17), and severely (<14) decreased groups and mildly (26–29), moderately (30–33), and severely (>30) increased groups, and the relationship of SB category with the frequency of complications (acute kidney injury/hepatorenal syndrome, portosystemic encephalopathy, gastrointestinal bleeding, ascites, and spontaneous bacterial peritonitis) and hospital metrics (length of stay [LOS], admission to an intensive care unit [ICU], and mortality) was assessed. A total of 2,693 patients were analyzed. Mean SB was 22.9 ± 4.5 mEq/L. SB was within the normal range (22–25 mEq/L) in 1,072 (39.8%) patients, and 955 patients (36%) had a low SB. As the SB category decreased, the incidence of complications progressively increased ( p < 0.001 ). Increased MELD-Na score and low serum albumin also correlated with frequency of complications ( p < 0.001 ). As the SB category decreased, LOS, ICU admission, and mortality progressively increased ( p < 0.001 ). On multivariate analysis, the association of decreased SB with higher odds of complications, LOS, ICU admission, and mortality persisted. Conclusion. Low admission SB in patients with cirrhosis is associated with cirrhotic complications, longer LOS, increased ICU admissions, and increased hospital mortality.

Riboflavin - properties, occurrence and its use in medicine

Riboflavin is built on an isoalloxazin ring, which contains three sixcarbon rings: benzoic, pyrazine and pyrimidine. Riboflavin is synthesized by some bacteria, but among humans and animals, the only source of flavin coenzymes (FAD, FMN) is exogenous riboflavin. Riboflavin transport in enterocytes takes place via three translocators encoded by the SLC52 gene. Deficiency of dietary riboflavin has wide ranging implications for the efficacy of other vitamins, the mechanism of cellular respiration, lactic acid metabolism, hemoglobin, nucleotides and amino acid synthesis. In studies it was found that, pharmacologic daily doses (100 mg) have the potential to react with light, which can have adverse cellular effects. Extrene caution should be exercised when using riboflavin as phototherapy in premature newborns. At the cellular level, riboflavin deficiency leads to increased oxidative stress and causes disorders in the glutathione recycling process. Risk factors for developing riboflavin deficinecy include pregnancy, malnutrition (including anorexia and other eating disorders, vegitarianism, veganism and alcoholism. Furthermore, elderly people and atheletes are also at risk of developing this deficiency. Widespread use of riboflavin in medicine, cancer therapy, treatment of neurodegenerative diseases, corneal ectasia and viral infections has resulted in the recent increased interest in this flavina.

Channel-mediated lactic acid transport: a novel function for aquaglyceroporins in bacteria

MIPs (major intrinsic proteins), also known as aquaporins, are membrane proteins that channel water and/or uncharged solutes across membranes in all kingdoms of life. Considering the enormous number of different bacteria on earth, functional information on bacterial MIPs is scarce. In the present study, six MIPs [glpF1 (glycerol facilitator 1)–glpF6] were identified in the genome of the Gram-positive lactic acid bacterium Lactobacillus plantarum. Heterologous expression in Xenopus laevis oocytes revealed that GlpF2, GlpF3 and GlpF4 each facilitated the transmembrane diffusion of water, dihydroxyacetone and glycerol. As several lactic acid bacteria have GlpFs in their lactate racemization operon (GlpF1/F4 phylogenetic group), their ability to transport this organic acid was tested. Both GlpF1 and GlpF4 facilitated the diffusion of D/L-lactic acid. Deletion of glpF1 and/or glpF4 in Lb. plantarum showed that both genes were involved in the racemization of lactic acid and, in addition, the double glpF1 glpF4 mutant showed a growth delay under conditions of mild lactic acid stress. This provides further evidence that GlpFs contribute to lactic acid metabolism in this species. This lactic acid transport capacity was shown to be conserved in the GlpF1/F4 group of Lactobacillales. In conclusion, we have functionally analysed the largest set of bacterial MIPs and demonstrated that the lactic acid membrane permeability of bacteria can be regulated by aquaglyceroporins.