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Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality. 5-Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation. The aim of this study is to investigate the role of 5-HT on cecal ligation and puncture- (CLP-) induced sepsis in the mouse model. CLP was performed on C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout (KO) mice. The results showed that the 5-HT-sufficient group mice had a significantly lower survival rate than the 5-HT-deficient group in CLP-induced sepsis and septic shock. The KO-CLP sepsis group received a lower clinical score than the WT-CLP sepsis group. Meanwhile, the body temperature of mice in the KO-CLP sepsis group was higher than that in the WT-CLP sepsis group and was much closer to the normal body temperature 24 hours after CLP. The tissue histopathology analysis revealed that 5-HT markedly exacerbated histological damages in the peritoneum, lung, liver, kidney, intestinal tissue, and heart in sepsis. Moreover, significant lower levels of TNF-α, IL-6, bacterial loads, MPO, and ROS were discovered in the KO-CLP sepsis group in contrast to the WT-CLP sepsis group. In conclusion, 5-HT drives mortality and exacerbates organ dysfunction by promoting serum cytokines and bacterial loads as well as facilitating oxidative stress in the process of sepsis.

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Acetaminophen (APAP) overdose is a major cause of acute liver failure. Peripheral 5-hydroxytryptamine (serotonin, 5-HT) is a cytoprotective neurotransmitter which is also involved in the hepatic physiological and pathological process. This study seeks to investigate the mechanisms involved in APAP-induced hepatotoxicity, as well as the role of 5-HT in the liver's response to APAP toxicity. We induced APAP hepatotoxicity in mice either sufficient of serotonin (wild-type mice and TPH1-/- plus 5- Hydroxytryptophan (5-HTP)) or lacking peripheral serotonin (Tph1-/- and wild-type mice plus p-chlorophenylalanine (PCPA)).Mice with sufficient 5-HT exposed to acetaminophen have a significantly lower mortality rate and a better outcome compared with mice deficient of 5-HT. This difference is at least partially attributable to a decreased level of inflammation, oxidative stress and endoplasmic reticulum (ER) stress, Glutathione (GSH) depletion, peroxynitrite formation, hepatocyte apoptosis, elevated hepatocyte proliferation, activation of 5-HT2B receptor, less activated c-Jun NH2-terminal kinase (JNK) and hypoxia-inducible factor (HIF)-1α in the mice sufficient of 5-HT versus mice deficient of 5-HT. We thus propose a physiological function of serotonin that serotonin could ameliorate APAP-induced liver injury mainly through inhibiting hepatocyte apoptosis ER stress and promoting liver regeneration.

BackgroundSialylated glycoconjugates play important roles in physiological and pathological processes. However, available sialylated oligosaccharides source is limited which is a barrier to study their biological roles. This work reports an efficient approach to produce sialic acid-modified lactuloses and investigates their inhibitory effects on Staphylococcus aureus (S. aureus).MethodsA one-pot two-enzyme (OPTE) sialylation system was used to efficiently synthesize sialylated lactuloses. Silica gel flash chromatography column was employed to purify the sialylated products. The purity and identity of the product structures were confirmed with mass spectrometry (MS) and nuclear magnetic resonance (NMR). The inhibitory effect of sialylated lactuloses against S. aureus was evaluated by using microplate assay, fluorescence microscopy, DAPI (4',6-diamidino-2-phenylindole) fluorescence staining and protein leakage quantification.ResultsNeu5Ac-containing sialylated lactuloses with either α2,3- or α2,6-linkages were efficiently synthesized via an efficient OPTE sialylation system using α-2,3-sialyltransferase or α-2,6-sialyltransferase, respectively. Neu5Ac-α2,3-lactulose and Neu5Ac-α2,6-lactulose significantly inhibited the growth of S. aureus. Fluorescence microscopy and DAPI fluorescence staining indicated that the sialylated lactuloses might disrupt nucleic acid synthesis of S. aureus.ConclusionsNeu5Ac-containing sialylated lactuloses had higher antibacterial activity against S. aureus than non-sialylated lactulose. The inhibitory effect of Neu5Ac-α2,3-lactulose was superior to that of Neu5Ac-α2,6-lactulose. The sialylated lactuloses might inhibit S. aureus by causing cell membrane leakage and disrupting nucleic acid synthesis.