Serotonin Deficiency Exacerbates Acetaminophen-Induced Liver Toxicity In Mice

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

Case Report: A papillary thyroid microcarcinoma patient with skip lymph node metastasis and multiple distant metastasis

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Papillary thyroid microcarcinoma (PTMC) is defined as PTC with a diameter less than 1 centimeter. Most lymph nodes of PTC patients have metastasized to the central neck, and a few lymph nodes have metastasized to the lateral neck. Skip lymph node metastasis, that is, lateral cervical lymph node metastasis without central lymph node metastasis, is even less common. Additionally, distant metastasis of PTMC is also rare, mainly occurring in the lung and bone. Here, we reported a case of PTMC patient with skip lymph node metastasis and multiple distant metastasis. The patient presented with a huge shoulder mass and the primary tumor was found to originate from the thyroid. However, the patient only suffered with PTMC via postoperative pathological results, and interestingly, the patient only had skip lymph node metastasis. Thus, we should focus on PTMC patients with lateral cervical lymph nodes metastasis, especially those with skip metastasis. In addition, this case provides a new perspective for us to understand of skip lymph metastasis and distant metastasis of PTMC

5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice

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