Sepsis is a systemic inflammatory response that may be induced by trauma, infection, surgery, and burns. With the aim of discovering novel treatment targets for sepsis, this current study was conducted to investigate the effect and potential mechanism by which microRNA‐30a (miR‐30a) controls sepsis‐induced liver cell proliferation and apoptosis. Rat models of sepsis were established by applying the cecal ligation and puncture (CLP) method to simulate sepsis models. The binding site between miR‐30a and suppressor of cytokine signaling protein 1 (SOCS‐1) was determined by dual luciferase reporter gene assay. The gain‐of‐and‐loss‐of‐function experiments were applied to analyze the effects of miR‐30a and SOCS‐1 on liver cell proliferation and apoptosis of the established sepsis rat models. The expression of miR‐30a, SOCS‐1, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), Bcl‐2 associated X protein (Bax), B cell lymphoma‐2 (Bcl‐2), toll‐like receptor 4 (TLR4), and high‐mobility group box 1 (HMGB1), and the extent of JAK2 and STAT3 phosphorylation were all determined. Sepsis led to an elevation of miR‐30a and also a decline of SOCS‐1 in the liver cells. SOCS‐1 was negatively regulated by miR‐30a. Upregulated miR‐30a and downregulated SOCS‐1 increased the expression of JAK2, STAT3, Bax, TLR4, and HMGB1 as well as the extent of JAK2 and STAT3 phosphorylation whereas impeding the expression of SOCS‐1 and Bcl‐2. More important, either miR‐30a elevation or SOCS‐1 silencing suppressed liver cell proliferation and also promoted apoptosis. On the contrary, the inhibition of miR‐30a exhibited the opposite effects. Altogether, we come to the conclusion that miR‐30a inhibited the liver cell proliferation and promoted cell apoptosis by targeting and negatively regulating SOCS‐1 via the JAK/STAT signaling pathway in rats with sepsis.

Background Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis. Methods First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3. Results Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway. Conclusion Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis.

As a serious and elusive syndrome caused by infection, sepsis causes a high rate of mortality around the world. Our investigation aims at exploring the role and possible mechanism of specificity protein-1 (SP1) in the development of sepsis. A mouse model of sepsis was established by cecal ligation perforation, and a cellular model was stimulated by lipopolysaccharide (LPS), followed by determination of the SP1 expression. It was determined that SP1 was poorly expressed in the intestinal tissues of septic mice and LPS-treated cells. Next, we examined the interactions among SP1, histone deacetylase 4 (HDAC4), and high mobility group box 1 (HMGB1) and found that SP1 bound to the HDAC4 promoter to upregulate its expression, thereby promoting the deacetylation of HMGB1. Meanwhile, gain- or loss-of-function approaches were applied to evaluate the intestinal barrier dysfunction, oxidative stress, and inflammatory response. Overexpression of SP1 or underexpression of HMGB1 was observed to reduce intestinal barrier dysfunction, oxidative stress, and inflammatory injury. Collectively, these experimental data provide evidence reporting that SP1 could promote the HDAC4-mediated HMGB1 deacetylation to reduce intestinal barrier dysfunction, oxidative stress, and inflammatory response induced by sepsis, providing a novel therapeutic target for sepsis prevention and treatment.

Patient: Female, 65Final Diagnosis: Adrenocortical insufficiencySymptoms: Anorexia and jaundiceMedication: Glucocorticoid replacementClinical Procedure: —Specialty: Gastroenterology and HepatologyObjective:Challenging differential diagnosisBackground:Adrenal insufficiency is mainly due to insufficient adrenal corticosteroid hormones secretion by the adrenal cortex, which leads to clinical manifestations such as weakness, weight loss, hyperpigmentation, hypotension, and vomiting. However, the clinical manifestations of adrenocortical insufficiency may be atypical: anorexia, ascites, impaired liver function, and alacrima have been reported. Jaundice and anorexia presenting together in the same patient as the main symptoms are rare.Case Report:We present a rare case of a 65-year-old woman diagnosed as having adrenocortical insufficiency with chief complaints of anorexia and jaundice. The patient had a history of hiatus hernia and gastroesophageal reflux disease, which can easily lead to a misdiagnosis in clinical practice, which is what happened with this patient at the beginning in our hospital and in the other hospitals that treated her previously. Hiatus hernia was considered the mostly likely cause of her vomiting, and a laparotomy was done to repair the hernia at the local hospital. However, there was no improvement. After regular glucocorticoid replacement, the patient’s symptoms all soon disappeared.Conclusions:Adrenal insufficiency can atypically present as anorexia and jaundice. In order to avoid misdiagnosis, physicians should pay attention to these atypical symptoms.