Artesunate alleviates the inflammatory response of ulcerative colitis by regulating the expression of miR-155.

CONTEXT: Ulcerative colitis (UC) is a recrudescent and chronic inflammatory disease. Artesunate (ART) has shown its anti-inflammatory and antioxidative properties in severe diseases, including UC. OBJECTIVE: The present study investigates the molecular mechanisms for effects of ART on UC, and the role of miR-155 in this process. MATERIALS AND METHODS: The in vitro UC model was established by using lipopolysaccharide (LPS)-induced RAW264.7 cells. For BALB/c mice model, different concentrations/doses of ART were treated once a day for 7 days. The apoptosis and viability were measured by CCK-8 and flow cytometry assay, respectively. The expressions and concentrations of inflammatory factors were detected by qRT-PCR and ELISA, respectively. Colon tissues of mice were used for detecting the activity of MPO, and the histological changes were observed by H&E staining. RESULTS: The IC50 of ART for RAW264.7 cells was 107.3 µg/mL. In LPS-induced cells, ART treatment inhibited the cell apoptosis and promoted cell viability compared with the model group. Besides, ART treatment also reduced the expressions of pro-inflammatory factors and miR-155. However, overexpression of miR-155 showed opposite effects and attenuated the effects of ART. Meanwhile, inhibiting miR-155 expression also improved the inflammatory response induced by LPS. In UC mice model, ART treatment also alleviated the mice's survival and alleviated the inflammatory response. In addition, the expression of p-NF-κB was suppressed by ART. CONCLUSION: ART reduced the inflammatory response by inhibiting the expression of miR-155 in UC to inhibit the NF-κB pathway. This research showed ART might have potential in UC treatment.

MiR-155 aggravated septic liver injury by oxidative stress-mediated ER stress and mitochondrial dysfunction via targeting Nrf-2.

OBJECTIVE: Liver is uniquely vulnerable during sepsis. MicroRNA-155 (miR-155) is confirmed to play crucial roles in septic liver injury. The present study aims to investigate the mechanisms of miR-155 in septic liver injury. METHODS: The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) in mice. Mice were divided into four groups: Vehicle, miR-155 antagomir, LPS, LPS+ miR-155 antagomir. The survival rate and body weight were monitored. Liver injury was assessed by H&E staining. The levels of serum ALT and inflammatory cytokines were determined by ELISA kits. Oxidative stress was detected by MDA and SOD detection kits. The miR-155, Nrf-2, and markers related to oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial injury and apoptosis were detected by western blotting and qPCR. Apoptosis in liver tissues was detected by TUNELstaining. RESULTS: MiR-155 antagomir alleviated liver injury as evidenced by enhancing survival rate and body weight, inhibiting inflammatory cell infiltration, liver cells necrosis and decreasing ALT level. The productions of TNF-α, IL-6 were suppressed, while anti-inflammatory cytokine IL-10 was promoted by miR-155 antagomir. Oxidative stress was inhibited by miR-155 antagomir via enhancing nuclear factor, erythroid 2-like 2 (Nrf-2) expression. ER stress and Cytochrome C (Cyto-C) release were restrained by miR-155 antagomir. Sepsis-induced apoptosis was repressed by miR-155 antagomir as manifested by the decreased levels of Bax, cleaved caspase-12, 9 and 3, and increased levels of Bcl-2 and uncleaved PARP. CONCLUSION: MiR-155 antagomir relieved septic liver injury through inhibiting oxidative stress-mediated ER stress, mitochondrial dysfunction and apoptosis via targeting Nrf-2, suggesting miR-155 as a therapeutic target for septic liver injury.

Case report: Features of hand, foot and mouth disease in neonates.

RATIONALE: Hand, foot and mouth disease (HFMD) is caused by enterovirus. The virus may exist in secretions. PATIENT CONCERNS: Five neonates had symptoms of fever and maculopapular rashes involving face, trunk, breech, arms, and legs, especially scattering on palms and feet. Blood, oropharyngeal fluid, urine, and cerebrospinal fluid (CSF) samples were collected and detected for further diagnoses with the consent of the infants' parents. Some of them suffered aseptic meningitis. DIAGNOSES: They were diagnosed as HFMD with CSF enterovirus positive. INTERVENTIONS: All of them continued breastfeed. Water bag was used during the pyrogenic stage. Antibiotics were administrated at first and withdrawn as soon as possible. OUTCOMES: None of them developed into brainstem encephalitis or pulmonary edema and they all recovered well. LESSONS: HFMD is more common in neonates than it has been thought. Enterovirus may exist in neonatal CSF and cause CSF cell to increase similar to purulent meningitis. Medical history, physical examination, and CSF enterovirus detection are important in making correct diagnosis. Unlike bacterial infection, HFMD is a self-limited disease. Once HFMD is determined and bacterial infection is ruled out, antibiotics should be avoided.

Risk factors that predict the requirement of aggressive therapy among Chinese patients with Crohn's disease.

OBJECTIVES: Crohn's disease is now increasingly considered as a disabling disease. Conventionally, the disease is managed by step-up therapy. In recent years, the top-down strategy has been proposed and is thought to benefit the patients in whom the condition is likely to rapidly deteriorate toward disabling. However, this strategy has severe adverse effects which have to be weighed against its benefits. The aim of this study is to identify the risk factors that can predict the requirement of top-down therapy among Chinese patients. METHODS: We included 207 Chinese patients who had histories of Crohn's disease for ≥ 5 years, or those who had Crohn's disease for <5 years and at least one criterion of disabling disease. The risk factors related to the 5-year disabling course and the 2-year disabling course of Crohn's disease were separately analyzed in the same cohort by logistic regression. RESULTS: Among the 207 patients, the rate of disabling disease was 80.19% for 5-year, and 71.01% for 2-year. The risk factors of age <40 years at diagnosis, steroids requirement for treating acute exacerbation, and presence of perianal disease at diagnosis were significantly associated with a 5-year disabling course. In the same cohort, the risk factors related to 2-year disabling course were likewise steroids requirement for treating acute exacerbation and presence of perianal disease at diagnosis. CONCLUSION: The risk factors associated with disabling Crohn's disease, which entails the requirement of top-down therapy in Chinese patients, are requirement of steroids for treating acute exacerbation and the presence of perianal disease at diagnosis.