An atypical winter outbreak of hand, foot, and mouth disease associated with human enterovirus 71, 2010.

BACKGROUND: To analyze the epidemiological characteristics and pathogenic molecular characteristics of an hand, foot, and mouth disease (HFMD) outbreak caused by enterovirus 71 in Linyi City, Shandong Province, China during November 30 to December 28, 2010. METHODS: One hundred and seventy three stool specimens and 40 throat samples were collected from 173 hospitalized cases. Epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. RESULTS: Among the 173 cases reported in December 2010, the male-female ratio was 1.88: 1; 23 cases (13.3%) were severe. The majority of patients were children aged < 5 years (95.4%). Some patients developed respiratory symptoms including runny nose (38.2%), cough (20.2%), and sore throat (14.5%). One hundred and thirty eight EV71 positive cases were identified based on real time reverse-transcription PCR detection and 107 isolates were sequenced with the VP1 region. Phylogenetic analysis of full-length VP1 sequences of 107 Linyi EV71 isolates showed that they belonged to the C4a cluster of the C4 subgenotype and were divided into 3 lineages (Lineage I, II and III). The two amino acid substitutions (Gly and Gln for Glu) at position 145 within the VP1 region are more likely to appear in EV71 isolates from severe cases (52.2%) than those recovered from mild cases (8.3%). CONCLUSION: This outbreak of HMFD was caused by EV71 in an atypical winter. EV71 strains associated with this outbreak represented three separate chains of transmission. Substitution at amino acid position 145 of the VP1 region of EV71 might be an important virulence marker for severe cases. These findings suggest that continued surveillance for EV71 variants has the potential to greatly impact HFMD prevention and control.

Fasudil alleviates acetaminophen-induced liver injury via targeting Rhoa/ROCK signal pathway.

Fasudil is an inhibitor of Rhoa/ROCK signaling, which is involved in anti-inflammatory and anti-injury effects. The purpose of this study was to explore the effects of Fasudil on acetaminophen (APAP)-induced liver injury and reveal its potential molecular mechanism. In this study, C57BL/6 J mice were divided into different groups and treated with APAP and specified dose of Fasudil. HE staining was used to detect the changes of liver pathological tissues induced by APAP. ELISA assay was performed to detected the level of related factors. Western blot was used to detect the expressions of Rhoa, ROCK1, ROCK2. CD86 and CD6 were determined by RT-PCR and immunohistochemical staining detected the difference in CD86 expression. Rhoa/ROCK expression was increased in APAP-induced liver injury, and Fasudil targeted the expression of Rhoa/ROCK. Fasudil inhibits APAP-induced hepatic pathological changes and liver function injury. Fasudil inhibits the release of APAP-induced systemic inflammatory factors in liver tissue. Fasudil inhibits the activity of antioxidant enzymes, lipid peroxidation and macrophage infiltration induced by APAP in liver tissues. Fasudil alleviates APAP-induced liver injury via targeting Rhoa/ROCK signal pathway, indicating the possibility for clinical use of Fasudil in APAP-induced liver injury.

TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway.

Toll-like receptors (TLRs) are key members of innate immunity, involved in the defense against diseases, and evidence has revealed that TLR4/5 is involved in the carcinogenesis of hepatic cancer. TLR7 belongs to the TLR family, and its roles in immune-associated hepatic diseases have been well characterized; however, the consequences of agonist targeting of TLR7 in hepatic cancer have not previously been reported. The present study aimed to investigate the effects and underlying mechanisms of Imiquimod, a TLR7 agonist, on hepatic carcinogenesis by affecting the self-renewal of hepatic cancer stem cells. To detect the effects of this TLR7 agonist on hepatic cancer cells an MTT assay, mammosphere formation assay, ALDEFLUOR™ fluorescence-based stem cell sorting was used, and the potential signaling involved in the mechanism was investigated by western blot analysis. The TLR7 agonist Imiquimod demonstrated inhibitory effects on the cell proliferation and mammosphere formation of hepatic cells and stem cells, and decreased stem cell number (P<0.01). These effects may be achieved via the TLR7/IκB kinase/nuclear factor-κB/interleukin-6 signaling pathway, with decreased levels of Snail expression. The present study demonstrated the effects and mechanisms of the TLR7 agonist on hepatic cancer occurred via suppression of the self-renewal of cancer stem cells, indicating novel potential functions of the TLR7 agonist in the treatment of HCC.

Acylglycerol kinase promotes the proliferation and cell cycle progression of oral squamous cell carcinoma.

Cell proliferation is a major underlying cause of mortality amongst patients with oral squamous cell carcinoma (OSCC); however, the underlying mechanisms have remained to be elucidated. Acylglycerol kinase (AGK) is a multisubstrate lipid kinase, which is known to be associated with the progression of various types of human cancer. The present study aimed to investigate the role of AGK in cell proliferation and cell cycle progression in OSCC. The expression levels of AGK were detected in cancerous and adjacent normal tissue samples from four patients with OSCC undergoing surgical resection, and in OSCC cell lines, using the polymerase chain reaction (PCR) and western blot analysis. The effects of AGK on the proliferation and cell cycle progression of OSCC cells were assessed using a short hairpin RNA lentivirus or expressed-plasmid transfection. In addition, the expression levels of cyclin D1 and p21, as well as cell proliferation- and cell cycle-associated proteins were detected by PCR and western blotting. The results of the present study demonstrated that the expression levels of AGK were significantly higher in the cancerous tissues and OSCC cell lines, compared with the adjacent normal tissues and control cells, respectively. Furthermore, MTT and colony formation assays, in addition to flow cytometric analysis were conducted, in order to assess the role of AGK in cell proliferation and cell cycle progression. The cell proliferation and cell cycle progression of an established OSCC cell line were demonstrated to be decreased following AGK knockdown, and enhanced by AGK overexpression in vitro. Aberrant AGK expression in OSCC was shown to be associated with cell proliferation and cell cycle progression. The results of the present study provide evidence that AGK may promote cell proliferation and cell cycle progression in OSCC.