Rare case of bacteremia due to Lysinibacillus sphaericus in a person living with HIV.

Lysinibacillus sphaericus, as an insect pathogen, is a ubiquitous Gram-positive bacterium present in the environment. It is often considered to be contaminating bacteria. L. sphaericus has been reported to cause infectious diseases in humans relatively rarely. We report a rare case of bacteremia due to L. sphaericus in a person living with HIV, which is also the first reported case of bacteremia caused by L. sphaericus in China. L. sphaericus easily causes infection in immunocompromised individuals. We found that L. sphaericus and Lysinibacillus fusiformis could not be distinguished by their 16S ribosomal RNA gene sequence. We performed a genome-wide analysis of the isolated strains of this case and predicted the virulence factors. Finally, L. sphaericus was confirmed. According to antimicrobial susceptibility test, the strain was found to be sensitive to levofloxacin and vancomycin but resistant to penicillin. Greater attention to L. sphaericus infection should be paid and immunocompromised populations should be protected from L. sphaericus infection.

The extract of Curcumae Longae Rhizoma suppresses angiogenesis via VEGF-induced PI3K/Akt-eNOS-NO pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumae Longae Rhizoma (CLR) is a safe natural herbal medicine, and which has been widely used for centuries as functional food and health products, but its effects on angiogenesis and related underlying mechanism remain unclear. AIM OF THE STUDY: The abnormal angiogenesis is closely related with various diseases, and therefore the precise control of angiogenesis is of great importance. The well-known angiogenic factor, vascular endothelial growth factor (VEGF), mediates angiogenesis and induces multiple signalling pathways via binding to VEGF receptor (VEGFR). The attenuation of VEGF-triggered angiogenic-related signalling pathways may relieve various diseases through suppression of angiogenesis. Here, we aimed to elucidate that CLR extract could exert striking anti-angiogenic activities both in vitro and in vivo. MATERIALS AND METHODS: The viability of human umbilical vascular endothelial cell (HUVEC) was examined by LDH and MTT assays. Migrative and invasive ability of the endothelial cells were independently evaluated by wound healing and transwell assays. The activities of CLR extract on in vitro angiogenesis was tested by tube formation assay. In vivo vascularization was determined by using zebrafish embryo model in the present of CLR extract. Western blotting was applied to determine the phosphorylated levels of VEGFR2, PI3K, AKT and eNOS. Besides, the levels of nitric oxide (NO) and reactive oxygen species (ROS) were separately evaluated by Griess assay and 2'7'-dichlorofluorescein diacetate reaction. In addition, the cell migrative ability of cancer cell was estimated by using cultured human colon carcinoma cells (HT-29 cell line), and immunofluorescence assay was applied to evaluate the effect of CLR extract on nuclear translocation of NF-κB p65 subunit in the VEGF-treated HT-29 cultures. RESULTS: CLR extract significantly suppressed a series of VEGF-mediated angiogenic responses, including endothelial cell proliferation, migration, invasion, and tube formation. Moreover, CLR extract reduced in vivo sub-intestinal vessel formation in zebrafish embryo model. Mechanistically, the extract of CLR attenuated the VEGF-triggered signalling, as demonstrated by decreased level of phosphorylated VEGFR2 and subsequently inactivated its downstream regulators, e.g. phospho-PI3K, phospho-AKT and phospho-eNOS. The production of NO and formation of ROS were markedly inhibited in HUVECs. Furthermore, CLR extract suppressed cell migration and NF-κB translocation in cultured HT-29 cells. CONCLUSIONS: These preclinical findings demonstrate that the extract of CLR remarkably attenuates angiogenesis and which has great potential as a natural drug candidate with excellent anti-angiogenic activity.

Circ_FURIN promotes trophoblast cell proliferation, migration and invasion in preeclampsia by regulating miR-34a-5p and TFAP2A.

Emerging evidence has shown that circular RNAs (circRNAs) play vital roles in the progression of diverse human diseases. However, the functions of circRNAs in preeclampsia (PE) are largely unknown. In this study, we aimed to explore the functions of the circRNA furin, paired basic amino acid cleaving enzyme (circ_FURIN) in PE development. qRT-PCR and western blot analyses were conducted to determine the levels of circ_FURIN, miR-34a-5p and transcription factor AP-2 alpha (TFAP2A). A Cell Counting Kit-8 (CCK-8) assay and a 5'-ethynyl-2'-deoxyuridine (EdU) incorporation assay were utilized to evaluate the cell proliferation ability. Transwell assays were adopted to estimate cell migration and invasion. A dual-luciferase reporter assay and an RNA pulldown assay were utilized to analyze the relationships among circ_FURIN, miR-34a-5p and TFAP2A. It was found that circ_FURIN was downregulated in PE placental tissues and hypoxia-treated placental trophoblast cells. Overexpression of circ_FURIN promoted trophoblast cell proliferation, migration and invasion under hypoxic conditions. Circ_FURIN functioned as the sponge for miR-34a-5p. MiR-34a-5p overexpression abrogated the effects of circ_FURIN on the proliferation, migration and invasion of trophoblast cells under hypoxic conditions. In addition, TFAP2A was demonstrated to be the target gene of miR-34a-5p. TFAP2A silencing ameliorated the promotive effects of miR-34a-5p inhibition on trophoblast cell proliferation, migration and invasion under hypoxic conditions. In conclusion, circ_FURIN enhanced trophoblast cell proliferation, migration and invasion under hypoxic conditions by elevating TFAP2A expression through sponging miR-34a-5p.

Lessons from an active surveillance pilot to assess the pneumonia of unknown etiology surveillance system in China, 2016: the need to increase clinician participation in the detection and reporting of emerging respiratory infectious diseases.

BACKGROUND: We sought to assess reporting in China's Pneumonia of Unknown Etiology (PUE) passive surveillance system for emerging respiratory infections and to identify ways to improve the PUE surveillance system's detection of respiratory infections of public health significance. METHODS: From February 29-May 29, 2016, we actively identified and enrolled patients in two hospitals with acute respiratory infections (ARI) that met all PUE case criteria. We reviewed medical records for documented exposure history associated with respiratory infectious diseases, collected throat samples that were tested for seasonal and avian influenza, and interviewed clinicians regarding reasons for reporting or not reporting PUE cases. We described and analyzed the proportion of PUE cases reported and clinician awareness of and practices related to the PUE system. RESULTS: Of 2619 ARI admissions in two hospitals, 335(13%) met the PUE case definition; none were reported. Of 311 specimens tested, 18(6%) were seasonal influenza virus-positive; none were avian influenza-positive. < 10% PUE case medical records documented whether or not there were exposures to animals or others with respiratory illness. Most commonly cited reasons for not reporting cases were no awareness of the PUE system (76%) and not understanding the case definition (53%). CONCLUSIONS: Most clinicians have limited awareness of and are not reporting to the PUE system. Exposures related to respiratory infections are rarely documented in medical records. Increasing clinicians' awareness of the PUE system and including relevant exposure items in standard medical records may increase reporting.