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INTRODUCTION: Rickettsioses are diseases caused by intracellular Gram-negative bacteria of the Rickettsiaceae family and transmitted through the bite of infected ticks or mites. AIM OF STUDY: To investigate the clinical and subclinical characteristics and prognostic severe factors of the disease caused by Rickettsiaceae. METHODS: A prospective, descriptive cross-sectional study was conducted at Department of Infectious Diseases of two military hospitals in Northern Vietnam from May 2013 to June 2019, in which 88 adult febrile patients caused by Orientia tsutsugamushi (50 patients) or Rickettsia spp. (38 patients) were enrolled. We recorded information regarding epidemiological characteristics (age, geography, residence, occupation), medical history, clinical and subclinical findings, life-threatening complications during treatment, outcomes and some factors predicting serious life-threatening complications in a case record form. RESULTS: Scrub typhus (ST) patients had eschar (70%), skin-conjunctiva congestion (60%) and lymphadenopathy (44%). Rickettsia patients had a higher rate of maculopapular rash (39.5%), no ulcers and no lymphadenopathy detected. The majority of patients had elevated PCT >0.05 ng/µL and increase in liver enzymes and thrombocytopenia. Major prognostic factors for severe complications included diffuse infiltrates on lung X-ray (OR: 19.5; p = 0.014), coarse crackles (OR: 18; p = 0.016), respiratory rate ≥25 cycles/minute (OR: 18; p = 0.016), shortness of breath (OR: 7.44; p = 0.003), pleural fluid (OR: 4.3; p = 0.035) and increase in AST ≥ 200 UI/l (OR: 4.42; p = 0.012). The PCT value is able to distinguish between the two groups with quite high reliability (the area under the ROC curve is 0.75). CONCLUSION: Eschar and peripheral lymphadenopathy were two valuable clinical symptoms for the diagnosis of scrub typhus and distinguishing 2 groups of diseases. Respiratory distress, increase in AST ≥ 200 UI/l and level of PCT were used as major prognostic factors in patients with Rickettsiaceae.
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The aberrant activation of Wnt/ß-catenin signaling plays an important role in the carcinogenesis and progression of hepatocellular carcinoma (HCC). Therefore, the Wnt/ß-catenin signaling molecules are attractive candidates for the development of targeted therapies for this disease. The present study showed that destruxin B (DB) inhibits the proliferation and induces the apoptosis of HCC cells by decreasing the protein expression of anti-apoptotic Bcl-2 and Bcl-xL and increasing the expression of the proapoptotic protein Bax. More importantly, DB also attenuates Wnt-signaling in HCC cells by downregulating ß-catenin, Tcf4, and ß-catenin/Tcf4 transcriptional activity, which results in the decreased expression of ß-catenin target genes, such as cyclin D1, c-myc, and survivin. Furthermore, DB affects the migratory and invasive abilities of Sk-Hep1 cells through the suppression of markers of the epithelial-mesenchymal transition (EMT). A synergistic anti-proliferative and migratory effect was achieved using the combination of DB and sorafenib in Sk-Hep1 cells. In conclusion, DB acts as a novel Wnt/ß-catenin inhibitor and reduces the aggressiveness and invasive potential of HCC by altering the cells' EMT status and mobility. DB in combination with sorafenib may be considered for future clinical use for the management of metastatic HCC.