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OBJECTIVE: Candida glabrata (C. glabrata) causes infections associated with severe sepsis and high mortality. This study describes the effects of micafungin (MCF), itraconazole (ICZ), and amphotericin B (AmB) on the function of macrophages during C. glabrata infection. METHODS: RAW264.1 macrophages were treated with MCF, ICZ, or AmB and then challenged with C. glabrata. Cytokines from infected macrophage supernatants and the levels of superoxide dismutase (SOD) in macrophages were measured at different time points after phagocytosis. RESULTS: The activity of SOD was significantly increased in RAW264.1 cells that phagocytized C. glabrata and reached a peak level at 6 hours (P < 0.05). ICZ and AmB did not affect the SOD activity in cells that phagocytized C. glabrata versus that in untreated macrophage. C. glabrata stimulated macrophages to secrete cytokines. Neither ICZ nor AmB affected the secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), or tumor necrosis factor-α (TNF-α) by C. glabrata-infected macrophages. However, MCF downregulated the secretion of TNF-α by infected macrophages and reduced the SOD activity of C. glabrata compared with those in untreated controls. CONCLUSION: Echinocandins may increase their antifungal efficacy by altering the innate immune response of macrophages and attenuating antioxidants of this organism.
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Background: Deep fungal infection is a type of life-threatening opportunistic infection. Its incidence has been increasing in recent years. This infection can affect the prognosis of patients, prolong hospital stays and raise costs for patients and their families. Objective: We aimed to understand the current situation of deep fungal infections in the First Affiliated Hospital of Kunming Medical University and to provide a basis for the clinical diagnosis and treatment of deep fungal infections. Methods: This was a retrospective analysis of 528,743 cases in the hospital from 2015 to 2019, including the epidemiological characteristics, treatment and prognosis of deep fungal infections. Results: A total of 274 cases (0.05%) with deep fungal infections were identified, accounting for 0.05% of the total number of hospitalizations. The incidence of deep fungal infections in the hospital showed an increasing trend from 2015 to 2019. The most commonly infected site was the respiratory tract (93.07%). Among patients with deep fungal infections, 266 specimens were positive for fungal culture, by which 161 cultured Candida albicans (C. albicans), accounting for 60.53%, the main pathogen causing deep fungal infection. From 2015 to 2019, the percentage of C. albicans cases showed a downward trend, while that of non-C. albicans showed an opposite trend. Antibiotics were the most common predisposing factor for deep fungal infections (97.45%). Among the underlying diseases of patients with deep fungal infections, infectious diseases (59.49%) were the most common. Those with underlying diseases such as renal insufficiency and neurological diseases had a worse prognosis. Indwelling catheters, nervous system disease and tumors were risk factors for a poor prognosis. Conclusions: We report for the first time the epidemiological data of deep fungal infections in a general hospital in southwestern China from 2015 to 2019. In the past 5 years, the number of patients with deep fungal infections in the First Affiliated Hospital of Kunming Medical University has been increasing. Although the clinical data are limited, these results can provide references for the diagnosis and treatment of deep fungal infections.
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Hospitales Generales , Micosis , Humanos , Incidencia , Pacientes Internos , Micosis/tratamiento farmacológico , Micosis/epidemiología , Micosis/microbiología , Estudios RetrospectivosRESUMEN
OBJECTIVE: To assess the distribution and systemic toxicity of podophyllotoxin-loaded nanostructured lipid carriers (POD-NLC) after topical application on the cervical mucosa in Tibet minipigs. METHODS: Twelve Tibet mini-pigs were randomized into test group and control group to receive topical application of 0.5% POD-NLC and 0.5% POD tincture, respectively, on the cervical mucosa. Cervical mucosal irritation, targeted distribution and systemic absorption of POD were observed at different time points within 24 h after the drug application. RESULTS: No local inflammation reaction was observed in the test group, while serious local irritations (swelling, blisters, blood blisters, erosion and ulceration) occurred in the control group. The fluorescence intensity of POD in the mucosal tissue reached the peak level at 4 h after drug application in the control group, while the POD fluorescence intensity increased slowly and reached the peak level at 16 h in the test group. The peak blood POD concentration occurred at 6 h after POD-NLC application in the test group (14.28∓0.33 ng/mL), as compared to 4 h in the control group (42.46∓0.32 ng/mL). At all the time points within 24 h, blood POD concentration remained significantly lower in the test group than in the control group (P<0.05), and the area under curve of blood POD concentration in the control group was 1.38-fold greater than that in the test group. CONCLUSION: POD-NLC allows sustained release of POD and achieves a higher POD concentration in the mucosal tissue without causing local irritation or obvious systemic toxicity in Tibet minipigs.
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Cuello del Útero/metabolismo , Portadores de Fármacos/farmacocinética , Membrana Mucosa/metabolismo , Podofilotoxina/farmacocinética , Animales , Femenino , Lípidos/química , Nanoestructuras/química , Tamaño de la Partícula , Porcinos , Porcinos Enanos , TibetRESUMEN
Although microRNA-1 (miR-1) is a known liver cancer suppressor, the role of miR-1 in apoptosis of hepatoma cells has remained largely unknown. Our study shows that ectopic miR-1 overexpression induced apoptosis of liver hepatocellular carcinoma (HepG2) cells. Apoptosis inhibitor 5 (API-5) was found to be a potential regulator of miR-1 induced apoptosis, using a bioinformatics approach. Furthermore, an inverse relationship between miR-1 and API-5 expression was observed in human liver cancer tissues and adjacent normal liver tissues. Negative regulation of API-5 expression by miR-1 was demonstrated to promote apoptosis of HepG2 cells. Our study provides a novel regulatory mechanism of miR-1 in the apoptosis of hepatoma cells.
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Proteínas Reguladoras de la Apoptosis/biosíntesis , Apoptosis , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroARNs/biosíntesis , Proteínas de Neoplasias/biosíntesis , Proteínas Nucleares/biosíntesis , ARN Neoplásico/biosíntesis , Proteínas Reguladoras de la Apoptosis/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , ARN Neoplásico/genéticaRESUMEN
To complement the molecular pathways contributing to Parkinson's disease (PD) and identify potential biomarkers, gene expression profiles of two regions of the medulla were compared between PD patients and control. GSE19587 containing two groups of gene expression profiles [6 dorsal motor nucleus of the vagus (DMNV) samples from PD patients and 5 from controls, 6 inferior olivary nucleus (ION) samples from PD patients and 5 from controls] was downloaded from Gene Expression Omnibus. As a result, a total of 1569 and 1647 differentially expressed genes (DEGs) were, respectively, screened in DMNV and ION with limma package of R. The functional enrichment analysis by DAVID server (the Database for Annotation, Visualization and Integrated Discovery) indicated that the above DEGs may be involved in the following processes, such as regulation of cell proliferation, positive regulation of macromolecule metabolic process, and regulation of apoptosis. Further analysis showed that there were 365 common DEGs presented in both regions (DMNV and ION), which may be further regulated by eight clusters of microRNAs retrieved with WebGestalt. The genes in the common DEGs-miRNAs regulatory network were enriched in regulation of apoptosis process via DAVID analysis. These findings could not only advance the understandings about the pathogenesis of PD, but also suggest potential biomarkers for this disease.