Vulvovaginal candidiasis (VVC) is a common observed infection, affecting approximately 75% of women of reproductive age. Drug resistance represents a troublesome stumbling block associated with VVC therapy. Thus the aim of the present study was to provide information regarding the selection of potential drug targets for VVC. CXCR3-, CXCR4-, or CXCR/CXCR4 double-deficient mouse models of VVC were subsequently established, with changes to the load of Candida Albicans evaluated accordingly. The biological behaviors of the vaginal epithelial cells were characterized in response to the CXCR3-, CXCR4-, or CXCR3/CXCR4 double-knockout in vivo. Our initial observations revealed that in mice with VVC, CXCR3-, CXCR4-, or CXCR3 - CXCR4 double-knockout resulted in a decreased load of C. Albicans as well as reduced levels and proportion of Th17 cells. Proinflammatory cytokine production was found to be inhibited by CXCR3-, CXCR4-, or CXCR3/CXCR4 double-knockout whereby the mRNA and protein expressions CXCR3, CXCR4, IL-17, IL-6, and TNF-α exhibited decreased levels. CXCR3-, CXCR4-, or CXCR3/CXCR4 double-knockout appeared to function as positive proliferation factors, while playing a negative role in the processes of apoptosis and the cell cycle of vaginal epithelial cells. Taken together, the key findings of the study suggested that CXCR3/CXCR4 double-knockout could act to hinder the progression of VVC, highlighting its promise as a novel therapeutic target in the treatment of VVC. CXCR3 and CXCR4 genes may regulate Th17/IL-17 immune inflammatory pathways to participate in antifungal immunity. 相似文献
Prediction of soft tissue aesthetics is important for achieving an optimal outcome in orthodontic treatment planning. Previously, applicable procedures were mainly restricted to 2-D profile prediction. In this study, a generic 3-D finite element (FE) model of the craniofacial soft and hard tissue was constructed, and individualisation of the generic model based on cone beam CT data and mathematical transformation was investigated. The result indicated that patient-specific 3-D facial FE model including different layers of soft tissue could be obtained through mathematical model transformation. Average deviation between the transformed model and the real reconstructed one was 0.47?±?0.77?mm and 0.75?±?0.84?mm in soft and hard tissue, respectively. With boundary condition defined according to treatment plan, such FE model could be used to predict the result of orthodontic treatment on facial soft tissue. 相似文献
Knowledge about the clinical and laboratory characteristics and prognosis of Talaromyces marneffei infection in children is limited. A retrospective study was conducted on pediatric patients with disseminated T. marneffei infection in a clinical setting. Extracted data included demographic information (age and sex), clinical features, laboratory findings, treatment, and prognosis. Eleven HIV-negative children were enrolled. The male/female ratio was 8:3. The median age of onset was 17.5 months (3.5–84 months). The mortality rate in these children was 36.36% (4/11). Seven children had underlying diseases. All of the children had multiple immunoglobulin abnormalities and immune cell decline. Ten children received voriconazole treatment, and most of the children (7/10) had a complete response to therapy at primary and long-term follow-up assessment; only three children died of talaromycosis. One patient recovered from talaromycosis but died of leukemia. The child who received itraconazole treatment also showed clinical improvement. No adverse events associated with antifungal therapies were recorded during and after the treatment. Talaromycosis is an indicator disease for undiagnosed severe immunodeficiencies in children. Awareness of mycoses in children by pediatricians may prompt diagnosis and timely treatment. Voriconazole is an effective, well-tolerated therapeutic option for disseminated T. marneffei infection in non-HIV-infected children.
Anchorage loss is very disturbing for orthodontists and patients during orthodontic treatment, which usually results in bad treatment effects. Despite the same treatment strategy, different patients show different tendencies toward anchorage loss, which influences the treatment results and should preferably be predicted before the treatment is begun. However, relatively little research has been conducted on which patients are more likely to lose anchorage. The mesial tipping of the first molar marks the onset of anchorage loss, and changes in the angulation of the first molar are closely related to anchorage loss. This cross-sectional study aimed to determine how the mesiodistal angulation of the upper first molars changes during general orthodontic treatment and to identify the individual physiologic factors leading to these changes in a large sample of 1403 patients with malocclusion. The data indicate that the upper first molars tend to be tipped mesially during orthodontic treatment, and this constitutes a type of anchorage loss that orthodontists should consider carefully. Compared to treatment-related factors, patients'' physiologic characteristics have a greater influence on changes in the angulation of the upper first molars during orthodontic treatment. The more distally tipped the upper first molars are before treatment, the more they will tip mesially during treatment. Mesial tipping of the upper first molars, and therefore, anchorage loss, is more likely to occur in adolescents, males, patients with class II malocclusion and patients who have undergone maxillary premolar extraction. This finding is of clinical significance to orthodontists who wish to prevent iatrogenic anchorage loss by tipping originally distally tipped upper molars forward, and provides a new perspective on anchorage during orthodontic treatment planning. 相似文献
Human dihydrofolate reductase (DHFR) is a critical target in cancer chemotherapy. Previous studies showed that an 82-nt RNA fragment within the DHFR mRNA protein-coding region functions as a DHFR cis-acting response element. In this study, we further investigated the key elements contained within this sequence that are required for the DHFR mRNA-DHFR protein interaction. Using enzymatic foot-printing assays and RNA-binding experiments, we isolated a 27-nt sequence (DHFR27, corresponding to nts 407-433), which bound with high affinity and specificity to human DHFR to form a ribonucleoprotein complex. In vivo transient transfection experiments using a luciferase reporter system revealed that DHFR27 RNA could repress the luciferase expression in a DHFR-dependent manner when placed upstream of luciferase mRNA. This work provides new insights into the essential molecular elements that mediate RNA-protein interactions. 相似文献