The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 x 10(9)PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8(+) T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8(-/-) mice, and partially blocked in CD4(-/-) mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity. 相似文献
Staphylococcus aureus and Escherichia coli are among the most prevalent species of gram-positive and gram-negative bacteria, respectively, that induce clinical mastitis. The innate immune system comprises the immediate host defense mechanisms to protect against infection and contributes to the initial detection of and proinflammatory response to infectious pathogens. The objective of the present study was to characterize the different innate immune responses to experimental intramammary infection with E. coli and S. aureus during clinical mastitis. The cytokine response and changes in the levels of soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), two proteins that contribute to host recognition of bacterial cell wall products, were studied. Intramammary infection with either E. coli or S. aureus elicited systemic changes, including decreased milk output, a febrile response, and induction of the acute-phase synthesis of LBP. Infection with either bacterium resulted in increased levels of interleukin 1beta (IL-1beta), gamma interferon, IL-12, sCD14, and LBP in milk. High levels of the complement cleavage product C5a and the anti-inflammatory cytokine IL-10 were detected at several time points following E. coli infection, whereas S. aureus infection elicited a slight but detectable increase in these mediators at a single time point. Increases in IL-8 and tumor necrosis factor alpha were observed only in quarters infected with E. coli. Together, these data demonstrate the variability of the host innate immune response to E. coli and S. aureus and suggest that the limited cytokine response to S. aureus may contribute to the well-known ability of the bacterium to establish chronic intramammary infection. 相似文献
Journal of Public Health - To investigate the attack rate of active tuberculosis (TB) cases and detection rate of latent tuberculosis infection (LTBI) cases, and to identify possible factors... 相似文献
Intradialytic hypotension (IDH) is a serious complication in dialysis patients. Diuretics might reduce the incidence of IDH by decreasing ultrafiltration. However, the effect of diuretics on IDH in maintenance dialysis patients is still unclear.
Methods
We searched Medline, Embase, the Cochrane Library, China National Knowledge Infrastructure and clinical trials registries from 1945 to May 2019. Randomized controlled trials (RCTs) or observational studies about IDH in maintenance dialysis with diuretics were included.
Results
Seven studies including 28,226 patients were included, of which 4 were RCTs involving mineralocorticoid receptor antagonists (MRAs) and 3 were observational studies involving loop diuretics. There was a trend that a lower incidence rate of IDH in maintenance dialysis patients who used loop diuretics than control, although the result was not statistically significant (OR 0.65, 95% CI 0.34–1.22, P?=?0.18). Similarly, lower incidence rate of all-cause mortality (OR 0.92, 95% CI 0.87–0.99; P?=?0.02) and cardiovascular (CV) mortality (OR 0.86, 95% CI 0.75–0.99, P?=?0.03) in dialysis patients who used loop diuretics than control. On the contrary, there were no significant difference in the incidence of IDH (OR 1.35, 95% CI 0.78–2.34, P?=?0.29) and all-cause mortality (OR 0.73, 95% CI 0.26–2.01; P?=?0.54) and CV mortality (OR 0.57, 95% CI 0.14–2.25; P?=?0.42) in maintenance dialysis patients who used MRAs compared with control.
Conclusion
Loop diuretics, but not MRAs, might have a potential benefit to reduce the incidence rate of IDH, all-cause mortality and CV mortality. More high-quality studies are needed to strengthen the arguments.
We aimed to compare intracavernosal injection (ICI), tail vein injection (IV), and periprostatic injection (PPI) of adipose-derived stem cells (ADSCs) for their ability to improve erectile function in cavernous nerve injury-induced erectile dysfunction (CNIED) rats and to explore the possible mechanism. Eighty-four male SD rats were divided into the sham group (n = 6), BCNI group (bilateral CN crush injury, n = 6), PBS-ICI group (n = 6), PBS-IV group (n = 6), PBS-PPI group (n = 6), ADSC-ICI group (n = 18), ADSC-IV group (n = 18) and ADSC-PPI group (n = 18). ADSCs were labelled with 5-ethynyl-2′-deoxyuridine (EdU), and six rats each in the ADSC-ICI group, ADSC-IV group, and ADSC-PPI group were sacrificed 2, 7, and 28 days after injection. EdU-labelled ADSCs were tracked by immunofluorescence staining. The intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio, neuronal nitric oxide synthase (nNOS)-positive nerve fibres in the dorsal penile nerve and the smooth muscle/collagen ratio in the cavernosum between groups were also evaluated. ADSCs can significantly improve erectile function through ICI or IV. The two are similar in efficacy and superior to PPI. The mechanism may be that after CN injury, ADSCs are recruited to around the MPG and secrete a variety of neurotrophic factors that promote the repair of the CN, thereby improving erectile function. 相似文献