OBJECTIVEB lymphocytes play an important role in the immunopathogenesis of autoimmune diabetes. We hypothesized that the altered B-cell subset phenotype is associated with autoimmune diabetes.RESEARCH DESIGN AND METHODSPatients with type 1 diabetes (T1D) (n = 81), latent autoimmune diabetes in adults (LADA) (n = 82), or type 2 diabetes (T2D) (n = 95) and healthy control subjects (n = 218) with normal glucose tolerance (NGT) were recruited. We determined the percentage of circulating B-lymphocyte subsets, including CD19+CD23−CD21+ (marginal zone B [MZB]), CD19+CD23+CD21− (follicular B [FoB]), and CD19+CD5+CD1dhi (interleukin-10–producing regulatory B [B10]) cells by flow cytometry.RESULTSPatients with T1D or LADA had increased percentages of MZB cells and decreased percentages of FoB cells compared with healthy control subjects with NGT and patients with T2D. Moreover, patients with T1D showed the lowest frequency of B10 cells compared with patients with LADA or T2D, whereas healthy control subjects expressed the highest frequency of B10 cells. Of note, the frequency of MZB cells was negatively associated and the frequency of FoB cells was positively associated with fasting C-peptide (FCP). The frequency of B10 cells was positively correlated with FCP and negatively correlated with hemoglobin A1c.CONCLUSIONSThe data show that patients with T1D or LADA express an altered frequency of B-cell subsets, which is associated with islet function and glycemia. These findings suggest that B lymphocytes may be involved in loss of self-tolerance and β-cell destruction and could be used as a biomarker and potential target for immunological intervention.
Influenza is a major public health concern, and the high mortality rate is largely attributed to secondary bacterial infections. There are several mechanisms through which the virus increases host susceptibility to bacterial colonization, but the micro-environment in lower respiratory tract (LRT) of host, infected with influenza virus, is unclear. To this end, we analyzed the LRT microbiome, transcriptome of lung and metabolome of bronchoalveolar lavage fluid (BALF) in mice inoculated intra-nasally with H1N1 to simulate human influenza, and we observed significant changes in the composition of microbial community and species diversity in the acute (7 days post inoculation or dpi), convalescent (14 dpi) and the recovery (28 dpi) periods. The dominant bacterial class shifted from Alphaproteobacteria to Gammaproteobacteria and Actinobacteria in the infected mice, with a significant increase in the relative abundance of anaerobes and facultative anaerobes like Streptococcus and Staphylococcus. The dysbiosis in the LRT of infected mice was not normalized even in the recovery phase of the infection. In addition, the infected lung transcriptome showed significant differences in the expression levels of genes associated with bacterial infection and immune responses. Finally, the influenza virus infection also resulted in significant changes in the metabolome of the BALF. These alterations in the microbiome, transcriptome, and metabolome of infected lungs were not only appeared at the acute period, but also observed at the recovery period. Furthermore, the infection of influenza virus induced a long-term effect in LRT micro-environmental homeostasis, which may give a chance for the invasion of potential pathogens.
Background: Breast cancer is the leading cause of cancer death in women. Chemotherapy to inhibit the proliferation of cancer cells is considered to be the most important therapeutic strategy. The development of long-circulating PEG and targeting liposomes is a major advance in drug delivery. However, the techniques used in liposome preparation mainly involve conventional liposomes, which have a short half-life, high concentrations in the liver and spleen reticuloendothelial system, and no active targeting. Methods: Four kinds of paclitaxel liposomes were prepared and characterized by various analytical techniques. The long-term targeting effect of liposomes was verified by fluorescence detection methods in vivo and in vitro. Pharmacokinetic and acute toxicity tests were conducted in ICR mice to evaluate the safety of different paclitaxel preparations. The antitumor activity of ES-SSL-PTX was investigated in detail using in vitro and in vivo human breast cancer MCF-7 cell models. Results: ER-targeting liposomes had a particle size of 137.93±1.22 nm and an acceptable encapsulation efficiency of 88.07±1.25%. The liposome preparation is best stored at 4°C, and is stable for up to 48 hrs. Cytotoxicity test on MCF-7 cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. We used the near-infrared fluorescence imaging technique to confirm that ES-SSL-PTX was effectively targeted and could quickly and specifically identify the tumor site. Pharmacokinetics and acute toxicity in vivo experiments were carried out. The results showed that ES-SSL-PTX could significantly prolong the half-life of the drug, increase its circulation time in vivo, improve its bioavailability and reduce its toxicity and side effects. ES-SSL-PTX can significantly improve the pharmacokinetic properties of paclitaxel, avoid allergic reaction of the original solvent, increase antitumor efficacy and reduce drug toxicity and side effects. Conclusion: ES-SSL-PTX has great potential for improving the treatment of breast cancer, thereby improving patient prognosis and quality of life.
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