Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics. It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors, especially when combined with traditional therapy, such as radiotherapy. According to their different biological characteristics, bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues. Moreover, genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy. In this review, we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years, expounding that the bacteria, bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment (TME) and immune effects. Furthermore, some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory, anti-oxidation and apoptosis inhibition. In conclusion, the prospect of bacteria in radiotherapy will be very extensive, but its biological safety and mechanism need to be further evaluated and studied.

The aim of this study is to evaluate the effectiveness and safety of China Savin pollen extract which was used for skin prick test (SPT) in the diagnosis of China Savin pollen allergy. Patients with diagnosis of allergic diseases were collected from Allergy Department of Peking Union Medical College Hospital. All patients were given SPT with China Savin pollen extract, and the mean wheal diameter (MWD) was measured after 15 minutes. Receiver operating characteristic curve (ROC) analysis was performed based on the results of serum specific immunoglobulin E (sIgE). The effectiveness of SPT in the diagnosis of China Savin pollen allergy was evaluated under different diagnostic cutoff values. Adverse events were also recorded to evaluate the safety. A total of 1 029 patients were enrolled in this study without drop out case. There were 1 007 patients in full analysis set (FAS) and 765 patients in per protocol analysis set (PPS). The elimination rate was 25.66%. The area under the ROC curve of FAS is 0.814 (95%: 0.788-0.839); which of PPS is 0.829 (95%: 0.801-0.857). Based on the ROC curve of PPS, the optimal and the 95% specificity diagnostic cutoff values of MWD were 3.25 mm and 4.75 mm respectively. Based on different diagnostic cutoff value (3.00, 3.25 and 4.75 mm), the sensitivities of SPT with China Savin pollen extract were 0.740 0 (95%: 0.701 6-0.778 4), 0.700 (95%: 0.659 8-0.740 2) and 0.532 (95%: 0.488 3-0.575 7) respectively, whereas the specificity was gradually increased in sequence, which was 0.769 8 (95%: 0.719 1-0.820 5), 0.826 4 (95%: 0.780 8-0.872 0) and 0.950 9 (95%: 0.924 9-0.976 9) respectively. There were 7 adverse events observed among 6 patients (rate: 0.583%, 6/1 029). The manifestation was mild. There was no severe adverse event. SPT with China Savin pollen extract is an effective and safe tool for the diagnosis of China Savin pollen allergy. The effectiveness of diagnosis could be improved based on integration of medical history and different diagnostic threshold values of SPT.
Allergens ; adverse effects ; China ; Humans ; Immunoglobulin E ; Pollen ; adverse effects ; Rhinitis, Allergic, Seasonal ; diagnosis ; Skin Tests

AIM:To investigate the effect of insulin on vascular smooth muscle cells (VSMCs) proliferation and to evaluate the intracellular signaling pathways involved.METHODS:VSMCs separated from Sprague-Dawley rats were used in this study. The proliferation of VSMCs induced by insulin was assayed by [3H]-thymidin incorporation. The protein expression and activity of p-ERK1/2 were determined by immunblot and [?-32P]ATP incorporation.RESULTS:Insulin induced cell proliferation in a concentration-dependent manner. The proliferative effect of insulin on VSMCs was inhibited partly by LY294002 (48.8%),an inhibitor of PI-3 kinase,and the ERK1/2 inhibitor PD98059 (43.6%),respectively. Moreover,phosphorylation of ERK1/2 and activity of ERK1/2 induced by insulin were also inhibited partly by LY294002.CONCLUSION:PI-3 kinase and ERK1/2 are involved in insulin induced VSMCs proliferation.