Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

Objective To investigate the combined value of multimodal functional magnetic resonance imaging(fMRI)and magnetic resonance spectroscopy(MRS)in the differential diagnosis of postoperative recur-rence and pseudoprogression(PsP)of glioma.Methods One hundred and four patients with glioma confirmed by surgical pathology were selected from our hospital from September 2021 to March 2024,and the patients were divided into recurrence group(n=70)and PsP group(n=34)according to the revised glioma treatment response assessment criteria.Another group of 73 patients with glioma were selected for model validation.The general data,apparent diffusion coefficient(ADC)of multimodal fMRI parameters,standardized cerebral blood volume(CBV)and MRS indexes of the two groups were compared.The influencing factors of postoperative glioma recurrence were analyzed by logistic regression,and clinical efficacy of the combined treatment in the diagnosis of postoperative glioma recurrence and PsP was analyzed by receiver operating curve(ROC).Results The level of ADC in the recurrence group was lower than that in the PsP group(P<0.05),and the levels of CBV,choline(Cho)/creatine(Cr)and Cho/N-acetylaspartic acid(NAA)were higher(P<0.05).Logistic regression analysis showed that the levels of ADC,CBV,Cho/Cr and Cho/NAA were risk factors for postoperative recurrence of glioma(P<0.05).ROC showed that the combined use of multimodal fMRI and MRS in the differential diagnosis of postoperative glioma recurrence and PsP had an AUC of 0.916,outperforming the diagnostic accuracy of each individual modality.Validation of the combined model constructed with multimodal fMRI and MRS yielded an AUC of 0.929,95%CI(0.844～0.976),with a sensitivity of 88.46%and specificity of 91.49%.There was no statistical difference when compared to the AUC of the combined predictive model established in the earlier phase.Conclusion Multi-mode fMRI combined with MRS demonstrate high clinical value in the differential diagnosis of postoperative glioma recur-rence and PsP,and it is worth to be popularized.

Sepsis is a clinical syndrome resulting from infection followed by inflammation and is one of the significant causes of mortality worldwide. The underlying reason is the host′s uncontrolled inflammatory response to an infection, which leads to multiple organ dysfunction. It not only aggravates the condition, but also leads to a poor prognosis. Neutrophils are involved in many physiological and pathological processes in the human body and are forerunners to reach the site of infection/inflammation for clearing the infection and resolute the inflammation during sepsis. In addition, under the stimulation of pathogens, neutrophils can release a special network structure containing a variety of protein components and DNA as the skeleton, which is named neutrophil extracellular traps (NETs). Although NETs can kill pathogens, excess NETs have a significant influence on the pathogenesis of sepsis-induced multiple organ damage, including lung, kidney, and liver damage. This review aims to introduce the role of NETs in sepsis and organ dysfunction, hoping to provide new ideas for the treatment of sepsis.

Malignant pleural effusion(MPE)is a common complication in patients with advanced malignant tumors,which not only significantly reduces their quality of life but also shortens their survival duration.Despite the widespread use of traditional treatment methods such as thoracentesis and pleurodesis,their efficacy is limited accompanied by high recurrence rates.Therefore,exploring novel therapeutic strategies becomes particularly urgent.In recent years,immunotherapy has attracted extensive attention for its potential in cancer treatment.This article systematically reviews the roles of CD4+T cell subsets,including regulatory T cells(Treg),T helper cell(Th)17,Th9,and Th22 cells,within the immunosuppressive microenvironment of MPE.These cell subsets are involved in the formation of the immunosuppressive state of MPE through various mechanisms and play key roles in the occurrence and development of the disease.In addition,the article discusses in detail the role of immune checkpoint molecules,such as programmed death protein 1(PD-1),PD-1 ligand(PD-L1),and cytotoxic T-lymphocyte-associated protein 4(CTLA-4),in the immune evasion of MPE.The abnormal expressions of these molecules provide opportunity for tumor cells to evade immune system surveillance.At the same time,this article also summarizes the application prospects of novel immunotherapy strategies,such as adoptive cell therapy(ACT)and chimeric antigen receptor T cell(CAR-T)therapy,in the treatment of MPE.These innovative therapies offer possibilities for improving the prognosis of MPE patients through activating and enhancing the anti-tumor immune response.

AIM:To investigate the potential mechanisms by which cell division cycle protein 42(Cdc42)regulates endothelial-mesenchymal transition(EndMT)in pulmonary hypertension(PH).METHODS:The pulmonary hypertension(PH)model was established using Sugen-5416 combined with hypoxia.Twenty-four C57BL/6 mice were ran-domly divided into four groups:normoxia control(CON)group,normoxia+ML141(CON+ML141)group,Sugen-5416+hypoxia(SuHx)group,and SuHx+ML141 group,with 6 mice in each group.After 4 weeks,right ventricular systolic pressure(RVSP)and cardiac ultrasound parameters were measured,and lung tissues were collected for immunofluores-cence staining.Pulmonary microvascular endothelial cells(PMVECs)were isolated using magnetic bead sorting.Calcium imaging was performed to assess Ca2+signaling,and Western blot was used to detect EndMT-related proteins as well as stromal interaction molecule 1(STIM1)and Orai1 expression.RESULTS:In the SuHx group,mice exhibited signifi-cantly increased RVSP,Fulton index(right ventricle/left ventricle+septum),end-diastolic right ventricular free wall thick-ness(RVEDWT),and end-systolic right ventricular free wall thickness(RVESWT)(P<0.01).Conversely,pulmonary artery acceleration time/pulmonary artery ejection time(PAT/PET)and tricuspid annulus plane systolic excursion(TAPSE)were significantly reduced(P<0.01).The Cdc42 inhibitor ML141 ameliorated these changes.The SuHx group exhibited a significant decrease in CD31 fluorescence intensity in pulmonary vascular endothelial cells(P<0.01),a marked increase in α-smooth muscle actin(α-SMA)fluorescence intensity in smooth muscle cells(P<0.01),and the emergence of CD31/α-SMA co-localization.These alterations were reversed by ML141.Hypoxia induced EndMT in PM-VECs,characterized by decreased CD31 and vascular endothelial cadherin(VE-cadherin)along with increased α-SMA and vimentin(P<0.01),which was suppressed by ML141(P<0.01).Hypoxia activated store-operated calcium entry(SOCE),enhancing intracellular Ca2? release,extracellular Ca2? influx,and basal Ca2? levels(P<0.01),while upregulat-ing STIM1 and Orai1 expression(P<0.01).These changes were reversed by ML141.Furthermore,both ML141 and STIM1 knockdown inhibited the upregulation of EndMT-related transcription factors Snail and Twist(P<0.05).CON-CLUSION:Cdc42 may participate in EndMT in PH by regulating store-operated calcium channels in pulmonary microvas-cular endothelial cells.

AIM:To investigate the potential mechanisms by which cell division cycle protein 42(Cdc42)regulates endothelial-mesenchymal transition(EndMT)in pulmonary hypertension(PH).METHODS:The pulmonary hypertension(PH)model was established using Sugen-5416 combined with hypoxia.Twenty-four C57BL/6 mice were ran-domly divided into four groups:normoxia control(CON)group,normoxia+ML141(CON+ML141)group,Sugen-5416+hypoxia(SuHx)group,and SuHx+ML141 group,with 6 mice in each group.After 4 weeks,right ventricular systolic pressure(RVSP)and cardiac ultrasound parameters were measured,and lung tissues were collected for immunofluores-cence staining.Pulmonary microvascular endothelial cells(PMVECs)were isolated using magnetic bead sorting.Calcium imaging was performed to assess Ca2+signaling,and Western blot was used to detect EndMT-related proteins as well as stromal interaction molecule 1(STIM1)and Orai1 expression.RESULTS:In the SuHx group,mice exhibited signifi-cantly increased RVSP,Fulton index(right ventricle/left ventricle+septum),end-diastolic right ventricular free wall thick-ness(RVEDWT),and end-systolic right ventricular free wall thickness(RVESWT)(P<0.01).Conversely,pulmonary artery acceleration time/pulmonary artery ejection time(PAT/PET)and tricuspid annulus plane systolic excursion(TAPSE)were significantly reduced(P<0.01).The Cdc42 inhibitor ML141 ameliorated these changes.The SuHx group exhibited a significant decrease in CD31 fluorescence intensity in pulmonary vascular endothelial cells(P<0.01),a marked increase in α-smooth muscle actin(α-SMA)fluorescence intensity in smooth muscle cells(P<0.01),and the emergence of CD31/α-SMA co-localization.These alterations were reversed by ML141.Hypoxia induced EndMT in PM-VECs,characterized by decreased CD31 and vascular endothelial cadherin(VE-cadherin)along with increased α-SMA and vimentin(P<0.01),which was suppressed by ML141(P<0.01).Hypoxia activated store-operated calcium entry(SOCE),enhancing intracellular Ca2? release,extracellular Ca2? influx,and basal Ca2? levels(P<0.01),while upregulat-ing STIM1 and Orai1 expression(P<0.01).These changes were reversed by ML141.Furthermore,both ML141 and STIM1 knockdown inhibited the upregulation of EndMT-related transcription factors Snail and Twist(P<0.05).CON-CLUSION:Cdc42 may participate in EndMT in PH by regulating store-operated calcium channels in pulmonary microvas-cular endothelial cells.

Objective To investigate the combined value of multimodal functional magnetic resonance imaging(fMRI)and magnetic resonance spectroscopy(MRS)in the differential diagnosis of postoperative recur-rence and pseudoprogression(PsP)of glioma.Methods One hundred and four patients with glioma confirmed by surgical pathology were selected from our hospital from September 2021 to March 2024,and the patients were divided into recurrence group(n=70)and PsP group(n=34)according to the revised glioma treatment response assessment criteria.Another group of 73 patients with glioma were selected for model validation.The general data,apparent diffusion coefficient(ADC)of multimodal fMRI parameters,standardized cerebral blood volume(CBV)and MRS indexes of the two groups were compared.The influencing factors of postoperative glioma recurrence were analyzed by logistic regression,and clinical efficacy of the combined treatment in the diagnosis of postoperative glioma recurrence and PsP was analyzed by receiver operating curve(ROC).Results The level of ADC in the recurrence group was lower than that in the PsP group(P<0.05),and the levels of CBV,choline(Cho)/creatine(Cr)and Cho/N-acetylaspartic acid(NAA)were higher(P<0.05).Logistic regression analysis showed that the levels of ADC,CBV,Cho/Cr and Cho/NAA were risk factors for postoperative recurrence of glioma(P<0.05).ROC showed that the combined use of multimodal fMRI and MRS in the differential diagnosis of postoperative glioma recurrence and PsP had an AUC of 0.916,outperforming the diagnostic accuracy of each individual modality.Validation of the combined model constructed with multimodal fMRI and MRS yielded an AUC of 0.929,95%CI(0.844～0.976),with a sensitivity of 88.46%and specificity of 91.49%.There was no statistical difference when compared to the AUC of the combined predictive model established in the earlier phase.Conclusion Multi-mode fMRI combined with MRS demonstrate high clinical value in the differential diagnosis of postoperative glioma recur-rence and PsP,and it is worth to be popularized.

Sepsis is a clinical syndrome resulting from infection followed by inflammation and is one of the significant causes of mortality worldwide. The underlying reason is the host′s uncontrolled inflammatory response to an infection, which leads to multiple organ dysfunction. It not only aggravates the condition, but also leads to a poor prognosis. Neutrophils are involved in many physiological and pathological processes in the human body and are forerunners to reach the site of infection/inflammation for clearing the infection and resolute the inflammation during sepsis. In addition, under the stimulation of pathogens, neutrophils can release a special network structure containing a variety of protein components and DNA as the skeleton, which is named neutrophil extracellular traps (NETs). Although NETs can kill pathogens, excess NETs have a significant influence on the pathogenesis of sepsis-induced multiple organ damage, including lung, kidney, and liver damage. This review aims to introduce the role of NETs in sepsis and organ dysfunction, hoping to provide new ideas for the treatment of sepsis.

AIM: To observe the effects of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO) and transforming growth factor-β1 (TGF-β1) of radiation-induced lung injury rats by Kiwi fruit essence (unsaturated fatty acid of actinidia chinesis planch seed oil). METHODS: According to random number table, 90 Sprague-Dawley rats were divided into the control group, model group, 60 mg/kg unsaturated fatty acid of actinidia chinesis planch seed oil intervention group, 120 mg/kg unsaturated fatty acid of actinidia chinesis planch seed oil intervention group, 240 mg/kg unsaturated fatty acid of actinidia chinesis planch seed oil intervention group, 18 animals were included in each group. Except for the control group, rats in the remaining groups were constructed by 6MV-X-ray 18Gy full chest radiation, one week before modeling, the rats in the last 3 groups were given (60, 120, 240) mg/kg unsaturated fatty acid of actinidia chinesis planch seed oil. The first two groups were given 0.9% sodium chloride solution by gavage, once a day in each rat. 14 days, 28 days, and 56 days after radiation, the rats were randomly sacrificed and their chests were cut, and ave lung tissue was saved. HE and Masson staining were performed to observe the pathological changes, and the content of SOD, GSH-Px, MPO was determined. The expression of TGF-β1 was analyzed by immunohistochemical staining. RESULTS: Compared with the model group, (60, 120, 240) mg/kg unsaturated fatty acid of actinidia chinesis planch seed oil significantly reduced the degree of lung alveolitis and radiation pulmonary fibrosis, reduced the content of hydroxyproline (HYP), MPO, increased the antioxidant enzymes SOD and GSH-Px content, down-regulated the expression of TGF-β1.There were significant differences in the above-mentioned indicators among the intervention groups of (60, 120, 240) mg/kg unsaturated fatty acid of actinidia chinesis planch seed oil group, and it was positively correlated with dosage. CONCLUSION: Unsaturated fatty acid of actinidia chinesis planch seed oil has a preventive effect on radiation-induced lung injury, and its mechanism may be related to the reduction of oxidative stress damage and down-regulation of TGF-β1 expression.

Metastasis is the leading cause of mortality for cancer patients, and lymphatic metastasis is one of the main ways of tumor metastasis. The role of CCL21 and its receptor CCR7 in lymphatic metastasis has been increasingly concerned in recent years. CCR7 is mainly expressed by both dendritic cells and T cells for immune responses. CCL21, the chemokine ligand for CCR7, secreted from lymphatic endothelial cells binds CCR7 and recruits immune cells toward lymphatic vessels and lymphatic nodes. CCR7 expressed tumor cells can also metastasize to lymphatic system by the similar way as immune cells. Targeting CCL21/CCR7 axis to inhibit lymphatic metastasis but remain potent anti-tumor immune response has increasingly become a spot light of tumor immunotherapy. In this review, we summarize the role of CCL21/CCR7 axis in lymphatic metastasis, as well as preclinical trials and clinical trials in targeting CCL21/CCR7 axis for tumor metastasis therapy, hoping to accelerate the progress on tumor metastasis therapy by targeting CCL21/CCR7 axis.
Cell Line, Tumor ; Chemokine CCL21 ; Endothelial Cells ; Humans ; Lymphatic Metastasis ; Neoplasms/therapy* ; Receptors, CCR7/genetics*