Tumors are highly heterogeneous diseases, and tumor-associated macrophages(TAMs) are important immune cells in the tumor microenvironment, which are highly heterogeneous and plastic. Tumor recurrence and metastasis are an important cause of morbidity and mortality in cancer patients. Macrophage-derived exosomes(MDEs) act as messengers for cell-to-cell signaling and carry a variety of components of mother cells. A large number of studies have shown that the polarization state of macrophages plays a regulatory role in tumor progression, and MDE is closely related to tumor progression and macrophage polarization. As a new anti-tumor strategy, MDE provides new insights into tumor treatment. This paper summarizes recent research on engineered MDEs in anti-tumor and how M1 and M2 MDEs mediate tumor development, aiming to provide references for tumor treatment.

Objectives miR-207 has been identified as being expressed in natural killer (NK) cell exosomes that play a role in disease progression; however, to date, there are no studies specifically linking miR-207 to tuberculosis (TB). Methods Bioinformatics methods employed for prediction, followed by a dual luciferase reporter assay to determine whether lysosome-associated membrane protein 2 (LAMP2) is targeted by miR-207. The experiments were divided into four groups using the liposome transfection method (OP-LAMP2 group: co-transfected with miR-207 mimics and LAMP2 overexpression plasmid; EP group: co-transfected with mimics NC and null-loaded plasmid; siLAMP2 group: transfected with siLAMP2; and siLAMP2-NC group: transfected with siLAMP2-NC). TB infection was modeled using H37Ra-infected Ana-1 cells. The impact of LAMP2 on intracellular mycobacterial load and clearance of extracellular residual mycobacteria were assessed by tuberculosis colony-forming unit counting. Flow cytometry was used to assess the total apoptosis rate. Real-time fluorescent quantitative PCR was conducted to determine the relative expression of LAMP2, apoptosis genes, pyroptosis genes, and autophagy genes. Western blot analysis was performed to measure the relative expression of LAMP2 proteins, apoptosis proteins, pyroptosis proteins, and autophagy proteins. Results Dual luciferase reporter assay test showed that there was a targeting relationship between LAMP2 and miR-207. The transfection model was successfully constructed under real-time fluorescent quantitative PCR and Western blot statistical analysis, and microscopic observation. The infection model was successfully established under microscopic observation. Colony forming unit counting revealed that the number of colonies in the OP-LAMP2 group was lower than that in the EP group, while the number of colonies in the siLAMP2 group was higher than that in the siLAMP2-NC group. Flow cytometry assay revealed that the total apoptosis in OP-LAMP2 group was lower than that in EP group, and the total apoptosis in siLAMP2 group was higher than that in siLAMP2-NC group. Real-time fluorescence quantitative PCR and Western blot analysis revealed that the relative expression of apoptosis and pyroptosis-related proteins and genes in the control group was lower in the OP-LAMP2 group compared to the EP group, and higher in the siLAMP2 group compared to the siLAMP2-NC group. Real-time fluorescence quantitative PCR detected that the relative expression of autophagy positively regulated genes Microtubule-associated protein 1 light chain 3(LC3)and Beclin1 in the OP-LAMP2 group was higher in the OP-LAMP2 group compared to the EP group, and lower in the siLAMP2 group compared to the siLAMP2-NC group, while the relative expression of negatively regulated autophagy genes followed the opposite trend to that of autophagy positively regulated genes. The relative expression of autophagy-related proteins was consistent with the trend of autophagy genes. Conclusions miR-207 enhances macrophage apoptosis, cellular pyroptosis and inhibits autophagy, promoting survival of Mycobacterium tuberculosis by targeting the autophagy-related protein LAMP2, thus offering a novel therapeutic direction for tuberculosis.
Lysosomal-Associated Membrane Protein 2/metabolism* ; MicroRNAs/metabolism* ; Mycobacterium tuberculosis/physiology* ; Autophagy/genetics* ; Humans ; Macrophages/metabolism* ; Apoptosis/genetics* ; Tuberculosis/metabolism* ; Cell Line ; Pyroptosis/genetics*

Pulmonary diseases, as a prevalent category of respiratory system disorders, have become a significant global public health concern. The increasing incidence of these diseases, caused by environmental pollution and occupational hazards, poses a substantial threat to human health and the overall quality of life. Mesenchymal stem cells (MSCs) are known for their remarkable immunomodulatory, anti-bacterial, and anti-apoptotic capabilities. Exosomes derived from MSCs, carrying a diverse array of proteins, lipids, nucleic acids, and other bio-active molecules, have demonstrated considerable therapeutic potential in treating pulmonary diseases, and have come to the forefront of medical research. This review summarized the therapeutic role of exosomes derived from various sources of mesenchymal stem cells in the context of pulmonary diseases, aiming to provide a robust foundation for their clinical application in diagnosis and treatment.
Exosomes/transplantation* ; Humans ; Mesenchymal Stem Cells/metabolism* ; Lung Diseases/therapy* ; Animals

Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.

Ferroptosis is a newly discovered mode of programmed cell death characterized by the accumulation of intracellular iron-dependent lipid peroxidation.Current research has mainly focused on the role of ferroptosis in the field of cancer,but increasing evidence shows that ferroptosis is also related to the occurrence of infectious diseases.Ferroptosis has accordingly been detected in cases of COVID-19,tuberculosis,and cryptococcal meningitis,as well as other diseases.This article reviews the role of ferroptosis in infectious diseases,to provide new ideas for the prevention and treatment of ferroptosis-related infectious diseases.

Objective To investigate the effect of mechanical thrombectomy using Solitaire stent combined with dual antiplatelet therapy(DAPT)on limb function and vascular reocclusion in patients with acute cerebral infarction.Methods A total of 134 patients with acute cerebral infarction who received treatment in our hospital from February 2020 to August 2023 were selected as samples.According to whether the patients regularly took aspirin and clopidogrel every day one week before surgery,they were divided into observation group(taking the medications)and control group(without taking medications),with 67 cases in each.The control group was given mechanical thrombectomy,and the observation group was treated with DAPT combined with mechanical thrombectomy.Outcomes measured included revascularization one week after treatment,and neurological and limb function assessment using NIHSS and FMA scale at baseline,1 day,1 week,and 1 month after treatment.Brain hemodynamics(CVR,Qmean,and Vmean)and thrombosis markers(TXB2,CD62P,and 6-keto-PGF1α)were evaluated pre-treatment and one month after treatment.Vascular reocclusion three months after treatment and its correlation with hemody-namics and thrombosis factors were analyzed.Results After treatment,higher revascularization rate,FMA score,Qmean,Vmean,and 6-keto-PGF1α level,and lower NIHSS score,CVR,TXB2,and CD62P level were found in the observation group(P<0.05).The incidence of vascular reocclusion was also lower in the observation group.Logistic analysis indicated that brain hemodynamic indicators and the level of thrombosis-related factors influenced vascular reocclusion occurrence(P<0.05).Conclusion Mechanical thrombectomy using Solitaire stent combined with DAPT helps the recovery of limb function in patients with acute cerebral infarction and reduces the risk of vascular reocclusion.

OBJECTIVE: To explore the clinical and genetic characteristics of a patient with hypertrophic cardiomyopathy as the initial manifestation of Mucopolysaccharidosis type Ⅲ A (MPS Ⅲ A). METHODS: A female patient with MPS Ⅲ A who was admitted to the Affiliated Hospital of Jining Medical University in January 2022 and her family members (seven individuals from three generations) were selected as the study subjects. Clinical data of the proband were collected. Peripheral blood samples of the proband was collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Heparan-N-sulfatase activity was determined for the disease associated with the variant site. RESULTS: The proband was a 49-year-old woman, for whom cardiac MRI has revealed significant thickening (up to 20 mm) of left ventricular wall and delayed gadolinium enhancement at the apical myocardium. Genetic testing revealed that she has harbored compound heterozygous variants in exon 17 of the SGSH gene, namely c.545G>A (p.Arg182His) and c.703G>A (p.Asp235Asn). Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PM2_Supporting +PM3+PP1Strong+PP3+PP4; PS3+PM1+PM2_Supporting +PM3+PP3+PP4). Sanger sequencing confirmed that her mother was heterozygous for the c.545G>A (p.Arg182His) variant, whilst her father, sisters and her son were heterozygous for the c.703G>A (p.Asp235Asn) variant. Determination of blood leukocyte heparan-N-sulfatase activity suggested that the patient had a low level of 1.6 nmol/(g·h), whilst that of her father, elder and younger sisters and son were all in the normal range. CONCLUSION The compound heterozygous variants of the SGSH gene probably underlay the MPS ⅢA in this patient, for which hypertrophic cardiomyopathy is an associated phenotype.
Female ; Humans ; Cardiomyopathy, Hypertrophic ; Contrast Media ; East Asian People ; Gadolinium ; Mucopolysaccharidosis III ; Mutation ; Pedigree ; Male ; Middle Aged

Objective:To investigate the predictive value of neutrophil to lymphocyte ratio (NLR) for hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS).Methods:Consecutive patients with AIS without performing intravenous thrombolysis and mechanical thrombectomy admitted to the Cerebrovascular Disease Treatment Center, the Affiliated Brain Hospital of Nanjing Medical University from December 2015 to December 2020 were enrolled. The clinical, imaging and laboratory examination data were collected. HT was defined as the first imaging examination of AIS patients without finding bleeding signs, but the imaging reexamination after hospitalization found intracranial hemorrhage. Multivariate logistic regression analysis was used to determine the independent correlation between NLR and HT. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of NLR for HT. Results:A total of 805 patients with AIS were included. The median age was 67 years (interquartile range, 63-71 years), the median National Institutes of Health Stroke Scale (NIHSS) score was 4 (interquartile range, 2-9), the median NLR was 3.84 (interquartile range, 2.66-5.30). Seventy-ywo patients (8.9%) had HT. There were significant differences in age, baseline systolic blood pressure, baseline NIHSS score, time from onset to admission, time from onset to blood collection, time from onset to imaging reexamination, NLR, atrial fibrillation, history of previous stroke and transient ischemic attack and stroke etiology between the HT group and the non-HT group (all P<0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for HT in patients with AIS after adjusting for confounding factors (odds ratio 1.355, 95% confidence interval 1.099-1.672; P=0.005). The ROC curve analysis showed that the area under the curve of NLR predicting HT was 0.852, and the optimal cut-off value was 4.75. Its sensitivity and specificity of predicting HT were 88.3% and 71.8% respectively. Conclusion:High NLR is an independent risk factor for HT in patients with AIS during hospitalization, and had better predictive value for HT risk.

Objective:To investigate the effect of exosomes (Exo) secreted by brain vascular endothelial cell bEnd.3 after ischemic preconditioning (IPC) on neurons suffering from oxygen and glucose deprivation (OGD).Methods:bEnd.3 was exposed to OGD for 3 h to simulate IPC in vivo. After 48 h of reoxygenation, the Exo (IPC Exo) in the conditioned medium were extracted and identified by Western blot and transmission electron microscopy. IPC Exo were incubated with primary cultured mouse cortical neurons for 24 h. Confocal microscope was used to observe whether Exo could be uptaked by primary cultured mouse cerebral cortical neurons. The primary cultured cortical neurons were divided into control group, OGD group, OGD+ IPC Exo (5 μg/ml, 10 μg/ml, 20 μg/ml) groups and sham OGD group (treated with Exo secreted by bEnd.3 cultured under normoxia conditions). The cell viability was detected by CCK-8 and cell survival/death detection kit.Results:Transmission electron microscopy showed that the extract of bend.3 culture medium showed typical morphology of Exo, i. e., a double concave disc-shaped vesicle with a diameter of 30-100 nm. Western blot analysis showed that the extract of bEnd.3 medium highly expressed Exo markers Alix and Tsg101. Confocal microscopy showed that Exo could be uptaked by primary cultured mouse cortical neurons, and the uptake of Exo was widely distributed in the cytoplasm and synapses. Compared with the OGD group, the addition of 10 and 20 μg/ml IPC Exo could significantly increased the neuronal viability ( P<0.05), while the addition of sham Exo had no neuroprotective effect. Conclusion:Exo released by cerebral vascular endothelial cells after IPC have protective effect on neurons suffering from OGD.