Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.

Objective:To analyze the influencing factors related to the prognosis of delayed replantation of avulsed permanent teeth.Methods:A retrospective study was conducted on the clinical data of 35 patients with 38 affected teeth underwent delayed replantation of permanent teeth.According to the prognosis after 12 to 108 months of follow-up,the replantation results of the cases were divided into-success,survival and failure groups.Survival curves were plotted using Kaplan-Meier method,Log-Rank test was used for univariate analysis,and Cox proportional risk regression models were used for multivariate analysis to assess the effects of gender,age,degree of tooth development,mode of tooth preservation and mode of endodontic treatment on the survival rate of replanted teeth.Results:Of the 38 replanted teeth,3 were successful,28 remained and 10 failed.The 9-year cumulative survival rate of the replanted teeth was 34.7％.The results showed that there were no statistically significant differences in the survival rate of the replanted teeth in the groups with different sex,age,degree of tooth development and the mode of preservation of avulsed teeth(P＞0.05).There were statistically significant differences in the cumulative survival rate of the replanted teeth among the groups with different endodontic treatment(P＜0.01),which showed that the cumulative survival rate in the root canal filling group＞continuous root canal sealing group＞pulp preserva-tion treatment group.Conclusion:For the delayed replantation of avulsed premanent teeth,survival prognosis of the teeth treated with pulp preservation is poor,early pulp extraction and root canal filling are recommended.

Objective: This ex vivo study evaluated the effect of ultrasound and Er:YAG laser irrigation activation techniques on the penetration of sodium hypochlorite solution into infected human root canal dentin, providing a reference for clinical infection control of infected root canals. Methods : Thirty-six cases of infected root canals were collected and randomly divided into three groups according to the irrigation technique: 12 cases in the conventional syringe irrigation (CSI) group, 12 cases in the passive ultrasonic irrigation (PUI) group, 12 cases in the Er:YAG laser and photon-induced photoacoustic streaming (PIPS) group and 36 cases of clean root canals (12 cases in the CSI group, 12 cases in the PUI group, 12 cases in the PIPS group). All of the selected root canals were straight root canals of posterior teeth. After standardizing the root length, all canals were subjected to instrumentation and dynamic irrigation. 2% methylene blue solution was used to visualize the penetration of the irrigant. EXAKT cutting and grinding equipment was used to take transverse sections of 100-150 μm at the coronal, middle and apical thirds of the root canals. The data (maximum penetration depth, average penetration depth, and penetration percentage) were observed under a light microscope to evaluate the effect of dye penetration. Results : With the three irrigation techniques, the maximum penetration depth, average penetration depth and penetration percentage of the infected root canals were significantly lower than those of clean root canals in the full length of the root canal (P<0.05). The penetration percentage, average penetration depth and maximum penetration depth of the PIPS group were significantly higher than those of the CSI group in the coronal, middle and apical thirds of the infected root canal, respectively (P<0.05). There was no significant difference in the maximum penetration depth, average penetration depth or penetration percentage between the PUI and CSI groups (P>0.05). There was also no significant difference in the maximum penetration depth, average penetration depth or penetration percentage between the PIPS and PUI groups (P>0.05). Conclusion The dentine permeability of infected root canals was weaker than that of clean root canals. Er:YAG laser-assisted irrigation activation technology could significantly improve the penetration of sodium hypochlorite solution into infected dentin, but passive ultrasonic irrigation did not significantly improve the penetration.

Objective : To evaluate the anti⁃inflammatory effect of tissue inhibitor of metalloprotease (TIMP1) on a rat model of irreversible pulpitis. Methods : An irreversible pulpitis model was established by pulp exposure on maxillary first molars of 8 ⁃10 weeks old male rats , and pulpotomy was performed at 24 h , 36 h and 48 h after pulp exposure , with TIMP⁃1 covering the pulp section (TIMP⁃1 group) and saline as control (NS group) . Coronal obturation were performed with glass⁃ionomer cement. Histological and immunohistochemical analysis were performed at 24 and 48 h after administration. Results : Quantitative histopathological analysis of HE⁃stained sections showed that the inflammation score (inflammatory cellular response of the root pulp , morphological changes in root pulp tissue and extent of root pulp necrosis) of the pulp were higher in the TIMP⁃1 group than those in the NS group (P < 0. 001 or P < 0. 01) . Immunofluorescence staining (CD68⁃labeled) sections showed that the intensity of CD68 immunofluorescence was higher in the TIMP⁃1 group than that in the NS group (P < 0. 001) . Conclusion TIMP⁃1 had no anti⁃inflammatory effect in a rat model of irreducible pulpitis and increased the degree of inflammation in the root pulp.

Objective : To evaluate the effect of 2. 5% NaClO solution as irrigating agent on the healing of dental pulp after preservation treatment in rats with inflammatory pulp. Methods : 48 maxillary molars of 24 8 ⁃week⁃old male SD rats were selected and pulpitis models were established by pulp cavity exposure for 24 hours. Then part of the crown pulp was removed and divided into two groups according to different irrigation methods : 2. 5% NaClO flushing group (NaClO) and saline flushing group (NS) . The pulp was covered with iRoot BP Plus and the cavity was sealed with glass ionomer. Four animals in the two groups were killed on the 1st , 7th and 28th day after opera⁃ tion , respectively. And the inflammatory reaction , tissue destruction and hard tissue formation of residual dental pulp tissue were observed and evaluated by histopathology. Results : The pulp inflammatory reaction , tissue de⁃ struction and restorative dentin formation in 2. 5% NaClO irrigation group and saline irrigation group were similar on the 1st , 7th and 28th day after operation , there was no significant difference between the two groups. Conclusion 2. 5% NaClO used as a hemostatic before iRoot BP Plus pulp capping after partial pulpotomy has similar effect with normal saline on the inflammatory pulp model of rats , and does not affect the healing of pulp inflammation.

Animals ; Cell Differentiation ; Cell Lineage ; Dendritic Cells ; Mice

The infiltration of immune cells into the hepatocellular carcinoma microenvironment is the main reason why hepatocellular carcinoma patients are prone to carcinoma recurrence and the disease are incurable. Notably, the infiltration of Treg cells is the main trigger. Dahuang Zhechong pill (DHZCP) is a traditional Chinese herbal compound successful in the treatment of hepatitis and hepatocellular carcinoma. DHZCP can heal and nourish while slowing the onset of the disease, thereby strengthening the body's immune function. It can localize tumors and ultimately achieve the goal of eliminating tumors. In this study, an orthotopic liver cancer model of mice was used to explore the mechanism of DHZCP enhancing anti-tumor immunity, which showed more Th1 cells in the peripheral blood and spleen after DHZCP treatment, while more IFN-γ was secreted to activate CD8⁺ T cells and Treg cell production was inhibited, thereby suppressing the growth of HCC. Finally, we also analyzed the potential components of DHZCP from the perspective of modern targets using network pharmacology methods and experimental results.
Animals ; CD8-Positive T-Lymphocytes ; Carcinoma, Hepatocellular/drug therapy* ; Drugs, Chinese Herbal ; Humans ; Liver Neoplasms/drug therapy* ; Mice ; T-Lymphocytes, Regulatory ; Tumor Microenvironment

Objective To study the immune efficacy of ginsenoside Re as the adjuvant of anti-caries subunit vac-cine rPAc. Methods 40 mice were randomly diveded into four groups:anti-caries vaccine group( rPAc group) ,gin- senoside Re groups( Re group) , Re+rPAc group, normal saline group( NS group) . Mice were intranasally immu-nized twice on weeks 0 and 2 with rPAc,Re,Re+rPAc or normal saline,respectively. Concentration of specific anti-bodies in serum and saliva were detected by enzyme-linked immunosorbent assay(ELISA). In addition, cytokine production of spleen lymphocyte responses were also evaluated. 24 Wistar rats,infected with S. mutans Ingbritt, were randomly diveded into four groups:rPAc group,Re group, Re+rPAc group, NS group. Rats were jmmunized intranasally with rPAc,Re, Re+rPAc or normal saline,respectively. The Keyes method was used to determine the caries activity. Results The level of serum specific anti-PAc IgG, IgG1,IgG2a and saliva anti-PAc IgA were sig-nificantly higher in Re+rPAc group (P＜0. 05). In addition, the expression of cytokines interluekin-4 and inter-feron-γ were significantly upregulated in Re+rPAc group than those in any other groups(P＜0. 01). Re+rPAc im-munized rats showed significantly fewer E,Ds and Dm lesions than rPAc-immunized rats,Re-immunized rats or NS-immunized rats(P＜0. 05). Conclusion Re as the adjuvant of anti-caries subunit vaccine rPAc triggers a stronger humoral and cellular response against dental caries,and Re is a promising adjuvant for anti-caries vaccine rPAc.

Dendritic cells (DCs) are important immune cells linking innate and adaptive immune responses. DCs encounter various self and non-self antigens present in the environment and induce different types of antigen specific adaptive immune responses. DCs can be classified into lymphoid tissue-resident DCs, migratory DCs, non-lymphoid resident DCs, and monocyte derived DCs (moDCs). Recent work has also established that DCs consist of developmentally and functionally distinct subsets that differentially regulate T lymphocyte function. The development of different DC subsets has been found to be regulated by a network of different cytokines and transcriptional factors. Moreover, the response of DC is tightly regulated to maintain the homeostasis of immune system. MicroRNAs (miRNAs) are an important class of cellular regulators that modulate gene expression and thereby influence cell fate and function. In the immune system, miRNAs act at checkpoints during hematopoietic development and cell subset differentiation, they modulate effector cell function, and are implicated in the maintenance of homeostasis. DCs are also regulated by miRNAs. In the past decade, much progress has been made to understand the role of miRNAs in regulating the development and function of DCs. In this review, we summarize the origin and distribution of different mouse DC subsets in both lymphoid and non-lymphoid tissues. The DC subsets identified in human are also described. Recent progress on the function of miRNAs in the development and activation of DCs and their functional relevance to autoimmune diseases are discussed.
Animals ; Autoimmune Diseases ; immunology ; Cell Differentiation ; immunology ; Dendritic Cells ; cytology ; immunology ; Humans ; MicroRNAs ; immunology ; Monocytes ; cytology ; immunology ; T-Lymphocytes ; cytology ; immunology

Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 3'-substituents at the 11-side chain were synthesized and evaluated for their anticancer activity from sophoridine (1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a-b, alkenes 7a-b and sophoridinic amines 14a-b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin (AMD)-susceptible and resistant MCF-7 breast carcinoma cells, indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.