Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Tissue-resident memory T (TRM) cells are a recently defined subtype of non-recirculating memory T cells with longevity and protective functions in peripheral tissues. As an essential frontline defense against infections, TRM cells have been reported to robustly patrol the tissue microenvironment in malignancies. Accumulating evidence also implicates that TRM cells in the relapse of chronic inflammatory skin diseases such as psoriasis and vitiligo. In light of these developments, this review aims to synthesize these recent findings to enhance our understanding of TRM cell characteristics and actions. Therefore, after providing a brief overview of the general features of the TRM cells, including precursors, homing, retention, and maintenance, we discuss recent insights gained into their heterogeneous functions in skin diseases. Specifically, we explore their involvement in conditions such as psoriasis, vitiligo, fixed drug eruption - dermatological manifestations of drug reactions at the same spot, cutaneous T cell lymphoma, and melanoma. By integrating these diverse perspectives, this review develops a comprehensive model of TRM cell behavior in various skin-related pathologies. In conclusion, our review emphasizes that deciphering the characteristics and mechanisms of TRM cell actions holds potential not only for discovering methods to slow cancer growth but also for reducing the frequency of recurrent chronic inflammation in skin tissue.
Humans ; Skin Diseases/immunology* ; Memory T Cells/immunology* ; Animals ; Vitiligo/immunology* ; Psoriasis/immunology* ; Immunologic Memory

OBJECTIVE: To evaluate the feasibility and accuracy of cone-beam CT (CBCT) images for radiotherapy dose calculation in pelvic tumors. METHODS: An improved volumetric density coverage method was used to establish CT value-relative electron density (RED) curves for CBCT images. The planning CT plans were transferred to the CBCT images, and the constructed density curves were applied to calculate doses for CBCT plans while maintaining the optimization parameters unchanged. Dose calculation deviations between the two plans were analyzed. RESULTS: The mean differences in dosimetric parameters for the target volume and organs at risk (OAR) between the two plans were less than 1% and 1.5%, respectively. The target conformity index (CI), homogeneity index (HI), and gamma passing rates were highly consistent, with no statistically significant differences. CONCLUSION CBCT images corrected by this method can be used for dose calculation in pelvic tumor radiotherapy planning.
Cone-Beam Computed Tomography/methods* ; Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy Dosage ; Pelvic Neoplasms/diagnostic imaging*

Recent studies have demonstrated that bitter taste receptors are distributed not only in oral cavity but also in non-gustatory systems,such as the respiratory,digestive,reproductive and cardiovascular systems.The physiological role of bitter taste receptors is to recognize bitter substances or bacterial secretions,to trigger the immune response and to maintain the internal environmental homeosta-sis.In addition,oral bitter taste receptors are expressed not only in taste buds,perceiving bitter taste,but also in many other parts of periodontal tissues,which is the potential treatment target for oral infectious diseases.This review summarized the expression and distri-bution of oral bitter taste receptors which was off the taste buds and their roles in regulating oral inflammation and oral bacteria,dis-cussed the effects of genetic polymorphism of bitter taste receptor 38 subtype(TAS2R38)on innate immunity and its relationship with the susceptibility of dental caries and periodontal,aimed to provide novel ideas for the better prevention and treatment of dental caries and periodontal diseases.

This study was designed to explore the transcription level,genome alteration,potential abnormal expression mechanism,prognostic value and the association with immune cells of the tetraspan MS4A6A(membrane-spanning 4A(MS4A)subfamily protein 6A)in pan-cancer.Public databases,such as UCSC Xena,cBioPortal and Timer2,were used to collect relative data,and thenbioinformatic approaches were used to analyze the correlation of MS4A6A genome and MS4A6A expression with immune infiltration,tumor mutation burden(TMB),microsatellite instability(MSI)etc.TMB and MSI were further calculated by R package maftools.Immune score,stromal score and ESTIMATE score were calculated by R package ESTIMATE.The correlation between immune score and MS4A6A expression was conducted based on Spearman correlation coefficient.Data showed that DNA methylation of MS4A6A in most cancer tissues was negatively correlated with its expression level,suggesting the possible relation of differential MS4A6A expression to the methylation level of its promoter region.Univariate Cox analysis revealed that high expression of MS4A6A was the risk factor for LGG,TGCT,UVM and THYM;MS4A6A expression was positively correlated with the immune score in 32 types of cancer;MS4A6A expression was positively correlated with the infiltration levels of various immune cells,such as tumor associated fibroblasts(CAF),regulatory T cells(Treg),B cells,neutrophils,macrophages,monocytes,and CD8+T cells.In conclusion,MS4A6A may participate in the development of cancer,suggesting it is a potential new biomarker for cancer treatment and prevention.

Atypical anti-glomerular basement membrane(GBM)disease is rare,and the atypical anti-GBM disease with membrane hyperplasia lesion is even rarer.The treatment plan for it is not clear.This article reports a case of atypical anti-GBM disease with a negative anti-GBM antibody test,but renal tissue biopsy showed"glomerular membrane hyperplasia lesions with positive IgG linearity",which provides a reference for clinical diagnosis and treatment.The patient exhibited massive proteinuria,hematuria,edema,and renal impairment.After ruling out secondary factors,the patient was diagnosed with"atypical anti-GBM nephritis"by renal tissue biopsy,and was treated with glucocorticoids combined with cyclophosphamide,after which the patient developed a lung infection and acute left heart failure,and received regular hemodialysis treatment.Then the patient progressed to the stage of end-stage renal disease and continued to receive regular hemodialysis treatment.

Objective To establish a human tonsil organoid model and investigate the immunological effects of this tonsil organoid infected by influenza virus.Methods Human tonsil tissue removed by adenoid hypertrophy surgery were subjected to gradient centrifugation,and then the obtain cells were cultured in vitro with using a 2.5D-Transwell chamber in combination with IL-2 and B cell activating factor(Baff)to construct a human tonsil organoid.Single cell transcriptome sequencing(scRNA-seq)was used to analyze the distribution of influenza virus receptors in different cell subsets of the tonsil organoid.Immunofluorescence assay and flow cytometry were applied to detect the immunological effects of the tonsil organoid in 48 h after influenza virus infection.Results The tonsil organoids were established successfully using this 2.5D-Transwell culture technique.scRNA-seq analysis showed that the receptors for influenza virus were extensively distributed in nearly all of cell subsets of tonsil organoids.In 48 h after influenza virus infection,the tonsil organoids could generate a large amount of plasma cells and memory B cells to produce specific IgG antibodies.In addition,direct infection of the virus promoted the production of TNF-α and IL-2 from CD8+T cells and the secretion of TNF-α,IFN-γ and IL-2 by CD4+T cells.Conclusion The tonsil organoids can be established successfully and reach maturity at about the 6th day after culture.The receptors for influenza virus are widely distributed in human tonsil organoids.Influenza virus directly infects human T cells,leading to T cell activation and cytokine releasing.Moreover,influenza virus infection also promotes B cells differentiate into plasma cells and induce the secretion of IgG as well as the formation of memory B cells.

Objective To observe the improved effect of propofol on vascular hyporeactivity in septic rats and its underlying mechanism.Methods A total of 96 SD rats(12 weeks old,both genders,weighing 200～220 g)were randomly divided into sham group(n=16),sepsis group(n=16,cecal ligation and puncture),propofol group(n=16),propofol+ROCK inhibitor Y-27632 group(n=16),propofol+PKCαinhibitor GO6976 group(n=16),propofol+IP3 inhibitor 2-APB group(n=8)and propofol+gap junction inhibitor metoclopramide sodium(Movens)group(n=8).In vitro vascular ring reactivity and vascular calcium sensitivity were measured to observe the improved effects of propofol on vascular hyporeactivity in septic rats and its relationships with RhoA/ROCK,PKCα,IP3 and cell gap junction.Results Determination of in vitro vascular ring and calcium sensitivity showed that the contractile reactivity to norepinephrine(NE)and to calcium sensitivity were significantly decreased in the arterial rings isolated from the septic rats compared with those from the sham group,with the dose-response curve shifting to the right,and most significant decrease by 51.42％in the superior mesenteric artery(SMA,P＜0.05).Propofol treatment significantly improved the hyporeactivity and calcium sensitivity of the vessels isolated from the septic rats,especially those of the femoral artery with a recovery rate of 89.57％(P＜0.05).In comparison with the propofol group,the dose-response curves of the propofol+Y-27632 group and the propofol+GO6976 group were shifting to right,indicating that Y-27632 and GO6976 could significantly inhibit the amelioration of propofol on calcium sensitivity of SMA in severely septic rats with an inhibitory rate of 146.95％and 88.63％(P＜0.05),respectively.Isolated vascular reactivity measurement demonstrated that Y-27632 and Movens treatment significantly antagonized the ameliorated role of propofol on hyporeactivity of blood vessels from the septic rats with an inhibitory rate of 40.79％and 169.90％(P＜0.05),separately,while no such effect was observed in the propofol+GO6976 and propofol+2-APB groups.Conclusion Propofol treatment can significantly improve vascular hyporeactivity of septic rats,which may attribute to the increase of vascular calcium sensitivity through RhoA/ROCK pathway.