期刊：
Journal of Cardiovascular Translational Research,2024年17(5):1067-1082 ISSN：1937-5387
通讯作者：
Peng, Tianhong;Xie, W;Li, L
作者机构：
[Hou, Qin] Univ South China, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan Pr, Med Res Ctr,Hunan Prov Cooperat Innovat Ctr Mol Ta, Key Lab Atherosclerol Hunan Prov,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Deng, Yunong; Guo, Jiamin; Li, Pin; Yu, Panpan; Xie, Zhongcheng; He, Yinling; Ma, Wentao; Ouyang, Siyu; Tan, Xiaoqian; Lin, Xiaoyan; Liu, Zhiyang] Univ South China, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Zhixia; Mo, Qinger; Yu, Jiang; Chen, Dandan] Univ South China, Hengyang Med Sch, Class Clin Med, Hengyang 421001, Hunan, Peoples R China.;[Chen, Xi; Xie, Wei; Peng, Tianhong; Peng, TH] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Li, Liang] Univ South China, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Xie, W ; Li, L ; Peng, TH] U;Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.
摘要：
Exosomes, nano-sized small extracellular vesicles, have been shown to serve as mediators between intercellular communications by transferring bioactive molecules, such as non-coding RNA, proteins, and lipids from secretory to recipient cells, modulating a variety of physiological and pathophysiological processes. Recent studies have gradually demonstrated that altered exosome charges may represent a key mechanism driving the pathological process of ferroptosis. This review summarizes the potential mechanisms and signal pathways relevant to ferroptosis and then discusses the roles of exosome in ferroptosis. As well as transporting iron, exosomes may also indirectly convey factors related to ferroptosis. Furthermore, ferroptosis may be transmitted to adjacent cells through exosomes, resulting in cascading effects. It is expected that further research on exosomes will be conducted to explore their potential in ferroptosis and will lead to the creation of new therapeutic avenues for clinical diseases.
摘要：
Selenium, an essential trace element of the human body, is pivotal in human health and disease prevention. Nevertheless, the narrow therapeutic index of selenium, where the toxic and therapeutic doses are close, limits its clinical utility. Significantly, nanoscale selenium synthesized by different methods using polysaccharides as stabilizers has low toxicity properties and exhibits excellent bioactivity. Its biological activities, such as anti-tumor, anti-inflammatory, antioxidant, antibacterial, and immune function enhancement, are improved compared with traditional organic and inorganic selenium compounds, conferring greater potential for application in biomedicine. Therefore, this review evaluates the advancements in various synthesis methodologies for polysaccharide selenium nanoparticles (Se NPs) and their biological activities. It aims to provide a comprehensive theoretical basis and research directions for the future development of highly efficient, minimally toxic, and biocompatible polysaccharide-Se NPs and the application of polysaccharide-Se NPs in biomedicine.
摘要：
BACKGROUND: E2F7 is a recently discovered member of the E2F family. Investigating the function and mechanism of E2F7 in the growth of tumors is significant for the clinical diagnosis and therapy of these malignancies. OBJECTIVE: The purpose of this review is to provide theoretical basis for the diagnosis and treatment of malignant tumors by exploring E2F7. METHODS: The relevant information was collected through the PubMed database using keyword searches "E2F7" and "cancer". RESULTS: On the one hand, E2F7 plays an essential role in embryonic development, angiogenesis, and the nervous system. On the other hand, E2F7 is also linked to the occurrence and growth of various malignant tumors. CONCLUSION: E2F7 has potential as a therapeutic target in future cancer treatments.
摘要：
Currently, the oncogenic mechanism of endoplasmic reticulum stress-CAF (ERS-CAF) subpopulation in chordoma remains unknown. Here, single-cell RNA sequencing, spatial transcriptomics, GeoMx Digital Spatial Profiler, data-independent acquisition proteomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence are used to unveil the precise molecular mechanism of how ERS-CAF affected chordoma progression. Results show that hypoxic microenvironment reprograms CAFs into ERS-CAF subtype. Mechanistically, this occurrs via hypoxia-mediated transcriptional upregulation of IER2. Overexpression of IER2 in CAFs promotes chordoma progression, which can be impeded by IER2 knockdown or use of ERS inhibitors. IER2 also induces expression of ERS-CAF marker genes and results in production of a pro-tumorigenic paracrine GMFG signaling, which exert its biological function via directly binding to ITGB1 on tumor cells. ITGB1 inhibition attenuates tumor malignant progression, which can be partially reversed by exogenous GMFG intervention. Further analyses reveal a positive correlation between ITGB1high tumor cell counts and SPP1+ macrophage density, as well as the spatial proximity of these two cell types. Clinically, a significant correlation of high IER2/ITGB1 expression with tumor aggressive phenotype and poor patient survival is observed. Collectively, the findings suggest that ERS-CAF regulates SPP1+ macrophage to aggravate chordoma progression via the IER2/GMFG/ITGB1 axis, which may be targeted therapeutically in future. The hypoxic chordoma microenvironment induces upregulation of IER2 in CAF to stimulate its ERS effect and then release GMFG cytokine. GMFG secreted by ERS-CAF reshapes the immune microenvironment possibly via recruiting SPP1+ macrophages to promote chordoma progression by binding to ITGB1 on tumor cells. This study elucidates the specific molecular mechanism by which ERS-CAF regulated chordoma progression. image
期刊：
Cancer Cell International,2024年24(1):1-21 ISSN：1475-2867
通讯作者：
Tan, Yeru;Li, YH
作者机构：
[Jiang, Baohong] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang, Hunan, Peoples R China.;[Zeng, Lijun; Tan, Yeru; Li, YH; Li, Yuehua; Tang, Yuanbin; Luo, Lunqi; Ouyang, Lianjie; Feng, Wenjie; Tan, YR; Wu, Sixuan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, Hengyang, Hunan, Peoples R China.;[Wu, Sixuan] Fujian Med Univ, Fujian Canc Hosp, Clin Oncol Sch, Fuzhou, Fujian, Peoples R China.
通讯机构：
[Li, YH ; Tan, YR] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, Hengyang, Hunan, Peoples R China.
关键词：
Breast cancer;NDUFAF6;NRF2;PD-L1;Immune infiltration;Prognosis
摘要：
Breast cancer is a major global health concern, and there is a continuous search for novel biomarkers to predict its prognosis. The mitochondrial protein NDUFAF6, previously studied in liver cancer, is now being investigated for its role in breast cancer. This study aims to explore the expression and functional significance of NDUFAF6 in breast cancer using various databases and experimental models. We analyzed breast cancer samples from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) databases, supplemented with immunohistochemistry (IHC) staining to assess NDUFAF6 expression. A breast cancer cell xenograft mouse model was used to evaluate tumor growth, apoptosis, and NDUFAF6 expression. Survival probabilities were estimated through Kaplan–Meier plots and Cox regression analysis. A Protein–Protein Interaction (PPI) network was constructed, and differentially expressed genes related to NDUFAF6 were analyzed using GO, KEGG, and GSEA. The relationship between NDUFAF6 expression, immune checkpoints, and immune infiltration was also evaluated. NDUFAF6 was found to be overexpressed in breast cancer patients and in the xenograft mouse model. Its expression correlated with worse clinical features and prognosis. NDUFAF6 expression was an independent predictor of breast cancer outcomes in both univariate and multivariate analyses. Functionally, NDUFAF6 is implicated in several immune-related pathways. Crucially, NDUFAF6 expression correlated with various immune infiltrating cells and checkpoints, particularly promoting PD-L1 expression by inhibiting the NRF2 signaling pathway. The study establishes NDUFAF6 as a potential prognostic biomarker in breast cancer. Its mechanism of action, involving the inhibition of NRF2 to upregulate PD-L1, highlights its significance in the disease's progression and potential as a target for immunotherapy.
摘要：
OBJECTIVES: To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD). METHODS: Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo. RESULTS: We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF(+) ECMO-neutrophil counts and ACKR3(+) effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors. CONCLUSIONS: These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies.
摘要：
PURPOSE: Voriconazole, a first-line therapeutic agent for chronic pulmonary aspergillosis, is metabolized by the cytochrome 450 enzymes, specifically CYP2C19 and CYP3A4. Rifampicin and rifapentine act as inducers of the cytochrome P450 enzyme. The current study explored the potential drug interactions arising from the co-administration of voriconazole with either rifampicin or rifapentine, as well as the duration of this effect on serum voriconazole levels after discontinuation of rifampicin or rifapentine. PATIENTS AND METHODS: A retrospective study was conducted in tuberculosis patients with chronic pulmonary aspergillosis. These patients underwent a combination therapy involving voriconazole and rifampicin or rifapentine, or they were treated with voriconazole after discontinuation of rifampicin or rifapentine. The serum concentrations of voriconazole at steady-state were monitored. Data on demographic characteristics and the serum voriconazole levels were used for statistical analyses. RESULTS: A total of 124 serum voriconazole concentrations from 109 patients were included in the study. The average serum concentration of voriconazole fell below the effective therapeutic range in patients treated with both voriconazole and rifampicin or rifapentine. Notably the co-administration of rifapentine led to a substantial (>70%) decrease in serum voriconazole levels in two patients. Moreover, this interfering effect persisted for at least 7 days following rifampicin discontinuation, while it endured for 5 days or more after discontinuation of rifapentine. CONCLUSION: Concomitant use of voriconazole and rifampicin or rifapentine should be avoided, and it is not recommended to initiate voriconazole therapy within 5 or 7 days after discontinuation of rifapentine or rifampicin. Therapeutic drug monitoring not only provides a basis for the adjustment of clinical dose, but also serves as a valuable tool for identifying drug interactions.
摘要：
We are honored by the comments made by Li et al.1 regarding our publication2 in Neuro-Oncology. Peer-to-peer communication fosters valuable exchanges that aid in promptly addressing issues, thereby enhancing the scientific rigor of research outcomes. In response to their inquiries, we have provided answers and conducted further investigations.
Firstly, they indicate that RNA-Seq data were obtained from formalin-fixed paraffin-embedded (FFPE) samples of skull base chordoma and spinal chordoma, and RNA degradation in FFPE samples may influence the results. However, obtaining and preserving fresh samples of chordoma, being a rare disease, is extremely challenging. Sequencing fresh frozen tissue from a large cohort of chordoma, such as the 126 cases in our study, typically requires several years and significant financial resources to accomplish. Additionally, with the continuous advancement of sequencing technologies, longer timelines can lead to significant batch effects between sequencing data. Moreover, recent studies have shown a high degree of similarity between transcriptomic data from FFPE samples of various tumor tissues and transcriptomic data from fresh frozen samples of the same tumor type, suggesting that FFPE samples could serve as alternatives to fresh frozen samples.3 Furthermore, Validating a prognostic signature using FFPE specimens would provide substantial additional utility for both prospective and retrospective studies reliant on archived data, given the widespread utilization of FFPE preservation in clinical practice.4
摘要：
Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application.
摘要：
Hydrophilic and biocompatible hydrogels are widely applied as ideal scaffolds in tissue engineering. The "smart" gelation material can alter its structural, physiochemical, and functional features in answer to various endo/exogenous stimuli to better biomimic the endogenous extracellular matrix for the engineering of cells and tissues. Light irradiation owns a high spatial-temporal resolution, complete biorthogonal reactivity, and fine-tunability and can thus induce physiochemical reactions within the matrix of photoresponsive hydrogels with good precision, efficiency, and safety. Both gel structure (e.g., geometry, porosity, and dimension) and performance (like conductivity and thermogenic or mechanical properties) can hence be programmed on-demand to yield the biochemical and biophysical signals regulating the morphology, growth, motility, and phenotype of engineered cells and tissues. Here we summarize the strategies and mechanisms for encoding light-reactivity into a hydrogel and demonstrate how fantastically such responsive gels change their structure and properties with light irradiation as desired and thus improve their applications in tissue engineering including cargo delivery, dynamic three-dimensional cell culture, and tissue repair and regeneration, aiming to provide a basis for more and better translation of photoresponsive hydrogels in the clinic.
摘要：
Necrostatin-1, a small molecular alkaloid, was identified as an inhibitor of necroptosis in 2005. Investigating the fundamental mechanism of Necrostatin-1 and its role in various diseases is of great significance for scientific and clinical research. Accumulating evidence suggests that Necrostatin-1 plays a crucial role in numerous neurological disorders. This review aims to provide a comprehensive overview of the potential functions of Necrostatin-1 in various neurological disorders, offering valuable insights for future research.
摘要：
Resveratrol is one of the most interesting naturally-occurring nonflavonoid phenolic compounds with various biological activities, such as anticancer, neuroprotection, antibacterial, and anti-inflammatory. However, there is no clinical usage of resveratrol due to either its poor activity or poor pharmacokinetic properties. Heteroarenes-modified resveratrol is one pathway to improve its biological activities and bioavailability, and form more modification sites. In this review, we present the progress of heteroaryl analogues of resveratrol with promising biological activities in the latest five years, ranging from the synthesis to the structure-activity relationship and mechanism of actions. Finally, introducing heteroarenes into resveratrol is an effective strategy, which focuses on the selectivity of structure-activity relationship in vivo.
作者机构：
[Li, Rong; Xu, Rui; Xu, Xiaoding; Liu, Xiangya; Li, R; Wu, Guo] Univ South China, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Li, Rong; Xu, Rui; Xu, Xiaoding; Liu, Xiangya; Li, R; Wu, Guo] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Huang, Linzhuo; Xu, Rui; Xu, Xiaoding; Liu, Xiangya; Zhang, Yuxuan; Wu, Guo] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China.;[Huang, Linzhuo; Xu, Rui; Xu, Xiaoding; Liu, Xiangya; Zhang, Yuxuan; Wu, Guo] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou Key Lab Med Nanomat, Guangzhou 510120, Peoples R China.
通讯机构：
[Xu, XD ; Li, R] U;Univ South China, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China.;Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou Key Lab Med Nanomat, Guangzhou 510120, Peoples R China.
摘要：
Repolarizing tumor-associated macrophages (TAMs) into tumor-inhibiting M1 macrophages has been considered a promising strategy for enhanced cancer immunotherapy. However, several immunosuppressive ligands (e.g., LSECtin) can still be highly expressed on M1 macrophages, inducing unsatisfactory therapeutic outcomes. We herein developed an antibody-decorated nanoplatform composed of PEGylated iron oxide nanoparticles (IONPs) and LSECtin antibody conjugated onto the surface of IONPs via the hydrazone bond for enhanced cancer immunotherapy. After intravenous administration, the tumor microenvironment (TME) pH could trigger the hydrazone bond breakage and induce the disassociation of the nanoplatform into free LSECtin antibodies and IONPs. Consequently, the IONPs could repolarize TAMs into M1 macrophages to remodel immunosuppressive TME and provide an additional anticancer effect via secreting tumoricidal factors (e.g., interlukin-12). Meanwhile, the LSECtin antibody could further block the activity of LSECtin expressed on M1 macrophages and relieve its immunosuppressive effect on CD8(+) T cells, ultimately leading to significant inhibition of tumor growth.
摘要：
OBJECTIVE: Little is known about the association between whole-blood nicotinamide adenine dinucleotide (NAD (+)) levels and nabothian cysts. This study aimed to assess the association between NAD (+) levels and nabothian cysts in healthy Chinese women. METHODS: Multivariate logistic regression analysis was performed to analyze the association between NAD (+) levels and nabothian cysts. RESULTS: The mean age was 43.0 ± 11.5 years, and the mean level of NAD (+) was 31.3 ± 5.3 μmol/L. Nabothian cysts occurred in 184 (27.7%) participants, with single and multiple cysts in 100 (15.0%) and 84 (12.6%) participants, respectively. The total nabothian cyst prevalence gradually decreased from 37.4% to 21.6% from Q1 to Q4 of NAD (+) and the prevalence of single and multiple nabothian cysts also decreased across the NAD (+) quartiles. As compared with the highest NAD (+) quartile (≥ 34.4 μmol/L), the adjusted odds ratios with 95% confidence interval of the NAD (+) Q1 was 1.89 (1.14-3.14) for total nabothian cysts. The risk of total and single nabothian cysts linearly decreased with increasing NAD (+) levels, while the risk of multiple nabothian cysts decreased more rapidly at NAD (+) levels of 28.0 to 35.0 μmol/L. CONCLUSION: Low NAD (+) levels were associated with an increased risk of total and multiple nabothian cysts.
