Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.

Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.

Evaluating nitric oxide produced by rat inflamed microglial cell Lline, CHME-5, under the effect of IMOD.

Nitric oxide (NO), as a free radical, is produced by inflamed microglia cells and is one of the destructive factors of the immune system and a factor in myelin degradation. Therefore, inhibition of microglia activity is a chief strategy in reducing neurotoxic damage to the central nervous system. In this study, an herbal Immunomodulatory Drug (IMOD) was used to evaluate the effects of this drug in controlling the amount of nitric oxide. Nitric oxide induction was performed by bacterial lipopolysaccharide (LPS) in rat inflamed microglial cell line, CHME-5. ELISA test was used to measure the produced nitric oxide at 24, 48, and 72 hours. The results showed that the high concentrations of IMOD (1.2, and 4% V/V) had anti-inflammatory effects on microglial cells and were able to reduce the amount of nitric oxide in these cells but the effective dose of IMOD was in the range of 1.2% V/V. Therefore, the safest dose and the best time for the effect of IMOD on inflammatory cell groups are 1.2% V/V and 72h, respectively. Hence, with further studies, IMOD can be considered as an herbal anti-inflammatory drug that is effective in controlling neurodegenerative diseases.

Inhibition of Notch signaling pathway reduces angiogenesis in hypertrophic scar. / 抑制Notch信号通路减少增生性瘢痕的血管生成.

OBJECTIVES: Hypertrophic scar (HS) is the most common pathological scar in clinical practice. During its formation, angiogenesis-related factors show dynamic expression. Modern studies have found that Notch signaling pathway has an extremely important role in maintaining the construction and remodeling of vascular endothelial cells and vascular network. The correlation between Notch signaling pathway and angiogenesis in hypertrophic scar has been rarely reported. This study aims to investigate correlation between Notch signaling pathway and the expression of angiogenic factors in a proliferative scar model. METHODS: A total of 81 Sprague Dawley rats (SPF grade) were randomly assigned into a blank control group, a model group, and a blocker group. In the blocker group, a 2 cm diameter circular scald head was placed on the back of the rats for 10 s at 75 ℃ by using a constant temperature and pressure electrothermal scalding apparatus to form a rat deep II° burn model, and a hyperplastic scar model rat was obtained after natural healing of the wound skin (21 to 23 day epithelialization). A syringe was used to inject a needle from the normal skin around the scar at the 1st, 3rd, 5th, 7th, and 14th days after modeling. The γ-secretase inhibitor was injected locally at 2 mg/kg in a dilution of 0.1 mL at the base of the scar. The rats in the model group was injected with the same amount of saline after modeling; the rats in the blank control group was injected with the same amount of saline. Nine rats in each group was randomly killed by air embolization at the 21st, 28th, and 35th days, respectively. The protein expressions of collagen type I (COL-I) and collagen type III (COL-III) were detected by immunohistochemistry. The protein expressions of vascular endothelial growth factor (VEGF), angiopoietin 1 (Ang1), transforming growth factor-ß1 (TGF-ß1), and matrix metalloproteinase-2 (MMP-2) were detected by Western blotting. RESULTS: Immunohistochemical results showed that, at the 21st,28th, and 35th days, the protein expressions of COL-I and COL-III in the model group were up-regulated compared with the blank control group (all P<0.05) and the protein expressions of COL-I and COL-III in the blocker group were decreased compared with the model group (all P<0.05). Western blotting showed that, at the 21st, 28th, and 35th days, the protein expressions of VEGF, Ang1, TGF-ß1, and MMP-2 in the model group were significantly higher than those in the blank control group (all P<0.05). Except for the 21st day, the protein expressions of VEGF, Ang1, TGF-ß1, and MMP-2 in the blocker group were lower than those in the model group at the 28th and 35th days (all P<0.05). CONCLUSIONS: In the Sprague Dawley rat proliferative scar model, inhibition of Notch signaling pathway could attenuate the expressions of COL-I and COL-III, reduce traumatic scar proliferation, down-regulate the expressions of VEGF, Ang1, TGF-ß1, and MMP-2, and inhibit angiogenesis. The expressions of angiogenesis-related factors appeare to be up-regulated during the formation of proliferative scar. When the Notch signaling pathway is inhibited, the up-regulated angiogenic factors show a decreasing trend and the proliferative scar is alleviated, which suggests that Notch signaling pathway may affect the formation of hyperplastic scar by regulating the expression of angiogenic factors.

Curcumin and nanodelivery systems: New directions for targeted therapy and diagnosis of breast cancer.

As the global incidence of breast cancer continues to surge, the pursuit of novel, low-toxicity, and highly efficacious therapeutic strategies has emerged as a pivotal research focus. Curcumin (CUR), an active constituent of traditional Chinese medicine (TCM) renowned for its antimicrobial, anti-inflammatory, antioxidant, and antitumor properties, exhibits immense potential in breast cancer therapy. Nevertheless, CUR's poor water solubility, chemical instability, and unfavorable pharmacokinetics have impeded its clinical utilization. To address these challenges, nano-delivery systems have been extensively exploited for CUR administration, enhancing its in vivo stability and bioavailability, and facilitating precise targeting of breast cancer lesions. Therefore, we elaborate on CUR's chemical foundations, drug metabolism, and safety profile, and elucidate its potential mechanisms in breast cancer therapy, encompassing inducing apoptosis and autophagy, blocking cell cycle, inhibiting breast cancer metastasis, regulating tumor microenvironment and reversing chemotherapy resistance. The review primarily emphasizes recent advancements in CUR-based nano-delivery systems for the treatment and diagnosis of breast cancer. Liposomes, nanoparticles (encompassing polymer nanoparticles, solid lipid nanoparticles, mesoporous silica particles, metal/metal oxide nanoparticles, graphene nanomaterials, albumin nanoparticles, etc.), nanogels, and nanomicelles can serve as delivery carriers for CUR, exhibiting promising anti-breast cancer effects in both in vivo and in vitro experiments. Furthermore, nano-CUR can be integrated with fluorescence imaging, magnetic resonance imaging, computed tomography imaging, ultrasound, and other techniques to achieve precise localization and diagnosis of breast cancer masses. While this article has summarized the clinical studies of nano-curcumin, it is noteworthy that the research literature on nano-CUR applied to breast cancer diagnosis and the translation of nano-CUR clinical studies in BC patients remain limited. Therefore, future research should intensify exploration in this direction.

Bibliometric analysis of global research trends between gut microbiota and breast cancer: from 2013 to 2023.

Background: Breast cancer is the most prevalent cancer globally and is associated with significant mortality. Recent research has provided crucial insights into the role of gut microbiota in the onset and progression of breast cancer, confirming its impact on the disease's management. Despite numerous studies exploring this relationship, there is a lack of comprehensive bibliometric analyses to outline the field's current state and emerging trends. This study aims to fill that gap by analyzing key research directions and identifying emerging hotspots. Method: Publications from 2013 to 2023 were retrieved from the Web of Science Core Collection database. The VOSviewer, R language and SCImago Graphica software were utilized to analyze and visualize the volume of publications, countries/regions, institutions, authors, and keywords in this field. Results: A total of 515 publications were included in this study. The journal Cancers was identified as the most prolific, contributing 21 papers. The United States and China were the leading contributors to this field. The University of Alabama at Birmingham was the most productive institution. Peter Bai published the most papers, while James J. Goedert was the most cited author. Analysis of highly cited literature and keyword clustering confirmed a close relationship between gut microbiota and breast cancer. Keywords such as "metabolomics" and "probiotics" have been prominently highlighted in the keyword analysis, indicating future research hotspots in exploring the interaction between metabolites in the breast cancer microenvironment and gut microbiota. Additionally, these keywords suggest significant interest in the therapeutic potential of probiotics for breast cancer treatment. Conclusion: Research on the relationship between gut microbiota and breast cancer is expanding. Attention should be focused on understanding the mechanisms of their interaction, particularly the metabolite-microbiota-breast cancer crosstalk. These insights have the potential to advance prevention, diagnosis, and treatment strategies for breast cancer. This bibliometric study provides a comprehensive assessment of the current state and future trends of research in this field, offering valuable perspectives for future studies on gut microbiota and breast cancer.

Updating the therapeutic role of ginsenosides in breast cancer: a bibliometrics study to an in-depth review.

Breast cancer is currently the most common malignancy and has a high mortality rate. Ginsenosides, the primary bioactive constituents of ginseng, have been shown to be highly effective against breast cancer both in vitro and in vivo. This study aims to comprehensively understand the mechanisms underlying the antineoplastic effects of ginsenosides on breast cancer. Through meticulous bibliometric analysis and an exhaustive review of pertinent research, we explore and summarize the mechanism of action of ginsenosides in treating breast cancer, including inducing apoptosis, autophagy, inhibiting epithelial-mesenchymal transition and metastasis, and regulating miRNA and lncRNA. This scholarly endeavor not only provides novel prospects for the application of ginsenosides in the treatment of breast cancer but also suggests future research directions for researchers.

Differential expression profiles of miRNA in granulomatous lobular mastitis and identification of possible biomarkers.

The etiology and pathogenesis of granulomatous lobular mastitis (GLM) remain largely elusive and the expression levels and regulatory roles of microRNAs (miRNAs or miRs) in GLM have remained mostly undetermined. In the present study, the miRNAs that were differentially expressed in breast biopsy samples from patients with GLM and normal tissue adjacent to fibroadenoma were analyzed, a comprehensive differential expression profile of miRNAs was provided and potential biomarkers were screened out. The expression profile of miRNAs was determined by high-throughput sequencing in the tissues of patients with GLM and healthy controls. Significantly differentially expressed miRNAs were screened by threshold setting and cluster analysis and their target genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, circulating differentially expressed miRNAs between the GLM and control groups were further analyzed by reverse transcription-quantitative PCR (RT-qPCR). A total of 31,077 miRNAs were detected by high-throughput sequencing. By using the cutoff criteria of |log2 fold change|>2.5 and q<0.001, 13 miRNAs that were indicated to be GLM biomarkers were screened out. The expression levels of these 13 miRNAs in the GLM group were higher than those in the control group. GO and KEGG enrichment analyses suggested that the occurrence and development of GLM may be associated with autoimmune inflammation, metabolism and pathogenic organisms. miR-451a and miR-5571-3p were confirmed to be significantly increased in the serum of patients with GLM compared with their levels in the serum of healthy volunteers, which suggests that they may be used as biomarkers of GLM. To the best of our knowledge, the present study was the first report detailing genome-wide miRNA profiling of patients with GLM compared with controls. The possible targets and pathways of GLM were evaluated by bioinformatics analysis. The present study identified 13 differentially expressed miRNAs with important theoretical significance and potential application. Furthermore, miR-451a and miR-5571-3p were verified by RT-qPCR as possible biomarkers of GLM.