Display omitted
•The structure, pharmacokinetics and pharmacological activities of cryptotanshinone.•The molecular target of cryptotanshinone and its intervention pathway mechanism.•Cryptotanshinoneh ...has anti-cancer, anti-inflammatory and immunomodulatory effects.•Cryptotanshinone interferes with cancer through JAK2/STAT3, PI3K/AKT pathway.
Cryptotanshinone (IUPAC name: (R)-1,2,6,7,8,9-hexahydro-1,6,6-trimethyl-phenanthro(1,2-b)furan-10,11-dione), a biologically active constituent extracted from the roots and rhizomes of the plant Salvia miltiorrhiza, has been studied in depth as a medicinally active compound and shown to have efficacy in the treatment of numerous diseases and disorders. In this review, we describe in detail the current status of cryptotanshinone research, including findings relating to the structure, pharmacokinetics, pharmacological activity, and derivatives of this compound. Cryptotanshinoneh as a diverse range of pharmacological effects, including anti-cancer, anti-inflammatory, immune regulatory, neuroprotective, and anti-fibrosis activities. Studies on the molecular mechanisms underlying the activities of cryptotanshinone have established that the JAK2/STAT3, PI3K/AKT, NF-κB, AMPK, and cell cycle pathways are involved in the inhibitory and pro-apoptotic effects of cryptotanshinone on different tumor cell lines, these molecular pathways interact in a coordinated manner to inhibit cell proliferation, migration and invasion,and induce transformation, autophagy, necrosis, and cellular immunity. The anti-inflammatory mechanisms of cryptotanshinone have been found to be associated with the TLR4-MyD88/PI3K/Nrf2 and TLR4-MyD88/NF-κB/MAPK pathways, whereasthe Hedgehog, NF-κB, and Nrf-2/HO-1 pathways are regulated by cryptotanshinone to reduce organ fibrosis, and its inhibitory effects on the PI3K/AKT-eNOS pathway have been linked to neuroprotective effects. Given the potential medicinal utility of cryptotanshinone, further research is needed to verify the efficacy and safety of this compound in clinical use, evaluate its pharmacological activity, and identify molecular targets.
The composition and structure of dissolved organic matter (DOM) play vital roles in the material cycle of river ecosystems. Based on ultraviolet-visible absorption spectroscopy, excitation-emission ...matrix fluorescence spectroscopy, and ultrahigh-resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry technology, this study comprehensively characterized the composition and structure of DOM in the overlying water of the Chaobai River in order to determine the potential environmental impact of DOM on the water quality. The results showed that the DOM content of the overlying water in the Chaobai River was between 10.94 and 28.13 mg/L. The main DOM component of the overlying water was humus (70.94%). The relative abundance of CHOS compounds in the Chaobai River was lower than Maozhou River (urbanized river) and significantly higher than Xiangxi Bay (suburban river). In addition, the DOM composition and structure of the overlying water were closely related to anthropogenic input, microbial activity, and phytoplankton. In particular, chlorophyll a can indirectly reflect fresh autochthonous DOM content and composition in the overlying water. The results of this study further reveal the characteristics of suburban rivers and provide theoretical basis and guidance for the water quality evaluation and pollution control of the Chaobai River and other suburban rivers worldwide.
With the rapid development of next-generation sequencing technology, several studies have shown that ncRNAs can act as competitive endogenous RNAs (ceRNAs) and are involved in various biological ...processes, such as proliferation, differentiation, apoptosis, and migration of breast cancer (BC) cells, and plays an important role in BC progression as a molecular target for its diagnosis, treatment, prognosis, and differentiation of subtypes and age groups of BC patients. Based on the description of ceRNA-related biological functions, this study screened and sorted the sequencing analysis and experimental verification conclusions of BC-related ceRNAs and found that the ncRNAs mediated ceRNA networks can promote the development of BC by promoting the expression of genes related to BC proliferation, drug resistance, and apoptosis, inducing the production of epithelial-mesenchymal transition (EMT) to promote metastasis and activating cancer-related signaling pathways.
Display omitted
•ncRNA-mediated ceRNA networks is involved in various biological processes of breast cancer.•ncRNA-mediated ceRNA networks play a crucial role in diagnosis of breast cancer.•ncRNA-mediated ceRNA networks may facilitate the development of new anti-tumor drugs and clinical interventions of breast cancer.
Potential of cucurbitacin as an anticancer drug Li, Yan; Li, Yingrui; Yao, Yan ...
Biomedicine & pharmacotherapy,
December 2023, 2023-12-00, 20231201, 2023-12-01, Letnik:
168
Journal Article
Recenzirano
Odprti dostop
In Chinese medicine, the Cucurbitaceae family contains many compounds known as cucurbitacins, which have been categorized into 12 classes ranging from A to T and more than 200 derivatives. ...Cucurbitacins are a class of highly oxidized tetracyclic triterpenoids with potent anticancer properties. The eight components of cucurbitacins with the strongest anticancer activity are cucurbitacins B, D, E, I, IIa, L-glucoside, Q, and R. Cucurbitacins have also been reported to suppress JAK-STAT 3, mTOR, VEGFR, Wnt/β-catenin, and MAPK signaling pathways, all of which are crucial for the survival and demise of cancer cells. In this paper, we review the progress in research on cucurbitacin-induced apoptosis, autophagy, cytoskeleton disruption, cell cycle arrest, inhibition of cell proliferation, inhibition of invasion and migration, inhibition of angiogenesis, epigenetic alterations, and synergistic anticancer effects in tumor cells. Recent studies have identified cucurbitacins as promising molecules for therapeutic innovation with broad versatility in immune response. Thus, cucurbitacin is a promising class of anticancer agents that can be used alone or in combination with chemotherapy and radiotherapy for the treatment of many types of cancer.Therefore, based on the research reports in the past five years at home and abroad, we further summarize and review the structural characteristics, chemical and biological activities, and studies of cucurbitacins based on the previous studies to provide a reference for further development and utilization of cucurbitacins.
•Cucurbitacin and its derivatives have a wide range of biological activities.•Cucurbitacin exerts anticancer effects through multiple targets in vivo and in vitro.•Cucurbitacin can greatly enhance the anticancer effect when used in combination with clinical chemotherapy or radiotherapy.•Cucurbitacin has a wide range of multifunctionality in immune response.
In recent years, the emergence of immunotherapy has provided a new perspective for the treatment and management of triple-negative breast cancer (TNBC). However, the relationship between tumor ...mutation burden (TMB) and immune infiltration and the prognosis of TNBC remains unclear. In this study, to explore the immunogenicity of TNBC, we divided patients with TNBC into high and low TMB groups based on the somatic mutation data of TNBC in The Cancer Genome Atlas (TCGA), and screened out genes with mutation rate ≥10. Then, Kaplan-Meier survival analysis revealed that the 5-year survival rate of the high TMB group was much higher than that of the low TMB group and the two groups also showed differences in immune cell infiltration. Further exploration found that the FAT3 gene, which displays significant difference and a higher mutation rate between the two groups, is not only significantly related to the prognosis of TNBC patients but also exhibits difference in immune cell infiltration between the wild group and the mutant group of the FAT3 gene. The results of gene set enrichment analysis and drug sensitivity analysis further support the importance of the FAT3 gene in TNBC. This study reveals the characteristics of TMB and immune cell infiltration in triple-negative breast cancer and their relationship with prognosis, to provide new biomarkers and potential treatment options for the future treatment of TNBC. The FAT3 gene, as a risk predictor gene of TNBC, is considered a potential biological target and may provide new insight for the treatment of TNBC.
Breast cancer is one of the deadliest malignant tumors worldwide. Due to its complex molecular and cellular heterogeneity, the efficacy of existing breast cancer risk prediction models is ...unsatisfactory. In this study, we developed a new lncRNA model to predict the prognosis of patients with BRCA.
BRCA-related differentially-expressed long non-coding RNA were screened from the Cancer Genome Atlas database. A novel lncRNA model was developed by univariate and multivariate analyses to predict the prognosis of patients with BRCA. The efficacy of the model was verified by TCGA-based breast cancer samples. Identified lncRNA-related mRNA based on the co-expression method.
We constructed a 7-lncRNA breast cancer prediction model including LINC00377, LINC00536, LINC01224, LINC00668, LINC01234, LINC02037, and LINC01456. The breast cancer samples were divided into high-risk and low-risk groups based on the model, which verified the specificity and sensitivity of the model. The Area Under Curve (AUC) of the 3- and 5-year Receiver Operating Characteristic curve were 0.711 and 0.734, respectively, indicating that the model has good performance.
We constructed a 7-lncRNA model to predict the prognosis of patients with BRCA, and suggest that these lncRNAs may play a specific role in the carcinogenesis of BRCA.
As one of the most common malignant tumors in humans, lung cancer has experienced a gradual increase in morbidity and mortality. This study examined prognosis-related methylation-driven genes ...specific to lung adenocarcinoma (LUAD) to provide a basis for prognosis prediction and personalized targeted therapy for LUAD patients.
The methylation and survival time data from LUAD patients in the TCGA database were downloaded. The MethylMix algorithm was used to identify the differential methylation status of LUAD and adjacent tissues based on the β-mixture model to obtain disease-related methylation-driven genes. A COX regression model was then used to screen for LUAD prognosis-related methylation-driven genes, and a linear risk model based on five methylation-driven gene expression profiles was constructed. A methylation and gene expression combined survival analysis was performed to further explore the prognostic value of 5 genes independently.
There were 118 differentially expressed methylation-driven genes in the LUAD tissues and adjacent tissues. Five of the genes, CCDC181, PLAU, S1PR1, ELF3, and KLHDC9, were used to construct a prognostic risk model. Overall, the survival time was significantly lower in the high-risk group compared with that in the low-risk group (P < 0.05). In addition, the methylation and gene expression combined survival analysis found that the combined expression levels of the genes CCDC181, PLAU, and S1PR1 as well as KLHDC9 alone can be used as independent prognostic markers or drug targets.
Our findings provide an important bioinformatic basis and relevant theoretical basis for guiding subsequent LUAD early diagnosis and prognosis assessments.
Background The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) ...immune traits and ADs complicated by NHL remains debated. Methods Aggregate data for 84 Treg-related immune traits were downloaded from the Genome-Wide Association Study (GWAS) catalog, and GWAS data for diffuse large B-cell lymphoma (DLBCL; n=315243), follicular lymphoma (FL; n=325831), sjögren’s syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn’s disease(CD; n=411973) and systemic lupus erythematosus (SLE; n=307587) were downloaded from the FinnGen database. The inverse variance weighting (IVW) method was mainly used to infer any causal association between Treg-related immune traits and DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD and SLE, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Moreover, we performed sensitivity analyses to assess the validity of the causal relationships. Results There was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed potential associations between CD25++ CD8br AC, CD28- CD25++ CD8br % T cell, CD39+ CD8br % CD8br, and the risk of FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) (adjusted FDR>0.1). Furthermore, SLE and CD exhibited a genetically predicted potential association with the CD39+ CD8+ Tregs subset. SS and DM were possibly associated with an increase in the quantity of the CD4+ Tregs subset; RA may have reduced the quantity of the CD39+ CD8+ Tregs subset, although no causal relationship was identified. Sensitivity analyses supported the robustness of our findings. Conclusions There existed a genetically predicted potential association between the CD39+ CD8+ Tregs subset and the risk of DLBCL, while SLE and CD were genetically predicted to be potentially associated with the CD39+ CD8+ Tregs subset. The CD39+ CD8+ Tregs subset potentially aided in the clinical diagnosis and treatment of SLE or CD complicated by DLBCL.
There has been increasing attention on immune-oncology for its impressive clinical benefits in many different malignancies. However, due to molecular and genetic heterogeneity of tumors, the ...activities of traditional clinical and pathological criteria are far from satisfactory. Immune-based strategies have re-ignited hopes for the treatment and prevention of breast cancer. Prognostic or predictive biomarkers, associated with tumor immune microenvironment, may have great prospects in guiding patient management, identifying new immune-related molecular markers, establishing personalized risk assessment of breast cancer. Therefore, in this study, weighted gene co-expression network analysis (WGCNA), single-sample gene set enrichment analysis (ssGSEA), multivariate COX analysis, least absolute shrinkage, and selection operator (LASSO), and support vector machine-recursive feature elimination (SVM-RFE) algorithm, along with a series of analyses were performed, and four immune-related genes (
APOD
,
CXCL14
,
IL33
, and
LIFR
) were identified as biomarkers correlated with breast cancer prognosis. The findings may provide different insights into prognostic monitoring of immune-related targets for breast cancer or can be served as reference for the further research and validation of biomarkers.
The Wnt/β-catenin pathway is abnormally activated in most lung cancer tissues and considered to be an accelerator of carcinogenesis and lung cancer progression, which is closely related to increased ...morbidity rates, malignant progression, and treatment resistance. Although targeting the canonical Wnt/β-catenin pathway shows significant potential for lung cancer therapy, it still faces challenges owing to its complexity, tumor heterogeneity and wide physiological activity. Therefore, it is necessary to elucidate the role of the abnormal activation of the Wnt/β-catenin pathway in lung cancer progression. Moreover, Wnt inhibitors used in lung cancer clinical trials are expected to break existing therapeutic patterns, although their adverse effects limit the treatment window. This is the first study to summarize the research progress on various compounds, including natural products and derivatives, that target the canonical Wnt pathway in lung cancer to develop safer and more targeted drugs or alternatives. Various natural products have been found to inhibit Wnt/β-catenin in various ways, such as through upstream and downstream intervention pathways, and have shown encouraging preclinical anti-tumor efficacy. Their diversity and low toxicity make them a popular research topic, laying the foundation for further combination therapies and drug development.
PDF
