The L-shaped relationship between composite dietary antioxidant index and sarcopenic obesity in elderly adults: a cross-sectional study.

Background: This study aimed to examine the associations of the Composite Dietary Antioxidant Index (CDAI) with sarcopenic obesity (SO) using the National Health and Nutrition Examination Survey (NHANES) database. Methods: Data were gathered from NHANES between 2001 and 2004. To examine the relationship between CDAI and the occurrence of SO, multiple logistic regression analyses were performed. Subgroup analyses were performed to demonstrate the stability of the results. Restricted cubic splines were utilized to examine the non-linear correlations. Results: A total of 2,333 elderly individuals were included in the study. In the multivariate logistic regression crude model, we revealed an odds ratio (OR) of 0.928 [95% confidence interval (CI), 0.891-0.965, p < 0.001] for the correlation between CDAI and SO. The ORs were 0.626 (95% CI, 0.463-0.842) and 0.487 (95% CI, 0.354-0.667) for CDAI tertiles 2 and 3, respectively (p for trend <0.001), after full adjustment. The subgroup analysis findings demonstrated a reliable and enduring connection between CDAI and SO across various subgroups. However, the strength of the correlation between CDAI and SO was significantly affected by diabetes (p for interaction = 0.027). Moreover, restricted cubic spline analysis revealed an L-shaped relationship. Conclusion: The present study identified an L-shaped correlation between CDAI and SO in elderly participants' demographics. The implications of these findings were significant for future studies and the formulation of dietary guidelines.

LncRNA HAGLROS promotes breast cancer evolution through miR-135b-3p/COL10A1 axis and exosome-mediated macrophage M2 polarization.

Long non-coding RNAs (lncRNAs) play an important role in breast cancer progression, but the function of lncRNAs in regulating tumor-associated macrophages (TAMs) remains unclear. As carriers of lncRNAs, exosomes play an important role as mediators in the communication between cancer cells and the tumor microenvironment. In this study, we found that lncRNA HAGLROS was highly expressed in breast cancer tissues and plasma exosomes, and its high expression was related to the poor prognosis of breast cancer patients. Functionally, breast cancer cell-derived exosomal lncRNA HAGLROS promotes breast cancer cell proliferation, migration, epithelial-mesenchymal transition (EMT) process and angiogenesis by inducing TAM/M2 polarization. Mechanistically, lncRNA HAGLROS competitively binds to miR-135-3p to prevent the degradation of its target gene COL10A1. Collectively, these results indicated that the lncRNA HAGLROS/miR-135b-3p/COL10A1 axis promoted breast cancer progression, and revealed the interactive communication mechanism between breast cancer cells and TAMs, suggesting that lncRNA HAGLROS may be a potential biomarker and therapeutic target for breast cancer.

The involvement of ROS-regulated programmed cell death in hepatocellular carcinoma.

Reactive oxidative species (ROS) is a crucial factor in the regulation of cellular biological activity and function, and aberrant levels of ROS can contribute to the development of a variety of diseases, particularly cancer. Numerous discoveries have affirmed that this process is strongly associated with "programmed cell death (PCD)," which refers to the suicide protection mechanism initiated by cells in response to external stimuli, such as apoptosis, autophagy, ferroptosis, etc. Research has demonstrated that ROS-induced PCD is crucial for the development of hepatocellular carcinoma (HCC). These activities serve a dual function in both facilitating and inhibiting cancer, suggesting the existence of a delicate balance within healthy cells that can be disrupted by the abnormal generation of reactive oxygen species (ROS), thereby influencing the eventual advancement or regression of a tumor. In this review, we summarize how ROS regulates PCD to influence the tumorigenesis and progression of HCC. Studying how ROS-induced PCD affects the progression of HCC at a molecular level can help develop better prevention and treatment methods and facilitate the design of more effective preventative and therapeutic strategies.

A Risk Model for Prognosis and Treatment Response Prediction in Colon Adenocarcinoma Based on Genes Associated with the Characteristics of the Epithelial-Mesenchymal Transition.

The epithelial-mesenchymal transition (EMT) is an important process during metastasis in various tumors, including colorectal cancer (CRC). Thus, the study of its characteristics and related genes is of great significance for CRC treatment. In this study, 26 EMT-related gene sets were used to score each sample from The Cancer Genome Atlas program (TCGA) colon adenocarcinoma (COAD) database. Based on the 26 EMT enrichment scores for each sample, we performed unsupervised cluster analysis and classified the TCGA-COAD samples into three EMT clusters. Then, weighted gene co-expression network analysis (WGCNA) was used to investigate the gene modules that were significantly associated with these three EMT clusters. Two gene modules that were strongly positively correlated with the EMT cluster 2 (worst prognosis) were subjected to Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. Then, a prognosis-related risk model composed of three hub genes GPRC5B, LSAMP, and PDGFRA was established. The TCGA rectal adenocarcinoma (READ) dataset and a CRC dataset from the Gene Expression Omnibus (GEO) were used as the validation sets. A novel nomogram that incorporated the risk model and clinicopathological features was developed to predict the clinical outcomes of the COAD patients. The risk model served as an independent prognostic factor. It showed good predictive power for overall survival (OS), immunotherapy efficacy, and drug sensitivity in the COAD patients. Our study provides a comprehensive evaluation of the clinical relevance of this three-gene risk model for COAD patients and a deeper understanding of the role of EMT-related genes in COAD.

Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer.

BACKGROUND: Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear. METHODS: The protein level of Sp1 in tumour tissues was determined by immunohistochemistry. The effect of Sp1 expression on the biological characteristics of cervical cancer cells was assessed by colony, wound healing, transwell formation, EdU, and TUNEL assays. Finally, the underlying mechanisms and effects of Sp1 on the mitochondrial network and metabolism of cervical cancer were analysed both in vitro and in vivo. RESULTS: Sp1 expression was upregulated in cervical cancer. Sp1 knockdown suppressed cell proliferation both in vitro and in vivo, while overexpression of Sp1 had the opposite effects. Mechanistically, Sp1 facilitated mitochondrial remodelling by regulating mitofusin 1/2 (Mfn1/2), OPA1 mitochondrial dynamin-like GTPase (Opa1), and dynamin 1-like (Drp1). Additionally, the Sp1-mediated reprogramming of glucose metabolism played a critical role in the progression of cervical cancer cells. CONCLUSIONS: Our study demonstrates that Sp1 plays a vital role in cervical tumorigenesis by regulating the mitochondrial network and reprogramming glucose metabolism. Targeting Sp1 could be an effective strategy for the treatment of cervical cancer.

PD-L1/p-STAT3 promotes the progression of NSCLC cells by regulating TAM polarization.

PD-L1 is closely related to the immune escape process of tumour cells, and targeted PD-L1 clinical immunotherapy has been implemented. However, whether PD-L1 is involved in TAM/M2 polarization in the TME of NSCLC and its specific mechanism remain unclear. In order to clarify the specific role of PD-L1 in NSCLC and to seek new treatments for NSCLC, we designed a series of experimental studies. After constructing the co-culture system and conditioned medium system, the proliferation, apoptosis, metastasis, angiogenesis, EMT process and stemness of NSCLC were detected by MTT, flow cytometry, Transwell, endothelial cell tube formation and western blot assays. The results showed that αPD-L1 reversed TAM/M2 polarization by suppressing STAT3 phosphorylation in TAM/M2, therapy inhibiting NSCLC cell migration, angiogenesis, EMT process and stemness. However, αPD-L1 had no effect on the proliferation and apoptosis abilities of NSCLC cells. In vivo experiments showed that αPD-L1 inhibited lung metastasis of NSCLC and reversed TAM/M2 polarization in TME. The study investigates the mechanism by which PD-L1 regulates TAMs polarization in TME and promotes malignant progression of NSCLC, providing a new theoretical basis for PD-L1 targeted therapy of NSCLC.

EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling.

CircBRWD3 is a newly discovered circRNA, and its potential function has not been probed. Here, we aimed to molecularly dissect the role of circBRWD3 in the tumorigenesis and progression of breast cancer (BC). qRT-PCR analysis revealed that circBRWD3 expression was dramatically upregulated in BC tissues, a feature that was positively correlated with the poor prognosis of patients with BC. CircBRWD3 knockdown repressed cell proliferation and metastasis, while promoting cell apoptosis in vitro. Consistently, an in vivo circBRWD3 deficiency model exhibited suppressed tumor metastasis and oncogenesis. On the other hand, circBRWD3 overexpression promoted cancer cell activity and tumorigenesis. Further, mechanistic studies elucidated that circBRWD3 sponged both miR-142-3p and miR-142-5p to modulate RAC1 expression, which subsequently activated the RAC1/PAK1 signaling to facilitate the tumorigenesis and progression of BC. Moreover, we discovered that EIF4A3 facilitated circBRWD3 expression by targeting the upstream of BRWD3 pre-mRNA. In conclusion, our study reveals that circBRWD3 facilitates BC tumorigenesis by regulating the circBRWD3/miR-142-3p_miR-142-5p /RAC1/PAK1 axis. In addition, circBRWD3 expression is positively regulated by an RNA-binding protein, EIFA3. Our results provide valuable scientific data for early diagnosis and therapy for breast cancer patients.

PD­L1 mediates triple­negative breast cancer evolution via the regulation of TAM/M2 polarization.

Tumor­associated macrophages/M2­type (TAM/M2) play a key role in the metastasis and angiogenesis of cancer, and are considered to be critical targets for cancer treatment. However, it remains unclear whether α­programmed death­ligand 1 (αPD­L1; PD­L1 inhibitor) inhibits tumor progression via targeting TAMs. In the present study, it was demonstrated that αPD­L1 significantly inhibited IL­13­induced TAM/M2 polarization in vitro. Moreover, αPD­L1 inhibited the epithelial­mesenchymal transition (EMT) process and the stemness of triple­negative breast cancer (TNBC) cells, which were mediated via the reversal of TAM/M2 polarization. This therefore inhibited the migration and angiogenesis of TNBC cells. Furthermore, αPD­L1 prevented STAT3 phosphorylation and nuclear translocation, which resulted in the arrest of TAM/M2 polarization. In vivo experiments further demonstrated that αPD­L1 reduced the number of lung metastases without affecting tumor growth. Moreover, αPD­L1 reduced the expression levels of TAM/M2, EMT, stemness and vascular markers in tumor tissues. In summary, these data suggest that αPD­L1 plays a vital role in the anti­metastasis and anti­angiogenesis of TNBC in vitro and in vivo via the inhibition of TAM/M2 polarization. These findings may thus provide a novel therapeutic strategy for clinically refractory TNBC.

[Ginsenoside Rg3 Regulates Cisplatin Resistance in Gastric Cancer by Wnt/ß-catenin Signaling Pathway].

Objective To investigate the inhibitory effect of ginsenoside Rg3 combined with cisplatin (DDP) on DDP-resistant cell line SGC-7901/DDP and their molecular mechanism.Methods SGC-7901/DDP cells were divided into four groups including a control group,a ginsenoside Rg3 (40 µg/ml) treatment group,a DDP (1.40 µg/ml) treatment group,and a drug combination treatment group.The proliferation ability of SGC-7901/DDP cells was detected by MTT,EdU,and colony formation assays.The apoptosis ability of SGC-7901/DDP cell was detected by flow cytometry and Hoechst 33342 staining.The protein levels of apoptosis-related markers were detected by Western blotting.The migration ability of SGC-7901/DDP cells was detected by wound healing and Transwell assays.The expression levels of proteins in epithelial-mesenchymal transformation (EMT) and Wnt/ß-catenin signaling pathway were determined by Western blotting and immunofluorescence staining.Results Compared with the ginsenoside Rg3 or the DDP treatment groups,the drug combination treatment group inhibited the proliferation (t=8.062,P=0.001;t=7.090,P=0.002),colony formation (t=8.062,P=0.001;t=6.144,P=0.004),and migration (t=7.424,P=0.002;t=4.317,P=0.013),and promoted the apoptosis (t=5.530,P=0.031;t=6.036,P=0.026) of SGC-7901/DDP cells.Compared with the ginsenoside Rg3 and the DDP treatment groups,the drug combination treatment group down-regulated the expression levels of EMT-associated proteins including vimentin (t=24.450,P<0.001;t=14.750,P<0.001),Snail (t=29.640,P<0.001;t=70.700,P<0.001),Slug (t=89.230,P<0.001;t=87.360,P<0.001),matrix metalloproteinase (MMP) 2 (t=84.540,P<0.001;t=67.120,P<0.001),and MMP9 (t=19.010,P<0.001;t=10.890,P<0.001),as well as those of Wnt/ß-catenin signaling pathway related proteins including Wnt (t=35.480,P<0.001;t=14.670,P<0.001),ß-catenin (t=155.800,P<0.001;t=118.100,P<0.001),C-myc (t=20.870,P<0.001;t=3.334,P=0.029),and cyclin D1 (t=5.007,P=0.008;t=8.347,P=0.001).Meanwhile,it up-regulated the expression of epithelial cells including E-cadherin (t=36.450,P<0.001;t=33.810,P<0.001) and ZO-1 (t=37.060,P<0.001;t=37.030,P<0.001).Conclusion Ginsenoside Rg3 enhanced the sensitivity of SGC-7901/DDP cells to DDP by inhibiting the activity of Wnt/ß-catenin signaling pathway.

Regulation of wheat bran feruloyl oligosaccharides in the intestinal antioxidative capacity of rats associated with the p38/JNK-Nrf2 signaling pathway and gut microbiota.

BACKGROUND: Feruloyl oligosaccharides (FOs), the ferulic acid ester of oligosaccharides, may possess the physiological functions of both ferulic acid and oligosaccharides, including antioxidative activity and gut microbiota modulation capacity. The present study aimed to investigate whether FOs could regulate the intestinal antioxidative capacity of rats by modulating the MAPKs/Nrf2 signaling pathway and gut microbiota. Thirty Wistar rats were randomly divided into five groups. Rats received a standard diet and were gavaged once daily with 0.85% normal saline, 100 mg kg-1 body weight vitamin C or FOs solution at doses of 20, 40 and 80 mg kg-1 body weight for 21 days. RESULTS: FOs strengthened the antioxidative capacity of the jejunum, as indicated by increased in contents of catalase, superoxide dismutase and glutathione peroxidase, as well as glutathione. Moreover, FOs administration upregulated the mRNA expression level of antioxidant-related genes (glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit and heme oxygenase-1) in the jejunum. Increases in phosphorylation levels of Nrf2, p38 and JNK were also observed. Administration with 40 mg kg-1 FOs altered the structure and composition of the cecal microbiota, which was indicated by the increased the relative abundances of Actinobacteria, Proteobacteria and Acidobacteriota, and the decreased the relative abundances of Firmicutes, Lachnospiraceae_NK4A136_group and Blautia. Furthermore, Spearman correlation analysis revealed that the altered cecal microbiota closely correlated with jejunal antioxidative capacity of rats. CONCLUSION: FOs could be used as an antioxidant for gut heath improvement through modulating the p38/JNK-Nrf2 signaling pathway and gut microbiota. © 2022 Society of Chemical Industry.

Macular Morphologic and Microvascular Analysis in Pseudophakic Children with Previous Pediatric Cataract Using Optical Coherence Tomography Angiography.

INTRODUCTION: The macular morphologic and microvascular changes in children with pseudophakia after pediatric cataract surgery remain unknown. The aim of this study was to analyze macular morphologic and microvascular remodeling in children with pseudophakia after pediatric cataract surgery using optical coherence tomography angiography (OCTA). METHODS: Consecutive cases between December 1, 2018, and November 31, 2020 were recruited. Sixty-one participants (31 pseudophakic children and 30 healthy controls) met the inclusion criteria and were included for final analysis. OCTA was used to measure macular vascular density, the foveal avascular zone (FAZ), and macular thickness. The parameters were compared between pseudophakic and healthy eyes using binary logistic regression, with adjustment for the effect of refractive error, age, and axial length. RESULTS: Compared with normal eyes, a significantly reduced area of the FAZ (p = 0.042), increased superficial foveal vascular density (p = 0.033), and increased inner and outer foveal thickness (p = 0.034 and 0.029, respectively) were noted in pseudophakic eyes. The deep parafoveal vascular density was generally lower in eyes with cataracts (p ≤ 0.044). The inner foveal thickness was positively correlated with the superficial foveal vascular density (r = 0.889, p < 0.001) and negatively correlated with the area of the FAZ (r = -0.903, p < 0.001). The outer foveal thickness was positively correlated with the deep foveal vascular density (r = 0.399, p = 0.002). CONCLUSIONS: Morphological and microvascular remodeling in children with previous pediatric cataract indicates foveal underdevelopment. The underlying mechanism requires further investigation.

An advanced network pharmacology study to explore the novel molecular mechanism of Compound Kushen Injection for treating hepatocellular carcinoma by bioinformatics and experimental verification.

BACKGROUND: Compound Kushen Injection (CKI) is a Chinese patent drug that exerts curative effects in the clinical treatment of hepatocellular carcinoma (HCC). This study aimed to explore the targets and potential pharmacological mechanisms of CKI in the treatment of HCC. METHODS: In this study, network pharmacology was used in combination with molecular biology experiments to predict and verify the molecular mechanism of CKI in the treatment of HCC. The constituents of CKI were identified by UHPLC-MS/MS and literature search. The targets corresponding to these compounds and the targets related to HCC were collected based on public databases. To screen out the potential hub targets of CKI in the treatment of HCC, a compound-HCC target network was constructed. The underlying pharmacological mechanism was explored through the subsequent enrichment analysis. Interactive Gene Expression Profiling Analysis and Kaplan-Meier plotter were used to examine the expression and prognostic value of hub genes. Furthermore, the effects of CKI on HCC were verified through molecular docking simulations and cell experiments in vitro. RESULTS: Network analysis revealed that BCHE, SRD5A2, EPHX2, ADH1C, ADH1A and CDK1 were the key targets of CKI in the treatment of HCC. Among them, only CDK1 was highly expressed in HCC tissues, while the other 5 targets were lowly expressed. Furthermore, the six hub genes were all closely related to the prognosis of HCC patients in survival analysis. Molecular docking revealed that there was an efficient binding potential between the constituents of CKI and BCHE. Experiments in vitro proved that CKI inhibited the proliferation of HepG2 cells and up-regulated SRD5A2 and ADH1A, while down-regulated CDK1 and EPHX2. CONCLUSIONS: This study revealed and verified the targets of CKI on HCC based on network pharmacology and experiments and provided a scientific reference for further mechanism research.

Effect of age and cycloplegia on the morphology of the human crystalline lens: swept-source OCT study.

PURPOSE: To evaluate the effect of age and cycloplegia on the morphology of the crystalline lens using a swept-source optical coherence tomography (SS-OCT) system. SETTING: Hospital. DESIGN: Prospective cross-sectional study. METHODS: The parameters including anterior chamber depth (ACD), the radii of curvature of the anterior and posterior surface of the crystalline lens (ALR and PLR), lens thickness (LT), lens equatorial diameter (LED), and lens vault (LV) were quantified by the SS-OCT before and after cycloplegia. The paired t test was used to compare the parameters before and after cycloplegia. A multivariate linear regression model was built to analyze the association between the parameters/cycloplegia-induced changes and age, while adjusting for the effect of axial length, refractive status, and sex. RESULTS: 76 individuals (age range, 18 to 86 years) were recruited. The ALR and ACD were negatively correlated with age (P ≤ .002), and the LT, LV, and LED were positively correlated with age (P ≤ .004). In participants younger than 60 years, the ALR and ACD significantly increased, whereas the LV and LT significantly decreased after cycloplegia (all P < .001). With aging, cycloplegia-induced differences of ALR (P = .001) and ACD (P = .014) significantly decreased, and of LT (P < .001), LT (P < .001), and LV (P = .001) significantly increased. CONCLUSIONS: The crystalline lens morphology measured by the SS-OCT revealed steepening anterior surface and increasing equatorial diameter with age. Cycloplegia caused a significant change of anterior surface morphology in participants younger than 60 years, and this effect diminished with age.

Prognostic value of Mortalin correlates with roles in epithelial-mesenchymal transition and angiogenesis in lung adenocarcinoma.

Mortalin is involved in the malignant phenotype of many cancers. However, the specific molecular mechanisms involving Mortalin in lung adenocarcinoma remain unclear. In this study, we showed that both Mortalin mRNA and protein are overexpressed in lung adenocarcinoma. In addition, Mortalin overexpression was positively correlated with poor overall survival. In vitro experiments showed that Mortalin silencing inhibited the proliferation, colony formation and migration abilities of A549 and H1299 cells. Mortalin promotes EMT progression, angiogenesis and tumor progression by activating the Wnt/ß-catenin signaling pathway. In vivo experiments further confirmed that Mortalin promoted malignant progression of lung adenocarcinoma. Taken together, our data suggest that Mortalin represents an attractive prognostic marker and therapeutic target in lung adenocarcinoma patients.

A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation.

BACKGROUND: Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated. METHODS: Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis. RESULTS: The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes (NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92 and SFN) associated with the development of PC, and survival analysis found 5 genes (TSPOAP1, ADGRG6, GPR87, FAM111B and MMP28) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found that CDK1, JAK1, EGFR, MAPK1 and MAPK3 served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis. CONCLUSIONS: Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI.

Age-related changes in crystalline lens tilt and decentration: swept-source OCT study.

PURPOSE: To investigate the age-related tilt and decentration of crystalline lenses using a swept-source optical coherence tomography biometer (SS-OCT) (CASIA2, Tomey Corp.). SETTING: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. DESIGN: Cross-sectional study. METHODS: The direction and magnitude of the crystalline lens were evaluated in 230 participants with ages ranging from 7 to 90 years using SS-OCT. The participants were divided into 4 age groups, and the differences among the groups were analyzed. Multiple linear regression was used to investigate the main factors influencing crystalline lens tilt and decentration. RESULTS: The natural crystalline lens tilted toward the inferotemporal direction with a mean magnitude of 4.3 ± 1.5 degrees (range 0.7 to 8.95 degrees). The mean decentration toward the superotemporal direction was 0.17 ± 0.12 mm (range 0.03 to 1.15 mm). There was mirror symmetry between the right and left eyes. There were statistically significant differences in the crystalline lens tilt and decentration among the age groups. Multiple linear regression showed that changes in crystalline lens tilt depended on angle α (P < .01) and anterior chamber depth (ACD; P = .008), whereas crystalline lens decentration depended on angle κ (P = .003), age (P < .01), and angle α (P = .002). CONCLUSIONS: Although there was a statistically significant difference in crystalline lens tilt and decentration among age groups, the variation in the crystalline lens position was partially affected by age. The crystalline lens tilt was greater in eyes with wider angle α and shallower ACD, whereas crystalline lens decentration was greater in younger eyes with wider angles κ and α.

Revealing the Common Mechanisms of Scutellarin in Angina Pectoris and Ischemic Stroke Treatment via a Network Pharmacology Approach.

OBJECTIVE: To investigate the shared mechanisms of scutellarin in angina pectoris (AP) and ischemic stroke (IS) treatment. METHODS: A network pharmacology approach was used to detect the potential mechanisms of scutellarin in AP and IS treatment by target prediction, protein-protein interaction (PPI) data collection, network construction, network analysis, and enrichment analysis. Furthermore, molecular docking simulation was employed to analyze the interaction between scutellarin and core targets. RESULTS: Two networks were established, including a disease-target network and a PPI network of scutellarin targets against AP and IS. Network analysis showed that 14 targets, namely, AKT1, VEGFA, JUN, ALB, MTOR, ESR1, MAPK8, HSP90AA1, NOS3, SERPINE1, FGA, F2, FOXO3, and STAT1, might be the therapeutic targets of scutellarin in AP and IS. Among them, NOS3 and F2 were recognized as the core targets. Additionally, molecular docking simulation confifirmed that scutellarin exhibited a relatively high potential for binding to the active sites of NOS3 and F2. Furthermore, enrichment analysis indicated that scutellarin might exert a therapeutic role in both AP and IS by regulating several important pathways, such as coagulation cascades, mitogen-activated protein kinase (MAPK) signaling pathway, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, Toll-like receptor signaling pathway, hypoxia inducible factor-1 (HIF-1) signaling pathway, forkhead box O (FoxO) signaling pathway, tumor necrosis factor (TNF) signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, insulin resistance, and estrogen signaling pathway. CONCLUSIONS: The shared underlying mechanisms of scutellarin on AP and IS treatment might be strongly associated with its vasorelaxant, anticoagulant, anti-inflammatory, and antioxidative effects as well as its effect on improving lipid metabolism.

Mortalin promotes breast cancer malignancy.

Mortalin is a member of the heat shock protein 70 (HSP70) family that promotes the development of many cancers. It is reportedly a tumor promoter, but the mechanism of Mortalin in breast cancer is unclear. We designed a series of experiments to explore the correlation between Mortalin and the malignancy of breast cancer, and to assess the potential of Mortalin as a novel therapeutic target in breast cancer. The expression level of Mortalin in breast cancer tissues was detected. Then, we did a series of functional experiment. The findings indicated that Mortalin facilitates the proliferation, metastasis, and endothelial-to-mesenchymal transition (EMT) process of breast cancer. In our research, Mortalin is regulated EMT process and malignant progression of breast cancer through Wnt/ß-Catenin signaling pathway. The findings imply that Mortalin significantly promotes the progression of breast cancer malignancy and reduces patient survival, suggesting that Mortalin as a biomarker and prognostic factor in breast cancer.

Identification of candidate biomarkers correlated with the pathogenesis and prognosis of breast cancer via integrated bioinformatics analysis.

BACKGROUND: This study was carried out to identify potential key genes associated with the pathogenesis and prognosis of breast cancer (BC). METHODS: Seven GEO datasets (GSE24124, GSE32641, GSE36295, GSE42568, GSE53752, GSE70947, GSE109169) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between BC and normal breast tissue samples were screened by an integrated analysis of multiple gene expression profile datasets. Hub genes related to the pathogenesis and prognosis of BC were verified by employing protein-protein interaction (PPI) network. RESULTS: Ten hub genes with high degree were identified, including CDK1, CDC20, CCNA2, CCNB1, CCNB2, BUB1, BUB1B, CDCA8, KIF11, and TOP2A. Lastly, the Kaplan-Meier plotter (KM plotter) online database demonstrated that higher expression levels of these genes were related to lower overall survival. Experimental validation showed that all 10 hub genes had the same expression trend as predicted. CONCLUSION: The findings of this research would provide some directive significance for further investigating the diagnostic and prognostic biomarkers to facilitate the molecular targeting therapy of BC, which could be used as a new biomarker for diagnosis and to guide the combination medicine of BC.

Comparative Efficacy of Chinese Herbal Injections Combined with Paclitaxel Plus Cisplatin for Non-Small-Cell Lung Cancer: A Multidimensional Bayesian Network Meta-Analysis.

INTRODUCTION: Considering the limitations of pure paclitaxel plus cisplatin chemotherapy in the treatment of non-small-cell lung cancer and the extensive exploration of Chinese herbal injections, this study performed a multidimensional network meta-analysis to systematically evaluate the clinical efficacy and safety of 12 Chinese herbal injections in the treatment of non-small-cell lung cancer. METHODS: Randomized controlled trials were obtained from several databases according to the eligibility criteria, and the study quality was assessed by the Cochrane risk of bias tool. Data analysis was performed by Stata 13.1 software and WinBUGS 14.0 software. Multidimensional cluster analysis was performed with the "scatterplot3d" package in R 3.6.1 software (PROSPERO ID: CRD42020163503). RESULTS: A total of 58 eligible randomized controlled trials involving 4578 patients and 12 Chinese herbal injections were included. Combined with paclitaxel plus cisplatin chemotherapy, Xiaoaiping injection exhibited a better impact on the clinical effective rate than paclitaxel plus cisplatin alone. Shenqifuzheng injection was associated with a preferable response in performance status and reduced leukopenia and gastrointestinal reactions. Kangai injection was dominant in the comprehensive results of the cluster analysis. CONCLUSIONS: Chinese herbal injections combined with paclitaxel plus cisplatin chemotherapy have a certain adjuvant effect in treating non-small-cell lung cancer, but the results of this study need to be verified by more well-designed, large-sample, multicenter randomized controlled trials.