Bibliometric and visualized analysis of applying tumor markers in lung cancer diagnosis from 2000 to 2022.

Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tumor marker (TM) detection can indicate the existence and growth of a tumor and has therefore been used extensively for diagnosing LC. Here, we conducted a bibliometric analysis to examine TM-related publications for LC diagnosis to illustrate the current state and future trends of this field, as well as to identify additional promising TMs with high sensitivity. Methods: Publications regarding TMs in LC diagnosis were downloaded from the Web of Science Core Collection. CiteSpace was applied to perform a bibliometric analysis of journals, cocitation authors, keywords, and references related to this field. VOSviewer was used to generate concise diagrams about countries, institutions, authors, and keywords. Changes in the TM research frontier were analyzed through citation burst detection. Results: A total of 990 studies were analyzed in this work. The collaboration network analysis revealed that the People's Republic of China, Yonsei University, and Molina R were the most productive country, institution, and scholar, respectively. Additionally, Molina R was the author with the most citations. The National Natural Science Foundation of China was the largest funding source. "Carcinoembryonic antigen (CEA) as tumor marker in lung cancer" was the top reference with the most citations, Lung Cancer was the core journal, and "serum tumor marker" experienced a citation burst over the past 5 years. Conclusion: This bibliometric analysis of TMs in LC diagnosis presents the current trends and frontiers in this field. We summarized the research status of this field and the methods to improve the diagnostic efficacy of traditional serum TMs, as well as provided new directions and ideas for improving the LC clinical detection rate. Priority should be given to the transformation of computer-assisted diagnostic technology for clinical applications. In addition, circulating tumor cells, exosomes, and microRNAs were the current most cutting-edge TMs.

Risk Factors Analysis for the Development of Hypocomplementemia in Rheumatoid Arthritis Patients: A Single-Center Retrospective Study.

Objective: The purpose of the research was to explore the possible risk factors for the development of hypocomplementemia (HC) in rheumatoid arthritis (RA) patients by analyzing their clinical and laboratory features. Methods: This retrospective research contained 501 RA patients, divided into RA patients with HC (n=78) and RA patients without HC (n=423). Demographic characteristics and laboratory test results of RA patients were collected and analyzed, such as age, sex, anti-mutated citrullinated vimentin antibody (Anti-MCV), serum complements (C3, C4), immunoglobulins (IgA, IgG, IgM), hemoglobin (Hb), platelets (PLT) and erythrocyte sedimentation rate (ESR), etc. Spearman correlation was served as assessing the correlations of the levels of serum C3 and C4 with each index. Receiver operating characteristic (ROC) curves were served as assessing the diagnostic efficacy of each index for RA patients with HC. Furthermore, risk factors for the occurrence of HC in RA patients were analyzed by employing binary logistic regression of single and multiple factors. Results: Compared RA patients with HC to without HC, the former were older and had a longer disease duration with increased levels of Anti-MCV, IgM and DAS28 and lower levels of Hb, PLT and ESR; Spearman correlation analysis verified the level of serum Anti-MCV was a negative correlation with C3 (r=-0.156); the area under the ROC curve (AUC) of PLT in diagnosing RA patients with HC was the largest at 0.65 (95% CI: 0.60-0.69); binary logistic regression analysis indicated that advanced age (>66 years), long disease duration (>62 months), high DAS28 value (>6.13), the levels of Anti-MCV>107.68IU/mL, IgM>1.54g/L, ESR≤69.00mm/h, Hb≤99.00g/L and PLT≤305.00×109/L were probable risk factors for the occurrence of HC in RA patients. Conclusion: Age and disease duration, DAS28, Anti-MCV, IgM, ESR, Hb, and PLT are closely related to the development of HC in RA patients. Timely monitoring of these indicators can help to evaluate disease activity of RA patients and further improve their prognosis.

Serum sirtuin-1 a potential marker in the diagnosis of rheumatoid arthritis.

Introduction: To explore the value of serum sirtuin-1 (SIRT1) in the diagnosis and evaluation of joint mobility of rheumatoid arthritis (RA). Materials and Methods: Serum was randomly obtained from 212 RA patients,210 non-RA patients and 58 healthy controls in a large tertiary first-class hospital in Jiangxi province from November 2021 to June 2022. The level of serum Sirt1,anti-cyclic citrulline polypeptide antibody (anti-CCP), anti-mutant citrulline vimentin antibody (anti-MCV), rheumatoid factor (RF),high-mobility group box 1 (HMGB1), collagen triple helix repeat containing 1 (CTHRC1), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by ELISA, to explore the correlation between them and their value in the diagnosis and evaluation of joint range of motion of RA and statistically analyse their diagnostic efficiency. Results: ① The level of all markers was higher in the RA group than in the non-RA group and the healthy controls (p < 0.05). ② The AUC of the SIRT1 was 0.882, second only to the anti-MCV and anti-CCP. ③ The anti-CCP showed the highest sensitivity to RA diagnosis of 0.948. The specificity and positive predictive value of SIRT1 for the diagnosis of RA were the highest, which are 0.959 and 0.934 respectively. ④ In serial combination, SIRT1/anti-CCP、SIRT1/anti-MCV showed the highest specificity.SIRT1/anti-CCP in parallel combination had the highest sensitivity. ⑤ SIRT1 showed a significant correlation with other markers and DAS28 scores (p < 0.01). Conclusion: SIRT1 can be used as a new serological marker for RA diagnosis, which has a significant correlation with RA joint mobility and has a certain reference value in RA differential diagnosis, providing a new detection basis for RA differential diagnosis.

The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing.

Poor wound healing in individuals with diabetes has long plagued clinicians, and immune cells play key roles in the inflammation, proliferation and remodeling that occur in wound healing. When skin integrity is damaged, immune cells migrate to the wound bed through the actions of chemokines and jointly restore tissue homeostasis and barrier function by exerting their respective biological functions. An imbalance of immune cells often leads to ineffective and disordered inflammatory responses. Due to the maladjusted microenvironment, the wound is unable to smoothly transition to the proliferation and remodeling stage, causing it to develop into a chronic refractory wound. However, chronic refractory wounds consistently lead to negative outcomes, such as long treatment cycles, high hospitalization rates, high medical costs, high disability rates, high mortality rates, and many adverse consequences. Therefore, strategies that promote the rational distribution and coordinated development of immune cells during wound healing are very important for the treatment of diabetic wounds (DW). Here, we explored the following aspects by performing a literature review: 1) the current situation of DW and an introduction to the biological functions of immune cells; 2) the role of immune cells in DW; and 3) existing (or undeveloped) therapies targeting immune cells to promote wound healing to provide new ideas for basic research, clinical treatment and nursing of DW.

Effects of ginkgo diterpene lactone on brain inflammation and oxidative stress in rats with cognitive impairment of cerebral small vessel disease.

PURPOSE: This study aims to investigate the effects of ginkgo diterpene lactone on brain inflammation and oxidative stress in rats with cognitive impairment of cerebral small vessel disease (CSVD). METHODS: We equally assigned 40 Sprague Dawley (SD) rats to the observation group (OG) and the control group (CG) and modeled them for cognitive impairment of CSVD. Rats in OG were given ginkgo diterpene lactone for treatment, while those in CG were injected with the same amount of normal saline. The learning and memorizing ability of rats was tested by the water maze. The oxidative stress and inflammatory response in rats were evaluated. The levels of vascular endothelial growth factor (VEGF) and endostatin (ES) mRNA in the hippocampus of rats were measured. Vascular smooth muscle cells of rats were sampled for cell viability and apoptosis assays. RESULTS: Rats from OG were superior to those from CG in the learning and memorizing ability. After treatment, rats from OG had markedly lower malondialdehyde (MDA) levels and higher levels of superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) than those from CG (all P < 0.05). Concentrations of interleukin-18 (IL-18), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), and amyloid ß-protein 1-40 (Aß1-40) were markedly lower in OG than in CG (all P < 0.05). Rats from OG had markedly higher VEGF levels and lower ES mRNA levels than those from CG (all P < 0.05). Cell viability gradually decreased in rats from OG after treatment and was markedly lower than that in rats from CG (P < 0.05). Cell apoptosis rate was markedly higher in OG than in CG (P < 0.05). CONCLUSION: Ginkgo diterpene lactone can inhibit oxidative stress and inflammatory response in rats with cognitive impairment of CSVD to a certain degree.

Knockdown of CDCA8 inhibits the proliferation and enhances the apoptosis of bladder cancer cells.

Bladder cancer is a tumour of the urinary system with high mortality, and there is also a great lack of therapeutic targets in the clinic. Cell division cycle associated 8 (CDCA8), an important component of the vertebrate chromosomal passenger complex, is highly expressed in various tumours and promotes tumour development. However, the role of CDCA8 in bladder cancer is not fully understood. This study aimed to reveal the function of CDCA8 in bladder cancer by determining the relationship between CDCA8 expression and proliferation, metastasis and apoptosis of bladder cancer cells. Firstly, we studied the mRNA expression of CDCA8 through the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases and analysed the correlation between CDCA8 expression and prognosis of patients with bladder cancer. We also verified CDCA8 expression in bladder cancer tissues by immunohistochemistry. In addition, CDCA8 expression was inhibited in bladder cancer T24 and 5637 cells, and the effects of CDCA8 on the proliferation, migration and invasion of bladder cancer cell lines were investigated using cell counting kit-8, colony formation, cell cycle, apoptosis, wound healing and Transwell invasion assays. Results showed that CDCA8 was highly expressed in bladder cancer compared with normal tissues, and the high CDCA8 expression was significantly correlated with the poor prognosis of patients. Inhibiting CDCA8 expression inhibited the proliferation, migration and invasion of T24 and 5637 cells and induced the apoptosis of bladder cancer cells. CDCA8 was involved in the regulation of the growth cycle of bladder cancer cells. Bioinformatics-based mechanism analysis revealed that high CDCA8 expression may affect the cell cycle and P53 signalling pathways. In conclusion, our results suggest that CDCA8 is highly expressed in bladder cancer and can promote tumour development. Hence, CDCA8 may serve as an effective therapeutic target for treatment of bladder cancer.

Prognostic significance of elevated pretreatment serum levels of CEA and CA-125 in epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer is a highly lethal gynecological malignancy. Accurate and cost-effective predictive tools to estimate the prognosis of patients with epithelial ovarian cancer before treatment are currently lacking. OBJECTIVE: The purpose of this study was to evaluate the prognostic significance of pretreatment serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) in primary epithelial ovarian cancer. METHODS: Between 2008 and 2016, 326 patients with a diagnosis of primary epithelial ovarian cancer were retrospectively reviewed. We attempted to identify an optimal cut-off value of CEA to predict survival using ROC curve analysis. Cox regression univariate and multivariate analyses were used to evaluate prognostic factors. RESULTS: The optimal cut-off value of CEA was 2.6 ng/mL. In univariate and multivariate analyses, FIGO stage and pretreatment CA-125 and CEA levels significantly predicted progression-free and overall survival. The 5-year progression-free survival rate for patients with both a CEA level < 2.6 ng/mL and CA-125 level < 35 U/mL was 84%, compared to only 33% for the patients with higher levels of both markers (p< 0.001). The 5-year cancer specific survival rate was 94% in those with a CEA level < 2.6 ng/mL and CA-125 level < 35 U/mL, and only 39% for those with higher levels of both markers (p< 0.001). CONCLUSIONS: In addition to traditional prognostic factors, a pretreatment serum CEA level ⩾ 2.6 ng/mL and CA-125 level ⩾ 35 U/mL were also independent prognostic factors for epithelial ovarian cancer. Patients with an elevated CEA and/or CA-125 level before treatment should be considered to be at high-risk of recurrence and death.

Identification of a four immune-related genes signature based on an immunogenomic landscape analysis of clear cell renal cell carcinoma.

Renal clear cell carcinoma (ccRCC) is the most common type of renal cell carcinoma, which has strong immunogenicity. A comprehensive study of the role of immune-related genes (IRGs) in ccRCC is of great significance in finding ccRCC treatment targets and improving patient prognosis. In this study, we comprehensively analyzed the expression of IRGs in ccRCC based on The Cancer Genome Atlas datasets. The mechanism of differentially expressed IRGs in ccRCC was analyzed by bioinformatics. In addition, Cox regression analysis was used to screen prognostic related IRGs from differentially expressed IRGs. We also identified a four IRGs signature consisting of four IRGs (CXCL2, SEMA3G, PDGFD, and UCN) through lasso regression and multivariate Cox regression analysis. Further analysis results showed that the four IRGs signature could effectively predict the prognosis of patients with ccRCC, and its predictive power is independent of other clinical factors. In addition, the correlation analysis of immune cell infiltration showed that this four IRGs signature could effectively reflect the level of immune cell infiltration of ccRCC. We also found that the expression of immune checkpoint genes CTLA-4, LAG3, and PD-1 in the high-risk group was higher than that in the low-risk group. Our research revealed the role of IRGs in ccRCC, and developed a four IRGs signature that could be used to evaluate the prognosis of patients with ccRCC, which will help to develop personalized treatment strategies for patients with ccRCC and improve their prognosis. In addition, these four IRGs may be effective therapeutic targets for ccRCC.

Knockdown of SLC35F2 Inhibits the Proliferation and Metastasis of Bladder Cancer Cells.

BACKGROUND: Many studies have shown that solute carrier family 35 member F2 (SLC35F2) plays a key role in the biological processes of multiple cancers. However, there have been no reports on the role of SLC35F2 in the occurrence and development of bladder cancer (BC). METHODS: SLC35F2 expression data and clinical and prognostic information from BC patients were obtained from databases. SLC35F2 expression in BC was verified by quantitative real-time PCR (qRT-PCR). The influence of SLC35F2 knockdown on the proliferation, apoptosis, migration and invasion in the 5637 and T24 cell lines was studied, and tumor formation experiments were performed in nude mice. Gene set enrichment analysis (GSEA) was used to predict the pathways and functions of SLC35F2 in BC. RESULTS: SLC35F2 was highly expressed in BC tissues and was associated with invasiveness and T stage in BC patients. SLC35F2 knockdown can inhibit the proliferation, migration and invasion of BC cells and can promote apoptosis. SLC35F2 knockdown significantly reduced tumorigenesis in nude mice. GSEA showed that BC, pathways in cancer, apoptosis and the P53 signaling pathway were significantly enriched in SLC35F2 high expression phenotype. CONCLUSION: SLC35F2 can promote malignant progression and is a potential therapeutic target in BC.

Effects of Gegen Dingxuan Capsule on behavior, X-Ray Signs of the Cervical Spine, and Humoral Factor Levels in a Rat Model of Cervical Vertigo.

OBJECTIVE: To investigate the effects of Gegen Dingxuan capsule on behavior, X-ray signs of the cervical spine, and levels of norepinephrine (NE), nitric oxide (NO), endothelin (ET-1), and calcitonin gene-related peptide (CGRP) in the plasma of a rat model of cervical vertigo and additionally to clarify the underlying mechanisms of action. METHOD: A total of 40 male SPF Sprague-Dawley rats were randomly assigned to blank control, model, Sibelium, and Gegen Dingxuan capsule groups, with 10 rats in each group. A rat model of cervical vertigo was produced by physically damaging the cervical spine, thereby perturbing its stability. After cervical spine surgery, rats in the Sibelium and Gegen Dingxuan capsule groups were administered Sibelium and Gegen Dingxuan capsule, respectively. After 4 and 8 weeks of administration, balance beam test was used to assess behavior, lateral X-ray images of the cervical spine were taken and scored, and the plasma levels of NE, NO, ET-1, and CGRP were measured. RESULTS: After 4 and 8 weeks of drug administration, the balance beam test scores in the Gegen Dingxuan capsule group were significantly higher than those in the Sibelium group. The radiographic scores were significantly lower in the Gegen Dingxuan capsule group than those in the Sibelium group at 8 weeks. Plasma NE, NO, ET-1 levels, and ET-1/CGRP ratio were significantly decreased in the Gegen Dingxuan capsule group compared with the model group. No significant difference was found between the Sibelium and Gegen Dingxuan capsule groups. Plasma CGRP levels were significantly increased in the Gegen Dingxuan capsule group compared with the model group and were significantly decreased compared with the Sibelium group. CONCLUSIONS: Gegen Dingxuan capsule improves behavior, radiographic scores, reduces plasma levels of NE, NO, ET-1, and the ET-1/CGRP ratio, and increases plasma CGRP levels. Gegen Dingxuan capsule may improve outcome in the rat model of cervical vertigo by ameliorating cervical facet joint disorder, relieving cervical muscle spasm and vasospasm, increasing blood supply, and regulating humoral factor levels.

Development of a novel six-long noncoding RNA signature predicting survival of patients with bladder urothelial carcinoma.

Bladder urothelial carcinoma is a malignant tumor with a high incidence in the uropoietic system. Considerable studies have shown that long noncoding RNA (lncRNA) plays an important role in the development and progression of bladder urothelial carcinoma. In this study, the lncRNA expression and clinical data of 377 bladder urothelial carcinoma patients were obtained from The Cancer Genome Atlas database and differentially expressed lncRNAs in cancer and normal groups were evaluated. Univariate COX and multivariate COX regression analyses of prognosis were performed on differentially expressed lncRNAs in the training data sets, six prognosis-related lncRNAs (LINC02195, LINC01484, LINC01468, SMC2-AS1, AC011298.1, and PTPRD-AS1) were assessed, and a six-lncRNA signature was constructed. The predictive capability of this six-lncRNA signature was validated in the testing data sets and entire data sets. The prognostic ability of the six-lncRNA signature was independent of other clinical elements after multivariate COX regression and stratified analyses of with other clinical elements. We performed functional enrichment analysis with the six prognosis-related lncRNAs. Results of functional enrichment revealed that these prognosis-related lncRNAs might promote the development and metastasis of bladder urothelial carcinoma. In summary, the six-lncRNA signature that we developed could effectively predict the prognosis of bladder urothelial carcinoma patients. This six-lncRNA signature might be a novel independent prognostic marker of bladder urothelial carcinoma. Moreover, it also provides novel insights into the mechanism of bladder urothelial carcinoma.

Cancer-associated methylated lncRNAs in patients with bladder cancer.

Epigenetic modifications via DNA methylation and long non-coding RNAs (lncRNAs) have been identified in bladder cancer (BC). However, DNA methylation of lncRNAs involved in BC has not been elucidated. Here, DNA immunoprecipitation-sequencing (MeDIP-seq) and RNA-sequencing (RNA-seq) were carried out using eight paired tumor and adjacent normal tissue samples from patients with BC. Differences in methylation patterns between tumors and controls were compared and the percentage of differentially methylated genes, including lncRNA genes, was calculated. RNA-seq data were subjected to gene ontology (GO), Kyoto encyclopedia of genes, and genomes (KEGG) analysis. The association between DNA methylation modification and lncRNA expression was determined by pairwise analysis of MeDIP-seq and RNA-seq data. The most enriched motifs in the promoter region, as well as the methylated density in the 3 kb region surrounding super-enhancers of lncRNA genes, were analyzed. A peak of 5mC methylation in the region 2 kb upstream of the transcription start site (TSS), with the lowest point in the TSS region, was observed. In total, 436 and 239 genes were identified to be hyper and hypomethylated, respectively, in BC tissue around the TSS region. RNA-seq revealed differentially expressed lncRNAs between tumor and normal tissues, many of which were cancer-associated lncRNAs based on GO and KEGG pathway analysis. Combined MeDIP-seq and RNA-seq analysis revealed that expression of 26 lncRNAs were candidates of 5mC controlled genes. The possible link between 5mC modification and differential lncRNAs may relate to enrichment of 5mC reads in the region surrounding super-enhancers of lncRNA. Survival analysis indicated that the methylated lncRNA, LINC00574, was associated with shorter overall survival time in patients with BC (HR = 1.7, p-value = 0.035). Taken together, these findings indicate that lncRNAs genes are under control of DNA methylation. Methylated lncRNA genes, which are transcripted to LINC00574, may serve as biomarkers for BC prognosis.

Identification of key candidate genes and biological pathways in bladder cancer.

BACKGROUND: Bladder cancer is a malignant tumor in the urinary system with high mortality and recurrence rates. However, the causes and recurrence mechanism of bladder cancer are not fully understood. In this study, we used integrated bioinformatics to screen for key genes associated with the development of bladder cancer and reveal their potential molecular mechanisms. METHODS: The GSE7476, GSE13507, GSE37815 and GSE65635 expression profiles were downloaded from the Gene Expression Omnibus database, and these datasets contain 304 tissue samples, including 81 normal bladder tissue samples and 223 bladder cancer samples. The RobustRankAggreg (RRA) method was utilized to integrate and analyze the four datasets to obtain integrated differentially expressed genes (DEGs), and the gene ontology (GO) functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) network and module analyses were performed using Cytoscape software. The OncoLnc online tool was utilized to analyze the relationship between the expression of hub genes and the prognosis of bladder cancer. RESULTS: In total, 343 DEGs, including 111 upregulated and 232 downregulated genes, were identified from the four datasets. GO analysis showed that the upregulated genes were mainly involved in mitotic nuclear division, the spindle and protein binding. The downregulated genes were mainly involved in cell adhesion, extracellular exosomes and calcium ion binding. The top five enriched pathways obtained in the KEGG pathway analysis were focal adhesion (FA), PI3K-Akt signaling pathway, proteoglycans in cancer, extracellular matrix (ECM)-receptor interaction and vascular smooth muscle contraction. The top 10 hub genes identified from the PPI network were vascular endothelial growth factor A (VEGFA), TOP2A, CCNB1, Cell division cycle 20 (CDC20), aurora kinase B, ACTA2, Aurora kinase A, UBE2C, CEP55 and CCNB2. Survival analysis revealed that the expression levels of ACTA2, CCNB1, CDC20 and VEGFA were related to the prognosis of patients with bladder cancer. In addition, a KEGG pathway analysis of the top 2 modules identified from the PPI network revealed that Module 1 mainly involved the cell cycle and oocyte meiosis, while the analysis in Module 2 mainly involved the complement and coagulation cascades, vascular smooth muscle contraction and FA. CONCLUSIONS: This study identified key genes and pathways in bladder cancer, which will improve our understanding of the molecular mechanisms underlying the development and progression of bladder cancer. These key genes might be potential therapeutic targets and biomarkers for the treatment of bladder cancer.

Effects of Chailong Jieyu Pill on Behavior, Monoamine Neurotransmitters, and Corticosteroid Receptors in a Rat Model of Anxiety Disorder.

Chailong Jieyu Pill (CJP) is composed of Radix Bupleuri, Radix Scutellariae, Rhizoma Pinelliae Preparata, Radix Codonopsis, Radix Glycyrrhizae preparata, keel, Concha Ostreae, Concha Margaritifera Usta, Rhizoma Zingiberis Recens, and Fructus Jujubae. CJP has shown good clinical effects on improving anxiety disorders. However, as the mechanism underlying such benefits remains unclear, the aim of this study was to investigate the mechanism of action for CJP on anxiety-related behaviors in a rat model of anxiety disorder. After establishing a rat model of anxiety disorder using uncertain empty bottle stimulation, rats were divided into control, model, citalopram, low-dose CJP, and high-dose CJP groups. After 1 month of administration, effects of treatments on rat appearance, body weight, and open-field test scores were observed. In addition, hippocampal monoamine neurotransmitter (5-hydroxytryptamine, dopamine, and norepinephrine) contents were measured with an enzyme-linked immunosorbent assay, and mRNA expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) were measured with reverse transcription-polymerase chain reaction. CJP increased rat weight, and this effect was increased in the high-dose CJP group compared with the citalopram group (P < 0.05). CJP also elevated open-field test scores compared with the citalopram group (P < 0.05). While CJP decreased monoamine neurotransmitter contents in rat hippocampus, the regulatory effect of CJP on 5-hydroxytryptamine was reduced compared with citalopram (P < 0.01). CJP upregulated GR mRNA expression in both low-dose (P < 0.05) and high-dose (P < 0.01) CJP groups, but only the latter significantly downregulated MR mRNA expression and showed enhanced effects compared with citalopram (P < 0.05). Thus, CJP likely exerted its significant antianxiety effect by diminishing monoamine neurotransmitters and regulating mRNA expression of MR and GR in the hippocampus of our rat model of anxiety disorder.

Isokotomolide A, a new butanolide extracted from the leaves of Cinnamomum kotoense, arrests cell cycle progression and induces apoptosis through the induction of p53/p21 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells.

This study is the first to investigate isokotomolide A (IKA), a butanolide compound isolated from the leaves of Cinnamomum kotoense Kanehira & Sasaki (Lauraceaee), which exhibits an anti-proliferative activity in human non-small cell lung cancer A549 cells. The results show that IKA inhibits the proliferation of A549 by blocking cell cycle progression in the G0/G1 phase and inducing apoptosis. Blockade of cell cycle was associated with increased p21/WAF1 levels and reduced amounts of cyclin D1, cyclin E, Cdk2, Cdk4, and Cdk6 in a p53-mediated manner. IKA treatment also increased p53 phosphorylation (Ser15) and decreased the interaction of p53-MDM2. IKA treatment triggered the mitochondrial apoptotic pathway, indicated by changing Bax/Bcl-2 ratios, cytochrome c release and caspase-9 activation. In addition, pre-treatment of cells with caspase-9 inhibitor inhibited IKA-induced apoptosis, indicating that caspase-9 activation was involved in A549 cells' apoptosis induced by IKA. Our study reports here for the first time that the induction of p53/p21 and the initiation of the mitochondrial apoptotic system may participate in the anti-proliferative activity of IKA in human non-small cell lung cancer cells.

Rugosin E, an ellagitannin, inhibits MDA-MB-231 human breast cancer cell proliferation and induces apoptosis by inhibiting nuclear factor-kappaB signaling pathway.

In this study, we first report the chemopreventive effect of rugosin E in human breast cancer cell line, MDA-MB-231. Treatment with rugosin E decreased the cell proliferation of MDA-MB-231 cells in a dose-dependent manner. Rugosin E treatment arrested MDA-MB-231 cells at G0/G1 phase. This effect was strongly associated with concomitant decrease in the level of cyclin D1, cyclin D2, cyclin E, cdk2, cdk4, and cdk6, and increase of p21/WAF1. In addition, rugosin E also induced apoptotic cell death. Rugosin E increased in the expression of Bax, Bak, and Bcl-Xs, but decreased the levels of Bcl-2 and Bcl-X(L), and subsequently triggered mitochondria apoptotic pathway (release of cytochrome c, activation of caspase-9, and caspase-3). In addition, pre-treatment of cells with caspase-9 inhibitor blocked rugosin E-induced cell proliferation and apoptosis, indicating caspase-9 activation was involved in rugosin E-mediated MDA-MB-231 cells apoptosis. Rugosin E inhibited the constitutively activated and inducible NF-kappaB in both its DNA-binding activity and transcriptional activity. Furthermore, rugosin E also inhibited the TNF-alpha-activated NF-kappaB-dependent reporter gene expression of cyclin D1, c-Myc, XIAP, Bcl-2, and Bcl-X(L) were all downregulated by rugosin E. Our results indicated that rugosin E inhibits the activation of NF-kappaB, and this may provide a molecular basis for drug development in the prevention and treatment of cancer by rugosin E.