Complementary and Integrative Health Information in the literature: its lexicon and named entity recognition.

OBJECTIVE: To construct an exhaustive Complementary and Integrative Health (CIH) Lexicon (CIHLex) to help better represent the often underrepresented physical and psychological CIH approaches in standard terminologies, and to also apply state-of-the-art natural language processing (NLP) techniques to help recognize them in the biomedical literature. MATERIALS AND METHODS: We constructed the CIHLex by integrating various resources, compiling and integrating data from biomedical literature and relevant sources of knowledge. The Lexicon encompasses 724 unique concepts with 885 corresponding unique terms. We matched these concepts to the Unified Medical Language System (UMLS), and we developed and utilized BERT models comparing their efficiency in CIH named entity recognition to well-established models including MetaMap and CLAMP, as well as the large language model GPT3.5-turbo. RESULTS: Of the 724 unique concepts in CIHLex, 27.2% could be matched to at least one term in the UMLS. About 74.9% of the mapped UMLS Concept Unique Identifiers were categorized as "Therapeutic or Preventive Procedure." Among the models applied to CIH named entity recognition, BLUEBERT delivered the highest macro-average F1-score of 0.91, surpassing other models. CONCLUSION: Our CIHLex significantly augments representation of CIH approaches in biomedical literature. Demonstrating the utility of advanced NLP models, BERT notably excelled in CIH entity recognition. These results highlight promising strategies for enhancing standardization and recognition of CIH terminology in biomedical contexts.

The mechanism of melatonin promotion on cucumber seedling growth at different nitrogen levels.

The supply level of exogenous nitrogen has a very important influence on the growth and development of cucumber. Insufficient or excessive nitrogen application will lead to metabolic disorders in the body and affect the formation of yield. Therefore, it is of great scientific and practical significance to explore the corresponding mitigation measures. Melatonin (MT) is a multi-regulatory molecule with pleiotropic effects on plant growth and development. A large number of studies have shown that the appropriate amount of melatonin supplementation is beneficial to plant growth and development by promoting root development, delaying leaf senescence, and improving fruit yield. However, the study of MT function combined with a detailed physiological analysis of nitrogen (N) absorption and metabolism in cucumber plants needs further strengthening. We performed hydroponic tests at different nitrogen levels to determine the metabolic processes associated with the enhanced tolerance to nitrogen in melatonin-treated cucumber (Cucucumis sativus L.) seedlings. Cucumber seedlings were sprayed with 100 µM melatonin or water and treated with different nitrogen in the growth chamber for 7 days. Nitrogen deficiency significantly inhibited seedling growth, and this growth inhibition was partially alleviated by melatonin. The expression analysis of related carbon and nitrogen genes showed that the genes whose expression was significantly altered by melatonin were mainly related to carbon (C) and nitrogen (N) metabolism. By enzyme activity and reactive oxygen content data analysis, melatonin-treated cucumber seedlings showed relatively stable carbon and nitrogen levels compared to untreated ones. In conclusion, MT can repair the impaired growth and development situation by regulating the nitrogen assimilation capacity and the balance between oxidation and oxidative metabolism and carbon metabolism in the cucumber under different nitrogen levels.

A multicenter survey on the current status of chronic cough and its impact on quality of life in Guangdong, China.

Background: Chronic cough is a troublesome clinical problem with long-term impacts at the patient level. However, the burden of chronic cough in China is largely unknown. Thus, we performed a multicenter cross-sectional survey on the current status of chronic cough and its impact on quality of life in Guangdong, south China. Methods: Using a standardized questionnaire, we extracted and analyzed the relevant data on demographics, number of visits to a doctor, previous diagnosis, previous medications used and initial diagnosis. Cough-specific quality of life was measured by the Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC). Results: Of 933 patients from 13 tertiary medical centers in Guangdong, 52.2% were female, the median age was 40.0 [interquartile range (IQR), 31.0-52.0] years, and the median duration of chronic cough was 6.0 (IQR, 3.0-24.0) months. Over half (n=452, 54.0%) of the patients had visited physicians ≥3 times for cough. In terms of previous diagnosis, bronchitis (n=432, 46.5%) had been most frequently diagnosed, followed by pharyngitis (n=246, 26.5%) and asthmatic cough (n=98, 10.5%). A majority of patients with chronic cough had used antitussive agents (n=539, 58.5%), antibiotics (n=374, 40.6%) and traditional Chinese medicine (TCM) (n=294, 31.9%). Among the three subscales of the LCQ-MC, we observed lower scores in the mental health domain than in the physical and social domains (both P<0.001). Additionally, lower LCQ-MC scores were found in females and patients who saw the doctor >3 times for both the total and three subscale scores (all P<0.05). Conclusions: Misdiagnosis and inappropriate treatment are prevalent in patients with chronic cough and lead to considerable antibiotic abuse. Chronic cough markedly affects suffers' quality of life, especially for women.

To Explore the Molecular Mechanism of Acupuncture Alleviating Inflammation and Treating Obesity Based on Text Mining.

Objective: To explore the related mechanism of acupuncture affecting obesity by regulating inflammation using bioinformatics methods. Methods: The genes related to obesity, inflammation, and acupuncture and inflammation were mined using GenCLiP 3, and the intersecting genes were extracted using Venn diagram. The DAVID database was employed for pathway enrichment analysis and functional annotation of coexpressed genes. Then, the protein-protein interaction (PPI) network was constructed with the STRING database and visualized by the Cytoscape software and screened out important hub genes. Finally, the Boxplot and Survival Analysis of the hub genes in various cancers were performed by GEPIA. Results: 755 genes related to obesity and inflammation and 38 genes related to acupuncture and inflammation were identified, and 24 coexpressed genes related to obesity, inflammation, and acupuncture were extracted from the Venn diagram. Eight hub genes including interleukin-6 (IL-6), interleukin-10 (IL-10), Toll-like receptor 4 (TLR4), signal transduction and transcriptional activation factor 3 (STAT3), C-X-C motif chemokine 10 (CXCL10), interleukin-17A (IL-17A), prostaglandin peroxide synthesis-2 (PTGS2), signal transistors, and transcriptional activation factor 6 (STAT6) were identified by gene ontology (GO), Kyoto Encyclopedia of Genes (KEGG), and PPI network analysis. Among them, IL-6 is suggested to play an essential role in the treatment of obesity and inflammation by acupuncture, and IL-6 was significant in both Boxplot and Survival Analysis of pancreatic cancer (PAAD). Therefore, in this study, the core gene, IL-6 was used as the breakthrough point to explore the possible mechanism of acupuncture in treating obesity and pancreatic cancer by regulating IL-6. Conclusion: (1) Acupuncture can regulate the expression of IL-6 through the TLR4/nuclear factor-κB (NF-κB) pathway, thereby alleviating inflammation, which can be used as a potential strategy for the treatment of obesity. (2) IL-6/STAT3 is closely related to the occurrence, development, and metastasis of pancreatic cancer. Acupuncture affecting pancreatic cancer through TLR4/NF-κB/IL-6/STAT3 pathway may be a potential method for the treatment of pancreatic cancer.

Discovering novel drug-supplement interactions using SuppKG generated from the biomedical literature.

OBJECTIVE: Develop a novel methodology to create a comprehensive knowledge graph (SuppKG) to represent a domain with limited coverage in the Unified Medical Language System (UMLS), specifically dietary supplement (DS) information for discovering drug-supplement interactions (DSI), by leveraging biomedical natural language processing (NLP) technologies and a DS domain terminology. MATERIALS AND METHODS: We created SemRepDS (an extension of an NLP tool, SemRep), capable of extracting semantic relations from abstracts by leveraging a DS-specific terminology (iDISK) containing 28,884 DS terms not found in the UMLS. PubMed abstracts were processed using SemRepDS to generate semantic relations, which were then filtered using a PubMedBERT model to remove incorrect relations before generating SuppKG. Two discovery pathways were applied to SuppKG to identify potential DSIs, which are then compared with an existing DSI database and also evaluated by medical professionals for mechanistic plausibility. RESULTS: SemRepDS returned 158.5% more DS entities and 206.9% more DS relations than SemRep. The fine-tuned PubMedBERT model (significantly outperformed other machine learning and BERT models) obtained an F1 score of 0.8605 and removed 43.86% of semantic relations, improving the precision of the relations by 26.4% over pre-filtering. SuppKG consists of 56,635 nodes and 595,222 directed edges with 2,928 DS-specific nodes and 164,738 edges. Manual review of findings identified 182 of 250 (72.8%) proposed DS-Gene-Drug and 77 of 100 (77%) proposed DS-Gene1-Function-Gene2-Drug pathways to be mechanistically plausible. DISCUSSION: With added DS terminology to the UMLS, SemRepDS has the capability to find more DS-specific semantic relationships from PubMed than SemRep. The utility of the resulting SuppKG was demonstrated using discovery patterns to find novel DSIs. CONCLUSION: For the domain with limited coverage in the traditional terminology (e.g., UMLS), we demonstrated an approach to leverage domain terminology and improve existing NLP tools to generate a more comprehensive knowledge graph for the downstream task. Even this study focuses on DSI, the method may be adapted to other domains.

Preparation of Centella asiatica loaded gelatin/chitosan/nonwoven fabric composite hydrogel wound dressing with antibacterial property.

Antibiotics abuse and the emergence of massive drug-resistant bacteria have become the major obstacles in the medical system. Thus, designing an antibiotic-free wound dressing with antibacterial activity and decent biocompatibility is urgently desired. Herein, the sandwich-like composite hydrogel wound dressings were developed by intercalating nonwoven fabrics (NF) as the middle layer, gelatin and chitosan (Gel-CS) hydrogel loaded with Centella asiatica (CA) as the base materials. In addition, soaking strategy was employed to improve the mechanical properties of hydrogels. The hydrogels exhibited uniform microporous structure, stable mechanical property, high water absorbency, as well as water vapor transmission rate. After loading with CA, the composite wound dressing showed the sustained drug release properties in vitro and excellent antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The cytotoxicity results demonstrated that the composite hydrogels had good biocompatibility. This work indicates that the nonwoven composite hydrogels have broad application prospects in the field of medical care in the future.

The effect of selenium on the autophagy of macrophage infected by Staphylococcus aureus.

Selenium can alleviate the inflammatory reaction infected by Staphylococcus aureus (S. aureus). However, the role of selenium on the autophagy in RAW264.7 macrophages infected by S. aureus has not been reported. The goal of this study was to clarify the effect of selenium on the autophagy and related inflammatory pathways (MAPK and NF-κB) in RAW264.7 macrophages infected by S. aureus. RAW264.7 macrophages were co-treated with Na2SeO3 and S. aureus. The expression of related inflammatory pathways (MAPK and NF-κB) and autophagy-related proteins were detected by Western blotting. The microtubule-binding protein light chain 3 (LC3) puncta were measured with immunofluorescence staining. The ultrastructure of RAW264.7 macrophages infected by S. aureus was detected by transmission electron microscope (TEM). And plate counting method was used to detect the proliferation of S. aureus in RAW264.7 macrophages. The results showed that the expression levels of LC3 II increased and the expression levels of p62 decreased after adding selenium, compared with S. aureus infection group. Compared with S. aureus infection group, the intracellular LC3 puncta and autophagic vesicles, autophagosomes, and autolysosomes increased with selenium supplementation. The number of S. aureus proliferation decreased with addition of selenium, compared with S. aureus infection group. Selenium could significantly inhibit the phosphorylation of MAPK and NF-κB signaling pathway key proteins, compared with S. aureus infection group. In summary, selenium could promote the autophagy in macrophages infected by S. aureus, alleviate the blockade of autophagic flow, depress the transcription of MAPK and NF-κB signaling pathways, and inhibit the proliferation of S. aureus in RAW264.7 macrophages.

The Roles of GSK-3ß in Regulation of Retinoid Signaling and Sorafenib Treatment Response in Hepatocellular Carcinoma.

Rationale: Glycogen synthase kinase-3ß (GSK-3ß) plays key roles in metabolism and many cellular processes. It was recently demonstrated that overexpression of GSK-3ß can confer tumor growth. However, the expression and function of GSK-3ß in hepatocellular carcinoma (HCC) remain largely unexplored. This study is aimed at investigating the role and therapeutic target value of GSK-3ß in HCC. Methods: We firstly clarified the expression of GSK-3ß in human HCC samples. Given that deviated retinoid signalling is critical for HCC development, we studied whether GSK-3ß could be involved in the regulation. Since sorafenib is currently used to treat HCC, the involvement of GSK-3ß in sorafenib treatment response was determined. Co-immunoprecipitation, GST pull down, in vitro kinase assay, luciferase reporter and chromatin immunoprecipitation were used to explore the molecular mechanism. The biological readouts were examined with MTT, flow cytometry and animal experiments. Results: We demonstrated that GSK-3ß is highly expressed in HCC and associated with shorter overall survival (OS). Overexpression of GSK-3ß confers HCC cell colony formation and xenograft tumor growth. Tumor-associated GSK-3ß is correlated with reduced expression of retinoic acid receptor-ß (RARß), which is caused by GSK-3ß-mediated phosphorylation and heterodimerization abrogation of retinoid X receptor (RXRα) with RARα on RARß promoter. Overexpression of functional GSK-3ß impairs retinoid response and represses sorafenib anti-HCC effect. Inactivation of GSK-3ß by tideglusib can potentiate 9-cis-RA enhancement of sorafenib sensitivity (tumor inhibition from 48.3% to 93.4%). Efficient induction of RARß by tideglusib/9-cis-RA is required for enhanced therapeutic outcome of sorafenib, which effect is greatly inhibited by knocking down RARß. Conclusions: Our findings demonstrate that GSK-3ß is a disruptor of retinoid signalling and a new resistant factor of sorafenib in HCC. Targeting GSK-3ß may be a promising strategy for HCC treatment in clinic.

Complete Defluorination and Mineralization of Perfluorooctanoic Acid by a Mechanochemical Method Using Alumina and Persulfate.

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant that has received concerns worldwide due to its extreme resistance to conventional degradation. A mechanochemical (MC) method was developed for complete degradation of PFOA by using alumina (Al2O3) and potassium persulfate (PS) as comilling agents. After ball milling for 2 h, the MC treatment using Al2O3 or PS caused conversion of PFOA to either 1-H-1-perfluoroheptene or dimers with a defluorination efficiency lower than 20%, but that using both Al2O3 and PS caused degradation of PFOA with a defluorination of 100% and a mineralization of 98%. This method also caused complete defluorination of other C3∼C6 homologues of PFOA. The complete defluorination of PFOA attributes to Al2O3 and PS led to the weakening of the C-F bond in PFOA and the generation of hydroxyl radical (•OH), respectively. During the MC degradation, Al2O3 strongly anchors PFOA through COO--Al coordination and in situ formed from Lewis-base interaction and PS through hydrogen bond. Meanwhile, mechanical effects induce the homolytic cleavage of PS to produce SO4•-, which reacts with OH group of Al2O3 to generate •OH. The degradation of PFOA is initiated by decarboxylation as a result of weakened C-COO- due to Al3+ coordination. The subsequent addition of •OH, elimination of HF, and reaction with water induce the stepwise removal of all carboxyl groups and F atoms as CO2 and F-, respectively. Thus, complete defluorination and mineralization are achieved.

Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells.

AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie (XTSJ) decoction on gastric cancer stem-like cells (GCSCs). METHODS: The gastric cancer cell line MKN-45 line was selected and sorted by FACS using the cancer stem cell marker CD44; the stemness of these cells was checked in our previous study. In an in vitro study, the expression of Notch-1, Hes1, Vascular endothelial growth factor (VEGF), and Ki-67 in both CD44-positive gastric cancer stem-like cells (GCSCs) and CD44-negative cells was measured by Western blot. The effect of XTSJ serum on cell viability and on the above markers was measured by MTT assay and Western blot, respectively. In an in vivo study, the ability to induce angiogenesis and maintenance of GCSCs in CD44-positive-MKN-45- and CD44-negative-engrafted mice were detected by immunohistochemical staining using markers for CD34 and CD44, respectively. The role of XTSJ decoction in regulating the expression of Notch-1, Hes1, VEGF and Ki-67 was measured by Western blot and real-time polymerase chain reaction. RESULTS: CD44(+) GCSCs showed more cell proliferation and VEGF secretion than CD44-negative cells in vitro, which were accompanied by the high expression of Notch-1 and Hes1 and positively associated with tumor growth (GCSCs vs CD44-negative cells, 2.72 ± 0.25 vs 1.46 ± 0.16, P < 0.05) and microvessel density (MVD) (GCSCs vs CD44-negative cells, 8.15 ± 0.42 vs 3.83 ± 0.49, P < 0.001) in vivo. XTSJ decoction inhibited the viability of both cell types in a dose-dependent manner in vitro. Specifically, a significant difference in the medium- (82.87% ± 6.53%) and high-dose XTSJ groups (77.43% ± 7.34%) was detected at 24 h in the CD44(+) GCSCs group compared with the saline group (95.42% ± 5.76%) and the low-dose XTSJ group (90.74% ± 6.57%) (P < 0.05). However, the efficacy of XTSJ decoction was reduced in the CD44(-) groups; significant differences were only detected in the high-dose XTSJ group at 48 h (78.57% ± 6.94%) and 72 h (72.12% ± 7.68%) when compared with the other CD44- groups (P < 0.05). Notably, these differences were highly consistent with the Notch-1, Hes1, VEGF and Ki-67 expression in these cells. Similarly, in vivo, XTSJ decoction inhibited tumor growth in a dose-dependent manner. A significant difference was observed in the medium- (1.76 ± 0.15) and high-dose XTSJ (1.33 ± 0.081) groups compared with the GCSCs control group (2.72 ± 0.25) and the low-dose XTSJ group (2.51 ± 0.25) (P < 0.05). We also detected a remarkable decrease of MVD in the medium- (7.10 ± 0.60) and high-dose XTSJ (5.99 ± 0.47) groups compared with the GCSC control group (8.15 ± 0.42) and the low-dose XTSJ group (8.14 ± 0.46) (P < 0.05). Additionally, CD44 expression was decreased in these groups [medium- (4.43 ± 0.45) and high-dose XTSJ groups (3.56 ± 0.31) vs the GCSC control (5.96 ± 0.46) and low dose XTSJ groups (5.91 ± 0.38)] (P < 0.05). The significant differences in Notch-1, Hes1, VEGF and Ki-67 expression highly mirrored the results of XTSJ decoction in inhibiting tumor growth, MVD and CD44 expression. CONCLUSION: Notch-1 may play an important role in regulating the proliferation of GCSCs; XTSJ decoction could attenuate tumor angiogenesis, at least partially, by inhibiting Notch-1.

Xiaotan Tongfu granules contribute to the prevention of stress ulcers.

AIM: To investigate the efficacy and potential mechanism of Xiaotan Tongfu granules (XTTF) in stress ulcers. METHODS: One hundred sixty rats were randomly divided into 4 groups (n = 10) as follows: the model group (MP group), the control group (CP group), the ranitidine group (RP group) and the XTTF granule group (XP group). Rats in the MP group received no drugs, rats in the CP group received 0.2 mL of a 0.9% sodium chloride solution via oral gavage, and rats in the RP and XP groups received the same volume of ranitidine (50 mg/kg) or XTTF granule (4.9 g/kg). The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration. Afterwards, rats were sacrificed at 0, 3, 6 and 24 h. Gastric pH was measured by a precise pH meter; gastric emptying rate (GER) was measured by using a methylcellulose test meal; myeloperoxidase activity (MPO), macrophage migration inhibitory factor (MIF), proliferating cell nuclear antigen (PCNA), and heat shock protein 70 (HSP70) were measured by immunohistochemical staining; and mucosal cell apoptosis was measured by transferase dUTP nick end labeling. RESULTS: In the cold-restraint stress model, the development of stress ulcers peaked at 3 h and basically regressed after 24 h. Gastric lesions were significantly different in the RP and XP groups at each time point. Interestingly, although this index was much lower in the RP group than in the XP group immediately following stress induction (7.00 ± 1.10 vs 10.00 ± 1.79, P < 0.05. Concerning gastric pH, between the RP and XP groups, we detected a statistically significant difference immediately after stress induction (0 h: 4.56 ± 0.47 vs 3.34 ± 0.28, P < 0.05) but not at any of the subsequent time points. For GER, compared to the RP group, GER was remarkably elevated in the XP group because a statistically significant difference was detected (3 h: 46.84 ± 2.70 vs 61.16 ± 5.12, P < 0.05; 6 h: 60.96 ± 6.71 vs 73.41 ± 6.16, P < 0.05; 24 h: 77.47 ± 3.17 vs 91.31 ± 4.34, P < 0.05). With respect to MPO and MIF, comparisons between the RP and XP groups revealed statistically significant differences at 3 h (MPO: 18.94 ± 1.20 vs 13.51 ± 0.89, P < 0.05; MIF: 150.67 ± 9.85 vs 122.17 ± 5.67, P < 0.05) and 6 h (MPO: 13.22 ± 1.54 vs 8.83 ± 0.65, P < 0.05; MIF: 135.50 ± 9.46 vs 109.83 ± 6.40, P < 0.05). With regard to HSP70, HSP70 expression was significantly increased in the RP and XP groups at 3 and 6 h compared to the MP and CP groups. In addition, comparing the RP and XP groups also showed statistically significant differences at 3 and 6 h. The expression of PCNA was higher in the RP and XP groups 3 h after stress induction. Between these two groups, small but statistically significant differences were observed at all of the time points (3 h: 69.50 ± 21.52 vs 79.33 ± 15.68, P < 0.05; 6 h: 107.83 ± 4.40 vs 121.33 ± 5.71, P < 0.05; 24 h: 125.33 ± 5.65 vs 128.50 ± 14.49, P < 0.05) except 0 h. With regard to apoptosis, the apoptotic activity in the RP and XP groups was significantly different from that in the MP and CP groups. The XP group exhibited a higher inhibition of cell apoptosis than the RP group at 3 h (232.58 ± 24.51 vs 174.46 ± 10.35, P < 0.05) and 6 h (164.74 ± 18.31 vs 117.71 ± 12.08, P < 0.05). CONCLUSION: The Xiaotan Tongfu granule was demonstrated to be similar to ranitidine in preventing stress ulcers. It exhibited multiple underlying mechanisms and deserves further study.

ß -Elemene-Attenuated Tumor Angiogenesis by Targeting Notch-1 in Gastric Cancer Stem-Like Cells.

Emerging evidence suggests that cancer stem cells are involved in tumor angiogenesis. The Notch signaling pathway is one of the most important regulators of these processes. ß -Elemene, a naturally occurring compound extracted from Curcumae Radix, has been used as an antitumor drug for various cancers in China. However, its underlying mechanism in the treatment of gastric cancer remains largely unknown. Here, we report that CD44+ gastric cancer stem-like cells (GCSCs) showed enhanced proliferation capacity compared to their CD44- counterparts, and this proliferation was accompanied by the high expression of Notch-1 (in vitro). These cells were also more superior in spheroid colony formation (in vitro) and tumorigenicity (in vivo) and positively associated with microvessel density (in vivo). ß -Elemene was demonstrated to effectively inhibit the viability of GCSCs in a dose-dependent manner, most likely by suppressing Notch-1 (in vitro). ß -Elemene also contributed to growth suppression and attenuated the angiogenesis capacity of these cells (in vivo) most likely by interfering with the expression of Notch-1 but not with Dll4. Our findings indicated that GCSCs play an important role in tumor angiogenesis, and Notch-1 is one of the most likely mediators involved in these processes. ß -Elemene was effective at attenuating angiogenesis by targeting the GCSCs, which could be regarded as a potential mechanism for its efficacy in gastric cancer management in the future.

YY1 is a novel potential therapeutic target for the treatment of HPV infection-induced cervical cancer by arsenic trioxide.

OBJECTIVE: YY1 is a zinc finger transcription factor involved in the regulation of cell growth, development, and differentiation. Although YY1 can regulate human papillomavirus-type (HPV) viral oncogenes E6 and E7, it remains unknown if YY1 plays a key role in carcinoma progression of HPV-infected cells. Here we sought to determine whether YY1 is upregulated in the cervical cancer tissues and YY1 inhibition contributes to apoptosis of cervical cancer cells, which is at least partly p53 dependent. Therefore, YY1 can be a potential therapeutic target for cervical cancer treatment by arsenic trioxide (As2O3). MATERIALS AND METHODS: The expression level of YY1 was examined and analyzed by Western blot in pathologically confirmed primary cervical cancer samples, in the adjacent normal samples, as well as in normal cervix samples. The effects of YY1 inhibition by specific small interfering RNA in HeLa cells were determined by Western blot analysis of p53 level, cell growth curve, colony formation assay, and apoptosis. The contribution of YY1 to As2O3-induced p53 activation and apoptosis was also examined by Western blot and cell cycle analysis. RESULTS: Here we report that the expression level of YY1 is significantly elevated in the primary cancer tissues. In HPV-positive HeLa cells, small interfering RNA-mediated YY1 inhibition induced apoptosis and increased the expression of p53. Treatment of HeLa cells with As2O3, a known anti-cervical cancer agent, reduced both protein and mRNA levels of YY1 in HeLa cells. YY1 knockdown significantly further enhanced As2O3-induced apoptosis. CONCLUSIONS: These results demonstrated that the expression of YY1 is upregulated in cervical carcinomas and that YY1 plays a critical role in the progression of HPV-positive cervical cancer. In addition, YY1 inhibition induces p53 activation and apoptosis in HPV-infected HeLa cells. Thus, YY1 is an As2O3 target and could serve as a potential drug sensitizer for anti-cervical cancer therapy.