Pan-cancer analyses reveal the molecular and clinical characteristics of TET family members and suggests that TET3 maybe a potential therapeutic target.

The Ten-Eleven Translocation (TET) family genes are implicated in a wide array of biological functions across various human cancers. Nonetheless, there is a scarcity of studies that comprehensively analyze the correlation between TET family members and the molecular phenotypes and clinical characteristics of different cancers. Leveraging updated public databases and employing several bioinformatics analysis methods, we assessed the expression levels, somatic variations, methylation levels, and prognostic values of TET family genes. Additionally, we explored the association between the expression of TET family genes and pathway activity, tumor microenvironment (TME), stemness score, immune subtype, clinical staging, and drug sensitivity in pan-cancer. Molecular biology and cytology experiments were conducted to validate the potential role of TET3 in tumor progression. Each TET family gene displayed distinct expression patterns across at least ten detected tumors. The frequency of Single Nucleotide Variant (SNV) in TET genes was found to be 91.24%, primarily comprising missense mutation types, with the main types of copy number variant (CNV) being heterozygous amplifications and deletions. TET1 gene exhibited high methylation levels, whereas TET2 and TET3 genes displayed hypomethylation in most cancers, which correlated closely with patient prognosis. Pathway activity analysis revealed the involvement of TET family genes in multiple signaling pathways, including cell cycle, apoptosis, DNA damage response, hormone AR, PI3K/AKT, and RTK. Furthermore, the expression levels of TET family genes were shown to impact the clinical staging of tumor patients, modulate the sensitivity of chemotherapy drugs, and thereby influence patient prognosis by participating in the regulation of the tumor microenvironment, cellular stemness potential, and immune subtype. Notably, TET3 was identified to promote cancer progression across various tumors, and its silencing was found to inhibit tumor malignancy and enhance chemotherapy sensitivity. These findings shed light on the role of TET family genes in cancer progression and offer insights for further research on TET3 as a potential therapeutic target for pan-cancer.

A Deep-Learning-Based CPR Action Standardization Method.

In emergency situations, ensuring standardized cardiopulmonary resuscitation (CPR) actions is crucial. However, current automated external defibrillators (AEDs) lack methods to determine whether CPR actions are performed correctly, leading to inconsistent CPR quality. To address this issue, we introduce a novel method called deep-learning-based CPR action standardization (DLCAS). This method involves three parts. First, it detects correct posture using OpenPose to recognize skeletal points. Second, it identifies a marker wristband with our CPR-Detection algorithm and measures compression depth, count, and frequency using a depth algorithm. Finally, we optimize the algorithm for edge devices to enhance real-time processing speed. Extensive experiments on our custom dataset have shown that the CPR-Detection algorithm achieves a mAP0.5 of 97.04%, while reducing parameters to 0.20 M and FLOPs to 132.15 K. In a complete CPR operation procedure, the depth measurement solution achieves an accuracy of 90% with a margin of error less than 1 cm, while the count and frequency measurements achieve 98% accuracy with a margin of error less than two counts. Our method meets the real-time requirements in medical scenarios, and the processing speed on edge devices has increased from 8 fps to 25 fps.

OTUD6B promotes cholangiocarcinoma growth by regulating STAT3 phosphorylation through deubiquitination of PTK2.

Cholangiocarcinoma (CCA) is a hepatobiliary carcinoma with uncontrolled cell proliferation, poor prognosis, and high mortality. The ovarian tumor structural domain (OTU) containing protein 6B (OTUD6B) belongs to the OTU deubiquitin family and is vital in tumor development. However, its expression and biological function in CCA remain unknown. The expression of OTUD6B in CCA was analyzed using TIMER2.0, UALCAN, and GEO databases. MTT, clonal formation assay, immunofluorescence staining, immunohistochemistry staining, and flow cytometry examined the regulation of OTUD6B on cell proliferation, cycle, and apoptosis. The effects of OTUD6B on tumor volume and weight were assessed using the xenograft tumor model. The activities of PTK2 and STAT3 were detected by western blot and CO-IP. The biological database identified that OTUD6B was upregulated in CCA. In CCA cells, OTUD6B knockdown reduced CCA cell proliferation and promoted apoptosis. Cell cycle analysis indicated that the cycle stopped at the G0/G1 phase after OTU6B downregulation. Furthermore, OTUD6B knockdown resulted in a decrease in tumor volume and weight in xenograft tumor models. Mechanistically, OTUD6B is involved in the deubiquitination of PTK2. PTK2 further affected the phosphorylation of STAT3 thereby regulating the CCA process. Our study demonstrates that OTUD6B knockdown participates in the ubiquitination of PTK2 and phosphorylation of STAT3 to alleviate the process of CCA. These results suggest that OTUD6B may be a potential new strategy for CCA treatment.

Ecological Niche Characteristics of the Diets of Three Sympatric Rodents in the Meili Snow Mountain, Yunnan.

Understanding the dietary preferences and ecological niche characteristics of mammals not only reveals their adaptive strategies under environmental changes but also reveals the interspecific relationships and coexistence mechanisms among sympatric species. Nevertheless, such data are scarce for rodents inhabiting areas spanning a wide altitude range. This study employed DNA metabarcoding technology to analyze the stomach contents of Apodemus ilex, Apodemus chevrieri, and Niviventer confucianus, aiming to investigate their dietary compositions and diversity in the Meili Snow Mountain in Yunnan Province, China. Levins's and Pianka's indices were used to compare the interspecific niche breadth and niche overlaps. The results revealed the following: (1) Insecta (relative abundance: 59.4-78.4%) and Clitellata (relative abundance: 5.2-25.5%) were the primary animal food sources for the three species, while Magnoliopsida (relative abundance: 90.3-99.9%) constitutes their main plant food source. Considerable interspecific differences were detected in the relative abundance of primary animal and plant foods among the three species; (2) There was partial overlap in the genus-level animal food between A. ilex and N. confucianus (Ojk = 0.4648), and partial overlap in plant food between A. ilex and A. chevrieri (Ojk = 0.3418). However, no overlap exists between A. chevrieri and N. confucianus, either in animal or plant food; (3) There were no significant interspecific differences in the α-diversity of animal and plant foods among the three species. The feeding strategies and ecological niche variations of these rodents support the niche differentiation hypothesis, indicating that they have diversified in their primary food sources. This diversification may be a strategy to reduce competition and achieve long-term coexistence by adjusting the types and proportions of primary foods consumed.

Establishment of a Risk Prediction Model for Metabolic Syndrome in High Altitude Areas in Qinghai Province, China: A Cross-Sectional Study.

Purpose: The prevalence of metabolic syndrome (MetS) is increasing worldwide, and early prediction of MetS risk is highly beneficial for health outcomes. This study aimed to develop and validate a nomogram to predict MetS risk in Qinghai Province, China, and it provides a methodological reference for MetS prevention and control in Qinghai Province, China. Patients and Methods: A total of 3073 participants living between 1900 and 3710 meters above sea level in Qinghai Province participated in this study between March 2014 and March 2016. We omitted 12 subjects who were missing diagnostic component data for MetS, ultimately resulting in 3061 research subjects, 70% of the subjects were assigned randomly to the training set, and the remaining subjects were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used for variable selection via running cyclic coordinate descent with 10-fold cross-validation. Multivariable logistic regression was then performed to develop a predictive model and nomogram. The receiver operating characteristic (ROC) curves was used for model evaluation, and calibration plot and decision curve analysis (DCA) were used for model validation. Results: Of 24 variables studied, 6 risk predictors were identified by LASSO regression analysis: hyperlipidaemia, hyperglycemia, abdominal obesity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). A prediction model including these 6 risk factors was constructed and displayed good predictability with an area under the ROC curve of 0.914 for the training set and 0.930 for the validation set. DCA revealed that if the threshold probability of MetS is less than 82%, the application of this nomogram is more beneficial than both the treat-all or treat-none strategies. Conclusion: The nomogram developed in our study demonstrated strong discriminative power and clinical applicability, making it a valuable reference for meets prevention and control in the plateau areas of Qinghai Province.

Preparation of berberine hydrochloride-Ag nanoparticle composite antibacterial dressing based on 3D printing technology.

In recent years, Ag nanoparticle (Ag NP)-loaded antibacterial dressings have attracted much attention in high-level medical dressings. However, the high cytotoxicity of Ag NP has always been a problem. In this paper, we examined the improvement of antibacterial activity of berberine hydrochloride (BBR) with Ag NP, the results showed that the combined use of BBR and Ag NP can effectively reduce the dosage of Ag NP while ensuring the inhibition of bacterial growth, thus an intermediate layer dressing containing combined drugs were prepared. At the same time, the top dressing of polyvinyl alcohol (PVA) solid film and the PVA bottom dressings with three kinds of leakage structures were prepared by 3D printing technology. Three kinds of PVA bottom dressings showed high quality consistency, and the greater the number of leak holes, the higher the porosity value of the dressing, while the swelling ratio value of the bottom layer dressing with three holes was the lowest. Finally, three types of BBR-Ag NP composite antibacterial dressings (3D-BBR-Ag NP) can be obtained by self-assembling of the top dressing, the intermediate layer dressing, and the bottom dressings with three kinds of leakage structures. The cumulative drug release results showed that dressing with more holes had a faster drug release rate compared to the other two ones with fewer leakage holes. Besides, five drug release kinetic models were used to investigate the cumulative BBR release profiles for three types of 3D-BBR-Ag NP. And the three types of composite dressings showed strong antibacterial activity after 6 h of cultivation with staphylococcus aureus. The study showed that the antibacterial activity of the self-assembled dressing prepared by combination of BBR with Ag NP can be improved, and the drug release rate of the hydrogel dressing can be flexibly controlled through 3D printing technology.

[Effect of vitamin D binding protein gene polymorphism on susceptibility and prognosis of severe acute pancreatitis].

OBJECTIVE: To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP). METHODS: A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence. RESULTS: The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (µg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (µg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05). CONCLUSIONS: The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.

[Ginkgo biloba Ketone Ester Tablets with different release rates prepared by fused deposition modeling 3D printing technology].

The present study prepared a new type of Ginkgo biloba ketone ester(GBE50) preparation from polyethylene glycol and croscarmellose sodium with good biocompatibility and a certain viscosity by fused deposition modeling(FDM)-type 3D printing technique. Firstly, a cylindrical 3D printing model with a diameter of 9.00 mm and a height of 4.50 mm was established. Subsequently, the 3D-GBE50 preparations with three paths(concentric, zigzag, and grid), different layer heights, and different filling gaps were designed and prepared after the optimization of the proportions of excipients. The morphology, size, chemical properties, and dissolution activity of the 3D-GBE50 preparations were fully characterized and investigated. The results showed that 3D-GBE50 preparations had smooth appearance, clear texture, standard friability, good thermal stability, and stable chemical properties. Moreover, the printing path, layer height, and filling gap were directly related to the release rate of 3D-GBE50 preparations. The dissolution of 3D-GBE50 tablets with zigzag printing path was the fastest, while the dissolution rates of 3D-GBE50 tablets with concentric circle and grid-shaped printing paths were slower than that of commercially available G. biloba Ketone Ester Tablets. In addition, the dissolution of 3D-GBE50 tablets was faster with higher layer height and wider filling gap. As revealed by the results, th FDM-type 3D printing technique can flexibly regulate the drug release activity via controlling the printing parameters, providing effective ideas and methods for the pre-paration of personalized pharmaceutical preparations.

The diagnostic role of CT, MRI/MRCP, PET/CT, EUS and DWI in the differentiation of benign and malignant IPMN: A meta-analysis.

PURPOSE: The objective of this study was to assess the diagnostic properties of computed tomography (CT), magnetic resonance imaging (MRI/MRCP) /Magnetic Resonance Cholangiopancreatography (MRCP), positron emission tomography/computed tomography (PET/CT), endoscopic ultrasound (EUS) and diffusion-weighted magnetic resonance imaging (DWI) in distinguishing benign and malignant intraductal papillary mucinous neoplasm (IPMN). MATERIALS AND METHODS: Eligible databases were searched for eligible studies, published through July 2020 on the diagnostic accuracy of these modalities. Diagnostic accuracy parameters, including sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic curves (SROC) were calculated. Meta-regression was performed to identify the source of heterogeneity. RESULTS: In total, 28 studies were included. Pooled sensitivities for CT, MRI/MRCP, PET/CT, EUS and DWI were 0.7, 0.76, 0.8, 0.6 and 0.72, respectively. Pooled specificities were 0.78, 0.83, 0.9, 0.8 and 0.97. The DORs were 8, 16, 35, 6 and 88. The areas under the curve (AUC) of SROC for CT, MRI/MRCP/MRCP, PET/CT, EUS and DW were 0.8, 0.87, 0.92, 0.79 and 0.82, respectively. CONCLUSION: PET/CT showed the highest AUC and the overall diagnostic accuracy results support the use of MRI/MRCP, PET/CT interchangeably as a first-line examination in the diagnosis of malignant IPMN. With regard to DWI, EUS and CT, each techniques have their advantages and supportive to MRI/MRCP.

miR-424-3p Contributes to the Malignant Progression and Chemoresistance of Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common and lethal malignancies worldwide. Therefore, a better understanding of the mechanism of its malignant progression and chemoresistance will be helpful for the treatment of patients with GC. METHODS: The gene expression profiles downloaded from GEO database and the TargetScan Human were used to identify the key regulation model based on miRNA by bioinformatics analyses. The regulation of miRNA to target was clarified by luciferase assay, qPCR, and Western blotting. Then, the in vitro and in vivo experiments were further conducted by overexpression or knockdown of miRNA and/or target to examine the regulation effects and clarify the mechanism. RESULTS: In the present study, miR-424-3p was identified to be differentially expressed among normal gastric, GC, and chemoresistant GC tissues. Target analysis results indicated that ABCC2, a chemoresistance-related gene, was a regulated target of miR-424-3p. The in vitro and in vivo experiment results further demonstrated that miR-424-3p relied on ABCC2-induced chemoresistance to promote GC proliferation and metastasis. CONCLUSION: Overall, this study revealed that miR-424-3p contributed to the malignant progression and chemoresistance of GC. Thus, miR-424-3p could be a potential target for the treatment of GC.

miR-212 as potential biomarker suppresses the proliferation of gastric cancer via targeting SOX4.

BACKGROUND: Circulating microRNAs that post-transcriptionally regulate gene expressions have been reported as promising biomarkers in cancer monitoring. This study was to identify the potential role of circulating miR-212 in gastric cancer and whether it could serve as a novel biomarker for gastric cancer. METHODS: We detected the serum levels of miR-212 in 100 health people and 110 gastric cancer patients and analyzed the relationships of the serum level of miR-212 with gastric cancer. We detected the expression of miR-212 in human gastric mucosal epithelial cell line (GES-1) and human gastric cancer cell lines (NCI-N87 and SNU-16) using qRT-PCR. Then, we detected the role of 5-aza-deoxycytidine on the epigenetic regulation of miR-212 in human gastric cancer cell lines. Furthermore, luciferase reporter assay was used to detect binding activity of miR-212 on SOX4 mRNA, and their functions on the cell proliferation and apoptosis. RESULTS: The expression of miR-212 was higher in health people than that in gastric cancer patients, higher in gastric mucosal epithelial cell line than that in gastric cancer cells. miR-212 can be a circulating biomarker and an independent prognostic factor of gastric cancer. Moreover, miR-212 can directly regulate the 3'UTR of SOX4 mRNA to suppress p53 and Bax, resulting gastric cancer cells proliferation inhibition and apoptosis induction. CONCLUSION: Our study demonstrated that miR-212 was epigenetically downregulated in gastric cancer, and resulting low level of miR-212 can be a potential circulating biomarker and poor prognosis predicator of gastric cancer.

DERL3 functions as a tumor suppressor in gastric cancer.

BACKGROUND: Gastric cancer is a common malignant tumor in the clinic with a high mortality rate, ranking the first among malignant tumors of the digestive system. Early gastric cancer exhibits no specific clinical symptoms and signs, and most of the patients were diagnosed as advanced gastric cancer. The prognosis is poor, and the 5-year overall survival rate is still lower than 30%, seriously threatening people's life and health. However, the pathogenesis of gastric cancer is still unclear. METHODS: This study aimed to identify methylated differentially expressed genes in gastric cancer and to study the cellular functions and pathways that may be involved in its regulation, as well as the biological functions of key methylated differentially expressed genes. The gene expression data set and methylation data set of gastric cancer genes based on TCGA were analyzed to identify prognostic methylated genes. RESULTS: This study showed that the methylation of the DERL3 promoter was correlated with the clinical analysis of tumors. Further studies were conducted on genes co-expressed with DERL3, whose functions and pathways to inhibit gastric cancer were adaptive immune response, T cell activation, immune response-regulating pathway, cell surface on molecules, and natural killer cell-mediated cytotoxicity. Finally, cell proliferation assay, cell scratch assay, and cell invasion assay confirmed that DERL3 as a tumor suppressor gene inhibited the malignant evolution of gastric cancer. CONCLUSIONS: The analysis of key methylated differentially expressed genes helped elucidate the epigenetic regulation mechanism in the development of gastric cancer. DERL3, as a methylation biomarker, has a predictive and prognostic value in the accurate diagnosis and treatment of gastric cancer and provides potential targets for the precision treatment of gastric cancer. TRIAL REGISTRATION: Not applicable.

Association of polymorphisms in bone morphogenetic protein receptor-1B gene exon-9 with litter size in Dorset, Mongolian, and Small Tail Han ewes.

OBJECTIVE: The present study was to investigate the association of polymorphisms in exon-9 of the bone morphogenetic protein receptor-1B (BMPR-1B) gene (C864T) with litter size in 240 Dorset, 232 Mongolian, and 124 Small Tail Han ewes. METHODS: Blood samples were collected from 596 ewes and genomic DNA was extracted using the phenol: chloroform extraction method. The 304-bp amplified polymerase chain reaction product was analyzed for polymorphism by single-strand conformation polymorphism method. The genotypic frequency and allele frequency of BMPR-1B gene exon-9 were computed after sequence alignment. The χ2 independence test was used to analyze the association of genotypic frequency and litter size traits with in each ewe breed, where the phenotype was directly treated as category. RESULTS: The results indicated two different banding patterns AA and AB for this fragment, with the most frequent genotype and allele of AA and A. Calculated Chi-square test for BMPR-1B gene exon-9 was found to be more than that of p value at the 5% level of significance, indicating that the population under study was in Hardy-Weinberg equilibrium for all ewes. The χ2 independence test analyses indicated litter size differences between genotypes was not the same for each breed. The 304-bp nucleotide sequence was subjected to BLAST analysis, and the C864T mutation significantly affected litter size in singletons, twins and multiples. The heterozygosity in exon-9 of BMPR-1B gene could increase litter size for all the studied ewes. CONCLUSION: Consequently, it appears that the polymorphism BMPR-1B gene exon-9 detected in this study may have potential use in marker assisted selection for litter size in Dorset, Mongolian, and Small Tail Han ewes.

miR-519d-3p Inhibits Cell Proliferation and Invasion of Gastric Cancer by Downregulating B-Cell Lymphoma 6.

miR-519d inhibits cell growth, migration, and invasion, but its role in gastric cancer (GC) cells is obscure. We showed that miR-519d-3p was lowly expressed in GC tissues and was associated with the clinical stage and lymph node metastasis of GC tissues. We found that miR-519d-3p repressed cell proliferation and invasion of MGC803 cells and delayed the G1/S phase transition, resulting in decreased cyclin B1 and MMP2 and increased E-cadherin levels. Furthermore, miR-519d-3p targeted and downregulated B-cell lymphoma 6 (BCL6) expression. BCL6 overexpression partially abrogated the suppressive function of miR-519d in MGC803 cells. In conclusion, our study demonstrated that miR-519d-3p functions as a tumor suppressor by targeting and downregulating the expression of BCL6 in GC cells.

miR-320a serves as a negative regulator in the progression of gastric cancer by targeting RAB14.

Gastric cancer (GC) is one of the most common types of malignancy worldwide, with high morbidity and mortality rates. The dysregulation of microRNAs (miRs) has been found to be involved in the carcinogenesis of GC. The present study aimed to investigate the underlying association between GC and miR-320a. Analysis using reverse transcription quantitative polymerase chain reaction indicated that the expression of miR-320a was downregulated and the expression of RAB14 was upregulated in GC tissues and cells, compared with the corresponding controls. MTT, colony formation assays, and flow cytometric analyses were used to evaluate the effect of miR-320a on cell proliferation and the cell cycle. The ectopic expression of miR-320a using miR-320a mimics suppressed cell viability, inhibited G1/S transition, and induced apoptosis in AGS and MKN45 cells. In addition, RAB14 was identified as a direct target gene of miR-320a, according to the results of bioinformatics analysis and a luciferase reporter assay. Downregulation of RAB14 by RAB14-small interfering RNA inhibited the viability of GC cells, which was similar to the phenotype of miR-320a mimics. Furthermore, the reintroduction of RAB14 partially abrogated the miR-320a-mediated downregulation of RAB14 and rescued the miR-320a-induced effects on GC cell growth. These findings suggest a potential novel therapeutic target for the treatment of GC.

Theaflavins suppress tumor growth and metastasis via the blockage of the STAT3 pathway in hepatocellular carcinoma.

Theaflavins, the major black tea polyphenols, have been reported to exhibit promising antitumor activities in several human cancers. However, the role of theaflavins in hepatocellular carcinoma (HCC) is still unknown. In this study, we found that theaflavins could significantly inhibit proliferation, migration, and invasion, and induce apoptosis in HCC cells in vitro. Furthermore, we found that theaflavins inhibited the growth and metastasis of HCC in an orthotopic model and a lung metastasis model. Immunohistochemical analyses and terminal deoxynucleotidyl transferase dUTP nick end-labeling assays showed that theaflavins could suppress proliferation and induce apoptosis in vivo. Theaflavins also suppressed constitutive and inducible signal transducer and activator of transcription 3 (STAT3) phosphorylation. The downstream proteins regulated by STAT3, including the antiapoptotic proteins (Bcl-2 and Survivin) and the invasion-related proteins (MMP-2, MMP-9), were also downregulated after theaflavins treatment. Theaflavins induced apoptosis by activating the caspase pathway. Together, our results suggest that theaflavins suppress the growth and metastasis of human HCC through the blockage of the STAT3 pathway, and thus may act as potential therapeutic agents for HCC.