Research Progress on the Synergistic Anti-Tumor Effect of Natural Anti-Tumor Components of Chinese Herbal Medicine Combined with Chemotherapy Drugs.

The application of chemotherapy drugs in tumor treatment has a long history, but the lack of selectivity of drugs often leads to serious side effects during chemotherapy. The natural anti-tumor ingredients derived from Chinese herbal medicine are attracting increased attention due to their diverse anti-tumor effects, abundant resources, and minimal side effects. An effective anti-tumor strategy may lie in the combination of these naturally derived anti-tumor ingredients with conventional chemotherapy drugs. This approach could potentially inhibit tumor growth and the development of drug resistance in tumor cells while reducing the adverse effects of chemotherapy drugs. This review provides a comprehensive overview of the combined therapy strategies integrating natural anti-tumor components from Chinese herbal medicine with chemotherapy drugs in current research. We primarily summarize various compounds in Chinese herbal medicine exhibiting natural anti-tumor activities and the relevant mechanisms in synergistic anti-tumor combination therapy. The focus of this paper is on underlining that this integrative approach, combining natural anti-tumor components of Chinese herbal medicine with chemotherapy drugs, presents a novel cancer treatment methodology, thereby providing new insights for future oncological research.

Big data sentiment analysis of business environment public perception based on LTP text classification --Take Heilongjiang province as an example.

At present, the research of business environment is limited to conducting surveys on specific groups or measuring data from official databases. The assessment of the business environment largely depends on public perception. Aiming to explore the public perception of business environment, this paper organically combines the big data text mining and sentiment analysis (SA). The results show that the combination of big data text mining and SA can reflect the theme characteristics, reduce the bias of sentiment and text analysis, and clearly show the public perception of the business environment. The empirical study found that the public perception of business environment depends on not only the four dimensions of business environment, but also the influence of public opinion that cannot be ignored. The public's low recognition of the business environment in Heilongjiang Province mainly includes backward economic development, serious brain drain, low government efficiency, imperfect policies, administrative law enforcement, regional climate and urban construction. In order to solve these problems, it is necessary to improve the high-standard market system to promote economic development, enhance the efficiency of government services, improve government policies, effectively enhance law enforcement, strengthen infrastructure construction and promote cultural innovation.

Pheromone effect of estradiol regulates the conjugative transfer of pCF10 carrying antibiotic resistance genes.

Horizontal gene transfer (HGT) mediated by conjugative plasmids greatly contributes to bacteria evolution and the transmission of antibiotic resistance genes (ARGs). In addition to the selective pressure imposed by extensive antibiotic use, environmental chemical pollutants facilitate the dissemination of antibiotic resistance, consequently posing a serious threat to the ecological environment. Presently, the majority of studies focus on the effects of environmental compounds on R plasmid-mediated conjugation transfer, and pheromone-inducible conjugation has largely been neglected. In this study, we explored the pheromone effect and potential molecular mechanisms of estradiol in promoting the conjugative transfer of pCF10 plasmid in Enterococcus faecalis. Environmentally relevant concentrations of estradiol significantly increased the conjugative transfer of pCF10 with a maximum frequency of 3.2 × 10-2, up to 3.5-fold change compared to that of control. Exposure to estradiol induced the activation of pheromone signaling cascade by increasing the expression of ccfA. Furthermore, estradiol might directly bind to the pheromone receptor PrgZ and promote pCF10 induction and finally enhance the conjugative transfer of pCF10. These findings cast valuable insights on the roles of estradiol and its homolog in increasing antibiotic resistance and the potential ecological risk.

Docosahexaenoic acid inhibits pheromone-responsive-plasmid-mediated conjugative transfer of antibiotic resistance genes in Enterococcus faecalis.

The rapid spread of antibiotic-resistance genes (ARGs) in Enterococcus faecalis (E. faecalis) poses a great challenge to human health and ecological and environmental safety. Therefore, it is important to control the spread of ARGs. In this study, we observed that the addition of 5 µg/mL docosahexaenoic acid (DHA) reduced the conjugative transfer of pCF10 plasmid by more than 95% in E. faecalis. DHA disturbed the pheromone transport by inhibiting the mRNA levels of the prgZ gene, causing the iCF10 pheromone to accumulate in the donor bacteria and bond to the PrgX receptor to form an inhibitory phase, which resulted in the down-regulation of the expression of genes related to conjugative transfer, inhibiting biofilm formation, reducing bacterial adhesion and thus inhibiting conjugative transfer. Collectively, DHA exhibited an admirable inhibitory effect on the transfer of ARGs in E. faecalis. This study provided a technical option to control the transfer of ARGs.

Sirtuin1 (SIRT1) is involved in the anticancer effect of black raspberry anthocyanins in colorectal cancer.

PURPOSE: Abnormal acetylation modification is a common epigenetic change in tumorigenesis and is closely related to the progression of colorectal cancer (CRC). Our previous studies have suggested that black raspberry (BRB) anthocyanins have a significant chemopreventive effect against CRC. This study investigated whether protein acetylation plays an important role in BRB anthocyanins-mediated regulation of CRC progression. METHODS: We used the AOM-induced CRC mouse model and the CRC cell lines SW480 and Caco-2 to explore the potential role of acetylation of histone H4 and NF-κB signaling pathway-related proteins (non-histone proteins) in the antitumor process mediated by BRB anthocyanins. The expression of related proteins was detected by western blot. ROS level was detected by immunofluorescence. RESULTS: BRB anthocyanins affected the acetylation level by down-regulating the expression of Sirtuin1 (SIRT1) and up-regulating the expression of MOF and EP300. The acetylation level of lysine sites on histone H4 (H4K5, H4K12 and H4K16) was increased. Furthermore, following BRB anthocyanins treatment, the expression of ac-p65 was significantly up-regulated and the NF-κB signal pathway was activated, which in turn up-regulated Bax expression and inhibited Bcl-2, cyclin-D1, c-myc and NLRP3 expression to promote CRC cell cycle arrest, apoptosis and relieve inflammation. CONCLUSION: The findings suggested that protein acetylation could play a critical role in BRB anthocyanins-regulated CRC development.

Bisphenols Promote the Pheromone-Responsive Plasmid-Mediated Conjugative Transfer of Antibiotic Resistance Genes in Enterococcus faecalis.

The enrichment and spread of antibiotic resistance genes (ARGs) induced by environmental chemical pollution further exacerbated the threat to human health and ecological safety. Several compounds are known to induce R plasmid-mediated conjugation through inducing reactive oxygen species (ROS), increasing cell membrane permeability, enhancing regulatory genes expression, and so forth. Up to now, there has been no substantial breakthrough in the studies of models and related mechanisms. Here, we established a new conjugation model using pheromone-responsive plasmid pCF10 and confirmed that five kinds of bisphenols (BPs) at environmentally relevant concentrations could significantly promote the conjugation of ARGs mediated by plasmid pCF10 in E. faecalis by up to 4.5-fold compared with untreated cells. Using qPCR, gene knockout and UHPLC, we explored the mechanisms behind this phenomenon using bisphenol A (BPA) as a model of BPs and demonstrated that BPA could upregulate the expression of pheromone, promote bacterial aggregation, and even directly activate conjugation as a pheromone instead of producing ROS and enhancing cell membrane permeability. Interestingly, the result of mathematical analysis showed that the pheromone effect of most BPs is more potent than that of synthetic pheromone cCF10. These findings provide new insight into the environmental behavior and biological effect of BPs and provided new method and theory to study on enrichment and spread of ARGs induced by environmental chemical pollution.

Rapid Quantitative Detection of Live Escherichia coli Based on Chronoamperometry.

The rapid quantitative detection of Escherichia coli (E. coli) is of great significance for evaluating water and food safety. At present, the conventional bacteria detection methods cannot meet the requirements of rapid detection in water environments. Herein, we report a method based on chronoamperometry to rapidly and quantitatively detect live E. coli. In this study, the current indicator i0 and the electricity indicator A were used to record the cumulative effect of bacteria on an unmodified glassy carbon electrode (GCE) surface during chronoamperometric detection. Through the analysis of influencing factors and morphological characterization, it was proved that the changes of the two set electrochemical indicator signals had a good correlation with the concentration of E. coli; detection time was less than 5 min, the detection range of E. coli was 104−108 CFU/mL, and the error range was <30%. The results of parallel experiments and spiking experiments showed that this method had good repeatability, stability, and sensitivity. Humic acid and dead cells did not affect the detection results. This study not only developed a rapid quantitative detection method for E. coli in the laboratory, but also realized a bacterial detection scheme based on the theory of bacterial dissolution and adsorption for the first time, providing a new direction and theoretical basis for the development of electrochemical biosensors in the future.

An Overview of Extracellular Matrix-Based Bioinks for 3D Bioprinting.

As a microenvironment where cells reside, the extracellular matrix (ECM) has a complex network structure and appropriate mechanical properties to provide structural and biochemical support for the surrounding cells. In tissue engineering, the ECM and its derivatives can mitigate foreign body responses by presenting ECM molecules at the interface between materials and tissues. With the widespread application of three-dimensional (3D) bioprinting, the use of the ECM and its derivative bioinks for 3D bioprinting to replicate biomimetic and complex tissue structures has become an innovative and successful strategy in medical fields. In this review, we summarize the significance and recent progress of ECM-based biomaterials in 3D bioprinting. Then, we discuss the most relevant applications of ECM-based biomaterials in 3D bioprinting, such as tissue regeneration and cancer research. Furthermore, we present the status of ECM-based biomaterials in current research and discuss future development prospects.

Characterization of a novel Vibrio parahaemolyticus host-phage pair and antibacterial effect against the host.

Vibrio parahaemolyticus is a widely recognized pathogen that has caused numerous outbreaks and is prevalent in the marine environment. In this study, we investigated the characteristics of the novel V. parahaemolyticus strain BTXS2 and its associated phage, VB_VpP_BT-1011, isolated from the Bohai Coast (Tianjin, China). Strain BTXS2 is a short coryneform bacterium with a terminal flagellum and is able to utilize and metabolize a wide variety of organic matter because of its unique carbon source utilization and enzyme activity. It grows well in medium between pH 5.0 and 9.0 and salinities of simulated freshwater, estuary water, and seawater (NaCl 0.5%-3%). Multiple antibiotic resistance genes and virulence genes that endanger human health were found in the BTXS2 genome. Phage VB_VpP_BT-1011, which infects BTXS2, is a 40,065-bp double-stranded DNA virus of the family Myoviridae with a latent time of 30 min and burst size of 24 PFU/cell. Like its host, the phage tolerates a broad range of environmental conditions (salinity, 0-3% NaCl; pH 5.0-9.0; temperature, 4-37°C). A host range test showed that the phage only infected and inhibited isolate BTXS2. In summary, we investigated a novel V. parahaemolyticus host-phage pair and the antibacterial effect of the phage on V. parahaemolyticus, providing insights into marine microbial ecology and risks.

Decorin deficiency promotes epithelial-mesenchymal transition and colon cancer metastasis.

The tumor microenvironment encompasses a complex cellular network that includes cancer-associated fibroblasts, inflammatory cells, neo-vessels, and an extracellular matrix enriched in angiogenic growth factors. Decorin is one of the main components of the tumor stroma, but it is not expressed by cancer cells. Lack of this proteoglycan correlates with down-regulation of E-cadherin and induction of ß-catenin signaling. In this study, we investigated the role of a decorin-deficient tumor microenvironment in colon carcinoma progression and metastasis. We utilized an established model of colitis-associated cancer by administering Azoxymethane/Dextran sodium sulfate to adult wild-type and Dcn-/- mice. We discovered that after 12 weeks, all the animals developed intestinal tumors independently of their genotype. However, the number of intestinal neoplasms was significantly higher in the Dcn-/- microenvironment vis-à-vis wild-type mice. Mechanistically, we found that under unchallenged basal conditions, the intestinal epithelium of the Dcn-/- mice showed a significant increase in the protein levels of epithelial-mesenchymal transition associated factors including Snail, Slug, Twist, and MMP2. In comparison, in the colitis-associated cancer evoked in the Dcn-/- mice, we found that intercellular adhesion molecule 1 (ICAM-1) was also significantly increased, in parallel with epithelial-mesenchymal transition signaling pathway-related factors. Furthermore, a combined Celecoxib/decorin treatment revealed a promising therapeutic efficacy in treating human colorectal cancer cells, in decorin-deficient animals. Collectively, our results shed light on colorectal cancer progression and provide a protein-based therapy, i.e., treatment using recombinant decorin, to target the tumor microenvironment.

Identification of potential hub genes via bioinformatics analysis combined with experimental verification in colorectal cancer.

Colorectal cancer (CRC) is a kind of malignant cancer with high morbidity and mortality. The purpose of this study was to explore potential regulated key genes involved in CRC through bioinformatics analysis and experimental verification. The gene expression profile data were downloaded from the Gene Expression Omnibus, and the differential expression genes were detected in cancerous and paracancerous samples of CRC patients, respectively. Then functional enrichment analysis, such as the Kyoto Encyclopedia of Genes and Genomes pathway analysis as well as the protein-protein interaction network were constructed, and the highly related genes were clustered by Molecular COmplex DEtection algorithm to find out the core interaction in different genes' crosstalk. The genes affecting CRC prognosis were screened by the Human Protein Atlas database. In addition, the expression level of core genes was detected by GEPIA database, and the core genes' changes in large-scale cancer genome data set were directly analyzed by cBioPortal database. The expression of the predicted hub genes DSN1, AHCY, and ERCC6L was verified by reverse-transcription quantitative polymerase chain reaction in CRC cells. The gene function of DSN1 was analyzed by wound healing and colony formation assays. The results showed that silencing of DSN1 could significantly reduce the migration and proliferation of CRC cells. Further, BUB1B, the potential interacting protein of DSN1, was also predicted via bioinformatics analysis. Above all, this study shows that bioinformatics analysis combined with experimental method verification provide more potential vital genes for the prevention and therapy of CRC.

Upregulation of DKK3 by miR-483-3p plays an important role in the chemoprevention of colorectal cancer mediated by black raspberry anthocyanins.

It is reported that black raspberry (BRB) anthocyanins could act as a potential chemopreventive agent for colorectal cancer (CRC). However, the underlying mechanism by which BRB anthocyanins inhibits the carcinogenesis of CRC cells has not been elucidated. The abnormal expression of microRNAs (miRNAs) that target important tumor suppressor genes is usually associated with CRC development. In this study, we explored whether BRB anthocyanins could affect the expression of certain miRNAs in an azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced CRC mouse model and human CRC cell lines. miRNA microarray analysis was used to determine the differences in miRNA expression between AOM/DSS-induced mice fed with a diet supplemented without or with BRB anthocyanins. The expression of one particular miRNA, miR-483-3p, was found to decrease dramatically in AOM/DSS-induced mice that were fed with a diet supplemented with BRB anthocyanins. Subsequent quantitative real-time polymerase chain reaction and Western blot analyses showed that the reduced expression of miR-483-3p was accompanied by an increased expression of Dickkopf 3 (DKK3), a potential target of miR-483-3p as predicted by bioinformatic analysis. The protein and messenger RNA levels of DKK3 were significantly upregulated when the miR-483-3p level was reduced by a miR-483-3p-specific inhibitor, suggesting that DKK3 might be the target gene of miR-483-3p. In addition, the downstream factors of the DKK3 signaling pathway, which included Wnt/ß-catenin, also played a role in the miR-483-3p-mediated anticancer effect of BRB anthocyanins. Thus, miR-483-3p might be a potential target in BRB anthocyanin-mediated prevention of CRC.

Taurine Promotes the Cartilaginous Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Vitro.

Taurine has been reported to influence osteogenic differentiation, but the role of taurine on cartilaginous differentiation using human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) remains unclear. In this study, we investigated the effect of taurine (0, 1, 5 and 10 mM) on the proliferation and chondrogenesis of hUC-MSCs by analyzing cell proliferation, accumulation of glycosaminoglycans and expression of cartilage specific mRNA. The results show though taurine did not affected the proliferation of hUC-MSCs, 5 mM of taurine is sufficient to enhanced the accumulation of glycosaminoglycans and up-regulate cartilage specific mRNA expression, namely collagen type II, aggrecan and SOX9. Taurine also inhibits chondrocyte dedifferentiation by reducing expression of collagen type I mRNA. Taken together, our study reveals that taurine promotes and maintains the chondrogenesis of hUC-MSCs.

Identification of new defective interfering RNA species associated with porcine reproductive and respiratory syndrome virus infection.

In the present study, seven new defective interfering (DI) RNA species of porcine reproductive and respiratory syndrome virus (PRRSV) were identified. RT-PCR, Northern blot and sequence analyses indicated that these DI RNA specie have deletions of 8513-9176 nucleotides located between Nsp1/Nsp2 and Nsp10. Compared with the previous DI RNAs of PRRSV reported, they have three distinct characteristics: much smaller deletion sizes; different nucleotide repeats (2-12nt) used in the junction sites and in-frame deletions. The results further suggested that the similarity-assisted RNA recombination may be the main cause of generation of DI RNAs in PRRSV and probably in other arteriviruses.