Quercetin inhibits the metabolism of arachidonic acid by inhibiting the activity of CYP3A4, thereby inhibiting the progression of breast cancer.

BACKGROUND: Recent years have witnessed impressive growth in applying natural medicine in tumor treatment. Saffron is reported to elicit an inhibitory property against BC. Herein, we sought to explore the specific components and mechanistic basis of saffron's anti-breast carcinoma (BC) function. METHODS: Bioinformatics analysis was employed to analyze saffron components' anti-BC activity and screen the corresponding target genes involved in BC. Then, the roles of the main saffron ingredient quercetin in the activity of BC cells were examined using CCK-8, MTS, flow cytometry, colony formation, Transwell, and Gelatin zymogram assays. Additionally, the interactions among Quercetin, EET, and Stat3 were assessed by immunofluorescence and Western blot, and LC-MS/MS determined the levels of AA, EETs, and CYP3A. Finally, BC xenograft mouse models were established to verify the anti-BC function of Quercetin in vivo. RESULTS: Quercetin, the main active component of saffron, inhibited BC progression. Quercetin suppressed BC cell growth, migration, and invasion and inhibited CYP3A4 expression and activity in BC. Mechanistically, Quercetin down-regulated CYP3A4 to block the nuclear translocation of Stat3 by decreasing the metabolization of AA to EETs, thereby alleviating BC. Moreover, exogenously added EETs counteracted the anti-tumor effect of Quercetin on BC. Quercetin also inhibited the tumor growth of tumor-bearing nude mice. CONCLUSION: Quercetin could inhibit the activity of CYP3A to down-regulate AA metabolites EETs, consequently hampering p-Stat3 and nuclear translocation, thus impeding BC development.

Honey on Basketball Players' Physical Recovery and Nutritional Supplement.

Sports injury is a subject that every athlete will face, and it is the easiest to happen in training and competition, especially for basketball players. Moreover, the excessive fatigue caused by sports not only reduces the person's ability to play sports, but also it reduces the person's participation in normal training and competition. Sugar and fat play a dominant role in energy metabolism, while protein only plays an auxiliary role. For competitive sports, sugar is the most important energy, and the main components of honey are glucose and fructose. Therefore, this paper attempts to explore the effect of honey on the physical recovery and nutritional supplement of basketball players. In this paper, 10 basketball players in our city were selected as the experimental objects and the data of their physiological and biochemical indexes were analyzed. The results showed that the average hemoglobin of the experimental group decreased from 14.45 g·100 ml-1 in the first week to 13.23 g·100 ml-1 in the second week, increased to 14.25·100 ml-1 in the third week, and increased to 15.79.100 ml-1 in the fourth week. Adding honey can improve the content of HB and CK of basketball players in higher vocational colleges and reduce the increase of BUN, to slow down fatigue and accelerate the speed of physical recovery.

CCL21 activation of the MALAT1/SRSF1/mTOR axis underpins the development of gastric carcinoma.

BACKGROUND: As a significant cause of malignancy mortality, gastric carcinoma (GC) has been well documented to be an often-fatal diagnosis. Despite the limitations of effective therapy, immunotherapy has emerged as a promising therapeutic approach capable of killing cancer cells via the immune system. The current study was conducted to investigate the effect of cytokine C-C motif chemokine ligand 21 (CCL21) on GC progression through the metastasis-associated lung adenocarcinoma transcript 1/serine arginine-rich splicing factor 1/mammalian target of rapamycin (MALAT1/SRSF1/mTOR) axis. METHODS: Bioinformatics analysis was conducted to identify the key genes associated with GC and to subsequently predict their downstream genes. The effect of CCL21, MALAT1, and SRSF1 on the malignant phenotypes and epithelial-mesenchymal transition (EMT) of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo were assessed by expression determination and plasmid transfection. Additionally, RNA pull-down and RNA binding protein immunoprecipitation experiments were performed to determine the MALAT1-microRNA-202-3p (miR-203-3p) interaction and miR-202-3p-SRSF1 interaction followed by the analysis of their effect on the mTOR pathway. RESULTS: CCL21 was identified as a key GC immune gene. Overexpressed CCL21, MALAT1, and SRSF1 along with poorly expressed miR-202-3p were identified in the GC cells. CCL21 induced the MALAT1 expression in a time- and dose-dependent manner. Functionally, MALAT1 targeted miR-202-3p but upregulated SRSF1 and activated mTOR. Crucially, evidence was obtained indicating that CCL21 promoted both the malignant phenotypes and EMT of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo by increasing the MALAT1-induced upregulation of SRSF1. CONCLUSIONS: Taken together, the key observations of our study provide evidence that CCL21 enhances the progression of GC via the MALAT1/SRSF1/mTOR axis, providing a novel therapeutic target for the treatment of GC.

Calcium-binding and coiled-coil domain 2 promotes the proliferation and suppresses apoptosis of prostate cancer cells.

Prostate cancer (PCa) is considered to be one of the most common tumors in men. Calcium-binding and coiled-coil domain 2 (CALCOCO2) is a known important xenophagy receptor, which mediates intracellular bacterial degradation. To the best of the authors' knowledge, the present study is the first to demonstrate that CALCOCO2 functions as an oncogene in PCa. The results of the current study indicated that CALCOCO2 knockdown suppressed cell proliferation and colony formation, whereas it promoted apoptosis of PCa cells. In addition, knockdown of CALCOCO2 in PCa cells reduced cyclin-E1 and increased p53 protein expression. Bioinformatics analysis revealed that CALCOCO2 was associated with 'autophagosome assembly', 'nucleophagy' and 'nucleic acid metabolic process' biological processes and interacted with sequestosome-1, microtubule-associated proteins 1A/1B light chain 3 (MAP1LC3)B, γ-aminobutyric acid receptor-associated protein, IκB kinase subunit γ and MAP1LC3C. Moreover, CALCOCO2 protein levels were indicated to be significantly increased in PCa samples compared with normal prostate tissues. These results suggested that CALCOCO2 may be of value as a diagnostic and therapeutic target in PCa.

Human Herpesvirus 6B U26 Inhibits the Activation of the RLR/MAVS Signaling Pathway.

U26 is one of the roseolovirus unique genes with unknown function. Human herpesvirus 6B (HHV-6B) pU26 is predicted to be an 8-transmembrane protein containing a mitochondrion location signal. Here, we analyzed U26 function during HHV-6B infection and find that (i) HHV-6B U26 is expressed at a very early stage during HHV-6B infection, and knockdown of it results in a significant decrease of HHV-6B progeny virus production; (ii) U26 inhibits the activation of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)/mitochondrial antiviral signaling protein (MAVS) signaling pathway, an important anti-HHV-6B infection innate immune response, by targeting MAVS protein for degradation; and (iii) a portion of U26 locates to the mitochondria, which could affect the mitochondrial membrane potential and finally leads to MAVS degradation. These findings indicate that HHV-6B U26 is a novel antagonistic viral factor against host innate antiviral immunity.IMPORTANCE HHV-6B (human herpesvirus 6B) is well known to evade host antiviral responses and establish a lifelong latent infection. How HHV-6B evades RNA recognition is still poorly understood. Our results indicate that HHV-6 U26 plays a vital role in RLR/MAVS signaling pathway activity. Knockout of endogenous MAVS could facilitate HHV-6B replication. The findings in this study could provide new insights into host-virus interactions and help develop a new therapy against HHV-6B infection.

Anti-CD206 antibody-conjugated Fe3O4-based PLGA nanoparticles selectively promote tumor-associated macrophages to polarize to the pro-inflammatory subtype.

M2 macrophages serve roles in inhibiting inflammation and promoting tumor development. Reversing tumor-associated macrophages (TAMs) from M2- to M1-type polarization may provide an important strategy for tumor immunotherapy. The present study aimed to enhance antitumor immunity by targeting the concentration of iron in macrophages. Fe3O4-based poly(lactic-co-glycolic) acid (PLGA) nanoparticles surface-modified with an anti-CD206 monoclonal antibody were prepared using the oil in water single-emulsion technique. Particle size was measured using a particle size analyzer, the ζ potential was determined using a ζ potential analyzer and the carrier rate of Fe3O4 was measured using an iron assay kit. The conjugation of anti-CD206, and the ability to target M2 macrophages were studied via immunofluorescence. Polarization indexes of the macrophages were detected using both western blotting and reverse transcription-quantitative PCR (RT-qPCR), and a mouse model with subcutaneous tumors was established to verify the antitumor effects of the nanoparticles in vivo. Nanoparticles had a mean diameter in the range of 260-295 nm, and the ζ potential values were between -19 and -33 mV. The Fe3O4 association efficiency ranged from 65-75%, whereas the anti-CD206 conjunction efficiency ranged from 65-70%. The immunofluorescence experiments were able to demonstrate the successful targeting of the M2 macrophages. The western blotting and RT-qPCR experiments identified that CD206-Fe3O4-PLGA and Fe3O4-PLGA promoted the expression of TNF-α, inducible nitric oxide synthase (iNOS) and IL-1ß in the macrophages. The in vivo studies indicated that CD206-Fe3O4-PLGA nanoparticles were able to promote CD86 expression in TAMs, with CD86 being a specific marker of the M1 subtype. In summary, nanoparticles were characterized in the present study by their mean particle size, polydispersity index, ζ potential and morphology, as well as by their association with Fe3O4 and conjugation with the anti-CD206 monoclonal antibody. Collectively, the present results suggested that the nanoparticles were able to both target M2 macrophages and reverse the M2 polarization of the macrophages to the M1 phenotype via the release of coated iron-oxide particles.

[Anti-CD206 antibody-conjugated Fe3O4-based PLGA nanoparticles selectively promotes M1 polarization of tumorassociated macrophages in mice].

OBJECTIVE: To enhance the anti-tumor immunity of macrophages by increasing iron concentration in the macrophages using nanospheres. METHODS: Anti-CD206 antibody-conjugated Fe3O4-based polylactic acid glycolic acid (CD206- Fe3O4-PLGA) nanoparticles were prepared with the W/O/W method. The particle diameter was measured using Malvern particle size detector, the Zeta potential was determined using Zeta potentiometry, and the encapsulation efficiency of Fe3O4 was determined using an iron determination kit. The macrophage-binding and targeting abilities of the conjugated nanoparticles were evaluated using immunofluorescence assay, and the polarization index of macrophages was determined with Western blotting and qRT-PCR. BALB/C-57 mouse models bearing subcutaneous tumors were used to verify the efficacy of the nanoparticles to promote polarization of the tumor-associated macrophages (TAMs). RESULTS: The conjugated nanoparticles had a mean diameter of 260-295 nm with Zeta potential values ranging from -19 mV to -33 mV, encapsulation efficiency of Fe3O4 ranging from 65% to 75%, and anti-CD206 conjunction efficiency of 65%-70%. Immunofluorescence assay verified the targeted binding ability of the nanoparticles with M2 macrophages. Western blotting and qRT-PCR confirmed that both CD206-Fe3O4-PLGA and Fe3O4-PLGA nanoparticles promoted the expression of TNF-α, iNOS and IL-1ß (P < 0.05). In the tumor-bearing mouse models, CD206-Fe3O4-PLGA nanoparticles were confirmed to promote CD86 expression in the TAMs. CONCLUSIONS: CD206-Fe3O4-PLGA nanoparticles are capable of targeted binding to M2 macrophages and reversing the M2 macrophages to M1 phenotype by releasing coated iron oxide particles.

High-Sensitivity and Wide-Linear-Range Thermoluminescence Dosimeter LiMgPO4:Tm,Tb,B for Detecting High-Dose Radiation.

High-sensitivity and wide-linear-range thermoluminescence dosimeter (TLD) is of importance for detecting high-dose radiation in industry, medicine, and agriculture as well as materials and food processing. In this work, we synthesize a series of LiMgPO4 doped with Tm3+, Tb3+, and B3+ via a high-temperature solid-state reaction technique. To observe the effect of dopants, we first investigate the structure by Rietveld refinement of high-quality X-ray diffraction (XRD) data and then study the thermoluminescence (TL) properties of samples radiated by ß-rays in detail. The TL signal of LiMgPO4:Tm,Tb,B is originated from Tm3+ 4f-4f transitions. The kinetic parameters are obtained through fitting the TL glow curve based on the general-order kinetics model, revealing that the dominant TL peak at ∼323 °C is related to ∼1.49 eV trap. Through constructing the vacuum-referred binding energy (VRBE) scheme, we uncover that this deep trap mainly originates from the Tb3+ dopant acted as the captured center of free hole. After codoping 0.6% B3+, the sensitivity of sample as TLD increases ∼170%. According to the radiation dose-dependent TL intensities, the sensitivity of LiMgPO4:Tm,Tb,B is about 200% larger than that of the commercial LiF:Mg,Cu,P at 0.08 Gy, and more sensitive at higher dose. Moreover, the studied sample has wider linear range (up to 10 000 Gy) toward high-dose side, good reproducibility (RSD ∼ 4.6%), and weak fading (∼8% after 34 days), and therefore has potential application as TLD for monitoring high-dose radiation.

Overexpression of NCAPH is upregulated and predicts a poor prognosis in prostate cancer.

Prostate cancer (PCa) is one of the most frequently diagnosed types of cancer worldwide. However, there remains a lack of accurate biomarkers to predict the outcome of PCa. Non-SMC condensin I complex subunit H (NCAPH) encodes a regulatory subunit of the non-structural maintenance of chromosomes condensin I complex. The present study aimed to investigate whether NCAPH may be a novel diagnostic marker for PCa by analyzing public datasets, including GSE17951, GSE55945 and a dataset from The Cancer Genome Atlas. The current results, to the best of our knowledge, demonstrated for the first time that NCAPH is significantly upregulated in PCa. Furthermore, it was identified that NCAPH expression is higher in stage T3/T4 and N1 PCa samples compared with stage T2 and N0 PCa samples, respectively. Kaplan-Meier analysis demonstrated that overexpression of NCAPH is associated with poor survival of patients with PCa. Bioinformatics analysis revealed that NCAPH is involved in regulating the PCa cell cycle by interacting with a number of proteins, including non-SMC condensin I complex subunit D2, non-SMC condensin I complex subunit G, structural maintenance of chromosomes 4, structural maintenance of chromosomes 2, Aurora kinase A, Aurora kinase B, cyclin-dependent kinase 1, H2A histone family member Z, POC1 centriolar protein A and histone cluster 2 H2A family member C. In summary, the present results suggest NCAPH may be a novel and beneficial diagnostic and therapeutic target in PCa.

THERMOLUMINESCENCE SPECTRA AND DOSE RESPONSES OF SrSO4 PHOSPHORS DOPED WITH RARE EARTHS (Eu, Dy, Tm) AND PHOSPHORUS.

The thermoluminescence (TL) spectra and dose responses of strontium sulphate doped with rare earth ions show that the SrSO4:Eu2+ phosphor might reasonably be assumed a isoelectronic trap sample which has unique TL characteristics: there is only one obvious glow peak at 385 nm, 489 K in the TL 3D emission spectra and its TL dose response is linear-sublinear. However, there are several elementary glow peaks in the TL 3D emission spectra and their TL dose responses are linear-supralinear for SrSO4:RE3+ (RE = Dy, Tm). These TL peaks occurred from low to high temperature indicate that the traps are distributed in different energy levels. When a suitable amount of other impurities co-doped into these SrSO4:RE3+, such as phosphorus, the relative intensities of these elementary glow peaks are changed significantly, especially the TL peak ~500 K is enhanced while the peaks at lower temperature are suppressed. The enhanced peak of SrSO4:RE3+,P is attributed to the deep traps. Their dose responses remain in nonlinearity when co-doped phosphorus. The above results and the luminescence properties of other sulphate doped rare earths impurities illustrate that the TL characteristics depend on the structure of defect complexes which can be assumed the basic elements in the TL multi-stage processes.

Spindle pole body component 25 regulates stemness of prostate cancer cells.

Spindle pole body component 25 (SPC25) is a component of NDC80 complex that controls spindle assembly checkpoint in the microtubule-binding domain of kinetochores. We recently showed that SPC25 is required for prostate cancer (PrC) cell proliferation and cell cycle progression, and here we investigated whether SPC25 may be a Cancer stem cell (CSC) marker in PrC. We found that the levels of SPC25 were higher in PrC samples than paired normal prostate tissue. The overall survival of PrC patients with high SPC25 was poorer than those with low SPC25. PrC cell lines were transduced with two vectors carrying a luciferase reporter and a mCherry fluorescent reporter under a cytomegalovirus promoter and a nuclear green fluorescent protein reporter under the control of a SPC25 promoter, respectively, to allow differentiating SPC25+ from SPC25- PrC cells by flow cytometry. Compared to SPC25- cells, SPC25+ cells formed significantly more tumor spheres in culture, appeared to be more resistant towards docetaxel-induced cell apoptosis, and generated larger tumors with higher frequency after serial adoptive transplantation. Thus, our data suggest that SPC25 may be highly expressed in the CSC-like cells in PrC and could be a promising target for effective treatment of PrC.

Overexpression of MCM10 promotes cell proliferation and predicts poor prognosis in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is one of the most malignant tumors of the male urogenital system. There is an urgent need to identify novel biomarkers for PCa. METHODS: In this study, we evaluated the expression levels of MCM10 in prostate cancer by analyzing public datasets (including The Cancer Genome Atlas and GSE21032). Furthermore, loss of function assays was performed to evaluate the effects of MCM10 on cell proliferation, apoptosis, and colony formation. Furthermore, we performed microarray and bioinformatics analyses to explore the potential mechanisms of MCM10. RESULTS: In the present study, we for the first time revealed MCM10 was significantly upregulated in PCa. Moreover, we found increased MCM10 expression was significantly associated with advanced clinical stage and high Gleason score PCa. Kaplan-Meier analysis demonstrated higher MCM10 expression was associated with a poorer patient prognosis in PCa. Furthermore, loss of function assays showed that MCM10 knockdown inhibited cell proliferation and colony formation, but promoted cell apoptosis. Additionally, we performed microarray and bioinformatics analysis and found MCM10 regulated PCa progression by regulating a series of biological processes including cancer, cell death, and apoptosis. CONCLUSIONS: These results suggest that MCM10 may be a potential diagnostic and therapeutic target for PCa.

Knockdown of spindle pole body component 25 homolog inhibits cell proliferation and cycle progression in prostate cancer.

Prostate cancer (PCa) is the most frequently diagnosed type of cancer in Chinese males. Cell-cycle aberration is a hallmark of cancer. Spindle pole body component 25 homolog (SPC25), a component of the Ndc80 complex, serves an important role in regulating mitotic chromosome segregation. However, the functional roles of SPC25 in PCa remain poorly understood. To the best of our knowledge, the present study was the first to demonstrate that SPC25 is significantly upregulated in PCa. In order to investigate the molecular roles of SPC25, a loss of function assay was performed, revealing that SPC25 knockdown inhibited cell proliferation, and induced a decrease in the number of cells in the S phase and an increase in the number of cells in the G2/M phase. Furthermore, SPC25 knockdown promoted the apoptosis of PCa cells. Additionally, bioinformatics analysis revealed multiple functional roles of SPC25 in regulating cell proliferation, apoptosis, invasion, transforming growth factor-ß signaling and the SUMOylation pathway in PCa. The present study also evaluated the potential prognostic value of SPC25 using The Cancer Genome Atlas RNA-seq data and demonstrated that SPC25 was upregulated in late stage PCa. Kaplan-Meier analysis demonstrated that lower SPC25 expression was associated with an improved survival rate in patients with PCa. Taken together, these results suggested that SPC25 serves an oncogenic role in PCa and may act as a novel diagnostic and therapeutic target for PCa.

Arsenite inhibits the function of CD133+ CD13+ liver cancer stem cells by reducing PML and Oct4 protein expression.

Cancer stem cells (CSCs) can form new tumors and contribute to post-operative recurrence and metastasis. We showed that CD133+CD13+ hepatocytes isolated from HuH7 cells and primary HCC cells display biochemical and functional characteristics typical of CSCs, suggesting that CD133+CD13+ hepatocytes in primary HCC tumors function as CSCs. We also found that arsenite treatment reduced the viability and stemness of CD133+CD13+ hepatocytes, enhanced the sensitivity of HuH7 cells to pirarubicin, and reduced the tumorigenicity of CD133+CD13+ hepatocytes xenografts in mice. The effects of sodium arsenite treatment in CD133+CD13+ hepatocytes were mediated by the post-transcriptional suppression of PML expression and the inhibition of Oct4, Sox2, and Klf4 expression at the transcriptional level. Incomplete rescue of Oct4 expression in arsenic-treated cells ectopically expressing an siRNA-resistant PML transcript suggested that OCT4 regulation in liver CSCs involves other factors in addition to PML. Our findings provide evidence of a specific role for PML in regulating Oct4 levels in liver CSCs and highlight the clinical importance of arsenic for improving the efficacy of other chemotherapeutic agents and the prevention of post-operative HCC recurrence and metastasis.

[Expression of RhoC and ROCK-1 and their effects on MAPK and Akt proteins in prostate carcinoma].

OBJECTIVE: To detect the expression of RhoC and Rho kinase 1 (ROCK-1) in prostate carcinoma, and explore the possible mechanism of RhoC/ROCK-1 in the pathogenesis of prostate carcinoma. METHODS: Tissue specimens from 73 patients with prostate carcinoma and corresponding paracancerous tissues were obtained by prostate cancer biopsy or radical prostatectomy. The expression of RhoC/ROCK-1 mRNA was detected by RT-PCR. Western blot and immunohistochemistry were performed to dertect the expression of RhoC/ROCK-1 protein. Eukaryotic expression plasmids of RhoC were constructed and transfected into PC-3M-2B4 cells. p-MAPK and p-Akt were detected by Western bolt. RESULTS: The expression levels of RhoC and ROCK-1 mRNA in the prostate carcinomas were significantly higher than those in corresponding paracancerous tissues [72.6% (53/73) vs. 34.2% (25/73); 68.5% (50/73) vs. 38.4% (28/73), P < 0.01], respectively. The results indicated that RhoC/ROCK-1 mRNA expression had no significant correlation with Gleason grade. However, the expression of RhoC/ROCK-1 mRNA showed a significant positive correlation with distant metastasis. The RhoC/ROCK-1 protein expression in prostate cancer was also higher than corresponding paracancerous tissues, and showed a significant positive correlation with p-MAPK and p-Akt expression levels. In addition, p-MAPK and p-Akt expression levels were up-regulated in the transcripts. CONCLUSION: Expression levels of RhoC and ROCK-1 in prostate carcinoma are higher than those in corresponding paracancerous tissues, showing a significant positive correlation with distant metastasis. RhoC/ROCK-1 may be involved in the development, invasion and metastasis of prostate carcinoma.