Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway.

BACKGROUND: Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating PCa. METHODS: Nude mice were genetically modified to develop tumors characteristic of PCa. The treatment of PCa mice involved the administration of a combination of astragaloside IV and peptides derived from scorpion venom (PESV). Feces were collected for both 16 S rDNA and metabolic analysis. Fecal supernatant was extracted and used for fecal transplantation in PCa mice. Tumor development was observed in both PCa mice and nude mice. Tumor histopathology was examined, and the expression of inflammatory factors and the AGE-RAGE axis in PCa tissues were analyzed. RESULTS: PCa mice treated with Astragaloside IV in combination with PESV showed a significant reduction in tumor volume and weight, and stabilization of gut microbiota and metabolites. At the Genus level, significant differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate. There was a correlation between gut microbiota and metabolites. After the fecal transplantation, tumor growth was effectively suppressed in the PCa mice. Notably, both the mRNA and protein levels of the receptor for advanced glycation end products (RAGE) were significantly decreased. Furthermore, the expression of inflammatory factors, namely NF-κB, TNF-α, and IL-6, in the tumor tissues was significantly attenuated. Conversely, upregulation of RAGE led to increased inflammation and reversed tumor growth in the mice. CONCLUSION: Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE.

PREX2 contributes to radiation resistance by inhibiting radiotherapy-induced tumor immunogenicity via cGAS/STING/IFNs pathway in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear. METHODS: RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts. PREX2 expression was scrutinized using Western blotting, real-time PCR, and immunohistochemistry. The radioresistant role of PREX2 was assessed through in vitro colony formation assay, apoptosis assay, comet assay, and in vivo xenograft tumor models. The mechanism of PREX2 was elucidated using RNA-seq and Western blotting. Finally, a PREX2 small-molecule inhibitor, designated PREX-in1, was utilized to enhance the efficacy of ionizing radiation (IR) therapy in CRC mouse models. RESULTS: PREX2 emerged as the most significantly upregulated gene in radioresistant CRC cells. It augmented the radioresistant capacity of CRC cells and demonstrated potential as a marker for predicting radioresistance efficacy. Mechanistically, PREX2 facilitated DNA repair by upregulating DNA-PKcs, suppressing radiation-induced immunogenic cell death, and impeding CD8+ T cell infiltration through the cGAS/STING/IFNs pathway. In vivo, the blockade of PREX2 heightened the efficacy of IR therapy. CONCLUSIONS: PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC.

Exploring the mechanism of action of Sparganii Rhizoma-Curcumae Rhizoma for in treating castration-resistant prostate cancer: a network-based pharmacology and experimental validation study.

Sparganii Rhizoma-Curcumae Rhizoma (SR-CR) is a classic drug pair for the treatment of castration-resistant prostate cancer (CRPC), but its mechanism has not been clarified. The study aims to elucidate the potential mechanism of SR-CR in the management of CRPC. The present study employed the TCMSP as well as the SwissTargetPrediction platform to retrieve the chemical composition and targets of SR-CR. The therapeutic targets of CRPC were identified through screening the GeneCards, Disgenet, and OMIM databases. Subsequently, the Venny online platform was utilized to identify the shared targets between the SR-CR and CRPC. The shared targets were enrichment analysis using the Bioconductor and Kyoto encyclopedia of genes and genomes (KEGG) databases. The active ingredients and core targets were verified through molecular docking and were validated using PC3 cells in the experimental validation phase. A total of 7 active ingredients and 1126 disease targets were screened from SR-CR, leading to a total of 59 shared targets. Gene Ontology (GO) analysis resulted in 1309 GO entries. KEGG pathways analysis yielded 121 pathways, primarily involving cancer-related signaling pathways. The results from molecular docking revealed stable binding interactions between the core ingredients and the core targets. In vitro cellular assays further demonstrated that SR-CR effectively suppressed the activation of the Prostate cancer signaling pathway in PC3 cells, leading to the inhibition of cell proliferation and promotion of apoptosis. The SR-CR exert therapeutic effects on CRPC by inhibiting cell proliferation and promoting apoptosis through the Prostate cancer signaling pathway.

[Effects of Xihuang Pills on proliferation and apoptosis of prostate cancer LNCaP cells based on AR/m TOR signaling pathway].

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.

Effectiveness of non-pharmaceutical intervention on sperm quality: a systematic review and network meta-analysis.

Infertility affects about 10% of the world's population and has been recognized by the WHO as a global public health problem. The aim of this network meta-analysis was to investigate the efficacy of non-pharmaceutical interventions on sperm quality. All randomized clinical trials (RCTs) from the PubMed, MEDLINE, Embase, China national knowledge infrastructure (CNKI), Wanfang database, and Cochrane Library databases evaluating the effectiveness of non-pharmaceutical interventions on semen parameters using network meta-analyses. Results of the ω-3 fatty acid, lycopene, acupuncture, and vitamin suggested evident advantages in improving sperm concentration (MD, 9.93 (95% CI, 7.21 to 12.65)), (MD, 8.79 (95% CI, 2.67 to 14.91)), (MD, 5.40 (95% CI, 2.32 to 8.49)) and (MD, 3.82 (95% CI, 0.70 to 6.94) respectively). Acupuncture has a significant advantage over placebo in improving sperm total motility (MD, 17.81 (95% CI, 10.32 to 25.29)), and the effect of lycopene was obviously greater than that of placebo (MD, 19.91 (95% CI, 2.99 to 36.83)). Lycopene, Coenzyme Q10 (CoQ10), acupuncture, ω-3 fatty acid, and vitamin suggested significant advantages in improving sperm forward motility (MD, 8.64 (95% CI, 1.15 to 16.13), MD, 5.28 (95% CI, 2.70 to 7.86), MD, 3.95 (95% CI, 3.23 to 4.67), MD, 3.50 (95% CI, 2.21 to 4.79)) and (MD, 2.38 (95% CI, 0.96 to 3.80) respectively). This review establishes that non-pharmaceutical interventions, particularly acupuncture, exercise, lycopene, ω-3 fatty acids, CoQ10, zinc, vitamins, selenium, carnitine, or foods rich in these supplements, profitably improve sperm quality that may be used to treat male infertility.

Long non-coding RNA CCL14-AS suppresses invasiveness and lymph node metastasis of colorectal cancer cells by regulating MEP1A.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in the biology of colorectal cancer (CRC). There are several lncRNAs associated with invasion and metastasis have been characterized in CRC. However, studies focusing on the precise molecular mechanisms by which lncRNAs function in lymph node (LN) metastasis in CRC are still limited. METHODS: In this study, by analyzing TCGA dataset, we identified that AC244100.2 (termed CCL14-AS), a novel lncRNA enriched in the cytoplasm, was negatively correlated with LN metastasis and unfavorable prognosis of CRC. In situ hybridization was used to examine CCL14-AS expression in clinical CRC tissues. Various functional experiments including migration assay and wound-healing assay were used to investigate the effects of CCL14-AS on CRC cells migration. The nude mice popliteal lymph node metastasis model assay further confirmed the effects of CCL14-AS in vivo. RESULTS: CCL14-AS expression was significantly downregulated in CRC tissues compared to adjacent normal tissues. In addition, low CCL14-AS expression was correlated with advanced T classification, LN metastasis, distant metastasis, and shorter disease-free survival of CRC patients. Functionally, CCL14-AS overexpression inhibited the invasiveness of CRC cells in vitro and LN metastasis in nude mice. On the contrary, knockdown of CCL14-AS promoted the invasiveness and LN metastasis abilities of CRC cells. Mechanistically, CCL14-AS downregulated the expression of MEP1A via interacting with MEP1A mRNA and reduced its stability. Overexpression of MEP1A rescued the invasiveness and LN metastasis abilities in CCL14-AS-overexpressing CRC cells. Moreover, the expression levels of CCL14-AS was negatively correlated with that of MEP1A in CRC tissues. CONCLUSIONS: We identified a novel lncRNA, CCL14-AS, as a potential tumor suppressor in CRC. Our findings supported a model in which the CCL14-AS/MEP1A axis serves as critical regulator in CRC progression, suggesting a novel biomarker and therapeutic target in advanced CRC.

High-efficiency adsorption removal of CR and MG dyes using AlOOH fibers embedded with porous CoFe2O4 nanoparticles.

Owing to the toxicity and difficulty in degradation, how to the effective separation for the residual dyes in the aqueous solution is still an issue with great challenge in the area of environmental protection. Now, to high-efficiency removal of organic dyes from the aqueous solution, we design a unique AlOOH/CoFe2O4 adsorbent with porous CoFe2O4 nanoparticles embedded on the AlOOH fibers using a simple hydrothermal technique and calcination process. The structural properties and surface characteristics of the AlOOH/CoFe2O4 composites are detailedly analyzed by XRD, FTIR, XPS, TEM and SEM. Here, the high SBET and specific porous structure are beneficial to improve the adsorption performance of AlOOH/CoFe2O4 adsorbents. Especially, when the molar ratio of AlOOH to CoFe2O4 in the AlOOH/CoFe2O4 fibers is 1:1, an optimal performance on adsorbing anionic Congo red (CR) and cationic methyl green (MG) dyes can be obtained at pH = 6.29, where the corresponding maximum adsorption capacities reach up to 565.0 and 423.7 mg g-1, respectively. Factors leading to the change in the ability of adsorbing CR and MG dyes are systematically discussed, including contact time, temperature, initial concentrations, and pH values of the solutions. Meanwhile, the uptake of CR and MG dyes can best conform to Langmuir isotherm model and pseudo-second-order adsorption kinetics. The thermodynamic analysis verifies that the dye adsorption process is spontaneous and endothermic. Moreover, from the point view of practical application, the good reusability further makes the as-synthesized magnetic AlOOH/CoFe2O4 composite be a perfect adsorbent with efficiently removing both anionic and cationic dyes from aqueous solutions.

Bioprinting and its Use in Tumor-On-A-Chip Technology for Cancer Drug Screening: A Review.

The rising global incidence of cancer and high attrition rates of anticancer drugs make it imperative to design novel screening platforms to increase the success rate of chemotherapeutic agents. Advances in cell culture models from two-dimensional to three-dimensional platforms, along with microfluidics, have resulted in the creation of tumor-on-a-chip technology, which enables high-throughput molecular screening and helps to simulate the dynamic tumor microenvironment. Furthermore, advancements in bioprinting have allowed the structural and physiological aspects of the tumor to be recreated accurately and help to mimic cell-cell interactions and cell-extracellular matrix. This paper provides a comprehensive review of three-dimensional bioprinting to fabricate a tumor-on-a-chip platform to advance the discovery and screening of anticancer agents and provides a perspective on the challenges and future directions associated with the adoption of this technology to advance cancer research.

FOXS1 Promotes Tumor Progression by Upregulating CXCL8 in Colorectal Cancer.

Background: Forkhead box S1 (FOXS1) is a member of the forkhead box (FOX) transcriptional factor superfamily. The biological roles and underlying regulatory mechanism of FOXS1 in CRC remain unclear. Methods: Bioinformatics analysis, Western blotting, real-time PCR, and immunohistochemistry (IHC) were used to detect the expression FOXS1 in CRC. MTT assay, transwell assay, human umbilical vein endothelial cell tube formation assay, and chicken chorioallantoic membrane assay were performed to investigate the effects of FOXS1 on proliferation, invasion, and angiogenesis. Additionally, tumor formation assay and orthotopic implantation assay were used to investigate the effects of FOXS1 on tumor growth and metastasis in vivo. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the correlation between FOXS1 and EMT or angiogenesis. The correlation between FOXS1 and CXCL8 expression was analyzed in clinical CRC samples using IHC. Results: The results showed that FOXS1 expression was upregulated in CRC tissues compared with adjacent normal intestine tissues. A high FOXS1 expression is positively correlated with poor survival. FOXS1 promoted the malignant behavior of CRC cancer cells in vitro, including proliferation, invasion, and angiogenesis. In addition, FOXS1 promoted tumor growth and metastasis in nude mice. Mechanistically, FOXS1 upregulated the expression of C-X-C motif chemokine ligand 8 (CXCL8) at the transcriptional level. Knockdown of CXCL8 blocked FOXS1 induced the enhancement of the EMT and angiogenesis. GSEAs in public CRC datasets revealed strong correlations between FOXS1 expression and EMT marker and angiogenesis markers. IHC showed that FOXS1 expression was positively correlated with CXCL8 expression and CD31 expression in clinical CRC samples. Conclusion: The results suggest that FOXS1 promotes angiogenesis and metastasis by upregulating CXCL8 in CRC. Interference with the FOXS1/CXCL8 axis may serve as a potential therapeutic target for the treatment of metastatic CRC.

Mechanistic analysis of erectile dysfunction in a depression rat model.

OBJECTIVE: Most men suffering from depression have different degrees of erectile dysfunction (ED), but the relationship between depression and ED is not clear. This study explored the effect of depression on erectile function in rats and the underlying mechanism. METHODS: The potential targets and key signaling pathways of depression and ED were predicted through bioinformatics analysis, and a depression rat model was established by inducing chronic restraint stress. Pathological changes in rat penis tissue were studied by hematoxylin and eosin staining. The serum dopamine level was quantified by an enzyme-linked immunosorbent assay. The expression of related proteins and mRNA was detected by western blotting and real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Hematoxylin and eosin staining showed pathological damage in the penile tissue of the model group rats. The serum dopamine level, dopamine receptor D2 (DRD2) and solute carrier family 6 member 3 (SLC6A3) protein levels in penile tissue, and DRD2 and SLC6A3 mRNA levels were lower in the model group than in the control group. CONCLUSION: The decrease in erectile function in the depression rat model was related to dysfunction of the dopamine system and dopaminergic synapse signaling pathway.

3D porous coral-like Co1.29Ni1.71O4 microspheres embedded into reduced graphene oxide aerogels with lightweight and broadband microwave absorption.

In this work, three-dimensional (3D) porous coral-like Co1.29Ni1.71O4 microspheres were successfully combined with reduced graphene oxide (rGO) to form Co1.29Ni1.71O4/rGO aerogels as an efficient microwave absorber by a facile calcination and hydrothermal method. The elemental composition, microstructure, and morphology of the as-synthesized composites were characterized, and the electromagnetic wave absorption performance were analyzed in the frequency range of 2.0-18.0 GHz. The results show that adjusting the mass ratio of Co1.29Ni1.71O4 microspheres and rGO in the composites can effectively tune the electromagnetic parameters, which in turn improves their microwave absorption performance. Here, the minimum reflection loss (RLmin) of the Co1.29Ni1.71O4/rGO aerogels is -51.76 dB with an effective absorption bandwidth (RL < -10 dB) of 7.04 GHz (10.96-18 GHZ) at the thickness of 2.66 mm and a low filling ratio of 15 wt%. It can be demonstrated that the superior microwave absorption performance is attributed to the synergistic effect of impedance matching and dielectric loss, the unique 3D porous structure as well as the abundant interface of the composites. In brief, this study provides a new strategy for the design of magnetic/dielectric high-performance microwave absorbing materials.

Tumor cell-derived SPON2 promotes M2-polarized tumor-associated macrophage infiltration and cancer progression by activating PYK2 in CRC.

BACKGROUND: Tumor-associated macrophages (TAMs) are key regulators of the complex interplay between cancer and the immune microenvironment. Tumor cell-derived spondin 2 (SPON2) is an extracellular matrix glycoprotein that has complicated roles in recruitment of macrophages and neutrophils during inflammation. Overexpression of SPON2 has been shown to promote tumor cell migration in colorectal cancer (CRC). However, the mechanism by which SPON2 regulates the accumulation of TAMs in the tumor microenvironment (TME) of CRC is unknown. METHODS: Immunohistochemistry was used to examine SPON2 expression in clinical CRC tissues. In vitro migration assays, transendothelial migration assays (iTEM), and cell adhesion assays were used to investigate the effects of SPON2 on monocyte/macrophage migration. Subcutaneous tumor formation and orthotopic implantation assays were performed in C57 BL/6 mice to confirm the effects of SPON2 on TAM infiltration in tumors. RESULTS: SPON2 expression is positively correlated with M2-TAM infiltration in clinical CRC tumors and poor prognosis of CRC patients. In addition, SPON2 promotes cytoskeletal remodeling and transendothelial migration of monocytes by activating integrin ß1/PYK2 axis. SPON2 may indirectly induce M2-polarization through upregulating cytokines including IL10, CCL2 and CSF1 expression in tumor cells. Blocking M2 polarization and Macrophage depletion inhibited the SPON2-induced tumors growth and invasion. Furthermore, blocking the SPON2/integrin ß1/PYK2 axis impairs the transendothelial migration of monocytes and cancer-promoting functions of TAMs in vivo. CONCLUSIONS: Our findings demonstrate that SPON2-driven M2-TAM infiltration plays an important role during CRC tumor growth and metastasis. SPON2 may be a valuable biomarker guiding the use of macrophage-targeting strategies and a potential therapeutic target in advanced CRC.

3D core-shell Fe3O4@SiO2@MoS2 composites with enhanced microwave absorption performance.

In this work, a 3D ternary core-shell Fe3O4@SiO2@MoS2 composite is synthesized by a hydrothermal technique and a modified Stöber method, where magnetic Fe3O4@SiO2 microsphere with the core of raspberry-like Fe3O4 nanoparticles is completely coated by the flower-like MoS2. Herein, the electromagnetic parameters of the composites are effectively tuned by the combination of magnetic Fe3O4 with dielectric SiO2 and MoS2. The obtained ternary composites exhibit remarkable enhancement of microwave absorption. The measurement results indicate that the minimum reflection loss (RL) of Fe3O4@SiO2@MoS2 composites reaches -62.98 dB at 1.83 mm with the effective absorption bandwidth (RL < -10 dB) of 5.76 GHz (from 11.28 to 17.04 GHz) at 1.92 mm, much higher than those of pure Fe3O4 particles and Fe3O4@SiO2 microsphere. It is believed that the improved performances come from the specific structural design and the plentiful interfacial construction. Further, the synergistic effect of the dielectric and magnetic loss as well as the promoted impedance matching also help to enhance the microwave absorption of the composites. The microwave absorption behavior of the composites conforms to the quarter-wavelength cancellation theory. Our study offers an effective and promising strategy in the structural design and interfacial construction of the novel magnetic/dielectric composites with high-efficiency microwave absorption.

Effects of Primary Varicocele and Related Surgery in Male Infertility: A Meta-Analysis.

Purpose: To investigate the effect of primary varicocele and related surgery in male infertility through meta-analysis. Methods: A systematic search of the literature was conducted using the Medline, Embase, Cochrane, and CNKI databases. The search was up to September 2019. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using RevMan 5.2. A random-effects model was used to calculate the overall combined risk estimates. Results: After screening 687 articles, 4 randomized controlled trials with 349 patients were included. One hundred seventy two patients were addressed in embolization/ligation, with 177 patient's observation treatment. The number of spontaneous pregnancies in the two groups was 41 and 40, respectively. There was no significant difference in pregnancy rate between the operation group and the control group. RR = 1.05 [0.72, 1.54]. Conclusion: There is not enough evidence to explain the surgical treatment of varicocele can improve the natural fertility of the infertile couples, and there is still a need for most of prospective randomized controlled trials to verify the efficacy of varicocele surgery for treating of male infertility. We do not deny the importance of this operation, we just want to call on everyone to strictly grasp the indications of the operation, avoid ineffective medical expenses, and avoid unnecessary pain to patients.

CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET.

BACKGROUND: cAMP responsive element binding protein 5 (CREB5) is a transcriptional activator in eukaryotic cells that can regulate gene expression. Previously, we found that CREB5 was involved in the occurrence and development of colorectal cancer (CRC) using bioinformatics analysis. However, the biological roles and underlying regulatory mechanism of CREB5 in CRC remain unclear. METHODS: Real-time PCR, western blotting, and immunohistochemistry were used to examine CREB5 expression. In vitro experiments including migration assay, wound-healing assay, chicken chorioallantoic membrane assay, and human umbilical vein endothelial cells tube formation assay were used to investigate the effects of CREB5 on CRC cell migration and tumor angiogenesis ability. Additionally, an orthotopic implantation assay was performed in nude mice to confirm the effects of CREB5 in vivo. Furthermore, gene set enrichment analysis was performed to explore the potential mechanism of CREB5 in CRC. RESULTS: We found that CREB5 expression was highly upregulated in CRC. CREB5 overexpression was positively correlated with advanced WHO stages and TNM stages and shorter survival in CRC patients. Moreover, CREB5 overexpression promoted while CREB5 silencing reduced the invasiveness and metastatic capacity of CRC cells both in vitro and in vivo. Furthermore, CREB5 directly interacted with the MET promoter and activated the hepatocyte growth factor-MET signalling pathway. Importantly, inhibition of MET reduced the invasion and metastasis of CREB5-overexpressing CRC cells, suggesting that CREB5 promotes metastasis mainly through activation of MET signalling. CONCLUSION: Our study demonstrates a crucial role for CREB5 in CRC metastasis by directly upregulating MET expression. CREB5 may be both a potential prognostic marker and a therapeutic target to effectively overcome metastasis in CRC.

A mobile app for Glaucoma diagnosis and its possible clinical applications.

BACKGROUND: Nowadays, the latent power of technology, which can offer innovative resolutions to disease diagnosis, has awakened high-level anticipation in the community of patients as well as professionals. An easy-to-use mobile app is developed by us, which is purposefully intended for those patients with glaucoma. METHODS: A mobile App has been invented for smartphones for the convenient use wherever and whenever. The corresponding experiments carried out by public retinal image database and real captured clinical data reveal the ideal classification accuracy of the App. Also, user feedback evaluation is also carried out in terms of performance test as well as and users' experience. RESULTS: For clinical test using Yanbao App, we found 274 patients for the identification with 648 retinal images to be evaluated by glaucoma classification. Of the 243 glaucoma patients, 191 were screened out with an accuracy of 0.7860 (sensitivity); the number of non-glaucoma patients was 310 of 405, and the accuracy reached 0.7654 (specificity).` The total Accuracy amounted to 0.7731, and the result is close to the test performance obtained on public dataset ORIGA and DRISHTI-GS1. CONCLUSIONS: Yanbao App can be applied as an innovative approach exploiting mobile technology to enhance the clinicians' efficiency and a balanced medical resources as well as a provided better tiered medical service system.

UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer.

BACKGROUND: Ubinuclein-2 (UBN2) is a nuclear protein that interacts with many transcription factors. The molecular role and mechanism of UBN2 in the development and progression of cancers, including colorectal cancer (CRC), is not well understood. The current study explored the role of UBN2 in the development and progression CRC. METHODS: Oncomine network and The Cancer Genome Atlas (TCGA) database were downloaded and Gene Set Enrichment Analysis (GSEA) was performed to compare the UBN2's expression between normal and tumor tissues, as well as the potential correlation of UBN2 expression with signaling pathways. Immunohistochemistry (IHC), qRT-PCR and Western blotting were performed to determine the expression of UBN2 in CRC tissues or cell lines. In vitro proliferation and invasion assays, and orthotopic mouse metastatic model were used to analyze the effect of UBN2 on the development and progression of CRC. RESULTS: The analysis of UBN2 expression using Oncomine network showed that UBN2 was upregulated in CRC tissues compared to matched adjacent normal intestinal epithelial tissues. IHC, qRT-PCR and Western blotting confirmed that UBN2 expression is higher in CRC tissues compared with matched adjacent normal intestinal epithelial tissues. In addition, analyses of TCGA data revealed that high UBN2 expression was associated with advanced stages of lymph node metastasis, distant metastasis, and short survival time in CRC patients. IHC showed that high UBN2 expression is correlated with advanced stages of CRC. Moreover, UBN2 is highly expressed in the liver metastatic lesions. Furthermore, knockdown of UBN2 inhibited the growth, invasiveness and metastasis of CRC cells via regulation of the Ras/MAPK signaling pathway. CONCLUSION: The current study demonstrates that UBN2 promotes tumor progression in CRC. UBN2 may be used as a promising biomarker for predicting the prognosis of CRC patients.

[Linggui Fang protects the reproductive system of asthenospermia rats: An experimental study based on the L-carnitine pathway].

OBJECTIVE: To explore the protective effect of the Chinese medicinal prescription Linggui Fang (LGF) on the reproductive system of the ornidazole-induced asthenospermia (AS) rat and its possible action mechanisms. METHODS: Forty male SD rats weighing 200－230 g were equally randomized into four groups, blank control, AS model control, LGF treatment and L-carnitine (LC) intervention. The AS models were made in the latter three groups by intragastrical administration of ornidazole at 400 mg/kg. Meanwhile, the rats in the LGF group were treated intragastrically with LGF at 17.5 g/kg, those in the LC group with LC at 100 mg/kg, and the control animals with 0.5% sodium carboxymethylcellulose (CMC-Na), all once a day for 4 successive weeks. Then, all the rats were sacrificed for examination of the semen parameters, determination of the LC content and OCTN2 mRNA expression in the epididymis and observation of the histopathological changes in the testis. RESULTS: Compared with the AS model controls, the rats in the other groups showed significantly higher percentages of progressively motile sperm and total motile sperm (P < 0.01) as well as a higher LC content in the epididymis (P < 0.01), but no statistically significant difference in sperm concentration (P > 0.05). The expression of OCTN2 mRNA was remarkably upregulated in the LGF and LC groups in comparison with that in the AS model control (P < 0.05). Compared with the rats in the blank control group, the AS model controls exhibited markedly increased morphologically abnormal seminiferous tubules, irregularly arranged, with narrowed lumens and reduced numbers of sperm and sperm cells, as well as significantly increased hollow seminiferous tubules with deficient and disorderly arranged spermatogenic cells and partial epithelial degeneration and vacuolization. Those in the LGF and LC groups, however, manifested almost normal testicular histomorphology, with basically regular arrangement of different layers of seminiferous tubules. CONCLUSIONS: ①Ornidazole induces AS in rats by reducing the LC content in the epididymis, while LGF can improve the sperm motility and testicular morphology of the rats and upregulate the expression of OCTN2 mRNA in the epididymis by increasing the LC concentration.