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Network neuroscience has broadly conceptualized the functions of the brain as complex communication within and between large‐scale neural networks. Nevertheless, whether and how the gut microbiota influence functional network connectivity that in turn impact human behaviors has yet to be determined. We collected fecal samples from 157 healthy young adults and used 16S sequencing to assess gut microbial diversity and enterotypes. Large‐scale inter‐ and intranetwork functional connectivity was measured using a combination of resting‐state functional MRI data and independent component analysis. Sleep quality and core executive functions were also evaluated. Then, we tested for potential associations between gut microbiota, functional network connectivity and behaviors. We found significant associations of gut microbial diversity with internetwork functional connectivity between the executive control, default mode and sensorimotor systems, and intranetwork connectivity of the executive control system. Moreover, some internetwork functional connectivity mediated the relations of microbial diversity with sleep quality, working memory, and attention. In addition, there was a significant effect of enterotypes on intranetwork connectivity of the executive control system, which could mediate the link between enterotypes and executive function. Our findings not only may expand existing biological knowledge of the gut microbiota‐brain‐behavior relationships from the perspective of large‐scale functional network organization, but also may ultimately inform a translational conceptualization of how to improve sleep quality and executive functions through the regulation of gut microbiota., Gut microbiota can modulate large‐scale inter‐ and intranetwork functional connectivity (especially the executive control system) in young adulthood. Some functional network connectivity may act as mediators of the effects of gut microbiota on sleep and executive functions.

Myocardial remodelling is a common phenomenon in cardiovascular diseases, which threaten human health and the quality of life. Due to the lack of effective early diagnosis and treatment methods, the molecular mechanism of myocardial remodelling should be explored in depth. In this study, we observed the high expression of MBNL1 in cardiac tissue and peripheral blood of an isoproterenol (ISO)‐induced cardiac hypertrophy mouse model. MBNL1 promoted ISO‐induced cardiac hypertrophy and fibrosis by stabilizing Myocardin mRNA in vivo and in vitro. Meanwhile, an increase in MBNL1 may induce the apoptosis of cardiomyocytes treated with ISO via TNF‐α signalling. Interestingly, MBNL1 can be activated by p300 in cardiomyocytes treated with ISO. At last, Myocardin can reverse activate the expression of MBNL1. These results suggest that MBNL1 may be a potential target for the early diagnosis and clinical treatment of myocardial remodelling.

Although many methods and new therapeutic drugs have been developed, the overall survival rate and long-term survival rate of patients with gastric cancer (GC) are still not satisfactory. In this study, we investigated the effects of microRNA miR-133a-3p and transcription factor FOXP3 on proliferation and autophagy of GC cells and their interactions. Our results showed that knockdown of FOXP3 increased the proliferation and autophagy of GC cells. The relationship between FOXP3 and autophagy has not been reported previously. In addition, FOXP3 could directly bind the promoter region of TP53 and inhibit its expression. miR-133a-3p increased the proliferation and autophagy via decreasing the protein level of FOXP3 by targeting its 3'-UTR. Our research provides new insights into the development of GC and provides new ideas and theoretical basis for the clinical treatment of GC and the development of new drug targets.

The fluid‐solid coupling simulation of fractured coal and rock is helpful to study the influence of the fracture structure on the stress sensitivity of the permeability. Therefore, a key factor in improving the reliability of such a numerical simulation is selecting parameters that match measured laboratory results. This paper firstly illustrates the use of a common inversion method to select the fluid‐solid coupling parameters through the constant joint stiffness method (CJSM). The main principle, application range, and the shortcomings of this method (CJSM) are analyzed: It can be used to simulate the measured results in a lower stress range. However, the stress sensitivity of permeability is zero when the stress reaches the critical stress (the stress where the hydraulic aperture reaches the residual hydraulic aperture). In order to solve this problem, a numerical simulation method for fluid‐solid coupling using the varying joint stiffness method (VJSM) is proposed based on the characteristic that the compressibility of a fracture decreases with increasing stress. In this method, the compressibility of the hydraulic aperture can be changed by increasing the joint stiffness during the loading process. Thus, the hydraulic aperture can continuously change and there is no need to set the residual hydraulic aperture. Finally, fluid‐solid coupling simulations under different stress states were performed using the VJSM in this study. The numerical simulation results were basically consistent with the experimental results, which indicated that a fluid‐solid coupling simulation using the VJSM can match experimental results very well and can be further used to study the influence of the persistent fracture angle on the permeability.

Understanding coal and rock permeability, and the corresponding influence on stress, is important in the field of energy development. In applied engineering, there is a tendency to employ three‐dimensional methods that are simpler, less time‐ and cost‐expensive, less computationally expensive, and larger scale. Thus, a numerical simulation fluid‐solid coupling method is proposed in this paper. The proposed numerical simulation method utilizes the stress‐permeability test results for elastic and plastic coal samples. The permeability models of the elastic and plastic coal samples under loading and unloading were obtained by fitting the experimental results and embedded them into FLAC3D software by using FISH language. The results of the uniaxial and triaxial flow simulations are consistent with the experimental results, thereby confirming the accuracy and feasibility of the numerical method proposed in this paper. This allows the permeability of the numerical reservoir model to be continuously updated according to the current stress level in the production process.

Geothermal resources provide green, low‐carbon, and renewable clean energy, with abundant reserves and massive potential for application. The in‐depth analysis of geothermal resources in China, including their distribution and breakdown by shallow, hydrothermal, and hot dry rock (HDR) resources, is made in this study. Using the recent economic reports and state‐of‐the‐art technological solutions, this survey outlines the latest trends in the geothermal power generation in China. The application of geothermal power generation in China is still at an early stage, with the total installed capacity of 27.78 MW. The geothermal power generation technologies, such as dry steam technology, flash technology, binary cycle technology, and enhanced geothermal system (EGS), are briefly discussed and linked to their lucrative implementation sites. In particular, Tibet's Yangbajing is considered to be the most lucrative site for the EGS pilot project. The comparative analysis of low‐cost/large‐scale geothermal power generation technologies, such as low‐ to medium‐temperature one, solar‐geothermal hybrid one, and geothermal power generation in mines, was made, whose results strongly indicated the EGS technical and economical advantages. The concentration of 96% of China's population in the area to the east of Hu line affects the perspectives of high‐cost geothermal projects and has to be accounted in the comprehensive analysis of available data. Based on the revealed trends of geothermal resources’ development in China, the following guidelines are strongly recommended: comprehensive incorporation of geothermal energy generation into China's national energy and climate improvement plans, the rapid implementation of HDR technology, as well as comprehensive adaptation of the geothermal‐related projects to the local conditions/biased distribution of power consumers and state‐of‐the‐art challenges of power consumption.

N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a critical negative regulator of fibrosis development in the liver. However, its extremely short half-life in vivo greatly compromises its potential applications. Here, we report an Ac-SDKP analog peptide with d-amino acid replacement (Ac-SDD KD P). The stability of Ac-SDD KD P and its prevention of liver fibrosis were investigated in vitro and in vivo. The stabilities of Ac-SDKP and Ac-SDD KD P exposed to angiotensin-1-converting enzyme (ACE) and their half-lives in rats and human sera were determined by high-performance liquid chromatography. The inhibitory effects of Ac-SDKP and Ac-SDD KD P on the proliferation and activation of hepatic stellate cells (HSC-T6) were evaluated using the Cell Counting Kit-8, Western blotting, reverse transcription quantitative polymerase chain reaction, and immunofluorescence assays. Finally, the protective effects of Ac-SDKP and Ac-SDD KD P on carbon tetrachloride (CCl4 )-induced liver fibrosis in rats were compared. d-Amino acid replacement significantly enhanced the stability of the peptide to ACE and prolonged the half-life of Ac-SDKP in rats and human sera. The Ac-SDKP-mediated inhibition of HSC-T6 cell proliferation was well preserved, and Ac-SDD KD P exerted inhibitory effects comparable to Ac-SDKP on α-smooth muscle actin (α-SMA), collagen I and III expression, and phosphorylated-Smad-2 expression. After intraperitoneal (i.p.) administration, Ac-SDD KD P exhibited significantly greater protection than Ac-SDKP against CCl4 -induced liver fibrosis in rats. The serum alanine aminotransferase, aspartate aminotransferase, albumin, and total protein levels of the Ac-SDD KD P-treated rats were significantly lower than those of the Ac-SDKP-treated rats. α-SMA, CD45, and collagen I and III expression, as well as Smad-2 phosphorylation were significantly attenuated in the livers of the Ac-SDD KD P-treated rats compared to those of the Ac-SDKP-treated rats. Furthermore, we showed that the Ac-SDD KD P concentration in the rat liver increased to a physiological level of 60 min after i.p. administration, although i.p. administration of Ac-SDKP failed to enhance the peptide concentration in the rat liver. Our findings indicate that d-amino acid replacement is a simple and effective method to enhance the stability of Ac-SDKP. Ac-SDD KD P represents potential application of Ac-SDKP in fibrosis treatment and provides a new potential treatment strategy for liver fibrosis. © 2019 IUBMB Life, 71(9):1302-1312, 2019.

Myocardin is an important factor that regulates cardiac hypertrophy, and its activity can be regulated by GATA4. However, the molecular mechanism of the above process remains unclear. This paper presents three kinds of possible molecular mechanisms of GATA4 inhibiting myocardin activity in the process of cardiac hypertrophy. First, a competitive combination of GATA4 and SRF with myocardin could reduce the formation of the myocardin-SRF-CarG box complex when GATA4 was overexpressed. Second, overexpression of GATA4 could inhibit the combination of myocardin and p300 and downregulate acetylated myocardin levels. Finally, GATA4 could upregulate the phosphorylation of myocardin protein upon activation of the ERK pathway. These findings may provide insight into the function of GATA4 and myocardin in the occurrence and development of cardiac hypertrophy.

Megakaryoblastic leukemia 1 (MKL1) was closely related to the pathogenesis of various human malignant cancers. MiR34a was reported to be closely related to cancer cell proliferation. Forkhead box protein 3 (FOXP3) was a transcription factor that played a different role in different cancer types. CDK6 was involved in cell cycle progression and was upregulated in several types of cancers. The present study investigated the effects of MKL1/miR34a/FOXP3 axis on cell proliferation in MGC803 gastric cancer cells. Our results demonstrated that overexpression of MKL1 promoted proliferation of MGC80-3 cells, MKL1 directly binding to the promoter of CDK6 to increase its expression. Knockdown of FOXP3 promoted proliferation of MGC80-3 cells and MKL1 inhibited the expression of FOXP3 via miR-34a. The finding can contribute to elucidating the regulatory mechanism involved in the cell cycle progression of gastric cancer cells and may aid in screening potential gene targets for the biological therapy of gastric cancer.

Aims and objectives To assess the effects of three different bowel preparation methods on the incidence of infectious complications in patients who underwent transrectal ultrasonography-guided prostate biopsy. Background The standard bowel preparation protocol for prostate biopsy has not been established. Design A retrospective study in a single centre. Methods From January 2013–December 2015, the clinical records of 1,130 patients who underwent prostate biopsy were, respectively, reviewed. All the patients received metronidazole prophylaxis before biopsy. The patients were divided into three groups according to the bowel preparation methods: patients in Group A (n = 402) received only soapy enema; patients in Group B (n = 413) received polyethylene glycol; while patients in Group C (n = 315) received polyethylene glycol plus povidone–iodine enema. Infectious complications were classified as fever (>37.5°C), urinary tract infection and sepsis. The postoperative adverse events were also observed. Results The overall postbiopsy infectious complications were observed in 48 (4.25%) patients of all the cases, including 23 (5.72%) cases in Group A, 20 (4.84%) cases in Group B and five patients (1.59%) in Group C. There was significant difference among the groups (p = .018). In detail, these infectious complications included 22 (1.95%) cases of fever and 26 (2.30%) cases of urinary tract infection. No sepsis was observed among the total patients. The incidence of adverse events was 14.43% (58/402) occurred in Group A, 25.91% (107/413) in Group B and 26.67% (84/315) in Group C. The difference was statistically significant. Conclusions Our study confirmed that combined preparation regimens of polyethylene glycol with povidone–iodine enema could significantly reduce the postbiopsy infection rate. Conventional soapy enema is associated with less adverse events. Relevance to clinical practice Findings of this study provide useful evidence-based information for healthcare professionals. The application of combined preparation regimens of polyethylene glycol with povidone–iodine enema resulted in better improvement in the prevention of postbiopsy infection.

Regulation of matrix metalloproteinases (MMPs) by collagen in the fibroblast-like synoviocytes (FLSs) plays a critical role in joint destruction in rheumatoid arthritis (RA). Our previous study indicated that discoidin receptor 2 (DDR2) mediated collagen upregulation of MMPs. However, the precise underlying mechanism remains unclear. We report here that CYR61, a secreted, extracellular matrix-associated signaling protein which is capable of regulating a broad range of cellular activities, including cell adhesion, migration, proliferation, and apoptosis, is significantly upregulated in collagen II-stimulated RA FLS. Further studies found that collagen II-activated phosphorylated-DDR2 induces CYR61 through activation of transcription factor activator protein 1 (AP-1). The elevated CYR61, in turn, accelerates MMP1 production via ETS1 (ETS proto-oncogene 1). In addition, CYR61 significantly promotes FLS invasion and migration. Blockade of CYR61 by an adenovirus expressing CYR61 shRNA (Ad-shCYR61) in vivo remarkably ameliorated the severity of arthritis, reduced inflammatory cytokine secretion, and attenuated bone erosion as detected by micro-computed tomography (μCT), in collagen-induced arthritis (CIA) rats. Taken together, we uncovered the Collagen II-DDR2-AP-1-CYR61-ETS1-MMP1 loop in RA FLS. In which, CYR61 acts as a hinge to promote cartilage damage through regulating FLS invasion, migration, and MMP1 production and the inflammatory cascade in RA. Thus, CYR61 may be a promising diagnostic and therapeutic target for RA treatment. © 2016 American Society for Bone and Mineral Research.

Background: Contamination of food and feed by aflatoxin B1 (AFB1) poses serious economic and health problems worldwide, so the development of biological methods for effective AFB1 degradation is strongly required.; Results: Among three AFB1-degrading microorganisms isolated from moldy peanut, Fusarium sp. WCQ3361 could remove AFB1 extremely effectively, with a degradation ratio of 70.20% after 1 min and 95.38% after 24 h. Its degradation ratio was not much affected by temperature change (0-90 °C) and it also displayed excellent thermostability, maintaining 99.40% residual activity after boiling for 10 min. Since protease K could reduce the AFB1 degradation ratio by 55.15%, it is proposed that the effective component for AFB1 degradation is a protein. The AFB1 degradation ability of Fusarium sp. WCQ3361 was further verified by feed stock detoxification and the MTT test with HepG2 cells. In addition, no degradation products were detected by preliminary liquid chromatography/mass spectrometry, suggesting that AFB1 might be metabolized to products with different chemical characteristics from AFB1.; Conclusion: Fusarium sp. WCQ3361 is the first reported AFB1 degradation fungus belonging to the genus Fusarium with broad working temperature range, excellent thermostability and high activity, which provides a potential highly useful solution for dealing with AFB1 contamination in the human diet and animal feed. © 2016 Society of Chemical Industry.; © 2016 Society of Chemical Industry.

Myocardin is frequently repressed during human malignant transformation, and restoration of myocardin expression in sarcoma cells contributes to the inhibition of malignant growth. However, its role in breast carcinoma has barely been addressed. Here, we reported that myocardin could inhibit the proliferation of MCF-7 cells. Notably, we show that myocardin inhibited ERα-mediated proliferation of breast cancer MCF-7 via impairing ER-dependent transcriptional activation, mainly through the inhibition of the activity of ERα. Importantly, the molecular mechanism for the inhibition of the ERα-mediated proliferation is that myocardin inhibited the transcription and expression of ERα-induced PCNA, Ki-67, and E2F1 to impair ERα-mediated proliferation of breast cancer MCF-7. Interestingly, myocardin significantly enhanced the transcription and expression of miR-885 depending on the CArG box in miR-885 promoter, and miR-885 targeted the 3' untranslated regions (UTR) of E2F1 to silence the expression of E2F1. Thus, our data provided important and novel insights into how myocardin may deeply influence ERα-mediated breast cancer proliferation. In conclusion, myocardin could be seen as a breast cancer tumor suppressor so that it will provide new ideas for the treatment of breast cancer. © 2016 IUBMB Life, 68(6):477-487, 2016.

In article number https://doi.org/10.1002/advs.201903307, Cun Zhang, Wei Wu, and co‐workers identify the adult perivascular adipose tissue (PVAT) as the dominant source of vascular progenitors in a rat abdominal aorta model and clarify the mechanism by which DTβ4 enhances arterial muscle remodeling in the aging body. Different from conventional synthetic grafts, DTβ4‐incorporated grafts exhibit enhanced vascular regenerative activity and effectively ameliorate aging induced defective regeneration, thus providing a rational strategy for clinical translation of vascular grafts.

Regenerating nonthrombotic and compliant artery, especially in the aging body, remains a major surgical challenge, mainly owing to the inadequate knowledge of the major cell sources contributing to arterial regeneration and insufficient bioactivity of delivered peptides in grafts. Ultrathin nanofibrous sheaths stented with biodegrading elastomer present opening channels and reduced material residue, enabling fast cell recruitment and host remodeling, while incorporating peptides offering developmental cues are challenging. In this study, a recombinant human thymosin β4 dimer (DTβ4) that contains two complete Tβ4 molecules is produced. The adult perivascular adipose is found as the dominant source of vascular progenitors which, when stimulated by the DTβ4‐loaded nanofibrous sheath, enables 100% patency rates, near‐complete structural as well as adequate functional regeneration of artery, and effectively ameliorates aging‐induced defective regeneration. As compared with Tβ4, DTβ4 exhibits durable regenerative activity including recruiting more progenitors for endothelial cells and smooth muscle cells, when incorporated into the ultrathin polycaprolactone sheath. Moreover, the DTβ4‐loaded interface promotes smooth muscle cells differentiation, mainly through promoting M2 macrophage polarization and chemokines. Incorporating artificial DTβ4 into ultrathin sheaths of fast degrading vascular grafts creates an effective interface for sufficient muscular remodeling thus offering a robust tool for vessel replacement., Adult perivascular adipose tissue (PVAT) is the dominant source of vascular progenitors in a rat abdominal aorta model. Furthermore, the mechanism by which DTβ4 enhances arterial muscle remodeling in the aging body is that the DTβ4‐incorporated nanofibrous interface facilitates macrophage polarization to the M2 subset, which in turn promotes myogenic differentiation of PVAT‐derived stem cells through secreting platelet‐derived growth factor‐BB (PDGF‐BB).

Breast cancer is the leading cause of cancer death in women worldwide which is closely related to metastasis. But the exact molecular mechanism of metastasis is still not fully understood. We now report that both MRTF-A and STAT3 play important roles in migration of MDA-MB-231 breast cancer cells. Moreover, MRTF-A and STAT3 synergistically increased MDA-MB-231 cell migration by promoting the expression of migration markers urokinase-type plasminogen activator (uPA) and osteopontin (OPN) and inhibiting the expression of breast cancer metastasis suppressor 1 (BRMS1). Luciferase reporter assays demonstrated that MRTF-A and STAT3 do not affect transcription of the BRMS1 promoter. Instead, we identified a newly molecular mechanism by which MRTF-A and STAT3 synergistically controlled MDA-MB-231 cell migration by recruiting DNMT1 to hypermethylate the promoter of BRMS1 and thus affect the expression of BRMS1. Interestingly, physical interaction between MRTF-A and STAT3 synergistically promotes the transactivity of DNMT1 by binding to the GAS element within the DNMT1 promoter. Our data thus provide important and novel insights into the roles of MRTF-A and STAT3 in regulating MDA-MB-231 cell migration. © 2015 IUBMB Life, 67(3):202–217, 2015

Forkhead box protein 3 (FOXP3) plays an important role in breast cancer as an X-linked tumor suppressor gene. However, the biological functions and significance of FOXP3 in breast cancer metastasis remain unclear. Here, we find that, clinically, nuclear FOXP3 expression is inversely correlated with breast cancer metastasis. Moreover, we demonstrate that FOXP3 significantly inhibits adhesion, invasion and metastasis of breast cancer cells in vivo and in vitro. In addition, the adhesion molecule CD44 is found to be suppressed by FOXP3 through transcriptome sequence analysis (RNA-seq). A luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay identify CD44 as a direct target of FOXP3. The expression of CD44 is downregulated by FOXP3 in breast cancer cells. Importantly, anti-CD44 antibody reverses the FOXP3 siRNA-induced effects on the breast cancer cells in vitro and FOXP3 expression level in the nucleus of breast cancer cells is inversely correlated with CD44 expression level in clinic breast cancer tissues. Taken together, the results from the present study suggest that FOXP3 is a suppressor of breast cancer metastasis. FOXP3 directly binds to the promoter of CD44 and inhibits its protein expression, thereby suppressing adhesion and invasion of human breast cancer cells. This finding highlights the therapeutic potential of FOXP3-CD44 signaling to inhibit breast cancer metastasis.

In this paper, a heart-cutting two-dimensional high-performance liquid chromatography coupled with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was established for controlling the quality of different batches of Hypericum ascyron extract for the first time. In comparison with the common one-dimensional fingerprint, the second-dimensional fingerprint compiled additional spectral data and was hence more informative. The quality of H. ascyron extract was further evaluated by similarity measures and the same results were achieved, the correlation coefficients of the similarity of ten batches of H. ascyron extract were ＞0.99. Furthermore, we also evaluated the quality of the ten batches of H. ascyron extract by antibacterial activity. The result demonstrated that the quality of the ten batches of H. ascyron extract was not significantly different by MTT. Finally, we demonstrated that the second-dimensional fingerprint coupled with the MTT method was a more powerful tool to characterize the quality of samples of batch to batch. Therefore the proposed method could be used to comprehensively conduct the quality control of traditional Chinese medicines.

Objective Discoidin domain receptor 2 (DDR-2)/matrix metalloproteinase (MMP) signaling is an important pathway involved in cartilage destruction in rheumatoid arthritis (RA). However, the molecular mechanisms of this pathway have not been clearly identified. This study was undertaken to screen key molecules involved in this pathway and evaluate their biologic functions in synovium invasion of RA. Methods DDR-2–interacting proteins were examined in vitro by immunoprecipitation and mass spectrometry, and annexin A2 was acquired. The effects of annexin A2 on fibroblast-like synoviocyte (FLS) migration were evaluated using a Transwell invasion assay and an Erasion trace test. In Ddr2−/− mice with collagen-induced arthritis (CIA), hematoxylin and eosin (H&E) staining, immunohistochemical analysis, and Western blot analysis were used to assess expression of DDR-2, annexin A2, and MMP-13, as well as synovial hyperplasia. Rats with CIA were treated with lentivirus annexin A2 small interfering RNA (siRNA), and annexin A2 siRNA effects on joint damage were analyzed based upon arthritis index scores and results of micro–computed tomography and H&E staining. The differences between annexin A2 expression in clinical samples from RA and osteoarthritis patients were compared using Western blotting. Results Annexin 2 was identified for the first time as a DDR-2 binding protein. It may be phosphorylated by phospho–DDR-2, leading to MMP-13 secretion. The annexin A2 phosphorylation level and MMP-13 expression level were decreased and collagen-induced joint damage greatly reduced in Ddr2−/− mice. Joint damage in rats with CIA was significantly ameliorated when annexin A2 was down-regulated. Annexin A2 expression and phosphorylation were elevated in human RA synovial tissue. Conclusion Annexin A2 is a key molecule in the DDR-2/annexin A2/MMP-13 loop, the activation of which contributes to joint destruction in RA, mainly through promoting invasion of FLS. Annexin A2 might therefore become a novel clinical target for RA treatment.

Human chorionic gonadotropin (hCG) is a glycoprotein produced by placental trophoblasts. Previous studies indicated that hCG could be responsible for the pregnancy-induced protection against breast cancer in women. It is reported that hCG decreases proliferation and invasion of breast cancer MCF-7 cells. Our research also demonstrates that hCG can reduce the proliferation of MCF-7 cells by downregulating the expression of proliferation markers, proliferating cell nuclear antigen (PCNA), and proliferation-related Ki-67 antigen (Ki-67). Interestingly, we find here that hCG elevates the state of cellular differentiation, as characterized by the upregulation of differentiation markers, β-casein, cytokeratin-18 (CK-18), and E-cadherin. Inhibition of hCG secretion or luteinizing hormone/hCG receptors (LH/hCGRs) synthesis can weaken the effect of hCG on the induction of cell differentiation. Furthermore, hCG can suppress the expression of estrogen receptor alpha. hCG activated receptor-mediated cyclic adenosine monophosphate/protein kinase A signaling pathway. These findings indicated that a protective effect of hCG against breast cancer may be associated with its growth inhibitory and differentiation induction function in breast cancer cells. © 2014 IUBMB Life, 66(5):352–360, 2014

Similarity assessment of complex chromatographic profiles is a potential tool for the identification and quality control of herbal medicinal products to guarantee the expected biological activity. In this paper, a high-performance liquid chromatography method was established for controlling the quality of extract of Hypericum ascyron for the first time. With this method, the correlation coefficients of similarity of 10 batches extract of H. ascyron were >0.97. The extract of H. ascyron displayed steadily inhibitorty activities on the growth of human cervical cancer Hela cell lines. Therefore, the present study successfully set up a sensitive efficient method which might confirm stable biological activity of the extract of H. ascyron.

High expression of estrogen receptor α (ERα) is associated with a poor prognosis that correlates closely with cellular proliferation in breast cancer. However, the exact molecular mechanism by which ERα controls breast cancer cell proliferation is not clear. Here we report that ERα regulates the cell cycle by suppressing p53/p21 and up-regulating proliferating cell nuclear antigen (PCNA) and proliferation-related Ki-67 antigen (Ki-67) to promote proliferation of MCF-7 cells. In addition, 17-β-estradiol (E2) enhances ERα-induced proliferation of MCF-7 cells by stimulating expression of PCNA and Ki-67. Knockdown of ERα significantly affects PCNA/Ki-67 and p53/p21 expression. Furthermore, ERα inhibits the transcriptional activity of p53/p21 in an estrogen response element-dependent manner. More importantly, we provide new evidence that ERα mediates proliferation of MCF-7 cells by up-regulating miR-17 to silence the expression of p21. Thus, these data provide new insights into the underlying effect of ERα on breast cancer proliferation.

Epithelial-mesenchymal transition is an important developmental process, participates in tumor's formation, invasion, and metastasis and has been extensively studied. Recently, endothelial-mesenchymal transition (EndMT), a newly recognized type of cellular transdifferentiation, has been demonstrated to participate in a number of diseases by causing morphology changes and pathological processes. Previous studies showed that EndMT was a critical process of embryonic cardiac development. Not only that recent advances also suggested that EndMT occurred postnatally in cancer and cardiac fibrosis and emerged as a possible source of cancer-associated fibroblasts (CAFs). CAFs were found to acquire properties that promoted tumor development and metastasis formation. Resident endothelial cells undergoing EndMT lose their endothelial markers, acquire a mesenchymal or myofibroblastic phenotype, express mesenchymal cell products such as α-smooth muscle actin and type I collagen and develop invasive and migratory abilities. EndMT-derived cells are believed to function as fibroblasts in damaged tissue and may therefore have an important role in pathological process. However, little is known about the signaling mechanisms that cause endothelial cells to transform into mesenchymal cells. Transforming growth factor-β, Notch, or other signaling pathways could direct or interact to mediate EndMT. Therefore, to explore the signaling mechanisms of EndMT may provide novel therapeutic strategies for treating cancer.

The palea and lemma are unique organs in grass plants that form a protective barrier around the floral organs and developing kernel. The interlocking of the palea and lemma is critical for maintaining fertility and seed yield in rice; however, the molecules that control the interlocking structure remain largely unknown. Here, we showed that when OsCR4 mRNA expression was knocked down in rice by RNA interference, the palea and lemma separated at later spikelet stages and gradually turned brown after heading, resulting in the severe interruption of pistil pollination and damage to the development of embryo and endosperm, with defects in aleurone. The irregular architecture of the palea and lemma was caused by tumour-like cell growth in the outer epidermis and wart-like cell masses in the inner epidermis. These abnormal cells showed discontinuous cuticles and uneven cell walls, leading to organ self-fusion that distorted the interlocking structures. Additionally, the faster leakage of chlorophyll, reduced silica content and elevated accumulation of anthocyanin in the palea and lemma indicated a lesion in the protective barrier, which also impaired seed quality. OsCR4 is an active receptor-like kinase associated with the membrane fraction. An analysis of promoter::GUS reporter plants showed that OsCR4 is specifically expressed in the epidermal cells of paleas and lemmas. Together, these results suggest that OsCR4 plays an essential role in maintaining the interlocking of the palea and lemma by promoting epidermal cell differentiation.