Exploring the underlying mechanism by transcriptome sequencing in rats with high-voltage electrical burns and the role of iron metabolism.

BACKGROUND: Clinically, the condition of skeletal muscle injury is the key to the process of high voltage electrical burn (HVEB) wound repair. The aim of this study was to identify the potential mechanisms and intervention targets of skeletal muscle injury after HVEB. METHODS: A skeletal muscle injury model in SD rats with HVEB was made. Pathological examination and transcriptome sequencing of injured skeletal muscles were performed, and the expression levels of key proteins and genes in related signaling pathways were verified. RESULTS: Skeletal muscle injury was progressively aggravated within 48 h, then the injury was gradually repaired with scar formation occurring within 1 week. The mechanism of skeletal muscle injury is complex and varied, and ferroptosis is one of the mechanisms. The ferrous iron content in the injured skeletal muscle tissue of model rats increased significantly at 24 h after injury. After 24 h, damage to injured skeletal muscle tissue could be alleviated by increasing iron storage and blocking lysosomal phagocytosis of autophagy. CONCLUSIONS: Skeletal muscle injury caused by HVEB is characterized by adjacent endangered tissue progression after injury. Ferroptosis is involved in the mechanism of HVEB, and iron metabolism-related proteins may be potential targets for preventing progressive skeletal muscle injury.

Inhibition of CISD1 alleviates mitochondrial dysfunction and ferroptosis in mice with acute lung injury.

The NET family member, CDGSH iron-sulfur domain-containing protein 1 (CISD1), is located in theoutermembrane of mitochondria, where it regulates energy and iron metabolism. CISD1 has vital functions in certain human diseases; however, its function in acute lung injury (ALI) is unknown. ALI pathogenesis critically involves mitochondrial dysfunction and ferroptosis, which might be regulated by CISD1. Therefore, we investigated CISD1's function in mitochondrial dysfunction and ferroptosis regulation in lipopolysaccharide (LPS)-induced ALI. We found that CISD1 was upregulated in LPS-induced ALI,and silencing Cisd1 prevented cell apoptosis and increased cell viability. When CISD1was inhibited by mitoNEET ligand-1 (NL-1) there was a significant mitigation of pathological injury and lung edema, and reduced numbers of total cells, polymorphonuclear leukocytes, and a decreased protein content in the bronchoalveolar lavage fluid (BALF). Moreover, inhibition of CISD1 markedly decreased the interleukin (IL)6, IL-1ß, and tumor necrosis factor alpha (TNF-α) levels in the lungs and BALF of ALI-model mice. Silencing of Cisd1 prevented LPS-induced mitochondrial membrane potential depolarization, cellular ATP reduction, and reactive oxygen species (ROS) accumulation, suggesting mitochondrial protection. ALI activated ferroptosis, as evidenced by the increased lipid-ROS, intracellular Fe2+ level, reduced Gpx4 (glutathione peroxidase 4) expression, and the glutathione/glutathione disulfide ratio. Interestingly, inhibition of CISD1 reduced LPS-induced ferroptosis in vivo and in vitro. In conclusion, inhibition of CISD1 alleviated mitochondrial dysfunction and ferroptosis in LPS-induced ALI, identifying CISD1 as possible target for therapy of LPS-induced ALI.

Fractional CO2 Laser for Vulvar Tissue Rejuvenation: A Prospective Study.

Objective: Aging and changes in hormone levels influence the appearance of the vulva, including the texture, pigmentation, and other manifestations, all of which may largely affect the physical and mental health of women. This study aimed to evaluate the efficacy and safety of fractional carbon dioxide (CO2) laser treatment for vulvar rejuvenation in Chinese women. Background: The limited options currently available for vulvar rejuvenation raise concerns. There is insufficient evidence to determine whether the fractional CO2 laser can safely and effectively rejuvenate the vulvar area for women of various ages and races. Methods: The study included 17 patients (mean age = 36.4 years) treated three times by continuous fractional CO2 laser with an interval of 1 month between each session. The primary outcomes were changes in vulva texture and pigmentation. Treatment was evaluated using images of the patients. Baseline and posttreatment images were collected and evaluated using a scoring system from 0 to 3 to grade the vulvar texture and pigmentation changes. In addition, patients rated their degree of vaginal rejuvenation after the treatment using a scoring system from 0 to 3. Results: Fractional CO2 laser treatment effectively and significantly increased vulvar texture and decreased vulvar pigmentation after three sessions (p < 0.05). Patients also self-reported noticeable improvement. There were no adverse reactions during the treatment and follow-up. Conclusions: Fractional CO2 laser treatment is a safe and effective method for vulvar rejuvenation in women.

Infectious Granuloma With Mycobacterium abscessus After Facial Injection of Botulinum Toxin: A Case Report.

Botulinum toxin injections have garnered increasing employment in facial rhytidectomy due to their demonstrable efficacy and safety profile. In this study, the authors present the case of a 39-year-old woman who manifested painful crimson nodules and multiple abscesses on her face, which manifested 1 week postinjection. Subsequent histopathological scrutiny unveiled the development of histiocytic granulomas accompanied by infiltrates of inflammatory cells, and microbiological investigation and polymerase chain reaction assays identified the causative agent as Mycobacterium abscessus .

Vascular Compromise and Alopecia After Hyaluronic Acid Filler Injection in Temple Region.

Hyaluronic acid filler injection is widely applied in facial shaping and facial filling. Although hyaluronic acid injection is thought to be relatively safe and effective, there are still incidents being reported occasionally. The authors report here a case of alopecia at vascular compromise area after receiving hyaluronic acid filler injection in the left temple region, skin necrosis, and alopecia were well recovered with the treatment of hyaluronidase and external application of minoxidil.

The use of traditional Chinese medicines in relieving exercise-induced fatigue.

Exercise-induced fatigue is a non-pathological fatigue and indicated by a reduction of muscle performance that is caused by excessive physical activity. It seriously affects the daily lives of people, in particular athletes, military personnel, and manual laborers. In recent years, increasing attention has been paid to improving the adverse effect of exercise-induced fatigue on people's daily activities. Thus, studies and applications of traditional Chinese medicines (TCMs) in relieving exercise-induced fatigue have become the focus because of their good curative effects with fewer side effects. This review aims to document and summarize the critical and comprehensive information about the biological processes of exercise-induced fatigue, and to know the types of TCMs, their active components, and possible molecular mechanisms in alleviating exercise-induced fatigue. The peripheral and central mechanisms that cause exercise-induced fatigue have been summarized. A total of 47 exercise-induced fatigue relief TCMs have been collected, mostly including the types of visceral function regulation and emotional adjustment TCMs. Polysaccharides, terpenes, flavonoids/polyphenols are demonstrated to be the major bioactive components. The underlying molecular mechanisms are mainly related to the improvement of energy metabolism, elimination of excess metabolites, inhibition of oxidative stress and inflammatory response, regulation of HPA axis and neurotransmitters. Although current results are obtained mostly from animal models, the clinic trials are still insufficient, and a very few TCMs have been reported to possess potential hepatotoxicity. These findings still offer great reference value, and the significant efficacy in relieving exercise-induced fatigue is impossible to ignore. This review is expected to give insights into the research and development of new TCMs-derived drugs and health care products in relieving exercise-induced fatigue.

Aconitum pendulum and Aconitum flavum: A narrative review on traditional uses, phytochemistry, bioactivities and processing methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Composed of dried Aconitum pendulum and Aconitum flavum roots, Tiebangchui, is an important Tibetan medicine and has been traditionally and widely used as a remedy for cold and pain for thousands of years because of its extraordinary pharmacological activities. The toxicity and efficacy of Tiebangchui as a typical toxic traditional Tibetan medicine, are interdependent, and thus to make sure its safe use in clinics is also noteworthy. AIM OF THE STUDY: This review aims to document and summarize critical and comprehensive information about traditional uses, phytochemistry, pharmacology, toxicology and processing methods of Tiebangchui. Perspectives for possible future investigations have been discussed. MATERIALS AND METHODS: Relevant information about Tiebangchui (A. pendulum and A. flavum) was collected from internationally recognized electronic scientific databases, such as Web of Science, PubMed, Science Direct, Springer Link, ACS, and CNKI. Then, classic Tibetan medical books, such as Four Medical Tantra, and Jing Zhu Materia Medica, and official drug standards were reviewed. RESULTS: A total of 95 chemical constituents have been isolated and identified from Tiebangchui, and most of them were diterpenoid alkaloids. These phytochemicals showed a wide range of pharmacological properties, such as anti-inflammation, anti-rheumatoid arthritis, analgesic, local anesthetic, anti-cancer and anti-bacterial activities. Hence, Tiebangchui is broadly used in hundreds of preparations to treat fever, arthritis, rheumatic arthralgia, traumatic injury, furuncle and swelling. Cardiotoxicity, neurotoxicity and gastrointestinal toxicity are the main toxic effects caused by the Aconitum alkaloids of Tiebangchui. Various processing methods, including steaming, decocting and sand-frying, and traditional Tibetan medicine processing methods, such as processing with Hezi decoction, Qingke wine and Zanba, are effective in attenuating toxicity while retaining efficacy. CONCLUSIONS: The present review provides primary information of Tiebangchui, particularly for its traditional uses, botanical characteristics, phytochemicals, outstanding bioactivities and processing methods. However, studies that explored the in vivo pharmacokinetics and mechanism of Tiebangchui, as well as its quality markers, qualitative and quantitative analysis are still insufficient. Processing methods that attenuate toxicities, evaluations of efficacy, in vivo processes and biological effects, the mechanisms of processed products should be further explored.

LncRNA GAS5 suppresses CD4+ T cell activation by upregulating E4BP4 via inhibiting miR-92a-3p in systemic lupus erythematosus.

Increasing evidence reveals that long noncoding RNAs (lncRNAs) are associated with autoimmune and inflammatory diseases, such as systemic lupus erythematosus (SLE). In this study, we aimed to explore the role of lncRNA growth arrest specific 5 (GAS5) in the pathogenesis of SLE. We found that lncRNA GAS5 was decreased in CD4+ T cells and plasma from SLE patients. Overepression of GAS5 inhibited activation of normal CD4+ T cells and attenuated the self-reactivity of SLE CD4+ T cells. Additionally, we demonstrated that adenovirus E4 binding protein 4 (E4BP4) was involved in lncRNA GAS5-mediated inhibition of CD4+ T cell activation. GAS5 could upregulate E4BP4 by inhibiting miR-92a-3p. Taken together, our results indicate that the GAS5/miR-92a-3p/E4BP4 pathway plays an important role in inhibiting CD4+ T cell activation in SLE, thus providing a potential therapeutic target for SLE treatment.

Twin-arginine signal peptide of Bacillus licheniformis GlmU efficiently mediated secretory expression of protein glutaminase

Background: Protein glutaminase specifically deamidates glutamine residue in protein and therefore significantly improves protein solubility and colloidal stability of protein solution. In order to improve its preparation efficiency, we exploited the possibility for its secretory expression mediated by twin-arginine translocation (Tat) pathway in Bacillus licheniformis. Results: The B. licheniformis genome-wide twin-arginine signal peptides were analyzed. Of which, eleven candidates were cloned for construction of expression vectors to mediate the expression of Chryseobacterium proteolyticum protein glutaminase (PGA). The signal peptide of GlmU was confirmed that it significantly mediated PGA secretion into media with the maximum activity of 0.16 U/ml in Bacillus subtilis WB600. A mutant GlmU-R, being replaced the third residue aspartic acid of GlmU twin-arginine signal peptide with arginine by site-directed mutagenesis, mediated the improved secretion of PGA with about 40% increased (0.23 U/ml). In B. licheniformis CBBD302, GlmU-R mediated PGA expression in active form with the maximum yield of 6.8 U/ml in a 25-l bioreactor. Conclusions: PGA can be produced and secreted efficiently in active form via Tat pathway of B. licheniformis, an alternative expression system for the industrial-scale production of PGA.

AR-PDEF pathway promotes tumour proliferation and upregulates MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative breast cancer.

BACKGROUND: Androgen receptor (AR) is expressed in 60%~ 70% oestrogen receptor (ER)-negative breast cancer (BC) cases and promotes the growth of this cancer subtype. Expression of prostate-derived Ets factor (PDEF), a transcription factor, is highly restricted to epithelial cells in hormone-regulated tissues. MYC and its negative regulator MAD1 play an important role in BC progression. Previously, we found that PDEF expression is strongly correlated with AR expression. However, the relationship between AR and PDEF and the function of PDEF in ER-negative BC proliferation are unclear. METHODS: AR and PDEF expression in ER-negative BC tissues and cell lines was determined by performing immunohistochemistry or western blotting. Protein expression levels and location were analysed by performing western blotting, RT-qPCR and immunofluorescence staining. Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to validate the regulation of AR-PDEF-MAD1-MYC axis. Moreover, the effect of AR and PDEF on BC progression was investigated both in vitro and in vivo. RESULTS: We found that PDEF was overexpressed in ER-negative BC tissues and cell lines and appeared to function as an oncogene. PDEF expression levels were strongly correlated with AR expression in ER-negative BC, and PDEF transcription was positively regulated by AR. PDEF upregulated MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative BC. Finally, we found that compared with the inhibition of AR expression alone, simultaneous inhibition of AR and PDEF expression further suppressed tumour proliferation both in vitro and in vivo. CONCLUSIONS: Our data highlight the role of the AR-PDEF-MAD1-MYC axis in BC progression and suggest that PDEF can be used as a new clinical therapeutic target for treating ER-negative BC.

Clinical significance of PDEF factor expression and its relation to androgen receptor in ER- breast cancer.

AIMS: The mechanism of androgen receptor (AR) promoting tumour growth in oestrogen receptor-negative (ER- ) breast cancer (BC) is undetermined. Prostate-derived ETS factor (PDEF) is highly restricted to the hormone-regulated tissues of epithelial cells, such as those in the prostate, breast and other tissues. It has been demonstrated that PDEF expression is associated with AR in prostate cancer. In this research, we aimed to investigate the relationship between PDEF and AR in ER- BC. METHODS AND RESULTS: We immunohistochemically evaluated the correlation between PDEF and AR expression in 246 cases of ER- invasive BC, and investigated their relationship in ER- BC cell lines. The expression of PDEF was associated with the positive expression of AR (P < 0.001) and a worse survival rate (P = 0.006). PDEF+ tumours were significantly more often AR+ (P < 0.001). AR and PDEF were more often co-expressed and the series of AR+ PDEF+ (126 of 246, 51.2%) had a poor survival rate (P = 0.046). In Cox models, PDEF expression (P = 0.028) was an independent predictor for overall survival (OS). At the cellular protein and mRNA levels, our experiments also showed a statistically significant positive correlation between PDEF and AR, and that PDEF may be regulated by AR. CONCLUSIONS: PDEF is associated with markers of bad prognosis, supporting its role as a growth promoter in ER- BC. Our findings also provide evidence that PDEF is strongly correlated with AR expression in ER- breast cancer; it may be a downstream target gene of AR and a potential prognostic factor in ER- BC.

The importance of EGFR as a biomarker in molecular apocrine breast cancer.

Molecular apocrine breast cancer (MABC) is a molecular subtype with a poor prognosis, and there is urgent need to find new therapeutic targets. Epidermal growth factor receptor (EGFR) plays an important part in regulating the biological behavior of tumor cells, and EGFR-targeted drugs have already been used in therapy for lung and colorectal cancers. The purpose of this study was to analyze the significance of EGFR expression in MABC. A total of 400 patients with invasive breast cancer were analyzed, including 200 MABC and 200 non-MABC cases. Immunohistochemistry and immunofluorescence were carried out to evaluate the expression of estrogen receptor, progesterone receptor, androgen receptor (AR), EGFR, epidermal growth factor receptor 2 (HER2), and other biomarkers. Two hundred twelve (53%) cases were positive for EGFR expression, including 173 MABC and 39 non-MABC cases. EGFR expression was positively associated with AR expression in MABC, as well as with more advanced tumor stage and high Ki67 expression. Patients with EGFR expression had worse outcomes than those without. As a prognosis biomarker, EGFR was significantly associated with poorer clinical outcomes, and the co-expression of EGFR and HER2 often predicted worse outcomes in MABC. This study suggests that the identification of new targets such as HER2 and EGFR may help with assessing the prognosis of patients with MABC. Using both AR and EGFR as therapeutic targets may be especially important in MABC and may help to guide the choice of suitable treatments for individual breast cancer patients.

The immunohistochemical expression and potential prognostic value of HDAC6 and AR in invasive breast cancer.

Previous studies have investigated the role of histone deacetylase 6 (HDAC6) in the regulation of androgen receptor (AR) in prostate cancer; however, the role of HDAC6 has not yet been clearly identified in breast cancer. The aim of this study was to examine the expression of HDAC6 and AR, determine the correlation between HDAC6 and AR, and assess the prognostic value of HDAC6 and AR in breast cancer. A total of 228 cases of invasive breast cancer were randomly selected. The expression of HDAC6 and AR was analyzed by immunohistochemistry. χ2 Tests were performed to determine the association between conventional clinicopathological factors and HDAC6, AR, and HDAC6/AR co-expression. Spearman correlation methods were performed to determine the correlation between HDAC6 and AR, and Kaplan-Meier analyses were performed to determine the prognostic impact of HDAC6, AR and HDAC6/AR co-expression; 58.8% (134/228) patients exhibited high expression of HDAC6. High HDAC6 expression was significantly associated with high histologic grade (G3) (P<.001) and p53 overexpression (P=.002). HDAC6 and AR expression levels were significantly associated (r=0.382, P<.01). In estrogen receptor (ER)-negative samples, high expression of HDAC6 was more common in the AR+ groups (P<.001) and correlated with high histologic grade (G3) (P=.009), as well as higher HER2 (P=.006) and p53 levels (P=.012). Higher expression of AR and HDAC6 and HDAC6/AR co-expression had a worse clinical prognosis. The expression levels of HDAC6 and AR are correlated in breast cancer; moreover, HDAC6 and AR have prognostic value in predicting the overall survival (OS) of ER-negative breast cancer patients.

Generalized eruptive keratoacanthoma with vitiligo followed by the development of prurigo nodularis: A case report and published work review.

Herein, we report a unique case of generalized eruptive keratoacanthoma (GEKA) in a 47-year-old Chinese man presenting with extensive pruritic papules and nodules accompanied by oral lesions. He also had a 2-year history of vitiligo and long-term experience of working outdoors. Biopsies were consistent with keratoacanthoma . Interestingly, prurigo nodularis (PN) was found in histopathology at 1-year follow up. To our knowledge, this is the first report describing a case of GEKA with oral lesions complicated with vitiligo and developed with PN.

Downregulation of miRNA-26b inhibits cancer proliferation of laryngeal carcinoma through autophagy by targeting ULK2 and inactivation of the PTEN/AKT pathway.

Laryngeal carcinoma is one of the most common tumors of the head and neck cancers, the pathogenesis of which remains yet unclear. It has been discovered through research that microRNAs (miRNAs) play an important role during the genesis of laryngeal carcinoma. In the present study we investigated the effect of miRNA-26b on the proliferation of laryngeal carcinoma and elucidated the potential underlying mechanisms in order to provide new targets for laryngeal carcinoma. Firstly, we found that miRNA-26b expression was significantly increased in patients with laryngeal carcinoma, compared with normal volunteers. The downregulation of miRNA-26b inhibited cell proliferation and induced apoptosis of Hep-2 cells. Furthermore, downregulation of the expression of miRNA­26b promoted Bax, LC3 and p62 protein expression, decreased ULK2 mRNA and protein expression, as well as PTEN protein expression and increased phosphorylated­AKT protein expression in Hep-2 cells as determined using quantification by real-time PCR and western blotting. The concomitant downregulation of ULK2 and miRNA-26b futher enhanced the miRNA­26b-induced autophagy and apoptosis in addition to the miRNA-26b-inhibited cell proliferation of Hep-2 cells by targeting ULK2 and inactivating the PTEN/AKT pathway as determined by immunocytofluorescence. These findings revealed that miRNA-26b may play a key role in cell growth and death of laryngeal carcinoma through ULK2 and the PTEN/AKT pathway, and thus may be a new target for gene therapy in laryngeal carcinoma.

miR-124 suppresses proliferation and invasion of nasopharyngeal carcinoma cells through the Wnt/ß-catenin signaling pathway by targeting Capn4.

BACKGROUND: Recent studies have demonstrated that microRNA 124 (miR-124) acts as a tumor suppressor in nasopharyngeal carcinoma (NPC); however, the exact molecular mechanism by which miR-124 exerts tumor suppression has not been well elucidated. MATERIALS AND METHODS: We performed quantitative real-time PCR (qRT-PCR) to measure the expression of metastasis associated lung adenocarcinoma transcript 1, miR-124, and calpain small subunit 1 (Capn4) mRNAs in NPC cell lines. We also performed western blot analysis to detect the levels of Capn4. Furthermore, we performed MTT assay and transwell invasion assay to determine the proliferation and invasion ability of two NPC cell lines, namely, HONE1 and CNE2 cells, respectively. The verification of targets of miR-124 was performed using prediction softwares and luciferase reporter analysis. RESULTS: According to our results, the expression of Capn4 was found to be elevated, whereas the expression of miR-124 was lowered in NPC cell lines compared with normal nasopharyngeal cells. When we preformed overexpression of miR-124, it suppressed the proliferation and invasion of NPC cells. Moreover, miR-124 suppressed the expression of Capn4 by targeting Capn4 in HONE1 and CNE2 cells. When we preformed overexpression of Capn4, it reversed the inhibitory effect of miR-124 on the proliferation and invasion of NPC cells. Furthermore, miR-124-Capn4 axis decreased the levels of ß-catenin, cyclin D1, and c-Myc, the components of the Wnt/ß-catenin signaling pathway. CONCLUSION: The suppression of proliferation and invasion of NPC cells by miR-124 were achieved by the regulation of Wnt/ß-catenin signaling pathway by targeting Capn4. The results of this study revealed a novel miR-124-Capn4 regulatory axis in NPC cell lines, providing a better understanding of the pathogenesis of NPC and a promising therapeutic target for patients with NPC.

MiR-183 overexpression inhibits tumorigenesis and enhances DDP-induced cytotoxicity by targeting MTA1 in nasopharyngeal carcinoma.

MicroRNA 183 (miR-183) was identified to be downregulated in nasopharyngeal carcinoma spheroids and served as a tumor suppressor in nasopharyngeal carcinoma. However, the regulatory mechanism of miR-183 and its role in cisplatin (DDP) resistance in nasopharyngeal carcinoma cells are still unclear. The expression of miR-183 and metastasis-associated protein 1 at messenger RNA and protein levels in nasopharyngeal carcinoma tissues and cells was evaluated using quantitative reverse transcription real-time polymerase chain reaction and western blotting, respectively. CNE1 and CNE2 cells were transfected with miR-183 mimic, miR-183 inhibitor, pcDNA-metastasis-associated protein 1, or respective controls. The effects of miR-183 and metastasis-associated protein 1 overexpression on cell proliferation, invasion, and DDP-induced apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Transwell invasion assay, and flow cytometry analysis, respectively. Luciferase reporter assay was performed to explore whether miR-183 directly targeted metastasis-associated protein 1. Xenograft tumor experiment was applied to confirm the biological function of miR-183 in vivo. MiR-183 was downregulated in nasopharyngeal carcinoma tissues and cells and negatively correlated with metastasis-associated protein 1 expression. Ectopic expression of miR-183 markedly suppressed cell proliferation and invasion and strikingly enhanced DDP-induced apoptosis in nasopharyngeal carcinoma cells, whereas metastasis-associated protein 1 overexpression partially reversed these effects. Luciferase reporter assay demonstrated that metastasis-associated protein 1 was a direct target of miR-183. MiR-183 negatively regulated the expression of metastasis-associated protein 1 at both the messenger RNA and protein levels. Xenograft tumor experiment indicated that miR-183 overexpression repressed tumor growth and improved DDP-induced cytotoxicity in nasopharyngeal carcinoma cells in vivo. MiR-183 overexpression inhibited tumorigenesis and enhanced DDP-induced cytotoxicity by targeting metastasis-associated protein 1 in nasopharyngeal carcinoma, contributing to the development of novel therapeutic approaches for the treatment of clinical nasopharyngeal carcinoma patients.

Lin28A activates androgen receptor via regulation of c-myc and promotes malignancy of ER-/Her2+ breast cancer.

Having previously demonstrated the co-expression status of the Lin28A and androgen receptor (AR) in ER-/Her2+ breast cancer, we tested the hypothesis that Lin28A can activate AR and promotes growth of ER-/Her2+ breast cancer. The expression of Lin28A and AR were examined after Lin28A siRNA and Lin28A plasmid were transfected into ER-/Her2+ breast cancer cells. Chromatin immune-precipitation (ChIP) analysis and Luciferase Assays were used to evaluate the effect of Lin28A and c-myc on AR promoter activity. MTT assays, Boyden chamber invasion assays, colony formation assays and flow cytometry analysis were performed. ER-/Her2+ breast cancer cells which transfected with Lin28A siRNAs and Lin28A plasmid were injected into nude mice, and tumorigenesis was monitored. Our data showed that Lin28A can induced AR expression in ER-/Her2+ breast cancer cells. ChIP analysis showed that Lin28A stimulates the recruitment of c-Myc to the promoter of the AR gene. Lin28A enhanced growth ability, colonies ability, cells proliferation activities, invasive ability and inhibited cells apoptosis of ER-/Her2+ breast cancer cells. Lin28A high expression cells exhibited significantly higher tumorigenic ability in vivo. Our study demonstrates that Lin28A can activates androgen receptor via regulation of c-myc and promotes malignancy of ER-/Her2+ breast cancer. Our findings underline a novel role for Lin28A in breast cancer development and activation of the AR axis.

Phenanthrenes from Juncus effusus.

A chemical investigation of the EtOAc-soluble fraction from the ethanol extract of the medullae of Juncus effusus led to the isolation of three new 9,10-dihydrophenanthrenes, juncuenins E-G (1-3); two new phenanthrenes, dehydrojuncuenins D-E (4-5); one new feruloylated glycoside (6); and one known 9,10-dihydrophenanthrene (7). The structures of these compounds were determined by analyzing their spectroscopic data. Metabolites 1-4 and 7 were further evaluated for their in vitro cytotoxic activities against seven human cancer lines (A549, MCF-7, BEL-7402, HeLa, COLO205, BGC-823, and SK-OV-3). Among them, compound 1 exhibited weak cytotoxicity against MCF-7 and HeLa cell lines. Compound 7 showed moderate cytotoxicity against MCF-7 and HeLa cell lines, with IC50 values of 9.17 and 19.6 µM, respectively.

Influence of changes in hydrodynamic conditions on cadmium transport in tidal river network of the Pearl River Delta, China.

With rapid economic development, the Pearl River Delta (PRD) of China has experienced a series of serious heavy metal pollution events. Considering complex hydrodynamic and pollutants transport process, one-dimensional hydrodynamic model and heavy metal transport model were developed for tidal river network of the PRD. Then, several pollution emergency scenarios were designed by combining with the upper inflow, water quality and the lower tide level boundary conditions. Using this set of models, the temporal and spatial change process of cadmium (Cd) concentration was simulated. The influence of change in hydrodynamic conditions on Cd transport in tidal river network was assessed, and its transport laws were summarized. The result showed the following: Flow changes in the tidal river network were influenced remarkably by tidal backwater action, which further influenced the transport process of heavy metals; Cd concentrations in most sections while encountering high tide were far greater than those while encountering middle or low tides; and increased inflows from upper reaches could intensify water pollution in the West River (while encountering high tide) or the North River (while encountering middle or low tides).