Flavin mononucleotide regulated photochemical isomerization and degradation of zeatin.

cis-Zeatin (cZ), a cytokinin often overlooked compared to trans-zeatin (tZ), can now be controlled in live cells and plants through a new biocompatible reaction. Using flavin photosensitizers, cZ can be isomerized to tZ or degraded, depending on the presence of a reducing reagent. This breakthrough offers a novel approach for regulating plant growth through chemical molecules.

A Novel Ultrafiltrate Extract of Propolis Exerts Anti-inflammatory Activity through Metabolic Rewiring.

Thousands of years ago, humans started to use propolis because of its medicinal properties, and modern science has successfully identified several bioactive molecules within this resinous bee product. However, a natural propolis extract which has been removed the adhesive glue and preserved propolis bioactive compounds is urgently needed to maximise the therapeutic opportunities. In this study, a novel ultrafiltrate fraction from Brazilian green propolis, termed P30K, was demonstrated with anti-inflammatory properties, both in vitro and in vivo. Total flavonoids and total phenolic acids content in P30K were 244.6 mg/g and 275.8 mg/g respectively, while the IC50 value of inhibition of cyclooxygenase-2 (COX-2) was 8.30 µg/mL. The anti-inflammatory activity of P30K was furtherly corroborated in experimental models of lipopolysaccharides (LPS)-induced acute liver and lung injury. Mechanistically, integrated GC-MS and LC-MS based serum metabolomics analysis revealed that P30K modulated citrate cycle (TCA), pyruvate, glyoxylate and dicarboxylate metabolism pathways to inhibit secretion of pro-inflammatory cytokines. Results of network pharmacology and molecular docking suggested that P30K targeted catechol-O-methyltransferases (COMT), 11ß-hydroxysteroid dehydrogenases (HSD11B1), and monoamine oxidases (MAOA and MAOB) to promote cellular metabolomic rewiring. Collectively, our work reveals P30K as an efficient therapeutic agent against inflammatory conditions and its efficacy is related to metabolic rewiring.

[Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing].

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

[Correlation between appearance characteristics and intrinsic quality of Gastrodiae Rhizoma].

Totally 21 batches of Gastrodiae Rhizoma pieces from various habitats with different appearance characteristics were analyzed. Five active components( gastrodin,4-hydroxybenzyl alcohol,parishin B,parishin C,and parishin A) were determined by UPLC. Polysaccharide content was determined by phenol sulfuric acid method. And the content of alcohol extracts was determined. The correlation between appearance characteristics and active components,polysaccharide content and amount of alcohol extracts of Gastrodiae Rhizoma pieces was statistically analyzed by SPSS 19. 0 software. And the five active components in the 21 Gastrodiae Rhizoma pieces were clustered by using the Ward' s method in SPSS 19. 0 software. The study found that inconspicuous keratinous Gastrodiae Rhizoma had a low content of each component,and the degree of keratin was positively correlated with the content of each component and the extract,with no significant correlation with the polysaccharide content. In the cluster analysis,the 21 batches were divided into three groups,except the second group whose gastrodin content was significantly higher than the special conditions of other groups. According to the content of the five active components,19 batches of Gastrodiae Rhizoma pieces were classified into two groups with obvious keratin and no obvious keratin. In terms of color,with the deepening of brown color,the content of each component showed a downward trend. The grading of decoction pieces of Gastrodiae Rhizoma shall give full consideration to the color and texture. And the combination of chemical composition and appearance characteristics is an indicator to evaluate the product specification standards.

[Study on quality of standard decoction of Coptidis Rhizoma based on traditional decoction process].

In order to determine the quality evaluation method for standard decoction of Coptidis Rhizoma,15 batches of standard decoction of Coptidis Rhizoma were prepared by using standardized process. Parameters such as traits,p H value,indicative component content,fingerprint similarity,composition transfer rate and dry extract rate were selected as the indexes for quality evaluation. Similarity evaluation and cluster analysis were performed for HPLC fingerprint of standard decoction,and mathematical model was used to study the correlation between dry extract rate,berberine content,berberine transfer rate in standard decoction and berberine content in decoction pieces. The results showed that the similarity of fingerprints was greater than 0. 99 for these 15 batches of standard decoctions of Coptidis Rhizoma. In cluster analysis,the standard decoctions of Coptidis Rhizoma from 4 producing areas were classified into 3 categories,consistent with the content determination results,indicating that there were quality differences among different producing areas.R2 in three linear regression mathematical models established was all greater than 0. 9,with significant difference. The validation of three batches of data showed that the models had good accuracy. Therefore,this model can be used to predict the quality of standard decoction prepared from different Coptidis Rhizoma pieces. In the standard decoction process established in this study,the integrity of the traditional process was greatly preserved,and the established quality evaluation method could be used to comprehensively examine the quality of the standard decoction,which can provide a demonstration for the related research of water extraction preparation containing Coptidis Rhizoma pieces.

[Quality evaluation of multi-components simultaneous determination and fingerprint of Gardeniae Fructus from different regions].

An analysis method was established by UPLC fingerprint and then applied to simultaneous determination of multiple compounds in Gardeniae Fructus from different areas in China. Samples were separated on a Waters Acquity UPLC BEH C18( 2. 1 mm×50 mm,1. 7 µm) column with 0. 1% formic acid-water and acetonitrile solution as gradient mobile phase at a flow rate of 0. 4 m L·min-1 at various wavelengths. The similarity of samples was over 0. 95 with ″Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine( 2012 edition) ″. The UPLC common fingerprints for 32 batches were established with 19 common peaks identified. The samples were divided into 3 groups analyzed by HCA and PCA. Five components were identified as the main compositions which caused the differences of chemical constituents in the samples from different areas with partial least squares discriminant analysis( PLS-DA). The content of the total components in each area was Zhejiang > Fujian > Jiangxi > Sichuan. This method was accurate and viable,could be used to evaluate the quality of Gardeniae Fructus.

[Technology optimization of Gardeniae Fructus processed with ginger juice and composition changes after processing].

To optimize the technology of Gardeniae Fructus processed with ginger juice,establish fingerprints and simultaneously determine seven compounds( geniposidic acid,chlorogenic acid,genipin-1-ß-D-gentiobioside,geniposide,rutin,crocin Ⅰ,and crocin Ⅱ) by using ultra high performance liquid chromatography( UPLC). Waters ACQUITY UPLC BEH C18( 2. 1 mm×50 mm,1. 7µm) column was used with acetonitrile and 0. 1% formic acid solution as mobile phase for gradient elution at the flow rate of 0. 4 m L·min-1. The data was comprehensively processed and analyzed with similarity evaluation,principal component analysis( PCA) and partial least squares discriminant analysis( PLS-DA) methods. Twenty common peaks were identified in this study,and the similarity of samples was over 0. 97. The results of PCA and PLS-DA showed that there were differences in chemical compositions and contents between the raw Gardeniae Fructus and those processed with ginger juice,with 9 potential differentiated chromatographic peaks. After being processed with ginger juice,the contents of chlorogenic acid,crocin Ⅰ and crocin Ⅱ were less than before and the contents of other four compositions were higher than before. The optimized preparation for Gardeniae Fructus processed with ginger juice was stable and feasible. The methods of UPLC fingerprints and simultaneous determination of seven components can be effectively carried out to distinguish Gardeniae Fructus and Gardeniae Fructus processed with ginger juice.

Weighted Measurement Fusion Particle Filter for Nonlinear Systems with Correlated Noises.

The multi-sensor information fusion particle filter (PF) has been put forward for nonlinear systems with correlated noises. The proposed algorithm uses the Taylor series expansion method, which makes the nonlinear measurement functions have a linear relationship by the intermediary function. A weighted measurement fusion PF (WMF-PF) was put forward for systems with correlated noises by applying the full rank decomposition and the weighted least square theory. Compared with the augmented optimal centralized fusion particle filter (CF-PF), it could greatly reduce the amount of calculation. Moreover, it showed asymptotic optimality as the Taylor series expansion increased. The simulation examples illustrate the effectiveness and correctness of the proposed algorithm.

[Antiemetic activity of effective extract and bioactive compounds in ginger].

To investigate the antiemetic effect of the active extract (ginger ether extract, GEE) and its bioactive compounds in ginger, the pica vomiting model in rats and the gastric emptying model in mice were used to observe the antiemetic effect of GEE in cisplatin-induced pica and gastric emptying, and the main components in GEE were detected by RP-HPLC; in vitro, the antagonist effect of GEE and the four components in it were explored by the contraction of guinea-pig ileum induced by SR57227A and carbachol. The results showed that the amount of Kaolin ingested by rats were declined significantly in all the three groups of GEE (25,50,100 mg•kg⁻¹) (P<0.01), while cisplatin-induced gastric emptying in mice was also suppressed in all the three groups (P<0.01), and 6-gingerol, 8-gingerol,10-gingerol and 6-shogaol were found mainly in GEE by RP-HPLC; the maximum contraction of isolated guinea-pig ileum could be reduced by addition of GEE (2.3, 4.6, 11.5 mg•L⁻¹), 6-gingerol,8-gingerol,10-gingerol or 6-shogaol (1, 2, 5 µmol•L⁻¹) when the concentration of SR5727A was 1×10⁻5 mol•L⁻¹ and that of carbachol was 1×10⁻4 mol•L⁻¹ (P<0.05, P<0.01). In conclusion, 5-HT3 and M3 receptors could be antagonized by GEE and its bioactive compounds 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol, which may be correlated with the antiemetic mechanism of ginger maybe related to it.

Insertion/deletion polymorphisms in the ΔNp63 promoter are a risk factor for bladder exstrophy epispadias complex.

Bladder exstrophy epispadias complex (BEEC) is a severe congenital anomaly; however, the genetic and molecular mechanisms underlying the formation of BEEC remain unclear. TP63, a member of TP53 tumor suppressor gene family, is expressed in bladder urothelium and skin over the external genitalia during mammalian development. It plays a role in bladder development. We have previously shown that p63(-/-) mouse embryos developed a bladder exstrophy phenotype identical to human BEEC. We hypothesised that TP63 is involved in human BEEC pathogenesis. RNA was extracted from BEEC foreskin specimens and, as in mice, ΔNp63 was the predominant p63 isoform. ΔNp63 expression in the foreskin and bladder epithelium of BEEC patients was reduced. DNA was sequenced from 163 BEEC patients and 285 ethnicity-matched controls. No exon mutations were detected. Sequencing of the ΔNp63 promoter showed 7 single nucleotide polymorphisms and 4 insertion/deletion (indel) polymorphisms. Indel polymorphisms were associated with an increased risk of BEEC. Significantly the sites of indel polymorphisms differed between Caucasian and non-Caucasian populations. A 12-base-pair deletion was associated with an increased risk with only Caucasian patients (p = 0.0052 Odds Ratio (OR) = 18.33), whereas a 4-base-pair insertion was only associated with non-Caucasian patients (p = 0.0259 OR = 4.583). We found a consistent and statistically significant reduction in transcriptional efficiencies of the promoter sequences containing indel polymorphisms in luciferase assays. These findings suggest that indel polymorphisms of the ΔNp63 promoter lead to a reduction in p63 expression, which could lead to BEEC.

Yak meat content in feed and its impact on the growth of rats.

To evaluate the effects of varying proportions of yak meat in feed on the growth of rats and provide a theoretical basis for selecting the optimal feed proportion suitable for rats. This study was designed as a one-variable experiment. Fifty male rats were divided into five groups. The ratios of yak meat to basal feed of rats in four dietary treatment groups were 2:8, 4:6, 6:4, and 8:2, respectively, while those in the control group were only provided a basal diet. In the feeding experiment, the body weights of the rats were recorded on Day 0 and subsequently in the first, second, third, and fourth weeks, along with quantities of feed intake. The body and tail lengths, as well as the waist circumference of the rats, were measured, and blood samples were collected in the fourth week for routine blood and biochemistry investigations. The rats in the 4:6 feed group had the best body condition. They had normal body and tail lengths, smaller waist circumferences, good posture, and were in better overall health than rats in the other groups. The results indicate that the 4:6 diet was optimal for enhancing rats' growth performance compared to the other diets.

Retrograde type A aortic dissection during or after thoracic endovascular aortic repair: a single center 16-year experience.

Objective: This article aims to investigate the incidence rate of retrograde type A aortic dissection (RTAD) and the risk factors of RTAD in relation to thoracic endovascular aortic repair (TEVAR). Methods: Patients with thoracic aortic disease who underwent TEVAR at Henan Provincial People's Hospital from January 2004 to December 2019 were enrolled in the present research. The risk factors associated with RTAD following TEVAR using univariate and multiple logistic regression analyses. Results: During the study period, A total of 1,688 TEVAR patients were included in this study, and of these, 1,592 cases were included in the type B aortic dissection (TBAD) group, and 96 cases were included in the non-TBAD group. There were 1,230 cases of aortic dissection and 362 cases of aortic intramural hematoma and/or penetrating ulcer in the TBAD group. The non-TBAD group included 68 cases of thoracic aortic aneurysm, 21 cases of thoracic aortic pseudoaneurysm, and seven cases of congenital aortic coarctation. The overall incidence rate of RTAD was 1.1% (18/1,688) in patients, all of which occurred in the TBAD group. The cohort comprised 18 RTAD patients with an average age of 56.78, consisting of 13 males and 5 females. Among them, 13 individuals exhibited hypertension. Ten instances happened within the TEVAR perioperative period, including two cases during the surgery, six cases occurred within three months, two cases occurred after one year, and the longest interval was 72 months following TEVAR. TEVAR was successfully implemented in 17 patients, while the operation technique was temporarily altered in one case. The new entry position for RTAD was identified as the proximal region of the stent graft (SG) in 13 patients, while in five cases, the entry site was more than 2 cm away from the proximal region of the SG. 17 cases were at the greater curvature of the aorta, and one case was at the lesser curvature. Multivariate logistic regression analysis revealed that the SG oversizing ratio is a relevant risk factor for RTAD. However, ascending aortic diameter, aortic arch type, SG type, and anchored region were not directly related to the occurrence of RTAD. Conclusion: RTAD is a rare yet catastrophic complication. It could occur both during the procedure, early and late postoperative periods. Maintaining an appropriate SG oversizing ratio is crucial to minimize the risk of RTAD.

[Protective effects of salidroside on vascular endothelial cells in rats with frostbite after chronic hypoxia].

Objective: To investigate the protective effects of salidroside on endothelial cells in rats with frostbite after chronic hypoxia. Methods: Healthy male SD rats, randomly divided into 3 groups with 10 rats in each group, which included the sham injury group, the model group, and the model +salidroside group. The rats in each group were placed in a composite low-pressure chamber to simulate a environment with a pressure of 54.1 kpa and a temperature of 23~25°C. The rats were exposed to hypoxia under these conditions for 14 days, during the experimental time the rats in the model+salidroside group were treated with 50 mg/kg salidroside daily. After the rats were removed from the low-pressure chamber, except for the sham injury group, frozen iron sheets were applied tightly to the back of the rats for 30 s, supplemented with low temperature for frostbite modeling. Blood and skin tissues were collected at 12 hours after modeling for testing. The structural changes in tissue and vascular endothelial cells were observed in the frostbite region. Vascular endothelial cell particulate EMP levels were detected. The levels of ICAM-1, sEPCR, vWF, ET-1 and NO secretion were determined. The expression levels of HIF-1α, p-PI3K, p-Akt and VEGF were detected by Western blot. Results: Salidroside could effectively reduce skin collapse in frostbitten areas. It could reduce the injury of frostbitten tissues, and improve the subcutaneous tissue necrosis and inflammatory cell infiltration. The autophagy of vascular endothelial cells was reduced. Compared with the model group (0.250±0.165)%, the expression of EMPs in the model+salidroside group (2.453±0.196)% was increased significantly (P＜0.01). In addition, the contents of NO (2.622±0.219)pg/ml was also significantly higher than that of the model group (1.616±0.152)pg/ml (P＜0.01), and the content of vWF (233.50±13.43)pg/ml was lower than that of the model group (315.60±8.78)pg/ml (P＜0.05). There was no significant difference in the levels of ICAM-1, sEPCR and ET-1. Salidroside significantly decreased the expressions of p-PI3K, p-Akt, VEGF and HIF-1α protein in vascular endothelial cells of rats with frostbite (P＜0.01). Conclusion: Salidroside can reduce endothelial cell damage, reduce endothelial cell autophagy and promote endothelial cell regeneration. Based on the PI3K/Akt pathway, salidroside has a good protective effect on endothelial cells of rats with frostbite after chronic hypoxia.

Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis.

Action myoclonus-renal failure syndrome (AMRF) is an autosomal-recessive disorder with the remarkable combination of focal glomerulosclerosis, frequently with glomerular collapse, and progressive myoclonus epilepsy associated with storage material in the brain. Here, we employed a novel combination of molecular strategies to find the responsible gene and show its effects in an animal model. Utilizing only three unrelated affected individuals and their relatives, we used homozygosity mapping with single-nucleotide polymorphism chips to localize AMRF. We then used microarray-expression analysis to prioritize candidates prior to sequencing. The disorder was mapped to 4q13-21, and microarray-expression analysis identified SCARB2/Limp2, which encodes a lysosomal-membrane protein, as the likely candidate. Mutations in SCARB2/Limp2 were found in all three families used for mapping and subsequently confirmed in two other unrelated AMRF families. The mutations were associated with lack of SCARB2 protein. Reanalysis of an existing Limp2 knockout mouse showed intracellular inclusions in cerebral and cerebellar cortex, and the kidneys showed subtle glomerular changes. This study highlights that recessive genes can be identified with a very small number of subjects. The ancestral lysosomal-membrane protein SCARB2/LIMP-2 is responsible for AMRF. The heterogeneous pathology in the kidney and brain suggests that SCARB2/Limp2 has pleiotropic effects that may be relevant to understanding the pathogenesis of other forms of glomerulosclerosis or collapse and myoclonic epilepsies.

Sequestration and transport of lignin monomeric precursors.

Lignin is the second most abundant terrestrial biopolymer after cellulose. It is essential for the viability of vascular plants. Lignin precursors, the monolignols, are synthesized within the cytosol of the cell. Thereafter, these monomeric precursors are exported into the cell wall, where they are polymerized and integrated into the wall matrix. Accordingly, transport of monolignols across cell membranes is a critical step affecting deposition of lignin in the secondarily thickened cell wall. While the biosynthesis of monolignols is relatively well understood, our knowledge of sequestration and transport of these monomers is sketchy. In this article, we review different hypotheses on monolignol transport and summarize the recent progresses toward the understanding of the molecular mechanisms underlying monolignol sequestration and transport across membranes. Deciphering molecular mechanisms for lignin precursor transport will support a better biotechnological solution to manipulate plant lignification for more efficient agricultural and industrial applications of cell wall biomass.

Femoral epithelioid hemangioendothelioma detected with magnetic resonance imaging and positron emission tomography/computed tomography: A case report.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is an uncommon low-grade aggressive vascular tumor. It can occur in almost all locations, but is rarely encountered in bone. CASE SUMMARY: We report a 23-year-old man who presented with left hip pain with no obvious cause. X-ray revealed bone destruction in the left femoral neck with sclerosis at the edges of the lesions. Magnetic resonance imaging (MRI) showed bone destruction in the medullary cavity of the left femoral head and neck. 18F-deoxyglucose-positron emission tomography/computed tomography (PET/CT) imaging showed bone destruction in the left ischium, acetabulum, and left femoral head neck, accompanied by increased radioactive uptake; the maximum standard uptake value was 4.2. Histopathologic examination revealed spindle-shaped mesenchymal tissue hyperplasia with scattered epithelioid cells. The patient underwent left femoral head replacement surgery. No signs of recurrence were observed as of the 18-mo follow-up. CONCLUSION: The definitive diagnosis of femoral EHE can be established aided by the MRI and PET/CT findings.

IL­6 plays a crucial role in epithelial­mesenchymal transition and pro­metastasis induced by sorafenib in liver cancer.

Interleukin­6 (IL­6) is involved in various biological responses, including tumor progression, metastasis and chemoresistance. However, the role and molecular mechanism of IL­6 in the treatment of sorafenib in liver cancer remain unclear. In the present study, through western blot analysis, Transwell assay, flow cytometric assay, ELISA analysis and immunohistochemistry it was revealed that sorafenib promoted metastasis and induced epithelial­mesenchymal transition (EMT) in liver cancer cells in vitro and in vivo, and significantly increased IL­6 expression. Endogenous or exogenous IL­6 affected metastasis and EMT progression in liver cancer cells through Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling. Knocked out IL­6 markedly attenuated the pro­metastasis effect of sorafenib and increased the susceptibility of liver cancer cells to it. In conclusion, the present results indicated that IL­6/STAT3 signaling may be a novel therapeutic strategy for liver cancer.

Overexpression of Thellungiella halophila H(+)-PPase (TsVP) in cotton enhances drought stress resistance of plants.

An H(+)-PPase gene, TsVP from Thellungiella halophila, was transferred into two cotton (Gossypium hirsutum) varieties (Lumianyan19 and Lumianyan 21) and southern and northern blotting analysis showed the foreign gene was integrated into the cotton genome and expressed. The measurement of isolated vacuolar membrane vesicles demonstrated that the transgenic plants had higher V-H(+)-PPase activity compared with wild-type plants (WT). Overexpressing TsVP in cotton improved shoot and root growth, and transgenic plants were much more resistant to osmotic/drought stress than the WT. Under drought stress conditions, transgenic plants had higher chlorophyll content, improved photosynthesis, higher relative water content of leaves and less cell membrane damage than WT. We ascribe these properties to improved root development and the lower solute potential resulting from higher solute content such as soluble sugars and free amino acids in the transgenic plants. In this study, the average seed cotton yields of transgenic plants from Lumianyan 19 and Lumianyan 21 were significantly increased compared with those of WT after exposing to drought stress for 21 days at flowering stage. The average seed cotton yields were 51 and 40% higher than in their WT counterparts, respectively. This study benefits efforts to improve cotton yields in arid and semiarid regions.

Estradiol-17ß regulates the expression of insulin-like growth factors 1 and 2 via estradiol receptors in spotted scat (Scatophagus argus).

Insulin-like growth factors (Igf1 and Igf2) play a key role in growth and development of vertebrates. In mammals, the expression of IGFs is regulated by estradiol-17ß (E2) via estrogen receptors (ESRs). The expression of igfs can also be regulated by E2 in fish, while comparative study of this is still lacking. The present study examined tissue distribution of igfs and hepatic expression of igfs and esrs during gonad development in Scatophagus argus by real-time PCR. Serum E2 concentration was measured by enzyme-linked immunosorbent assay (ELISA). The hepatic expression of igfs and esrs at gonadal phase III, incubated with either E2 (0.1, 1 or 10 µM) alone or in combination with estrogen receptor antagonists-fulvestrant, MPP or PHTPP, was measured. igf1 and igf2 expressed highest in liver of both sexes. Igf1, esr1 and esr2b expressions and serum E2 concentration increased, while igf2 and esr2a expressions decreased, during ovary development. Igfs and esrs expressions increased while serum E2 concentration maintained low during testis development. In females, E2 incubation enhanced the expressions of igf1 and esr1 but inhibited that of igf2 and esr2a. Both fulvestrant and MPP inhibited up-regulation effect of E2 on igf1 and esr1. Fulvestrant enhanced down-regulation effect of E2 on igf2 and esr2a, but MPP conversely. In males, E2 incubation enhanced the expressions of igfs, esr1 and esr2a. Fulvestrant and MPP inhibited up-regulation effect of E2 on igfs and esr1. PHTPP inhibited igf1 and esr2 expressions in both sexes. Our results indicated that the expression of igfs is regulated by E2 via Esrs in S. argus.

miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a.

BACKGROUND: High frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown. METHODS: Real-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression. RESULTS: We showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3'-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/ß-catenin signaling by inhibiting the degradation of ß-catenin and enhancing the interaction between ß-catenin and TCF4 which was mediated by repressed FOXO3a. CONCLUSIONS: Consistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.