[The role and mechanism of multifunctional molecule SLPI in regulating ischemia-reperfusion induced acute kidney injury and repair].

The secretory leukocyte protease inhibitor (SLPI) is mainly produced by immune cells and various epithelial cells, and is regulated by a variety of cytokines, such as transforming growth factor ß1, interleukin 1ß and tumor necrosis factor α. In addition to commonly known anti-protease activity, it has been found in recent years that SLPI plays essential roles in anti-apoptosis, regulating cell cycle, cell differentiation and proliferation, and inhibiting inflammatory response. SLPI can also assist the immune system to clear pathogens/damaged cells by enhancing the phagocytic function of phagocytes, so as to ameliorate tissue damage and promote repair. Moreover, recent studies have shown that the change of SLPI level in the serum of patients post cardiovascular surgery has a high diagnostic value in predicting the occurrence of acute kidney injury, suggesting that SLPI is involved in ischemia-reperfusion (IR) induced acute kidney injury. In this review, we summarized the expression, regulation, signaling pathways and associated biological events of SLPI in different organ injury models, and also discussed and evaluated the potential role of SLPI in renoprotection against IR induced acute kidney injury and its potential as a new biomarker.

[Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway].

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

PPAR-γ alleviates the inflammatory response in TNF-α-induced fibroblast-like synoviocytes by binding to p53 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by synovial inflammation, synoviocyte expansion and damage to cartilage and bone. We recently reported that peroxisome proliferator-activated receptor (PPAR)-γ inhibited the proliferation and activation of fibroblast-like synoviocytes (FLS), and was downregulated in RA synovial. In this study we investigated the role of PPAR-γ in RA and the underlying mechanisms. Adjuvant-induced arthritis (AIA) was induced in rats; from D15, AIA rats were orally administered pioglitazone (30 mg·kg-1·d-1) or rosiglitazone (4 mg·kg-1·d-1) for 14 days. Collagen-induced arthritis (CIA) was induced in wild-type and Ppar-γ+/- mice. We showed that the expression of PPAR-γ was significantly reduced, whereas that of TNF-α was markedly increased in human RA FLS. In CIA mice, knockdown of PPAR-γ expression (Ppar-γ+/-) aggravated the ankle inflammation. Similarly, T0070907 (a PPAR-γ antagonist) or si-PPAR-γ promoted the activation and inflammation of TNF-α-induced FLS in vitro. On the contrary, administration of PPAR-γ agonist pioglitazone or rosiglitazone, or injection of ad-Ppar-γ into the ankle of AIA rat in vivo induced overexpression of PPAR-γ, reduced the paw swelling and inflammation, and downregulated activation and inflammation of FLS in RA. Interesting, injection of ad-Ppar-γ into the ankle also reversed the ankle inflammation in Ppar-γ+/- CIA mice. We conducted RNA-sequencing and KEGG pathway analysis, and revealed that PPAR-γ overexpression was closely related to p53 signaling pathway in TNF-α-induced FLS. Co-IP study confirmed that p53 protein was bound to PPAR-γ in RA FLS. Taken together, PPAR-γ alleviates the inflammatory response of TNF-α-induced FLS by binding p53 in RA.

[Update on the role and mechanism of erythropoietin receptor in acute kidney injury and repair or fibrosis].

Acute kidney injury (AKI) is a common critical disease clinically with high morbility and mortality and some survival patients also progress to chronic kidney disease. Renal ischemia-reperfusion (IR) is one of the main causes of AKI, in which, its repair and potential fibrosis, apoptosis, inflammation and phagocytosis play important roles. During the progression of IR-induced AKI, the expression of erythropoietin homodimer receptor (EPOR)2 and EPOR and ß common receptor formed heterodimer receptor (EPOR/ßcR) is changed dynamically. Moreover, (EPOR)2 and EPOR/ßcR may synergistically participate in renoprotection at the stage of AKI and early repair, whereas at the late stage of AKI, the (EPOR)2 induces renal fibrosis and the EPOR/ßcR facilitates repair and remodelling. The underlying mechanism, signaling pathways and the different effect turning point of (EPOR)2 and EPOR/ßcR have not been well defined. It has been reported that EPO, according to its 3D structure, derived helix B surface peptide (HBSP) and cyclic HBSP (CHBP) only bind to EPOR/ßcR. Synthesized HBSP, therefore, provides an effective tool to distinguish the different roles and mechanisms of both receptors, with the (EPOR)2 promoting fibrosis or the EPOR/ßcR leading to repair/remodelling at the late stage of AKI. This review discusses the similarities and differences of (EPOR)2 and EPOR/ßcR in their impacts on apoptosis, inflammation and phagocytosis in AKI, repair and fibrosis post IR, associated mechanisms, signaling pathways and outcomes.

Evolution of the frequency-comb structure and coherence from a Keldysh multiphoton into a tunneling regime.

We present a theoretical study of the characteristics of the frequency-comb structure and coherence via high-order harmonic generation (HHG) driven by the laser pulse trains when the ionization process is pushed from Keldysh multiphoton into tunneling regime. HHG is obtained by solving accurately the time-dependent Schrödinger equation by means of the time-dependent generalized pseudospectral method. We find that the nested comb structures are formed from each harmonic order in the Keldysh multiphoton ionization regime. But it is severely suppressed or even disappeared in the Keldysh tunneling ionization regime. It implies that the temporal coherence of the emitted frequency comb modes is very sensitive to the Keldysh ionization regime. To understand the evolution of frequency-comb structure and coherence, we perform the calculation of the time-dependent ionization probability and the spectral phase of frequency-comb HHG. We find that the frequency-comb HHG driven by the laser pulse trains in the Keldysh multiphoton regime has a good coherence because the ionization probability of the atom driven by each laser pulse is stable, leading to a phase-coherent frequency-comb structure rather than those cases in the Keldysh tunneling regime with high laser intensity. Our results shed light on current interest and significance to the experimental realization of controllable and frequency-comb vacuum-ultraviolet light sources.

A randomized double blind comparison of atosiban in patients with recurrent implantation failure undergoing IVF treatment.

BACKGROUND: Patients with recurrent implantation failure (RIF) may have more uterine contractions. Several observational studies suggested that atosiban administration around embryo transfer resulted in higher pregnancy rates in RIF patients. This study aimed to evaluate the effect of atosiban given before fresh embryo transfer on pregnancy outcomes of women with RIF. METHODS: A prospective, randomized, double-blind controlled clinical trial was performed in IVF center of Shanghai First Maternity and Infant Hospital. According to a computer-generated randomization list, 194 infertile women with RIF received fresh embryo transfer between July 2017 and December 2019 were randomly allocated into the atosiban (n = 97) and the placebo (n = 97) groups. Women in the treatment group received atosiban intravenously about 30 min before embryo transfer with a bolus dose of 6.75 mg over one minute. Those in the placebo group received only normal saline infusion for the same duration. RESULTS: There was no significant difference in the live birth rate between the atosiban and placebo groups (42.3% vs 35.1%, P = 0.302, RR = 1.206 (0.844-1.723)). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and implantation rates. Similar results were found when stratified by the number of embryos previously transferred, number of previous failed embryo transfers, frequency of endometrial peristalsis on embryo transfer day (≥ 3 waves/min) or serum estradiol (E2) on the day of hCG above the median level. And, there was no correlation between the serum E2 level on the day of hCG and the frequency of endometrial peristalsis on embryo transfer day. The frequency of endometrial peristalsis on embryo transfer day, total FSH/HMG dosage and duration were the significant factors which independently predicted the likelihood of a live birth. CONCLUSIONS: These results suggested that atosiban treatment before fresh embryo transfer might not improve the live birth rate in RIF patients. TRIAL REGISTRATION: The study had been approved by the Institutional Review Board of the hospital (2017 ethics No.43) and was registered under Clinicaltrials.gov with an identifier NCT02893722.

Circular RNA circUbe2k promotes hepatic fibrosis via sponging miR-149-5p/TGF-ß2 axis.

Abundant regulatory genes and complex circuits involving non-coding RNAs (ncRNAs) monitor the formation and development of hepatic fibrosis (HF). Circular RNAs (circRNAs) are a class of RNAs generated from protein coding genes by back-splicing, playing crucial roles in various pathological processes, including HF. However, little is known about mechanisms of action of circRNAs, let alone in HF. In this study, we found circUbe2k enhanced in CCl4 -induced HF mice and LX-2 cells stimulated with TGF-ß1, regulating the development of HF. Restraining the expression of circUbe2k inhibited α-SMA and Col1α1 expression in CCl4 -induced HF mice and in LX-2 cells stimulated with TGF-ß1. Furthermore, inhibiting circUbe2k expression reduced hepatic stellate cells (HSCs) activation and proliferation in vivo and in vitro. Mechanistically, we demonstrated a direct interaction between circUbe2k and miR-149-5p, which results in the modulation of TGF-ß2 expressions. Together, circUbe2k may act as a "catalyst" of HSCs activation and HF through the circUbe2k/miR-149-5p/TGF-ß2 axis. Our results provide unprecedented evidence for a significant role for circUbe2k to serve as a potential biomarker for HF therapy.

Hesperetin derivative decreases CCl4 -induced hepatic fibrosis by Ptch1-dependent mechanisms.

Hepatic fibrosis (HF), a continuous wound-healing response of the liver to repeated injuries, is characterized by abnormal extracellular matrix (ECM) accumulation. Hepatic stellate cells (HSCs) are considered a major cell type for ECM production. However, recent evidence indicates the lack of effective treatments for HF. Hesperetin, a Traditional Chinese Medicine monomer, has been isolated from the fruit peel of Citrusaurantium L. (Rutaceae). Growing evidence suggests the partial function of hesperetin in HF treatment. A hesperetin derivative (HD) was synthesized in our laboratory to increase the bioavailability and the water solubility of hesperetin. In this study, we detected the functions of HD in a mouse model of CCl4 -induced HF and transforming growth factor-ß1-stimulated HSC-T6 cells, in vivo and in vitro. HD reduced histological damage and CCl4 -induced HF. Moreover, HD interference was associated with the activation of indicators in HSC-T6 cells, showing that HD is involved in HSCs activation in HF. Mechanistically, the Hedgehog pathway is involved in the HD treatment of HF, and HD may attenuate the aberrant expression of patched1. In conclusion, the studies indicate that HD may function as a potential antifibrotic Traditional Chinese Medicine monomer in HF therapy.

Critical cultural competence of clinical nurses in China: A cross-sectional survey.

AIM: To determine the level of critical cultural competence (CCC) among Chinese clinical nurses and explore its influencing factors. BACKGROUND: Previous research has only focused on the theoretical model of CCC and the development of assessment tools; however, no large-scale study has been conducted on the level of clinical nurses' CCC and its influencing factors. METHOD: Clinical nurses in 14 Level A tertiary hospitals (n = 3858) were surveyed using Almutairi's critical cultural competence scale (CCCS). Descriptive, univariate and multivariate analyses were performed. RESULTS: The mean score of CCC was 4.44 (SD = 0.33). Critical empowerment (M = 4.85, SD = 0.58) and critical awareness (M = 3.57, SD = 0.99) had the highest and lowest scores, respectively. Female nurses, nurses in the nursing department and nurses with higher positions had higher CCC. CONCLUSION: The CCC of clinical nurses can be strengthened through targeted training, especially considering the fact that male and low-ranking nurses who had the lower level of CCC work in different departments. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital administrators should pay attention to the importance of culture and cultural differences among different countries or ethnic groups. Creating an equal and fair nursing environment and encouraging nurses to provide critical cultural nursing is important.

Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways.

BACKGROUND: Trophoblast cells are required for the establishment of pregnancy and fetal development. Apoptosis is an essential feature for trophoblast invasion. Uncontrolled trophoblast apoptosis is related to some complicate pregnancies. Oxidative stress (OS) is an important inducer of trophoblast apoptosis. Cyclosporin A (CsA) has been shown to promote the activity of trophoblast cells and reduce OS-induced oxidative injury. We investigated the role and mechanism of CsA in oxidative stress-induced trophoblast cell apoptosis. METHODS: JEG-3 cells were cocultured with H2O2 and CsA. Cell viability and morphology were measured by MTT assay and DAPI staining. Cell apoptosis was tested with annexin V/PI staining. The expression of Bcl-2-associated X protein (Bax), B-cell lymphoma/leukemia-2 (Bcl-2), cleaved poly (ADP-ribose) polymerase (PARP) and pro-caspase-3 was assayed by western blotting. The protein expression and phosphorylation of p53 and mitogen-activated protein kinase (MAPK) kinases (JNK, ERK1/2 and p38) were examined by western blotting. RESULTS: CsA increased the viability, alleviated morphological injury and reduced cell apoptosis of the H2O2-treated JEG-3 cells. CsA also attenuated the activation of p53, decreased the expression of Bax and cleavage of PARP, and increased the expression of Bcl-2 and pro-caspase-3 in the JEG-3 treated with H2O2. Furthermore, CsA reduced the activation of JNK and P38 but had no significant effect on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the H2O2-treated JEG-3 cells. Promoting the activation of JNK and p38 impaired the protective effect of CsA on OS-induced trophoblast apoptosis. CONCLUSIONS: These results suggested that CsA protected trophoblast cells from OS-induced apoptosis via the inhibition of the p53 and JNK/p38 signaling pathways.

Knockout of Selenoprotein V Affects Regulation of Selenoprotein Expression by Dietary Selenium and Fat Intakes in Mice.

BACKGROUND: The metabolic function of selenoprotein V (SELENOV) remains unknown. OBJECTIVES: Two experiments were conducted to determine effects of the Selenov knockout (KO) on selenium concentration and mRNA, protein, and/or activity of 4 major selenoproteins [glutathione peroxidase (GPX) 1, GPX4, thioredoxin reductase-1 (TXNRD1), and selenoprotein P (SELENOP)] in the serum, liver, testis, and/or white adipose tissue (WAT) of mice fed different dietary selenium and fat concentrations. METHODS: In Experiment (Expt) 1, 40 KO and 40 wild-type (WT) mice (males, 8 wk old) were fed (n = 10/genotype) a casein-sucrose basal diet plus 0, 0.3, 1, or 3 mg Se/kg (as sodium selenite) for 32 wk . In Expt 2, 20 KO and 20 WT mice (males, 8 wk old) were fed (n  = 10/genotype) a normal-fat diet (NF; 10% calories from fat) or a high-fat diet (HF; 60% calories from fat) for 19 wk. RESULTS: In Expt 1, the KO caused consistent or substantial decreases (P < 0.05) of mRNA amounts of Gpx1, Txnrd1, and Selenop in the testis (≤52%), but selenium concentrations (19-29%) and GPX activities (≤ 50%) were decreased in the liver across different dietary selenium concentrations . Hepatic and testis GPX1 protein was elevated (≤31%) and decreased (≤45%) by the KO, respectively. In Expt 2, the genotype and dietary fat intake exerted interaction effects ( P < 0.05) on Gpx1 mRNA amounts in the WAT; Gpx1, Txnrd1, and Selenop mRNA amounts and TXNRD activities in the testis; and selenium concentrations in the serum and liver. However, these 2 treatments produced largely independent or additive effects (P < 0.05) on the GPX1 and SELENOP protein amounts in the liver and testis (up to ± 50% changes). CONCLUSIONS: The KO-mediated changes in the tissue selenium concentrations and functional expression of 3 major selenoproteins implied potential for SELENOV in regulating body selenium metabolism in the mouse.

Cinnamic acid derivatives: inhibitory activity against Escherichia coli ß-glucuronidase and structure-activity relationships.

Gut microbial ß-glucuronidase (GUS) is a potential therapeutic target to reduce gastrointestinal toxicity caused by irinotecan. In this study, the inhibitory effects of 17 natural cinnamic acid derivatives on Escherichia coli GUS (EcGUS) were characterised. Seven compounds, including caffeic acid ethyl ester (CAEE), had a stronger inhibitory effect (IC50 = 3.2-22.2 µM) on EcGUS than the positive control, D-glucaric acid-1,4-lactone. Inhibition kinetic analysis revealed that CAEE acted as a competitive inhibitor. The results of molecular docking analysis suggested that CAEE bound to the active site of EcGUS through interactions with Asp163, Tyr468, and Glu504. In addition, structure-activity relationship analysis revealed that the presence of a hydrogen atom at R1 and bulky groups at R9 in cinnamic acid derivatives was essential for EcGUS inhibition. These data are useful to design more potent cinnamic acid-type inhibitors of EcGUS.

Embryonic transcriptome and proteome analyses on hepatic lipid metabolism in chickens divergently selected for abdominal fat content.

BACKGROUND: In avian species, liver is the main site of de novo lipogenesis, and hepatic lipid metabolism relates closely to adipose fat deposition. Using our fat and lean chicken lines of striking differences in abdominal fat content, post-hatch lipid metabolism in both liver and adipose tissues has been studied extensively. However, whether molecular discrepancy for hepatic lipid metabolism exists in chicken embryos remains obscure. RESULTS: We performed transcriptome and proteome profiling on chicken livers at five embryonic stages (E7, E12, E14, E17 and E21) between the fat and lean chicken lines. At each stage, 521, 141, 882, 979 and 169 differentially expressed genes were found by the digital gene expression, respectively, which were significantly enriched in the metabolic, PPAR signaling and fatty acid metabolism pathways. Quantitative proteomics analysis found 20 differentially expressed proteins related to lipid metabolism, PPAR signaling, fat digestion and absorption, and oxidative phosphorylation pathways. Combined analysis showed that genes and proteins related to lipid transport (intestinal fatty acid-binding protein, nucleoside diphosphate kinase, and apolipoprotein A-I), lipid clearance (heat shock protein beta-1) and energy metabolism (NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 and succinate dehydrogenase flavoprotein subunit) were significantly differentially expressed between the two lines. CONCLUSIONS: For hepatic lipid metabolism at embryonic stages, molecular differences related to lipid transport, lipid clearance and energy metabolism exist between the fat and lean chicken lines, which might contribute to the striking differences of abdominal fat deposition at post-hatch stages.

Efficacy and Safety of Opioids for the Prevention of Etomidate-Induced Myoclonus: A Meta-Analysis.

Etomidate is a widely used hypnotic drug for induction of general anesthesia and sedation, especially in elderly patients and hemodynamically unstable patients. Myoclonus, however, is the most prominent problem during induction of anesthesia with etomidate. Many agents have been used to prevent it and opioid is one of them. This meta-analysis was to evaluate effects of opioids pretreatment for preventing etomidate-induced myoclonus. We searched the PubMed, EMBASE, and the Cochrane Library databases and published studies in English updated to September 2015. Randomized controlled trials of opioids versus placebo/control in patients were included. We evaluated the prophylactic effect of opioids on etomidate-induced myoclonus. All statistical analysis was performed using RevMan 5.2 software. Nine randomized controlled trials involving 604 participants were included. The results indicated that compared with placebo/control, opioids allow more patients to experience no myoclonic movements after etomidate injection [risk ratio (RR) 2.76, 95% confidence interval (CI) 1.75-4.37, P < 0.0001]. The numbers of patients with mild myoclonus [(RR) 0.53, 95% (CI) 0.36-0.78, P = 0.001], moderate myoclonus [(RR) 0.36, 95% (CI) 0.23-0.55, P < 0.00001], and severe myoclonus [(RR) 0.20, 95% (CI) 0.08-0.52, P = 0.0009] after etomidate injection were significantly decreased with the pretreatment of opioids. This meta-analysis suggests that pretreatment with opioids before injecting etomidate was effective for preventing etomidate-induced myoclonus and can reduce the intensity of myoclonus without any adverse effects.

[Clinical and laboratory characteristics of juvenile myelomonocytic leukemia].

OBJECTIVE: To study the clinical and laboratory characteristics of juvenile myelomonocytic leukemia (JMML). METHODS: The clinical characteristics and laboratory results were retrospectively analyzed in 10 children with newly diagnosed JMML. They were compared with those of 28 children with myelodysplastic syndrome (MDS) and 44 children with chronic myeloid leukemia (CML). RESULTS: Compared with the children with CML or MDS, the children with JMML had significantly higher rates of skin rashes, ecchymosis, and lymphadenectasis, a significantly lower serum cholinesterase (ChE) level, and a significantly higher fetal hemoglobin level (P<0.05). The white blood cell count of children with JMML was significantly higher than that of children with MDS, but significantly lower than that of children with CML (P<0.05). In addition, the myeloid/erythroid ratio and rate of dyshaematopoiesis were significantly lower in children with JMML than those in children with CML or MDS. The children with JMML had a significantly higher expression of mature monocyte marker CD14 than those with CML or MDS (P<0.05). The levels of myeloid markers CD33, CD11b, CD13, and CD15 in children with JMML were significantly higher than those in children with MDS, but significantly lower than those in children with CML (P<0.05). The levels of CD2 and CD7 in children with JMML were higher than those in children with CML, but lower than those in children with MDS (P<0.05). CONCLUSIONS: Skin rashes, ecchymosis, lymphadenectasis, and ChE reduction are more common in children with JMML than in those with CML or MDS, while dyshaematopoiesis is less common. In addition, CD14 level increases significantly in children with JMML.

Aloe-emodin (AE) nanoparticles suppresses proliferation and induces apoptosis in human lung squamous carcinoma via ROS generation in vitro and in vivo.

Human lung squamous cell carcinoma is a deadly cancer for which present therapeutic strategies are inadequate. And traditional chemotherapy results in severe systemic toxicity. Compounds from living organisms often exert a biological activity, triggering several targets, which may be useful for the improvement of novel pharmaceuticals. Aloe-emodin (AE), a well-known natural compound, is a primary component of anthraquinones in Aloe vera and exhibits anti-proliferative and apoptotic effects on various tumor cells. However, the translational and clinical use of AE has been limited owing to its rapid degradation and poor bioavailability. To improve its efficacy, a poly (lactic-co-glycolic acid) based AE nanoparticle formulation (NanoAE) was prepared. Our study indicated that compared to the free AE, nanoAE significantly suppressed cancer cell proliferation, induced cell cycle arrest and apoptosis, evidenced by high cleavage of Caspase-3, poly (ADP-ribose) polymerase (PARP), Caspase-8 and Caspase-9. NanoAE enhanced reactive oxygen species (ROS) production, along with Mitogen-activated protein kinases (MAPKs) activation and PI3K/AKT inactivation. Cell proliferation, apoptosis and MAPKs and PI3K/AKT were dependent on ROS production in nanoAE-treated groups. In vivo, nanoAE exhibited inhibitory effects on the tumor growth with little toxicity. Together, our results indicated that nanoAE might be an effective treatment for human lung squamous cell carcinoma.

New Mitogenomes of Two Chinese Stag Beetles (Coleoptera, Lucanidae) and Their Implications for Systematics.

Although conspicuous and well-studied, stag beetles have been slow to join the genomic era. In this study, mitochondrial genomes of two stag beetles, Sinodendron yunnanense and Prosopocoilus confucius, are sequenced for the first time. Both of their genomes consisted of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNAs (rRNAs), and a control region. The mitogenome of S. yunnanense was 16,921 bp in length, and P. confucius was 16,951 bp. The location of the gene trnL(UUR), between the A + T-rich and control region in S. yunnanense, is the first observed in Lucanidae. In P. confucius, an unexpected noncoding region of 580 bp was discovered. Maximum likelihood and Bayesian inference on the 13 mitochondrial PCGs were used to infer the phylogenetic relationships among 12 representative stag beetles and three scarab beetles. The topology of the two phylogenetic trees was almost identical: S. yunnanense was recovered as the most basal Lucanid, and the genus Prosopocoilus was polyphyletic due to P. gracilis being recovered sister to the genera Dorcus and Hemisodorcus. The phylogenetic results, genetic distances and mitogenomic characteristics call into question the cohesion of the genus Prosopocoilus. The genetic resources and findings herein attempts to redress understudied systematics and mitogenomics of the stag beetles.

[Interaction between gomizine D and α-glucosidase].

This paper describes a study exploring the interaction between gomizine D and α-glucosidase. The inhibitory activity of α-glucosidase by gomizine D was determined using PNPG as substrates Gomizine D gave the IC50 value of 0.59 mmol•L⁻¹, which was higher than that of acarbose (1.95 mmol•L⁻¹). Gomizine D was a reversible and non-competitiveα-glucosidase inhibitor with an inhibition constant Ki=4.026 g•L⁻¹. The binding mode between gomizine D and α-glucosidase was analyzed by AutoDock Vina molecular docking software. The lowest energy of Gomizine D binding to α-glucosidase was -7.7 kcal•mol⁻¹, which was lower than that of acarbose (-6.6 kcal•mol⁻¹). After binding with gomizine D, UV spectroscopy analysis displayed that the microenvironment of aromatic residue in the secondary structure of α-glucosidase was changed, and the polarity of protein was reduced.

Comparative proteome analysis of abdominal adipose tissues between fat and lean broilers.

BACKGROUND: The molecular mechanism underlying broiler fat deposition is still poorly understood. METHOD: Currently, we used two-dimensional gel electrophoresis (2DE) to identify differentially expressed proteins in abdominal adipose tissues of birds at 4 week of age derived from Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF). RESULTS: Thirteen differentially expressed protein spots were screened out and identified by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The protein spots were matched to thirteen proteins by searching against the NCBInr database. These identified proteins were apolipoprotein A-I (Apo A-I), cytokeratin otokeratin, ATP synthase subunit alpha, peptidyl-prolyl cis-trans isomerase FKBP4 (PPIase FKBP4), aspartate aminotransferase, carbonic anhydrase II (CA-II), prostaglandin-H2 D-isomerase precursor, fibrinogen alpha chain, lamin-A (LMNA), superoxide dismutase [Mn] (MnSOD), heat shock protein beta-1 (HSPß1) and two predicted proteins. These differentially expressed proteins are involved mainly in lipid metabolism, amino acid metabolism, signal transduction, energy conversion, antioxidant, and cytoskeleton. Differential expression of Apo A-I, PPIase FKBP4, and cytokeratin otokeratin proteins were further confirmed by Western blot analysis. Quantitative real-time RT-PCR analyses showed that, of these 13 differentially expressed proteins, only PPIase FKBP4 and cytokeratin otokeratin were differentially expressed at mRNA level between the two lines. CONCLUSIONS: Our results have provided further information for understanding the basic genetics control of growth and development of broiler adipose tissue.

Identification of Suitable Candidate Reference Genes for Gene Expression Analysis by RT-qPCR in Peripheral Blood Mononuclear Cells of CHB Patients.

BACKGROUND: Quantitative polymerase chain reaction (qPCR) analysis is a precise and effective method for the study of mRNA expression throughout the field of peripheral blood mononuclear cell (PBMC) research. However, the use of suitable reference genes for data normalization is critical to obtain meaningful and reproducible results. The present study aimed to identify the greatest reference genes for further research in PBMC of Chronic Hepatitis B (CHB) patients. METHODS: We assessed the expression stability of four commonly used reference genes (beta actin, beta-tubulin, 18S rRNA, GAPDH) in PBMC of CHB patients. Then we employed geNorm, BestKeeper, and Normfinder to evaluate the expression stability of these reference genes. RESULTS: All four genes displayed no significant differences between patient and control groups except beta actin and thus beta actin should not be used as a normalizing gene in a discussed experimental setup. GAPDH and beta-tubulin composed the best pair of reference genes for normalization purposes in future studies of gene expression in PBMC of CHB patients according to three algorithms. CONCLUSIONS: GAPDH and beta-tubulin were the best combination of two reference genes in this study for RT-qPCR analysis.