Search

Background. Systemic lupus erythematosus (SLE) is an autoimmune disease with strong heterogeneity, leading to variable clinical symptoms, which makes diagnosis and activity evaluation difficult. Methods. The original dataset of GSE88884 was analyzed to screen differentially expressed genes (DEGs) of SLE and the correlation between DEGs and clinical parameters (SLEDAI, anti-dsDNA, C3, and C4). The result was validated by microarray GSE121239 and SLE patients with RT-qPCR. Next, receiver operator characteristic (ROC) analysis, correlation analysis, and ordinal logistic regression were applied, respectively, to evaluate the capability of diagnosis and prediction of the candidate biomarker. Subsequently, the biological functions of the candidate biomarker were investigated through KEGG and GO enrichment, protein–protein interaction network, and the correlation matrix. Results. A total of 283 DEGs were screened, and seven of them were overlapped with SLE-related genes. DDX60 was identified as the candidate biomarker. Analyses of GSE88884, GSE121239, and SLE patients with RT-qPCR indicated that DDX60 expression level is significantly higher in patients with high disease activity. ROC analysis and the area under the ROC curve (AUC = 0.8818) suggested that DDX60 has good diagnostic performance. DDX60 expression level was positively correlated with SLEDAI scores (r = 0.24). For every 1-unit increase in DDX60 expression value, the odds of a higher stage of activity of SLE disease are multiplied by 1.47. The function of DDX60 mainly focuses on IFN-I-induced antiviral activities, RIG-I signaling, and innate immune. Moreover, DDX60 plays a synergistic role with DDX58, IFIH1, OASL, IFIT1, and other related genes in the SLE pathogenesis. Conclusions. DDX60 is differently expressed in SLE, and it is significantly related to both serological indicators and the disease activity of SLE. We suggested that DDX60 might be a potential biomarker for SLE diagnosis and management. [ABSTRACT FROM AUTHOR]

Biologically active bacterial cellulose (BC) was efficiently synthesized in situ using wine pomace and its hydrolysate. The structural and biomechanical properties together with the biological functions of the BC were investigated. Functional BC from wine pomace and its enzymatic hydrolysate were of high purity and had higher crystallinity indexes (90.61% and 89.88%, respectively) than that from HS medium (82.26%). FTIR results proved the in-situ bindings of polyphenols to the functionalized BC. Compared to BC from HS medium, wine pomace-based BC had more densely packed ultrafine fibrils, higher diameter range distributions of fiber ribbon, but lower thermal decomposition temperatures, as revealed by the SEM micrographs and DSC data. Meanwhile, wine pomace-based BC exhibited higher loads in tensile strength and higher hardness (4.95 ± 0.31 N and 5.13 ± 0.63 N, respectively) than BC in HS medium (3.43 ± 0.14 N). Furthermore, BC synthesized from wine pomace hydrolysate exhibited a slower release rate of phenolic compounds, and possessed more antioxidant activities and better bacteriostatic effects than BC from wine pomace. These results demonstrate that BC synthesized in situ from wine pomace (especially from enzymatic hydrolysate) is a promising biomolecule with a potential application in wound dressing, tissue engineering, and other biomedical fields. [Display omitted] • Bacterial cellulose was synthesized in-situ using wine pomace. • The phenolics bind to the bacterial cellulose from wine pomace in-situ. • The cellulose from wine pomace hydrolysate had slower phenolic release rate. • The cellulose has excellent antibacterial and antioxidant properties. [ABSTRACT FROM AUTHOR]

A cellulose-producing bacterium Komagataeibacter rhaeticus K15 was isolated from kombucha tea, and its metabolic pathways and cellulose synthesis operon were analyzed by genome sequencing. Different from the reported K. rhaeticus , the K15 produced little gluconic acid (2.26 g/L) when glucose was the sole carbon source and has the capacity for high cellulose production (4.76 g/L) with other carbon sources. Furthermore, six nitrogen-fixing genes were found to be responsible for the survival of K15 on a nitrogen-free medium. Based on its fermentation characteristics, K15 was cultured in a kitchen waste medium as a strategy for green and sustainable bacterial cellulose production. The SEM, XRD, and FTIR results indicated that synthesized cellulose has a mean diameter of 40–50 nm nanofiber, good crystallinity, and the same chemical structure. The K15 strain provides a highly viable alternative strategy to reduce the costs of bacterial cellulose production using agro-industrial residues as nutrient sources. [Display omitted] • Strain K15 produces little gluconic acid when glucose as the sole carbon source. • Metabolic pathways and cellulose synthesis operon of K15 are analyzed. • Six nitrogen fixing genes support the survival of K15 on nitrogen-free medium. • K15 utilizing kitchen waste is a novel strategy for enhancing cellulose production. [ABSTRACT FROM AUTHOR]

Background: Toxocara canis, the most prevalent helminth in dogs and other canines, is one of the socioeconomically important zoonotic parasites, particularly affecting pediatric and adolescent populations in impoverished communities. However, limited information is available regarding the proteomes of female and male adult T. canis. To address this knowledge gap, we performed a comprehensive proteomic analysis to identify the proteins with differential abundance (PDAs) and gender-specifically expressed proteins between the two sexes adult T. canis. Methods: The comparative proteomic analysis was carried out by the Orbitrap mass spectrometry (MS) with asymmetric track lossless (Astral) analyzer. The difference analysis was conducted using t-test and the proteins verification was achieved through parallel reaction monitoring (PRM). The potential biological functions of identified adult T. canis proteins and PDAs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The domain, transcription factor and subcellular localization of the identified proteins and PDAs were analyzed by InterPro, AnimalTFDB 4.0 and Cell-mPLOC 2.0 databases, respectively. Results: A total of 8565 somatic proteins of adult T. canis were identified. Compared to male adult, 682 up-regulated PDAs and 844 down-regulated PDAs were identified in female adult with P-values < 0.05 and |log2FC| > 1, including 139 proteins exclusively expressed in female and 272 proteins exclusively expressed in male. The GO annotation analysis using all PDAs revealed that the main biological processes, cellular components and molecular functions corresponded to aminoglycan metabolic process, extracellular region and protein tyrosine phosphatase activity, respectively. The KEGG analysis using all PDAs showed that the pathways were mainly associated with adipocytokine signaling pathway, proximal tubule bicarbonate reclamation and PPAR signaling pathway. Conclusions: This study reveals the differential protein expression between female and male adult T. canis, providing valuable resource for developing the novel intervention strategies against T. canis infection in humans and animals, especially from the perspective of sexual development and reproduction. [ABSTRACT FROM AUTHOR]

This paper presents an experimental study on the effects of the Reynolds number (Resj = 300, 600, and 900) and porosity (ϕ = 20%–85%) on synthetic jet vortex rings impinging onto a porous wall. Laser-induced fluorescence and particle image velocimetry are used to acquire flow information qualitatively and quantitatively. When Resj is low (Resj = 300), ϕ plays a key role in determining the formation of transmitted vortex rings downstream. For the first time, a row of individual small-scale vortex rings that form at the lowest porosity (ϕ = 20%) have been observed in the synthetic jet/porous wall interaction. As Resj increases to 900, the triggered Kelvin–Helmholtz instability promotes the vorticity cancellation at a low porosity (ϕ = 30%), and thus contributes to the formation of a transmitted vortex ring. It is concluded that the vorticity cancellation is the dominant factor affecting the generation of a transmitted vortex ring. Time-averaged characteristics indicate that for a low Resj, the incoherence of the vortex ring is mainly due to the viscous effects. However, for a high Resj, it is the transition that leads to a significant enhancement in the turbulent kinetic energy. Measurements of flow macroscopic parameters show that the loss of the momentum flux exhibits a linear relationship with ϕ for all Resj, while the loss of the kinetic energy transport is nonlinearly dependent on ϕ. Incorporating ϕ, this study presents a more comprehensive similarity parameter, ϕln(Resj2 d h * 3 ), to characterize the synthetic jet/porous wall interaction. [ABSTRACT FROM AUTHOR]

Hong Kong has launched reforms to advocate child-centred pedagogies in kindergartens since 2000. This study examined the actual pedagogical interactions in eight kindergarten classrooms via videotaped observations. The teachers were surveyed before the observation and interviewed after receiving the observational report. Evidence revealed that the Hong Kong teachers used various scaffolding strategies to maintain a reciprocal interaction, and teacher-directed instruction dominated the pedagogical interactions. Most teachers had a positive attitude towards teacher–child interactions, yet traditional beliefs persisted. Teachers' pedagogical interactions were associated with their age, years of teaching experience and educational level, but not with the age group they taught. [ABSTRACT FROM AUTHOR]

Background: In predicting the risk for posthepatectomy complications, hepatectomy is traditionally classified into minor or major resection based on the number of resected segments. Recently, a new hepatectomy complexity classification was proposed. This study aimed to compare the value of the traditional and that of the new classification in perioperative outcomes prediction.Methods: Demographics, perioperative laboratory tests, intraoperative and postoperative outcomes, and follow-up data of patients with hepatocellular carcinoma who underwent liver resection were retrospectively analyzed.Results: A total of 302 patients were included in our study. Multivariable analysis of intraoperative variables showed that the complexity classification could independently predict the occurrence of blood loss > 800 mL, operation time > 4 h, intraoperative transfusion, and the use of Pringle's maneuver (all p < 0.05). For postoperative outcomes, the high-complexity group was independently associated with severe complications, and hepatic-related complications (all p < 0.05); the traditional classification was independently associated only with posthepatectomy liver failure (PHLF) (p = 0.004).Conclusions: Complexity classification could be used to assess the difficulty of surgery and was independently associated with postoperative complications. The traditional classification did not reflect operation complexity and was associated only with PHLF. [ABSTRACT FROM AUTHOR]

Time-resolved particle image velocimetry was applied to investigate turbulent vortex rings generated by a synthetic jet impacting porous walls. By varying the nondimensional diameter of the hole ( d h * = 0.067–0.20), we chose four porous walls with a constant porosity (ϕ = 75%) to examine the effect of their geometry on this vortex rings/porous wall interaction. In upstream flow, the strength of the wall shear layer induced by the vortex rings decreased as d h * increased, and so did the radial spreading of the primary vortex ring. In downstream flow, with an increase in d h * , the coherence of the transmitted vortex rings gradually weakened owing to insufficient vorticity cancellation and enhanced Kelvin-Helmholtz (K–H) instability. For d h * = 0.20 (the largest hole diameter), the transmitted vortex rings downstream were the most disrupted and lost coherence quickly to survive the shortest axial distance. The results of velocity triple decomposition show that in the case of the impact of a turbulent synthetic jet on a porous wall, the wall can effectively reduce the ratio of fluctuation energy to total flow kinetic energy. Because of the low contribution of fluctuation energy to the total kinetic energy, the porous wall with the largest hole ( d h * = 0.20) exhibited the best quality of the downstream flow field. Therefore, for flow control, we propose using a porous wall with a hole of a large diameter to effectively disrupt vortical structures and achieve a better quality of flow under the given conditions. [ABSTRACT FROM AUTHOR]

• Reynolds number (Re sj) effect on vortex rings/porous wall interaction is investigated. • Both the flow evolutions and time-mean flow characteristics are influenced by Re sj. • Synthetic jet vortex rings at a high Re sj are easier to pass through a porous wall. • Formation of K-H vortices accelerates incoherence of the vortex ring at a high Re sj. The interaction of synthetic jet vortex rings with a porous wall was investigated using laser-induced fluorescence (LIF) and particle image velocimetry (PIV) techniques. The synthetic jet Reynolds number (Re sj) varied from 309 to 1238, where the vortex rings underwent transition from laminar to turbulent flow. For the lowest Reynolds number (Re sj = 309), the flow is almost laminar; the primary vortex ring (VR1) induces and pairs with a well coherent secondary vortex ring (VR2) in the upstream side of the porous wall, leading to a conventional "rebound" and "reversal" in VR1's trajectory. As Re sj increases, the induced VR2 becomes weaker and loses coherence quickly after rolling up; even at Re sj = 1238, VR2 becomes indistinguishable. During the vortex ring interacting with the porous wall, some fluid penetrates through the wall to form a transmitted vortex ring (VRT) in the downstream region. The circulation of VRT increases with the growth of Re sj. In particular, for a higher Re sj , the synthetic jet tends to pass through a porous wall more easily with less losses in both vortex ring circulation and jet momentum. Velocity triple decomposition shows that VRT for all tested cases has lost coherence completely before it moves out of the field of view. Moreover, for Re sj = 309, the incoherence of VRT is caused by the vorticity diffusion and viscous dissipation since both the upstream and downstream flow are almost laminar. But for the high Re sj (619, 928 and 1238), VRT lost coherence is mainly due to the transition, which results in a relatively large ratio of the fluctuation kinetic energy (FKE) to the total flow kinetic energy (KE). In particular, for Re sj = 928 and 1238, it is observed that some small-scale Kelvin-Helmholtz vortices are formed in the trailing jet, and entrained into the primary vortex core, which accelerates the loss of coherence for the primary vortex ring. This observation can explain why the vortex ring at high Reynolds number is less coherent. [ABSTRACT FROM AUTHOR]

• Parent's epistemological beliefs about the nature of mathematics were not related to how often children engaged with numeracy activities at home. • Parents' dynamic belief about the nature of mathematics were positively related to their use of indirect teaching strategies. • Frequency of home numeracy activities and parents' use of indirect teaching strategies were linked with children's numeracy abilities through numeracy interest. • This study demonstrated the importance of helping parents to appreciate the dynamic nature of mathematics, and of coaching parents how to guide children's numeracy learning. Many existing home numeracy models focus only on the roles of home activities in children's numeracy abilities. Parents' beliefs, teaching strategies, and children's numeracy interest are seldom considered. As such, this study investigated the relations between parents' epistemological beliefs about mathematics, how often children engaged with numeracy activities at home, parents' use of indirect teaching strategies, children's early interest and ability in numeracy. Three hundred twenty-seven Hong Kong kindergarteners and their parents participated in the study. After controlling for the children's gender, age, non-verbal intelligence and language abilities, results showed that parents' dynamic beliefs about the nature of mathematics were associated with their use of indirect teaching strategies. The frequency of home numeracy activities and parents' use of indirect teaching strategies were linked with children's numeracy abilities through numeracy interest. Our findings demonstrate the importance of helping parents to appreciate the dynamic nature of mathematics, and of coaching parents how to guide children's numeracy learning. [ABSTRACT FROM AUTHOR]

Silent information regulator factor 2-related enzyme 1 (Sirt1) is involved in the regulation of cell senescence, gene transcription, energy balance and oxidative stress. However, the effect of Sirt1 on atrial natriuretic factor (ANF) secretion, especially under hypoxic conditions is unclear. The present study aimed to investigate the effect of Sirt1, regulated by NADPH oxidase 4 (NOX4), on ANF secretion in isolated beating rat atria during hypoxia. ANF secretion was analyzed using radioimmunoassays and protein expression levels were determined by western blotting and immunofluorescence staining. Intra-atrial pressure was recorded using a physiograph. Hypoxia significantly upregulated Sirt1 and nuclear factor erythroid-2-related factor 2 (Nrf2) protein expression levels, together with significantly increased ANF secretion. Hypoxia-induced protein expression of Sirt1 was significantly blocked by a NOX4 inhibitor, GLX351322, and Nrf2 protein expression levels were significantly abolished using the Sirt1 inhibitor, EX527. Hypoxia also significantly elevated the protein expression levels of phosphorylated-Akt and sequestosome 1 and significantly downregulated Kelch-like ECH-associated protein 1 protein expression levels. These effects were significantly blocked by EX527, preventing hypoxia-induced Nrf2 expression. An Nrf2 inhibitor, ML385, significantly abolished the hypoxia-induced upregulation of activating transcription factor (ATF)3, ATF4, T cell factor (TCF)3 and TCF4/lymphoid enhancer factor 1 (LEF1) protein expression levels, and significantly attenuated hypoxia-induced ANF secretion. These results indicated that Sirt1 and Nrf2, regulated by NOX4, can potentially stimulate TCF3 and TCF4/LEF1 signaling via ATF3 and ATF4 activation, thereby potentially participating in the regulation of ANF secretion in beating rat atria during hypoxia. In conclusion, intervening with the Sirt1/Nrf2/ATF signaling pathway may be an effective strategy for resisting oxidative stress damage in the heart during hypoxia. [ABSTRACT FROM AUTHOR]

The work in this paper is based on the optimization software, using the exactly optimization technique. The hypersonic aerodynamic performance is calculated by numerically solving the Euler equations and the maximum surface heat flux is calculated by solving the Fay-Riddell equation. To test our method, the CTV is optimized. The Spaceship reentry capsule has been optimized as a particular instance. This research work can be as the groundwork for the reentry capsule optimization. [ABSTRACT FROM AUTHOR]

Chylothorax is a rare complication of neck dissection. We report three cases of chylothorax after neck dissections for thyroid carcinoma and attribute this relatively high incidence to the assumption that most patients are asymptomatic. Thus, conventional chest X-ray or ultrasonography in the early postoperative period may be warranted to exclude asymptomatic chylothorax, especially if the thoracic duct is injured and ligated during the operation. We suggest that for chylothorax induced by ligation of the thoracic duct, which may be transient and resolve quickly, short-term thoracic drainage is enough. [ABSTRACT FROM AUTHOR]

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT). [Display omitted] [ABSTRACT FROM AUTHOR]

Hydrogen donors were employed to replace pure hydrogen as a hydrogen source for in-situ gas phase HDO due to their low storage and transportation cost. A series of catalysts have been prepared by modifying the zeolite HZSM-5 with polymetallic and multi-carriers. Gas-phase hydrodeoxygenation (HDO) of guaiacol was conducted under a pressure 2 MPa and a temperature at 350 °C. The effect of polymetallic and multi-carrier modification on HDO activity was investigated. The physicochemical properties of catalysts were characterized by BET, XRD, SEM, H 2 -TPR, XPS and NH 3 -TPD. The characterization results showed that when La was loaded, the catalyst Ni/HZSM-5&La obtained a stronger medium-strong acidity. The electronic transfer of the elemental nickel was promoted. After HDO, the catalyst Ni/HZSM-5&La exhibited the highest HDO rate and BTX selectivity, reaching 97.79% and 34.25%, respectively. The real bio-oil HDO under a hydrogen donor were also analyzed. The results showed the content of the hydrocarbon compound were over 95%. The reaction mechanism was discussed through the distribution of liquid product species. Direct demethoxylation pathway (DMO) and methylation pathway (ME) were considered as the main pathways. Synopsis: A series of molecular sieve supported catalysts with different modification methods were prepared and the effect on the HDO of guaiacol was investigated under the action of hydrogen donor. Image 1 • Introduction of isopropanol as hydrogen donor in HDO of guaiacol in gaseous phase. • Catalyst Ni/HZSM-5&La demonstrates outstanding BTX and hydrocarbon selectivity. • The mechanism of HDO of guaiacol under hydrogen donor conditions was studied. • The content of hydrocarbon was over 95% after gas phase HDO of bio-oils. [ABSTRACT FROM AUTHOR]

Background and Purpose: Indoleamine 2,3-dioxygenase 1 (IDO1) is emerging as an important new therapeutic target for treatment of malignant tumours characterized by dysregulated tryptophan metabolism. However, the antitumour efficacy of existing small-molecule inhibitors of IDO1 is still unsatisfactory and the underlying mechanism remains largely undefined. Hence, we discovered a novel potent small-molecule inhibitor of IDO1, LW106, and studied its antitumour effects and the underlying mechanisms in two tumour models.Experimental Approach: C57BL6 mice, athymic nude mice or Ido1-/- mice were inoculated with IDO1-expressing and -nonexpressing tumour cells and treated with vehicle, epacadostat or increasing doses of LW106. Xenografted tumours, plasma, spleens and other vital organs were harvested and subjected to kynurenine/tryptophan measurement and flow cytometric, histological and immunohistochemical analyses.Key Results: LW106 dose-dependently inhibited the outgrowth of xenografted tumours that were inoculated in C57BL6 mice but not nude mice or Ido1-/- mice, showing a stronger antitumour efficacy than epacadostat, an existing IDO1 inhibitor. LW106 substantially elevated intratumoural infiltration of proliferative Teff cells, while reducing recruitment of proliferative Treg cells and non-haematopoietic stromal cells such as endothelial cells and cancer-associated fibroblasts. LW106 treatment resulted in a reduced subpopulation of cancer stem cells (CSCs) in xenografted tumours in which fewer proliferative/invasive tumour cells and more apoptotic tumour cells were observed.Conclusions and Implications: LW106 inhibits tumour outgrowth by limiting stroma-immune crosstalk and CSC enrichment in the tumour micro-environment. LW106 has potential as a immunotherapeutic agent for use in combination with immune checkpoint inhibitors and (or) chemotherapeutic drugs for cancer treatment. [ABSTRACT FROM AUTHOR]

The antioxidant efficacy of protein hydrolysates prepared from large yellow croaker (Pseudosciaena crocea) by enzymatic hydrolysis using neutral protease was evaluated in D-galactose-induced aging mice. Animals were divided into normal and model control groups, and low-, middle-, and high-dose groups (50, 100, and 300 mg/kg; LYCHs), as well as tocopherol (VE) and antagonistic (LYCHs + VE) groups. The study was carried out for 30 days. Administration of D-galactose induced oxidative damage with a significant rise (p< 0.01) in malondialdehyde and a reduction in several endogenous antioxidant enzymes and glutathione (GSH). Treatment with large yellow croaker protein hydrolysates stimulated an increase in superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities, increased levels of reduced glutathione, and decreased malondialdehyde, compared with the model control group. Additionally, hepatocellular damage was evaluated by measuring aspartate aminotransferase and alanine aminotransferase levels. These results demonstrate the protective role of large yellow croaker protein hydrolysates in D-galactose-induced oxidative stress, as well as their potential as nutraceuticals or adjuvant agents for disease prevention. [ABSTRACT FROM PUBLISHER]

[Display omitted] • Low-dose telmisartan inhibited glioma proliferation and migration in co-cultures. • Astrocyte-derived IL-6 promoted glioma cell proliferation and migration. • Telmisartan inhibits IL-6/STAT3 pathway between astrocyte and glioma. • Telmisartan exerts the anti-tumor effects via PPARγ activation. Telmisartan, an angiotensin II type 1 receptor (AT1R) blocker, exhibits broad anti-tumor activity. However, in vitro, anti-proliferative effects are shown at doses far beyond the therapeutic plasma concentration. Considering the role of tumor microenvironment in glioma progression, glioma-astrocyte co-cultures were employed to test the anti-tumor potential of low-dose telmisartan. When a high dose was required for a direct anti-proliferative effect on glioma cell lines, a low dose significantly inhibited glioma cell proliferation and migration in the co-culture system. Under co-culture conditions, upregulated IL-6 expression in astrocytes played a critical role in glioma progression. Silencing IL-6 in astrocytes or IL-6R in glioma cells reduced proliferation and migration. Telmisartan (5 μM) inhibited astrocytic IL-6 expression, and its anti-tumor effects were reversed by silencing IL-6 or IL-6R and inhibiting signal transducer and activator of transcription 3 (STAT3) activity in glioma cells. Moreover, the telmisartan-driven IL-6 downregulation was not imitated by losartan, an AT1R blocker with little capacity of peroxisome proliferator-activated receptor-gamma (PPARγ) activation, but was eliminated by a PPARγ antagonist, indicating that the anti-glioma effects of telmisartan rely on its PPARγ agonistic activity rather than AT1R blockade. This study highlights the importance of astrocytic IL-6-mediated paracrine signaling in glioma growth and the potential of telmisartan as an adjuvant therapy for patients with glioma, especially those with hypertension. [ABSTRACT FROM AUTHOR]

Background Conflicting results about the prognostic value of surgical margin status in patients with intrahepatic cholangiocarcinoma (ICC) have been reported. We aimed to assess the association between surgical margin status and prognosis in ICC through a meta-analysis. Materials and methods We conducted a literature search of the articles evaluating the prognostic value of surgical margin status in patients with ICC. The pooled estimation of the hazard ratio (HR) with the 95% confidence interval (CI) was performed to determine the influence of surgical margin status on the survival outcome. Results A total of 21 studies involving 3201 patients were finally included into the meta-analysis. The percentage of patients with positive surgical margin ranged from 7.2% to 75.9% in the enrolled studies. The pooled estimates showed that patients with positive surgical margin had inferior overall survival (HR: 1.864; 95% CI: 1.542–2.252; P < 0.001) and progression-free survival (HR: 2.033; 95% CI: 1.030–4.011; P = 0.041) than patients with negative ones. The subgroup analyses and sensitivity analyses were consistent with the overall results. Conclusions Patients with negative surgical margin had significantly favorable overall survival and progression-free survival after surgical resection for ICC. The notion of achieving the R0 resection should be emphasized. [ABSTRACT FROM AUTHOR]

The mammalian cardiac myocytes not only synthesize and secrete atrial natriuretic peptide (ANP), but also express cholecystokinin (CCK) and its receptors (CCK 1 R and CCK 2 R). However, atrial CCK expression patterns and its effects on ANP secretion during hypoxia are unclear. Therefore, this study is aimed to investigate the effect of hypoxia on the expression levels of CCK and its receptors, as well as the underlying mechanisms involved in regulating hypoxia-induced ANP secretion in isolated beating atria. The results of this study showed that acute hypoxia significantly upregulated expression of CCK and CCK 1 R as well as CCK 2 R through activation of hypoxia-inducible factor 1α–apelin signaling. Endogenous CCK induced by hypoxia markedly upregulated the expression of silent information regulator factor 2-related enzyme 1 (Sirt1) and its downstream nuclear factor erythroid‑2‑related factor 2 (Nrf2) via the activation of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), leading to increase of activating T cell factor (TCF) 3 and TCF4/ lymphoid enhancer factor (LEF) 1, ultimately promoting hypoxia-induced ANP secretion. In addition, siRNA-mediated knockdown of LEF1 dramatically attenuated hypoxia-induced increase of ANP expression in HL-1 atrial myocytes. These results indicated endogenous CCK induced by hypoxia promoted hypoxia-induced ANP secretion by activation of NOX4–Sirt1–TCF3/4–LEF1 signaling pathway. • HIF-1α-apelin enhanced the expression of endogenous CCK and its receptors, increasing ANP secretion under hypoxic conditions. • NOX4-Sirt1 controlled by CCK regulated ANP secretion under hypoxic conditions. • TCF/LEF regulated by Nrf2 was associated with hypoxia-induced ANP secretion. • The correlation of CCK regulating ANP under hypoxic conditions can be delineated as follows: CCK NOX4 Sirt1 Nrf2 TCF3/4/LEF1. [ABSTRACT FROM AUTHOR]

A simple and efficient method was developed for the synthesis of 4-quinolone-3-carboxylic esters and 4-quinolone-3-carbonitriles under microwave (MW) activation using anilines and acrylates as materials. All reactions demonstrated the benefits of microwave reactions: convenient operation, short reaction time, and good yields. [ABSTRACT FROM AUTHOR]

A facile and efficient synthetic method of esters from their corresponding carboxylic acids and amino acids is described. The esterification reaction of carboxylic acids and amino acids could be greatly accelerated under microwave irradiation because the reactions described in this article took place in only 5 min with almost quantitative yields, and distinct acidity of catalytic acids was well tolerated. Unlike the racemation problem in microwave-assisted N-acylation reactions, the esters of chiral amino acids could be achieved with retention of configuration under this condition. [ABSTRACT FROM AUTHOR]

Abstract: Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 8 inhibited both enzymes with the IC50 values of 34.8nM and 26.7μM. Several compounds also showed moderate anti-proliferation at 10μM against colon and liver cancer cell lines. [Copyright &y& Elsevier]

Abstract: Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heteroarylamino-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, prepared, and evaluated for blocking multiple signaling pathways in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds could inhibit both enzymes, and several of them showed potent inhibition activity against different cancer cell lines. The best compound 20 (CPU-Y020) showed the IC50 values of 6.58 and 7.61μM toward colon cancer HT-29 and liver cancer HepG2 cell lines. [Copyright &y& Elsevier]

Background: Percutaneous radiofrequency ablation (RFA) is used as a first‐line treatment for colorectal liver metastases that recur after first liver resection in our institution. We aim to evaluate its therapeutic efficacy compared to repeated surgical resection. Methods: A retrospective review was performed in 104 patients treated with curative intent for resectable recurrent colorectal liver metastases. Results: Sixty‐one patients underwent RFA and 43 patients underwent surgery. The overall recurrence rates were 82% in the RFA group and 65.1% in the resection group (P = 0.05). The local recurrence rate on a lesion‐basis was markedly higher after RFA than that after resection (16.7% versus 7.3%, P = 0.04). The difference remained significant in patients with a maximum lesion diameter >3 cm (24.5% versus 7.6%, P = 0.01). RFA treatment was independently associated with recurrence on multivariate analyses (P = 0.01). 69.7% of RFA patients and 42.6% of surgery patients with intrahepatic recurrence were amenable to repeated local treatment (P = 0.05), leading to the equivalent actuarial 3‐year progression free survival rates (RFA: 29.1% versus Resection: 33.1%, P = 0.48) and 5‐year overall survival rates in the two treatment groups (RFA: 33% versus Resection: 28.4%, P = 0.36). Conclusions: Surgery remains the treatment of choice for resectable recurrence. RFA may offer similar benefit in selected patients. [ABSTRACT FROM AUTHOR]

Background: The neutrophil to lymphocyte ratio (NLR) is a marker of inflammation and is associated with poor outcomes. We aimed to evaluate the role of the pretreatment NLR in predicting the outcomes after preoperative chemotherapy in patients with colorectal liver metastases (CRLM).Methods: A retrospective review was performed for 183 patients with CRLM. The NLR was measured before chemotherapy, and a receiver operating characteristic (ROC) curve was used to estimate the cutoff value. Logistic regressions were applied to analyze potential predictors of the pathological response. The Cox proportional hazard method was used to analyze survival.Results: The pre-chemotherapy NLR was 2.4 ± 1.1, whereas the post-chemotherapy NLR was 2.1 ± 1.6 (p < 0.001). The pretreatment NLR of 2.3 was a significant predictive marker for the pathological response. The pathological response rates were 67.1% in the patients with an NLR ≤ 2.3 and 48.1% in patients with an NLR > 2.3 (p = 0.01). Multivariate analysis revealed that the factors independently associated with pathological responses were a low pretreatment NLR (p = 0.043), radiological response to chemotherapy (p < 0.001), first-line chemotherapy (p = 0.001), and targeted therapy (p = 0.002). The median overall survival (OS) and recurrence-free survival (RFS) were worse in the increased NLR cohort than in the low NLR cohort (OS: 31.1 vs. 43.1 months, p = 0.012; RFS: 6.5 vs. 9.4 months, p = 0.06). According to multivariate analyses, a high pretreatment NLR was a significant predictor for both worse OS (HR = 2.43, 95%CI = 1.49-3.94, p < 0.001) and RFS (HR = 1.53, 95%CI = 1.08-2.18, p = 0.017).Conclusions: An increased pretreatment NLR was a significant predictor of a poor pathological response and worse prognosis after preoperative chemotherapy. The NLR is a simple biomarker for assessing chemotherapy efficacy. [ABSTRACT FROM AUTHOR]

Two new prenylflavonoids, morusalbols A and B (1and2), were isolated from the branches and leaves ofMorus alba, together with three known compounds, kuwanon C (3), morusin (4), morusinol (5). The structures of these two prenylflavonoids were elucidated by extensive analyzes of the spectroscopic data. [ABSTRACT FROM PUBLISHER]

Aim The prognostic value of the newly raised objective liver function assessment tool, the albumin-bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child-Pugh (C-P) score in predicting prognosis in this study. Methods The clinical data of 491 C-P class A patients who underwent liver resection as initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) were retrospectively analyzed. The prognostic performances of ALBI and C-P score in predicting the short- and long-term clinical outcomes were compared. Results The ALBI score gained a significantly larger area under the receiver operating characteristic curve for predicting the occurrence of severe postoperative complications than that of C-P score. With a median follow-up of 57 months, the 1-year, 3-year, and 5-year overall survival rates of the patients were 92.1%, 65.8%, and 45.2%, respectively. Tumor number, tumor size, and ALBI grade were proved to be the independent prognostic factors for overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI grade when it was compared to C-P score in terms of both the Akaike information criterion value and χ2 value of likelihood ratio test. Conclusions The ALBI grade, which was featured by simplicity and objectivity, gained a superior prognostic value than that of C-P grade in patients with hepatocellular carcinoma who underwent liver resection. Future well-designed studies with larger sample sizes are warranted. [ABSTRACT FROM AUTHOR]

Integrin αIIbβ3 plays a crucial role in the process of platelet aggregation. Three integrin αIIbβ3 antagonists (abciximab, eptifibatide, and tirofiban) have been approved by FDA for clinical use. Unfortunately, they all showed severe side effects such as thrombocytopenia and bleeding risk. Thus, researches on the development of more effective and safer antiplatelet agents are needed. In this manuscript we reported a novel naphthalenic derivative compound ND-1 with potent antithrombotic effect and lower bleeding risk. ND-1 inhibited ADP-, collagen-, thrombin-, and U46619-induced platelet aggregation with IC50 values of 1.29, 14.46, 12.84, and 40.24 μM, respectively. Mechanism studies indicated that ND-1 inhibited the binding of fibrinogen to integrin αIIbβ3 in a dose-dependent manner with an IC50 value of 3.12 μM. ND-1 inhibited P-selectin expression induced by ADP, collagen, thrombin, and U46619 on the surface of platelets. Additionally, this compound reduced platelets spreading to the immobilized fibrinogen. In vivo, ND-1 potently decreased thrombus formation in an arteriovenous shunt thrombosis model in rats and slightly prolonged bleeding time in a tail cutting model in mice. Taken together, our results reveal that ND-1 is a novel antagonist of αIIbβ3 with strong antithrombotic effect and lower bleeding risk. [ABSTRACT FROM AUTHOR]

XK469 is identified as a potent quinoxaline antineoplastic agent based on its significant clinical efficacy. It probably exerts its activity via DNA topoisomerase II (topo II) inhibition. To obtain more effective antineoplastic agents, a spectrum of peptidomimetic-type quinoxaline analogues of XK469 was herein designed, synthesized, and evaluated. Few compounds ( e.g . 13a and 13b ) exhibited obvious cytotoxicity indicated by in vitro anti-proliferative assay. SAR investigation revealed that introducing of hydrophobic tert -butylamine or dodecylamine moiety at the 3-position of quinoxaline core is favorable for achieving a better anti-proliferative potency, while peptidomimetic derivatives only yielded moderate cytotoxicity. Compounds with improved anti-proliferative activities also demonstrated decent anti-metastatic potencies comparable with that of doxorubicin (Doxo) based on in vivo mouse model study. The topo II-mediated kinetoplast DNA ( k DNA) decatenation assay as well as molecular docking studies implicated that these compounds tend to be potent topo II inhibitors. Overall, compounds 13a and 13b , 13b in particular, standed out from various assessments and might be promising candidates for further chemical optimization. [ABSTRACT FROM AUTHOR]

Objective: The definite prognostic role of p-STAT3 has not been well defined. We performed a meta-analysis evaluating the prognostic role of p-STAT3 expression in patients with digestive system cancers. Methods: We searched the available articles reporting the prognostic value of p-STAT3 in patients with cancers of the digestive system, mainly including colorectal cancer, gastric cancer, hepatocellular carcinoma, esophagus cancer and pancreatic cancer. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) of overall survival (OS) and disease-free survival (DFS) were used to assess the prognostic role of p-STAT3 expression level in cancer tissues. And the association between p-STAT3 expression and clinicopathological characteristics was evaluated. Results: A total of 22 studies with 3585 patients were finally enrolled in the meta-analysis. The results showed that elevated p-STAT3 expression level predicted inferior OS (HR=1.809, 95% CI: 1.442-2.270, P<0.001) and DFS (HR=1.481, 95% CI: 1.028-2.133, P= 0.035) in patients with malignant cancers of the digestive system. Increased expression of p-STAT3 is significantly related with tumor cell differentiation (Odds ratio (OR) =1.895, 95% CI: 1.364-2.632, P<0.001) and lymph node metastases (OR=2.108, 95% CI: 1.104-4.024, P=0.024). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Funnel plots and Egger’s tests revealed there was no significant publication bias in the meta-analysis. Conclusion: Phospho-STAT3 might be a prognostic factor of patients with digestive system cancers. More well designed studies with adequate follow-up are needed to gain a thorough understanding of the prognostic role of p-STAT3. [ABSTRACT FROM AUTHOR]

Highlights: [•] A novel peptide with the sequence of Asp-Pro-Asp-Ala-Asp-IIe-Leu-Gln was isolated from stiff silkworm. [•] This peptide shows the strong potency in reducing platelet aggregation. [•] This peptide shows low cytotoxicity to venous endothelial cell. [Copyright &y& Elsevier]

Centipedes have been used as traditional medicine for thousands of years in China. Centipede venoms consist of many biochemical peptides and proteins. Factor Xa (FXa) is a serine endopeptidase that plays the key role in blood coagulation, and has been used as a new target for anti-thrombotic drug development. A novel FXa inhibitor, a natural peptide with the sequence of Thr-Asn-Gly-Tyr-Thr (TNGYT), was isolated from the venom of Scolopendra subspinipes mutilans using a combination of size-exclusion and reverse-phase chromatography. The molecular weight of the TNGYT peptide was 554.3 Da measured by electrospray ionization mass spectrometry. The amino acid sequence of TNGYT was determined by Edman degradation. TNGYT inhibited the activity of FXa in a dose-dependent manner with an IC value of 41.14 mg/ml. It prolonged the partial thromboplastin time and prothrombin time in both in vitro and ex vivo assays. It also significantly prolonged whole blood clotting time and bleeding time in mice. This is the first report that an FXa inhibiting peptide was isolated from centipedes venom. [ABSTRACT FROM AUTHOR]

In this study, we examined anti-fungal and anti-inflammatory effects of the synthetic melanocortin peptide (Ac-Cys-Lys-Pro-Val-NH2)2 or (CKPV)2 against Candida albicans vaginitis. Our in vitro results showed that (CKPV)2 dose-dependently inhibited Candida albicans colonies formation. In a rat Candida albicans vaginitis model, (CKPV)2 significantly inhibited vaginal Candida albicans survival and macrophages sub-epithelial mucosa infiltration. For mechanisms study, we observed that (CKPV)2 inhibited macrophages phagocytosis of Candida albicans. Meanwhile, (CKPV)2 administration inhibited macrophage pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) release, while increasing the arginase activity and anti-inflammatory cytokine IL-10 production, suggesting macrophages M1 to M2 polarization. Cyclic AMP (cAMP) production was also induced by (CKPV)2 administration in macrophages. These above effects on macrophages by (CKPV)2 were almost reversed by melanocortin receptor-1(MC1R) siRNA knockdown, indicating the requirement of MC1R in the process. Altogether, our results suggest that (CKPV)2 exerted anti-fungal and anti-inflammatory activities against Candida albicans vaginitis probably through inducing macrophages M1 to M2 polarization and MC1R activation. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective case series. Objective: To evaluate the accuracy of screw fixation using intraoperative three-dimensional fluoroscopy-based navigation (ITFN) and to assess the clinical outcomes of this treatment regimen. Summary Of Background Data: The surgical management of symptomatic os odontoideum poses considerable difficulties due to the highly variable anatomy of the upper cervical spine and surrounding neurovascular structures. Various methods have been described for the treatment of symptomatic os odontoideum, all of which have limitations. Methods: Nineteen patients with symptomatic os odontoideum were investigated. Pain scores were assessed using the visual analogue scale. Myelopathy was assessed using the Nurick scale and Odom's criteria. Radiological imaging was carried out in all patients for diagnosis and to assess the atlantodens interval, space available for cord, and presence of intramedullary hyperintensity signals on T2-weighted images at the C1-C2 level. Posterior stabilization was performed for all patients by using ITFN. Results: The mean Nurick score improved from 2.3 before surgery to 0.7 at the time of follow-up. The mean follow-up period was 34.7 months (range, 12-65 mo). According to Odom's criteria, outcomes were as follows: excellent, 47%; good, 37%; fair, 11%; and poor, 5%. All patients with preoperative neck pain had symptom relief or improvement, with all of these patients having more than 83.7% improvement in visual analogue scale scores. The mean preoperative space available for cord value of 9.3 mm improved to 17.7 mm. Solid fusion and reduction of atlantoaxial dislocation were achieved in every patient without screw failure. Sixty screws were placed in 19 patients. Two C2 polyaxial screws in 2 patients and 1 transarticular screw in 1 patient slightly penetrated the transverse foramen with no vascular injury and clinical sequelae. Conclusion: ITFN is a safe, accurate, and effective tool for screw placement in patients with symptomatic os odontoideum. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the efficacy and accuracy of posterior screw fixation for unstable Hangman's fracture using intraoperative 3D fluoroscopy-based navigation. Methods: 14 patients with unstable Hangman's fractures (11 males and 3 females), ranging in age from 21 to 59 years, received posterior fixation assisted by an intraoperative 3D fluoroscopy-based navigation system: 11 Levine-Edwards type II and three type IIA cases. The American Spine Injury Association grade was D in 2 and E in 12 cases. Results: Operation time was 110 min (range 90-140 min). Hospital stay was 7.6 days (range 5-12 days). All the patients were observed for an average of 28.8 months (range 15-50 months). No screw-related injury to nerve, or vertebral artery was observed intraoperatively. An average of four screws/patient were inserted. Pedicle screws were placed into C2 and C3, and 5 screws were into the lateral mass of C3. Screw placement accuracy was evaluated using postoperative CT, according to the modified classification of Gertzbein and Robbins; one screw was grade 2 in C2, and three screws were grade 2 in the pedicle of C3. No grade 3 misplacement or clinical deficits were noted. C3 lateral mass screws were successfully inserted. Neck pain was relieved in each case. Neurologic status improved from D to E in 2 cases. Solid fusion was demonstrated in all the cases by static and dynamic films during the final follow-up. Conclusions: This case series demonstrates that intraoperative 3D fluoroscopy-based navigation is a safe, accurate, and effective tool for screw placement in patients with unstable Hangman's fracture. [ABSTRACT FROM AUTHOR]

Abstract: A new synthetic flavonoid DHF-18, synthesized with a piperazine substitution, has been recently found to show potent anti-tumor activities both in vivo and in vitro. In this study, we demonstrated that DHF-18 significantly inhibited tumor growth in mice inoculated with Heps hepatoma cells without evident toxicity. After the treatment of 40mg/kg DHF-18, the inhibitory rate of tumor weight was 53.69%. To investigate whether apoptosis induction contributed to the anti-tumor effects of DHF-18, DAPI (diamidino-phenyl-indole) staining and Annexin V/PI (Propidium iodide) double staining were performed in our tests. The data showed that DHF-18 could induce the apoptosis cell death in HepG2 cells. Moreover, the apparent increase of intracellular reactive oxygen species levels and the reduction of mitochondria ΔΨm were both observed in HepG2 cells after DHF-18 treatment. Meanwhile, the transposition of apoptotic inducing factor (AIF) from mitochondria to nuclei, the release of cytochrome c from mitochondria and the activation of caspase-3, -9 were also detected, indicating that DHF-18 may induce apoptosis through a mitochondrial-mediated pathway. Additionally, DHF-18 decreased the expression of Bcl-2 protein, whereas the levels of Bax and Bak were found to increase after DHF-18 treatment. Moreover, the activation of caspase-8, the increase of TNF-R1 (Tumor necrosis factor receptor) and Bid were found. Taken together, our results suggested that DHF-18 may induce HeG2 cells apoptosis through a mitochondrial-dependent and independent pathway. [ABSTRACT FROM AUTHOR]

Abstract: Previously, we demonstrated that LYG-202, a newly synthesized flavonoid with a piperazine substitution, exhibited obvious antitumor activity in vivo and in vitro. The exact mechanism of this new compound remains unclear. In the present study, we examined the effects of LYG-202 on reactive oxygen species (ROS) production and the downstream signaling pathway in the apoptosis of human hepatocellular carcinoma HepG2 cells. Pretreatment with NAC (N-acetylcysteine), a ROS production inhibitor, partly inhibited the apoptosis induced by LYG-202 via blocking the ROS generation. Further data revealed that LYG-202 induced ROS accumulation followed by a decrease in mitochondrial membrane potential (MMP), release of cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) to cytosol, which induced apoptosis of the cells. Moreover, the mitogen-activated protein kinases (MAPK), the downstream effect of ROS accumulation including c-Jun N-terminal kinase (JNK) and p38 MAPK, could be activated by LYG-202. Taken together, the generation of ROS might play an important role in LYG-202-induced mitochondrial apoptosis pathway, which provided further support for LYG-202 as a novel anticancer therapeutic candidate. [Copyright &y& Elsevier]

Abstract: LYG-202 is a newly synthesized flavonoid with a piperazine substitution. We investigated the antitumor effect of LYG-202 in vivo and in vitro. We show that, LYG-202 significantly decreases tumor growth in mice inoculated with S180 sarcoma cells, compared with the control group. Meanwhile, the viabilities of various kinds of tumor cells were inhibited by LYG-202 with IC50 values in the range of 4.80 to 27.70μM. Then apoptosis induced by LYG-202 in HepG2 cells was characterized by DAPI staining and Annexin V/PI double staining and degradation of PARP was observed. Activation of the caspase cascade for both the extrinsic and intrinsic pathways was demonstrated, including caspase-8, -9, and -3. The results also showed that the expression of Bcl-2 protein decreased whereas that of Bax protein increased, leading to an increase of the Bax/Bcl-2 ratio. Our results demonstrated that LYG-202 exhibited strong antitumor effect in vivo and in vitro, involving with apoptosis induction. [Copyright &y& Elsevier]

Abstract: Oroxylin A is a flavonoid that is found in the roots of Scutellaria baicalensis Georgi. Here, we investigated the antitumor effect of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. We found that after inoculated with the HeLa cells the mice treated with oroxylin A showed a significant decrease of tumor volumes and tumor weight compared with the control. Meanwhile, the growth inhibition of oroxylin A on HeLa cells were observed by MTT assay and the value of IC50 was 19.4±0.7μM after treatment for 48h. Upon our previous research, the inhibition by oroxylin A might be through apoptosis. Then apoptosis induced by oroxylin A in HeLa cells was characterized by DAPI staining and Annexin V/PI double staining, and degradation of PARP (poly-ADP–ribose polymerase) was both found in HeLa cells and tumor tissue. Next, activation of the caspase cascade for both the extrinsic and intrinsic pathways were demonstrated in vivo and in vitro, including caspase-8, -9 and -3. We also found that the expression of Bcl-2 protein decreased, which leading to an increase of the Bax/Bcl-2 ratio. Our results showed that oroxylin A exhibited strong antitumor effect in HeLa cell line and apoptosis induction involved in it. [Copyright &y& Elsevier]

Androgenetic alopecia (AGA) is the most common type of hair loss dysfunction. Secreted frizzled related protein 1 (SFRP1) is found to be associated with hair loss, but its role in AGA and the regulation mechanism of its transcription level is unclear. The aim of our study is to explore the expression of SFRP1 in AGA samples and its transcriptional mechanism. Male frontal and occipital scalp hair follicles from AGA patients were collected, and human dermal papilla cells (DPCs) were isolated and cultured. SFRP1 gene was cloned and constructed into recombinant plasmids to perform dual-luciferase reporter assay. Transcription factor binding sites were predicted through the Jaspar website and further confirmed by the chromatin immunoprecipitation (ChIP) assay. Expression of genes in DPCs was determined by immunofluorescence (IF) staining, quantitative real-time PCR (qRT-PCR) and western blotting. Our findings showed that SFRP1 was highly expressed in DPCs of AGA patients. The core promoter region of SFRP1 was from −100 to +50 bp and was found to be positively regulated by forkhead box C1 (FOXC1), a transcription factor related to hair growth, both at mRNA and protein level in DPCs. Our study suggests that FOXC1 plays an important role in regulating SFRP1 transcription, which may provide new insights into the development of therapeutic strategies for the treatment of AGA. [ABSTRACT FROM AUTHOR]

As found using comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry, the main components (92.01 vol%) of Neroli oil are terpenoid compounds, such as linalool, b-pinene, a-terpineol, limonene, sabinene, nerol, nerolidol and linalyl acetate. [ABSTRACT FROM AUTHOR]