Abstract Background Dermal papilla cells (DPCs), which exhibit a multilayer aggregative growth character in in vitro culture, are closely related to induction of hair follicles (HFs) formation, and ...are associated with the development and cycle regulation of HFs. Versican, a large chondroitin sulfate proteoglycan and one of the major components of the extracellular matrix, plays an essential role in hair follicle formation. And also the Wnt/β-catenin signaling pathway performs a crutial function in induction during hair follicle growth and embryogenesis. Objective To characterize the role of versican and β-catenin in regulating DPCs aggregative growth, and to explore the versican gene expression regulation mechanism by TCF-4/β-catenin signaling pathway. Methods We first cultured DPCs at different passages, and detected the change in β-catenin and versican expression in DPCs of various passages by RT-PCR and Western blot. Then we knockdowned the versican and β-catenin gene, evaluated and verificated the binding capability of TCF-4/β-catenin to TOP elements in versican gene promoter region at varied passage DPCs by EMSA and ChIP Assay, finally observed the effect of Wnt/β-catenin pathway inhibition on DPC aggregative growth. Results With the increase of passage, DPCs lost the aggregative property, the versican mRNA and protein level in DPCs was on a gradual decline, while not significant declining tendency of β-catenin. The mRNA of both β-catenin and versican reduced simultaneously after β-catenin siRNA transfection. The binding ability of TCF-4/β-catenin of varied-passage DPCs to cultured versican promoters diminished with the increase of DPC passages. And versican inhibition or Wnt/β-catenin pathway blocking could both produce considerable effect on the aggregative growth of low-passage DPCs. Conclusion Wnt/β-catenin signal transducting system regulates DPC aggregative growth through modifying versican expression by means of acting on the versican gene upstream promoter.
Abstract Background In some psoriatic patients, impaired function of FOXP3+ regulatory T cells has been identified without well-uncovered mechanism(s). Meanwhile, dysregulation of FOXP3 nuclear ...translocation has been observed in some autoimmune syndromes and in some cancer cells. Objective To investigate whether there is dysregulation of FOXP3 nuclear translocation in some psoriatic patients and to explore the signal pathway responsible for FOXP3 nuclear translocation. Methods CD4+CD25+ T cells were purified from peripheral blood mononuclear cells by magnetic-bead-based method. FOXP3 expression pattern in psoriasis was analyzed by immunohistochemical staining. Transient and stable cell lines were established by exogenous construct transfection and retrovirus infection respectively. Cytoplasmic and nuclear FOXP3 was analyzed by immunoprecipitation, western blot and immunofluorescence. Results We observed that some psoriatic patients showed cytoplasmic retention of FOXP3 and these patients had higher serum IL-17 and disease severity. We found that c-Jun N-terminal kinase (JNK) was essential to FOXP3 nuclear translocation. Inhibition of JNK pathway caused cytoplasmic retention of FOXP3. This inhibition could also impair the promotion of FOXP3 nuclear translocation by UVB. Next we found that phospho-c-JUN (ser63/73), main downstream of JNK pathway, could interact with FOXP3 and promoted FOXP3 nuclear translocation. Conclusion Our study demonstrated that JNK-phospho-c-JUN (ser63/73) pathway was essential for FOXP3 nuclear translocation in psoriasis. Our study suggested selective manipulation of JNK in Tregs seems to be a promising choice for the development of drugs in the treatment of autoimmune inflammatory diseases.
The aim of the study was to investigate whether the type of arrhythmia recurrence after ablation of persistent atrial fibrillation (AF) has an impact on the maintenance of sinus rhythm after the ...repeat ablation procedure.
Included were 78 consecutive patients (82% men; mean age, 61±10 years; mean left atrial diameter, 47±4 mm) with persistent AF who underwent ≥1 repeat ablation. The initial ablation procedure had consisted of pulmonary vein isolation with additional substrate modification (ablation of complex fractionated atrial electrograms n=63 or linear lesions n=15). Patients presented for reablation either with persistent atrial tachycardia (AT) (group 1, n=36), persistent AF (group 2, n=37), or paroxysmal AF (group 3, n=5). The primary end point was freedom from any arrhythmia off antiarrhythmic drugs 6 and 9 months after the reablation procedure. Estimated proportions of patients reaching the primary end point were 59% for group 1, 28% for group 2, and 100% for group 3 at 6 months and 51%, 23%, and 100%, for groups 1, 2, and 3, respectively, at 9 months (P=0.002).
In patients presenting for a repeat procedure after ablation of persistent AF, the occurrence of AT is associated with a significantly better outcome compared with recurrent persistent AF. These results suggest that AT might be considered as a step toward sinus rhythm.
We sought to understand the clinical course and molecular defects of infantile-onset Pompe disease (IOPD) among mainland Chinese patients.
Twenty-five Chinese patients with IOPD were enrolled and ...clinical data were retrospectively reviewed. The entire coding region of the GAA gene was amplified by polymerase chain reaction and analyzed by direct sequencing.
The median age at symptom onset was 3.4 months (range: 1.0-7.1 months) and 4.9 months (range: 2.7-8.3 months) at diagnosis. Only one patient received enzyme replacement therapy (ERT) and this child survived beyond the age of 2 years. Of the 24 patients not receiving ERT, all, but one patient, died at a median age of 8.3 months (range: 4.0-12.2 months). Thirteen novel and two common GAA mutations were identified in this study. The allelic frequency of c.2662G > T (p.Glu888X) was 23.1% in northern Chinese patients and 4.2% in southern Chinese patients, whereas the allelic frequency of c.1935C > A (p.Asp645Glu) was 20.8% in southern and 3.8% in northern Chinese patients.
We identified the most common mutations in southern and northern Chinese patients with IOPD.
The purpose of this trial was to compare the long-term efficacy of low-dose amiodarone with losartan and perindopril (both combined with low-dose amiodarone) for the prevention of atrial fibrillation ...(AF) recurrence in patients with lone paroxysmal AF.
One-hundred and seventy-seven patients with lone paroxysmal AF were randomly assigned to three treatment groups: group 1 received low-dose amiodarone alone, group 2 received low-dose amiodarone plus losartan, and group 3 received low-dose amiodarone plus perindopril. Left atrial diameter was measured with transthoracic echocardiogram at baseline and 6, 12, 18, and 24 months after randomization. The primary endpoint was the incidence of AF documented by 12-lead ECG or Holter after 14 days and within 24 months after randomization. The primary endpoint was reached in 24 patients (41%) in group 1, 11 (19%) in group 2, and 14 (24%) in group 3 (P = 0.02). The Kaplan-Meier survival analysis demonstrated a significant reduction in AF recurrence in group 2 (P = 0.006, log-rank test) as well as in group 3 (P = 0.04, log-rank test) when compared with group 1. No difference in the AF recurrence-free survival was found between group 2 and group 3. After 24 months follow-up, the left atrial diameter in group 2 and group 3 was significantly smaller than that in group 1 (36 +/- 2.3 and 35 +/- 2.4 vs. 38 +/- 2.4 mm, P < 0.001 for both comparisons).
The results of this study suggest that the combination of perindopril or losartan with low-dose amiodarone is more effective than low-dose amiodarone alone for the prevention of AF recurrence in patients with lone paroxysmal AF. Adding losartan or perindopril to amiodarone can inhibit left atrial enlargement in this group of patients.
To explore the genetic basis for 7 patients with Alström syndrome.
DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the ...patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis.
Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549C>T (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819C>T (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379C>T (p.Gln3127*), c.12115C>T (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825C>T (p.Arg3609*) and c.3902C>A (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379C>T, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379C>T and c.12115C>T variants of the ALMS1 gene wer
Two series of novel triazolo-pyridazine/-pyrimidine derivatives were designed, synthesized, and evaluated for their inhibitory activity against c-Met kinase, as well as three c-Met overexpressed ...cancer cell lines (A549, MCF-7, and HeLa) and one normal human hepatocytes cell line LO2 in vitro. The pharmacological data indicated that most of the tested compounds showed moderate cytotoxicity, and the most promising compound 12e exhibited significant cytotoxicity against A549, MCF-7, and HeLa cell lines with IC50 values of 1.06 ± 0.16, 1.23 ± 0.18, and 2.73 ± 0.33 μM, respectively. Moreover, the inhibitory activity of compound 12e against c-Met kinase (IC50 = 0.090 μM) was equal to that of Foretinib (IC50 = 0.019 μM). The result of the acridine orange (AO) single staining test demonstrated that compound 12e could remarkably induce apoptosis of A549 cells. The results of apoptosis and cycle distribution of cells showed that compound 12e could induce late apoptosis of A549 cells and stimulate A549 cells arresting in the G0/G1 phase. Structure–activity relationships (SARs), pharmacological results, and docking studies indicated that the introduction of 5-methylthiazole fragment to the five-atom moiety was beneficial for the activity. So far, the existing data indicated that compound 12e may become a potential class II c-Met inhibitor.
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•Ternary NiO-SnO2-rGO nanocomposites was successfully prepared for room-temperature NO2 sensing.•Largely enhanced response and fast recovery rate based on ternary nanocomposites were ...obtained.•The room-temperature sensing mechanism based on the ternary nanocomposites was proposed.•The potential application of ternary nanocomposites in room-temperature NO2 sensing was shown.
Recently, metal oxide semiconductors (MOS)-reduced graphene oxide (rGO) nanocomposites have attracted great attention for room-temperature gas sensing applications. Here, to further improve the room-temperature NO2 sensing properties of NiO-rGO, ternary NiO-SnO2-rGO nanocomposites was successfully prepared. The gas-sensing studies revealed that the ternary nanocomposites exhibited a remarkably higher response to NO2 at room temperature, and the response of the ternary nanocomposites to 60ppm NO2 is 10 times larger than that of the NiO-rGO under the circumstance of the equal specific surface area, indicating the important role of heterojunction. Significantly, the recovery rate of ternary nanocomposites was also accelerated compared to the bare NiO and the NiO-rGO. Here, we hope this work could provide a proper approach for further improvement of MOS-rGO based nanocomposites with even higher sensing performances.
Abstract Background Whether ZES can further improve angiographic and clinical outcomes compared to SES still remains uncertain. Objectives The aim of this study was to assess the efficacy and safety ...of zotarolimus-eluting stents (ZES) compared with sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary interventions (PCI). Methods Major electronic information sources were explored for randomized controlled trials comparing ZES with SES among patients undergoing PCI during at least 9 months follow-up. The primary efficacy outcomes were target lesion revascularization (TLR), target vessel revascularization (TVR), and major adverse cardiac events (MACE); safety outcomes were stent thrombosis (ST), myocardial infarction (MI), and cardiac death. Results Seven comparative studies were identified (a total of 5983 patients). When compared with ZES at 12-month follow‐up, SES significantly reduced risk of MACE (relative risk RR: 0.74, 95% confidence interval CI: 0.61 to 0.89, p = 0.002), and TLR (RR:0.39; 95% CI: 0.29 to 0.52; p < 0.00001), without significant differences in terms of TVR (RR:0.68, 95% CI: 0.38 to 1.20; p = 0.18), ST (RR:0.71; 95% CI: 0.39 to 1.31; p = 0.28), cardiac death (RR:0.83; 95% CI: 0.49–1.42, p = 0.50) or MI (RR:1.08; 95%CI: 0.80 to 1.45; p = 0.62). Conclusions At 12-month follow-up, SES are superior to ZES in reducing the incidences of TLR and MACE in patients undergoing PCI, without significant differences in terms of TVR, ST, cardiac death, and MI.
Enzyme-mediated nanostructures have gained increasing interests and shown promising applications in functional delivery for food and pharmaceuticals. In our previous study, we fabricated three types ...of spherical soy protein nanoparticles (SPNP) by flavorzyme to different degree of hydrolysis (DH, 3%, 7% and 11%). These SPNPs exhibited similar subunit composition, secondary structure and surface properties, but differ in size, which is 89 nm, 106 nm and 151 nm, respectively. This study further applied them in emulsion systems for functional delivery. We systematically studied the emulsifying activities, interfacial properties including wettability, interfacial packing pattern, interfacial adsorption and dilatational rheological behavior of SPNPs, and their performance in modulating lipolysis of the emulsions under the influence of lipase, bile salts, pepsin and trypsin. All SPNPs behaved as Pickering-like stabilizers with moderate wettability at oil-water interface with three phase contact angle of 92–101°, and the SPNP with the smallest size has better emulsifying activities (D3,2 = 3.22 ± 0.00 μm in SDS solution) than native soy protein isolate (SPI) (D3,2 = 4.04 ± 0.03 μm in SDS solution). These SPNPs formed similar viscoelastic oil-water interfaces (Ed' = 20.2–21.5 mN/m), which were more glassy-like with weak in-plane interactions compared to SPI (Ed' = 28.6 ± 0.5 mN/m). All SPNPs can delay lipolysis of emulsions by lowering the access/replacement of lipase and bile salts and depressing the proteolysis by trypsin at interface in similar ways. Our work elucidated the role of particle size of enzyme-mediated plant protein-based particle in emulsion stabilization and lipolysis control, and is expected to give the theoretical support for the design of functional food emulsions with controllable energy intake.
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•Flavorzyme-mediated soy protein nanoparticles (SPNP) are Pickering-like stabilizers.•SPNPs with smaller size have higher emulsifying activities.•SPNPs behave similarly in interfacial rheology and emulsion digestion.•SPNPs form glassy-like and weak interface compared to native soy protein.•SPNPs are resistant to proteolysis at interface and can delay lipolysis of emulsions.
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