The effect of thick fibers and large pores of electrospun poly(ε-caprolactone) vascular grafts on macrophage polarization and arterial regeneration

The vascular grafts prepared by electrospinning often have relatively small pores, which limit cell infiltration into the grafts and hinder the regeneration and remodeling of the grafts into neoarteries. To overcome this problem, macroporous electrospun polycaprolactone (PCL) scaffolds with thicker fibers (5–6 μm) and larger pores (∼30 μm) were fabricated in the present study. In vitro cell culture indicated that macrophages cultured on thicker-fiber scaffolds tended to polarize into the immunomodulatory and tissue remodeling (M2) phenotype, while those cultured on thinner-fiber scaffolds expressed proinflammatory (M1) phenotype. In vivo implantation by replacing rat abdominal aorta was performed and followed up for 7, 14, 28 and 100 d. The results demonstrated that the macroporous grafts markedly enhanced cell infiltration and extracellular matrix (ECM) secretion. All grafts showed satisfactory patency for up to 100 days. At day 100, the endothelium coverage was complete, and the regenerated smooth muscle layer was correctly organized with abundant ECM similar to those in the native arteries. More importantly, the regenerated arteries demonstrated contractile response to adrenaline and acetylcholine-induced relaxation. Analysis of the cellularization process revealed that the thicker-fiber scaffolds induced a large number of M2 macrophages to infiltrate into the graft wall. These macrophages further promoted cellular infiltration and vascularization. In conclusion, the present study confirmed that the scaffold structure can regulate macrophage phenotype. Our thicker-fiber electrospun PCL vascular grafts could enhance the vascular regeneration and remodeling process by mediating macrophage polarization into M2 phenotype, suggesting that our constructs may be a promising cell-free vascular graft candidate and are worthy for further in vivo evaluation.     

Evaluation and clinical significance of the stomach age model for evaluating aging of the stomach-a multicenter study in China

Background

A higher prevalence of chronic atrophic gastritis (CAG) occurs in younger adults in Asia. We used Stomach Age to examine the different mechanisms of CAG between younger adults and elderly individuals, and established a simple model of cancer risk that can be applied to CAG surveillance.

Methods

Stomach Age was determined by FISH examination of telomere length in stomach biopsies. Δψm was also determined by flow cytometry. Sixty volunteers were used to confirm the linear relationship between telomere length and age while 120 subjects were used to build a mathematical model by a multivariate analysis. Overall, 146 subjects were used to evaluate the validity of the model, and 1,007 subjects were used to evaluate the relationship between prognosis and Δage (calculated from the mathematical model). ROC curves were used to evaluate the relationship between prognosis and Δage and to determine the cut-off point for Δage.

Results

We established that a tight linear relationship between the telomere length and the age. The telomere length was obvious different between patients with and without CAG even in the same age. Δψm decreased in individuals whose Stomach Age was greater than real age, especially in younger adults. A mathematical model of Stomach Age (real age?+?Δage) was successfully constructed which was easy to apply in clinical work. A higher Δage was correlated with a worse outcome. The criterion of Δage >3.11 should be considered as the cut-off to select the subgroup of patients who require endoscopic surveillance.

Conclusion

Variation in Stomach Age between individuals of the same biological age was confirmed. Attention should be paid to those with a greater Stomach Age, especially in younger adults. The Δage in the Simple Model can be used as a criterion to select CAG patients for gastric cancer surveillance.

     

AKR1C3 Overexpression Mediates Methotrexate Resistance in Choriocarcinoma Cells

Background: Chemotherapy is typically used to treat choriocarcinoma, but a small proportion of tumors develop resistance to chemotherapy. Similarly, methotrexate (MTX) is a first-line chemotherapy used to treat choriocarcinoma; although ~30% of patients are drug-resistant for MTX mono-therapy. Thus, we sought to elucidate the mechanism of chemotherapeutic-resistance of MTX.Methods: RNA interference technology, colony formation, and MTT assays were used to investigate the role of aldo-keto reductase family 1, member C3 (AKR1C3) in MTX resistance in choriocarcinoma cells.Results: AKR1C3 expression was higher in JeG-3R cells compared to JeG-3 cells and targeted inhibition of AKR1C3 expression with shRNA suppresses growth of choriocarcinoma cells as measured by colony formation and MTT assays. Overexpression of AKR1C3 increased chemotherapeutic resistance in JeG-3 cells. Furthermore, AKR1C3 silencing increases sensitivity to MTX in JeG-3R choriocarcinoma cells. Increasing MTX sensitivity spears to be related to DNA damage induction by increased reactive oxygen species (ROS), apoptosis, and cell cycle arrest.Conclusions: Data show that AKR1C3 is critical to the development of methotrexate resistance in choriocarcinoma and suggest that AKR1C3 may potentially serve as a therapeutic marker for this disease.     

Long-term research of stem cells in monocrotaline-induced pulmonary arterial hypertension

Our previous studies have shown that bone marrow mesenchymal stem cells (BMSCs) can inhibit the progression of pulmonary artery hypertension (PAH) in the monocrotaline (MCT) model in the short term. The aim of this study was to further investigate the long-term effect of BMSCs on PAH and to explore the mechanism of the protective effect including the pulmonary vascular remodeling and cell differentiation. PAH model was established by subcutaneous injection of 50 mg/kg MCT as previously study. Postoperatively, the animals were randomly divided into three groups (n = 10 in each group): control, PAH group, and BMSCs implantation group. Six months after injection, immunology and immunohistochemistry analysis indicated the MCT-induced intima-media thickness in muscular arteries was reduced (P < 0.05); the area of collagen fibers in lung tissue was lower (P < 0.05), and the proliferating cell nuclear antigen level in pulmonary artery smooth muscle cells was decreased (P < 0.05). Immunofluorescence showed that the cells have the ability to differentiate between von Willebrand factor and vascular endothelial growth factor. Six months after intravenous injection, BMSCs could significantly improve pulmonary function by inhibiting the ventricular remodeling and the effect of cell differentiation.     

Development of active and intelligent films based on cassava starch and Chinese bayberry (Myrica rubra Sieb. et Zucc.) anthocyanins

Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruit is a functional food rich in anthocyanins. In this study, anthocyanin-rich bayberry extract (BBE) was added into cassava starch to develop food packaging films with antioxidant and pH-sensitive properties. Results showed the main anthocyanin in BBE was cyanidin-3-O-glucoside (95.6%). The addition of 1 wt% of BBE into the film matrix resulted in a dense and compact internal microstructure, which greatly improved the water vapor permeability and tensile strength of the film. However, the addition of 2, 3 and 4 wt% of BBE into film matrix produced heterogeneous inner microstructures due to the formation of agglomerated BBE. The intermolecular interactions between BBE and the starch film matrix were through hydrogen binding. As compared with the starch film, starch–BBE films exhibited higher thicknesses, tensile strength, UV-vis light barrier and antioxidant properties. Moreover, starch–BBE films presented significant color changes when exposed to hydrogen chloride and ammonia gases. The pH-sensitive starch–BBE films were able to monitor the freshness of pork. Our results suggested that starch–BBE films could be used as smart and active packaging materials in the food industry.

In this study, anthocyanin-rich Chinese bayberry extract (BBE) was added into cassava starch to develop food packaging films with antioxidant and pH-sensitive properties.     

White Matter Injuries Induced by MK‐801 in a Mouse Model of Schizophrenia Based on NMDA Antagonism

The etiology of schizophrenia (SZ) is complex and largely unknown. Neuroimaging and postmortem studies have suggested white matter disturbances in SZ. In the present study, we tested the white matter deficits hypothesis of SZ using a mouse model of SZ induced by NMDA receptor antagonist MK‐801. We found that mice with repeated chronic MK‐801 administration showed increased locomotor activity in the open field test, less exploration of a novel environment in the hole‐board test, and increased anxiety in the elevated plus maze but no impairments were observed in coordination or motor function on accelerating rota‐rod. The total white matter volume and corpus callosum volume in mice treated with MK‐801 were significantly decreased compared to control mice treated with saline. Myelin basic protein and 2′, 3′‐cyclic nucleotide 3′‐phosphodiesterase were also significantly decreased in the mouse model of SZ. Furthermore, we observed degenerative changes of myelin sheaths in the mouse model of SZ. These results provide further evidence of white matter deficits in SZ and indicate that the animal model of SZ induced by MK‐801 is a useful model to investigate mechanisms underlying white matter abnormalities in SZ. Anat Rec, 297:1498–1507, 2014. © 2014 Wiley Periodicals, Inc.     

Prevalence of renal dysfunction in patients with cirrhosis according to ADQI-IAC working party proposal

Background/Aims

A revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal.

Methods

The medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis.

Results

Six hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD.

Conclusions

Both AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.     

Ultrasensitive detection of Staphylococcal enterotoxin B in milk based on target-triggered assembly of the flower like nucleic acid nanostructure

A rapid and ultrasensitive method is described for the detection of Staphylococcal enterotoxin B (SEB). It is based on the formation of the flower like nucleic acid nanostructure by integrating (a) target-induced triggering of DNA release with (b) signal amplification by a hybridization chain reaction (HCR). Firstly, partially complementary pairing of aptamer and trigger DNA forms a duplex structure. The capture DNA (cpDNA) is then placed on the surface of gold electrode through gold-thiol chemistry. In the presence of SEB, the aptamer-target conjugate is compelled to form. This causes the release of trigger DNA owing to a strong competition between aptamer and SEB. Then, the trigger DNA is subsequently hybridized with the partial complementary sequences of the cpDNA to trigger HCR with three auxiliary DNA sequences (referred to as MB1, MB2, MB3). Finally, the flower like nucleic acid nanostructures are formed and allow numerous hexaammineruthenium(iii) chloride ([Ru(NH₃)₆]³⁺, RuHex) to be absorbed on the DNA by electrostatic interaction, and thus amplify electrochemical signal. Under optimal conditions, the chronocoulometry charge difference increases linearly with the logarithm of the SEB concentrations in the range from 5 pg mL⁻¹ to 100 ng mL⁻¹ with a detection limit as low as 3 pg mL⁻¹ (S/N = 3).

A rapid and ultrasensitive method is described for the detection of Staphylococcal enterotoxin B (SEB).     

Radiographic assessment of clinical root-crown ratios of permanent teeth in a healthy Korean population

PURPOSE

The aim of this study was to determine the absolute value of the root/crown ratio (R/C ratio) using panoramic radiographs (PRGs) in a healthy Korean population.

MATERIALS AND METHODS

In total, 99 patient radiographs (of 50 males and 49 females subjects; aged 16 to 24 years old) were examined, and 2,770 teeth were analyzed. Crown lengths and root lengths were measured with modified Lind''s measurements using PACS tools by two examiners in two separate sessions two months apart. All data were analyzed using SPSS. The independent t-test was used to assess for gender differences, and the paired t-test was used to compare both arches with a significance level of P<.05.

RESULTS

The mean R/C ratios varied from 1.29 to 1.89 (male: 1.28-1.84; females: 1.31-1.94). The highest R/C ratios were recorded for the mandibular canines (1.89), followed by the maxillary canines (1.79). The lowest R/C ratios were recorded for the maxillary second molars (1.31). In comparison with the maxillary teeth (1.29-1.78), the mandibular teeth yielded the higher R/C ratio (1.47-1.89), and this difference was significant in the females (P<.05). The difference between the genders was not statistically significant, except for the maxillary central incisors, mandibular canines and mandibular first premolars.

CONCLUSION

These data may enhance the understanding of the clinical R/C ratio as a useful guideline for determining the status of teeth and the ethnic difference.     

辛伐他汀对脓毒症患者降钙素原、C反应蛋白及预后的影响

目的拟用辛伐他汀干预脓毒症,观察辛伐他汀对脓毒症患者降钙素原(PCT)、C反应蛋白(CRP)及预后的影响,以探索辛伐他汀调节炎症反应的相关机制。方法采用前瞻性随机对照研究,以2013年10月-2016年12月ICU收治的82例脓毒症患者为研究对象并随机分组。测定两组患者入院后体温,血PCT、CRP水平,白细胞计数以及28 d病死率情况;在使用辛伐他汀(40 mg/d)第10天随访患者的肝功能指标丙氨酸转氨酶(ALT)和肌红蛋白(Myo),以评估辛伐他汀对相关脏器功能的影响。结果42例干预组和40例对照组患者年龄、性别、APACHEⅡ评分、入院最高体温、合并心力衰竭、肾功能等均无显著差异。干预组与对照组患者的炎症指标(PCT、CRP)在第3天开始都出现明显的下降,PCT第5天为(4.76±1.58)μg/L与(8.62±2.92)μg/L,P=0.038;第7天为(1.35±0.36)μg/L与(2.79±0.98)μg/L,P=0.017;第10天为(0.45±0.07)μg/L与(1.61±0.48)μg/L,P<0.001。CRP第3天为(81.95±7.63)mg/L与(123.17±12.29)mg/L,P=0.003;第5天为(45.12±4.17)mg/L与(67.93±7.15)mg/L,P=0.006;第7天为(21.73±2.55)mg/L与(34.72±4.81)mg/L,P=0.007等。两组患者28 d病死率无显著差异。两组患者的ALT和Myo随访数据无显著差异。结论辛伐他汀能显著降低脓毒症患者的PCT、CRP等炎症指标,两组患者全因死亡率无差异,希望对临床上干预脓毒症提供新思路。