Research Progress in Enzyme Biofuel Cells Modified Using Nanomaterials and Their Implementation as Self-Powered Sensors.

Enzyme biofuel cells (EBFCs) can convert chemical or biochemical energy in fuel into electrical energy, and therefore have received widespread attention. EBFCs have advantages that traditional fuel cells cannot match, such as a wide range of fuel sources, environmental friendliness, and mild reaction conditions. At present, research on EBFCs mainly focuses on two aspects: one is the use of nanomaterials with excellent properties to construct high-performance EBFCs, and the other is self-powered sensors based on EBFCs. This article reviews the applied nanomaterials based on the working principle of EBFCs, analyzes the design ideas of self-powered sensors based on enzyme biofuel cells, and looks forward to their future research directions and application prospects. This article also points out the key properties of nanomaterials in EBFCs, such as electronic conductivity, biocompatibility, and catalytic activity. And the research on EBFCs is classified according to different research goals, such as improving battery efficiency, expanding the fuel range, and achieving self-powered sensors.

Surface plasmonic coupling of Au nanoparticle arrays with ultrathin hexagonal boron nitride nanosheets for Raman enhancement.

Integration of hexagonal boron nitride (h-BN) with plasmonic nanostructures that possess nanoscale field confinement will enable unusual properties; hence, the manipulation and understanding of the light interactions are highly desirable. Here, we demonstrate the surface plasmonic coupling of Au nanoparticles (ANPs) with ultrathin h-BN nanosheets (BNNS) in nonspecific nanocomposites leading to a great enhancement of the Raman signal of E2g in both experimental and theoretical manner. The nanocomposites were fabricated from liquid-exfoliated atomically thin BNNS and diblock copolymer-based ANPs with excellent dispersion through a self-assembly approach. By precisely varying the size of ANPs from 3 to 9 nm, the Raman signal of BNNS was improved from 1.7 to 71. In addition, the underlying mechanism has been explored from the aspects of electromagnetic field coupling strength between the localized surface plasmons excited from ANPs and the surrounding dielectric h-BN layers, as well as the charge transfer at the BNNS/ANPs interfaces. Moreover, we also demonstrate its capability to detect dye molecules as a surface enhanced Raman scattering (SERS) substrate. This work provides a basis for the self-assembly of BNNS hierarchical nanocomposites allowing for plasmon-mediated modulation of their optoelectronic properties, thereby showing the great potential not only in the field of SERS but also in large-scale h-BN-based plasmonic devices.

Knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination among college students in China.

BACKGROUND: Cervical cancer is the fourth most common cancer in women. Up to 99% of cervical cancer cases are associated with high-risk human papillomavirus (HPV). Sexual behavior is a direct risk factor for HPV infection, and sexually active college students, therefore, receive attention for HPV vaccination. At present, most Chinese studies lack of in-depth research on influencing factors, and are limited to cervical cancer, HPV, or HPV vaccine, without comprehensive consideration. This study investigated Chinese college students' cervical cancer prevention and treatment knowledge level, and explored the influencing factors, and understood their willingness to receive HPV vaccination. The findings of this study will lay a foundation for promoting the early screening of cervical cancer and vaccination process. METHODS: A total of 800 college students from four universities in Zhengzhou, China were selected by multistage random sampling method. A self-administered questionnaire on the knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination was carried out. A logistic regression model was conducted to analyze factors influencing knowledge of cervical cancer prevention and treatment among college students. RESULTS: Up to 87.9% of college students said they had heard of cervical cancer. The proportion of college students with good knowledge of cervical cancer prevention and treatment was 46.7%. Logistic regression showed that gender, major, grade, level of education, the father's level of education, premarital sex attitude, and mother cervical cancer screening participation had a significant influence on cervical cancer prevention and treatment knowledge level (P < 0.05). In addition, 589 (74.0%) of college students had heard of HPV vaccine, and 92.8% of college students said they were willing to get vaccinated or recommended that their relatives and friends get vaccinated. CONCLUSIONS: The knowledge level of cervical cancer prevention and treatment knowledge among college students in Zhengzhou is low. Many of them had poor knowledge about HPV vaccine, but their willingness to vaccination is high. Various health education modes should be carried out for people with different characteristics, to improve their knowledge of cervical cancer prevention and promote the vaccination process.

Effective dispersion of oxidized multi-walled carbon nanotubes using a water-soluble N,O-carboxymethyl chitosan via non-covalent interaction.

Dispersible multi-walled carbon nanotubes (MWCNTs) in water have been widely applied in the nanotechnology field. This study reports a water-soluble N,O-carboxymethyl chitosan(N,O-CMCS) assisted individual dispersion of oxidized multi-walled carbon nanotubes (oMWCNTs) as a dispersant. First, the dispersing agent N,O-CMCS was successfully synthesized using the nucleophilic substitution of deacetylated chitosan with chloroacetic acid in an alkaline solution. It was further confirmed using Fourier transform infrared spectroscopy (FTIR). Second, after the treatment with the concentrated hydrochloric acid, the prepared oMWCNTs were dispersed in an aqueous solution of N,O-CMCS under ultrasonic vibrations. Finally, the dispersed aqueous solution was subjected to centrifugation to collect the supernatant of individually dispersed N,O-CMCS/oMWCNTs. In addition, transmission electron microscopy (TEM) further confirmed that the purity of oMWCNTs was improved after the acidification progress. Besides, the stability of the dispersion solution was evidenced by digital photos of oMWCNTs dispersed by N,O-CMCS before and after. Moreover, the UV-vis spectrum (the characteristic peak of dispersed oMWCNTs downshifted 13 nm) showed that the supernatant was enriched by the individual oMWCNTs. In particular, the analytical results of FTIR (the -NH2 band of N,O-CMCS downshifted 7 cm-1), resonance Raman spectroscopy (the I D/I G ratio of dispersed oMWCNTs only increased 0.14), and XRD identified the formation of a non-convalent interaction between N,O-CMCS and oMWCNTs. These findings reveal the dispersing nature of N,O-CMCS towards oMWCNTs in water media.

Compassion fatigue and compassion satisfaction among Chinese midwives working in the delivery room: A cross-sectional survey.

BACKGROUND AND AIMS: Compassion fatigue can negatively affect not only healthcare professionals' physical and mental health but also the quality of care they provide and organizational outcomes. However, little is known about compassion fatigue among Chinese midwives working in the delivery room. This study aimed to examine compassion fatigue and compassion satisfaction levels among Chinese midwives working in the delivery room and correlate their compassion fatigue and compassion satisfaction. METHODS: A multisite cross-sectional study with a convenience sampling approach was conducted at 62 hospitals in Henan Province, central China, from May to July 2020. The participants were recruited through an online survey. A self-designed sociodemographic and work-related data sheet, the Social Support Rating Scale (SSRS), and the Professional Quality of Life Scale (ProQoL) were used to measure the participants'basic information, level of social support, compassion fatigue(consists of burnout and secondary traumatic stress) and compassion satisfaction. Descriptive analysis was used to describe the characteristics of the participants' social support, compassion fatigue and compassion satisfaction. Multiple linear regression analysis was employed to identify associations with the participants' sociodemographic and professional characteristics, compassion fatigue and compassion satisfaction. RESULTS: A total of 213 questionnaires were completed, 206 of which were valid (96.71%). The majority of the participants reported moderate risks for compassion satisfaction (75.24%) and burnout (59.71%) and low risks for secondary traumatic stress (61.65%). Higher job satisfaction as a midwife, lower average working hours per week in the past year, higher social support, extroverted personality, and work recognition in the past month were positively associated with compassion satisfaction, explaining 48.7% of the total variance. Always considering giving up a midwifery career, lower social support, working a day-night shift, poor health condition, more exposure to traumatic birth events per month on average in recent years, and lower job satisfaction as a midwife were negative factors for burnout, explaining 35.3% of the total variance. Four factors, including more exposure to traumatic birth events per month on average in recent years, always considering giving up a midwifery career, working a day-night shift and poor sleep quality, were negatively related to secondary traumatic stress, explaining 14.2% of the variance. CONCLUSIONS: In this study, midwives showed moderate levels of compassion satisfaction and burnout and low levels of secondary traumatic stress which should attract the attention of health institutions. A healthy and supportive work environment is crucial to midwives' health, well-being and job satisfaction. Tailored strategies such as trauma management, emotional literacy, peer and social support networks should be implemented to support midwives' compassion satisfaction, while prevent and lower midwives' burnout and secondary traumatic stress.

Water-soluble carboxymethyl chitosan (WSCC)-modified single-walled carbon nanotubes (SWCNTs) provide efficient adsorption of Pb(ii) from water.

Nanocomposites play a key role in the removal of toxic metal(loid)s from environmental water. In this study, we investigated the adsorption capability of water-soluble carboxymethyl chitosan (WSCC)-modified functionally oxidized single walled carbon nanotubes (oSWCNTs) for rapid and efficient removal of toxic Pb(ii) from water. The WSCC-oSWCNTs nanocomposite was prepared by an acid treatment of SWCNTs followed by an ultrasonic dispersion process using WSCC as dispersant. The morphology and chemical characteristics of the WSCC-oSWCNTs nanocomposite were further identified using various characterization techniques (i.e., transmission electron microscopy, TEM; scanning electron microscopy, SEM; Raman spectra; Fourier transform infrared spectroscopy, FTIR; X-ray photoelectron spectroscopy, XPS; nitrogen adsorption-desorption isotherm test). The efficiency of the adsorption process in batch experiments was investigated via determining various factor effects (i.e. WSCC-oSWCNTs nanocomposite concentration, solution pH, initial Pb(ii) concentration, contact time, and reaction temperature). Kinetic results showed that the adsorption process followed a pseudo-second-order, while an isotherm results study showed that the adsorption process followed the Langmuir and Freundlich isotherm models at the same time. In addition, the van't Hoff equation was used to calculate thermodynamic parameters for assessing the endothermic properties and spontaneity of the adsorption process. The WSCC-oSWCNTs nanocomposite manifested a high adsorption capacity for Pb(ii) (113.63 mg g-1) via electrostatic interactions and ion-exchange, as its adsorption rate could reach up to 98.72%. This study, therefore, provides a novel adsorbent for the removal and detection of harmful residues (i.e. toxic metal(loid)s) from environmental water, such as industry wastewater treatment and chemical waste management.

Circulatory metabolites trigger ex vivo arterial endothelial cell dysfunction in population chronically exposed to diesel exhaust.

BACKGROUND: Chronic exposure to diesel exhaust has a causal link to cardiovascular diseases in various environmental and occupational settings. Arterial endothelial cell function plays an important role in ensuring proper maintenance of cardiovascular homeostasis and the endothelial cell dysfunction by circulatory inflammation is a hallmark in cardiovascular diseases. Acute exposure to diesel exhaust in controlled exposure studies leads to artery endothelial cells dysfunction in previous study, however the effect of chronic exposure remains unknown. RESULTS: We applied an ex vivo endothelial biosensor assay for serum samples from 133 diesel engine testers (DETs) and 126 non-DETs with the aim of identifying evidence of increased risk for cardiovascular diseases. Environmental monitoring suggested that DETs were exposed to high levels of diesel exhaust aerosol (282.3 µg/m3 PM2.5 and 135.2 µg/m3 elemental carbon). Surprisingly, chronic diesel exhaust exposure was associated with a pro-inflammatory phenotype in the ex vivo endothelial cell model, in a dose-dependent manner with CCL5 and VCAM as most affected genes. This dysfunction was not mediated by reduction in circulatory pro-inflammatory factors but significantly associated with a reduction in circulatory metabolites cGMP and an increase in primary DNA damage in leucocyte in a dose-dependent manner, which also explained a large magnitude of association between diesel exhaust exposure and ex vivo endothelial biosensor response. Exogenous cGMP addition experiment further confirmed the induction of ex vivo biosensor gene expressions in endothelial cells treated with physiologically relevant levels of metabolites cGMP. CONCLUSION: Serum-borne bioactivity caused the arterial endothelial cell dysfunction may attribute to the circulatory metabolites based on the ex vivo biosensor assay. The reduced cGMP and increased polycyclic aromatic hydrocarbons metabolites-induced cyto/geno-toxic play important role in the endothelial cell dysfunction of workers chronic exposure to diesel exhaust.

Polyhexamethylene guanidine aerosol triggers pulmonary fibrosis concomitant with elevated surface tension via inhibiting pulmonary surfactant.

Environmental chemicals inhalation exposure could induce pulmonary fibrosis, which is characterized by the excessive proliferation of fibroblasts and accumulation of extracellular matrix components, in which surface tension usually plays vital roles. Polyhexamethylene guanidine (PHMG) was first recognized as a potential hazard ingredient in humidifier disinfectants, which caused an outbreak of pulmonary fibrosis in South Korea. However, the underlying mechanisms involved in PHMG-induced pulmonary fibrosis have not yet been fully elucidated. Therefore, this study mainly focuses on the effect of PHMG on surface tension to unveil the influence and involved mechanisms in PHMG-induced pulmonary fibrosis. C57BL/6J mice were exposed to sub-acute PHMG aerosol for 8 weeks. The results indicated that PHMG induced pulmonary fibrosis combined with elevated surface tension. Results from in vitro study further confirmed PHMG elevated surface tension by inhibited pulmonary surfactant. Mechanistically, PHMG suppressed the key surfactant protein SP-B and SP-C by inhibiting protein expression and block their active sites. The present study, for the first time, revealed the molecular mechanism of PHMG-induced pulmonary fibrosis based on pulmonary surfactant inhibition mediated surface tension elevated. And pulmonary surfactant may be a potential target for further intervention to prevent PHMG-induced fibrosis or alleviate the symptom of relevant patients.

Time-course effect of ultrasmall superparamagnetic iron oxide nanoparticles on intracellular iron metabolism and ferroptosis activation.

Ferroptosis is an iron-dependent cell death caused by excessive peroxidation of polyunsaturated fatty acids. It can be activated by iron-based nanoparticles as a potential cancer therapeutic target. However, the intracellular transformation of iron-based nanoparticles is still ambiguous and the subsequent ferroptosis mechanism is also obscure. Here, we identified the time-course metabolism of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) in cells by using X-ray absorption near edge structure spectroscopy. Also, the integrated quantitative transcriptome and proteome data obtained from the cells exposed to USPIO exhibited hallmark features of ferroptosis. With the chemical species of iron oxide transforming to ferritin, the intracellular GPX4 down-regulated, and lipid peroxide began to accumulate. These results provide evidence that the intracellular metabolism of USPIO induced ferroptosis in a time-dependent manner, and iron over-loaded in cytoplasm along with lipid peroxidation of the membrane are involved in the detailed mechanism of ferroptosis signaling activation.

Power-Optimizing Repair for Distal Biceps Tendon Rupture: Stronger and Safer.

Purpose: Many approaches have been described to accomplish tendon reattachment to the radial tuberosity in a distal biceps tendon rupture, with significant success, but each is associated with potential postoperative complications, including posterior interosseous nerve (PIN) injury. To date, there has been no consensus on the best approach to the repair. The purpose of this study was to evaluate the supination strength and the distance of drill exit points from the PIN in a power-optimizing distal biceps repair method and compare the findings with those of a traditional anterior approach endobutton repair method. Methods: Cadaveric arms were dissected to allow for distal biceps tendon excision from its anatomic footprint. Each arm was repaired twice, first with the power-optimizing repair using an anterior single-incision approach with an ulnar drilling angle and biceps tendon radial tuberosity wraparound anatomic footprint attachment, then with the traditional anterior endobutton repair. Following each repair, the arm was mounted on a custom-built testing apparatus, and the supination torque was measured from 3 orientations. The PIN was then located posteriorly, and its distance from each repair exit hole was measured. Results: Five cadaveric arms, each with both the repairs, were included in the study. On average, the power-optimizing repair generated an 82%, 22%, and 13% greater supination torque than the traditional anterior endobutton repair in 45° supination, neutral, and 45° pronation orientations, respectively. On average, the power-optimizing repair produced drill hole exit points farther from the PIN (23 mm) than the traditional anterior endobutton repair (14 mm). Conclusions: The power-optimizing repair provides a significantly greater supination torque and produces a drill hole exit point significantly farther from the PIN than the traditional anterior endobutton approach. Type of study/level of evidence: Therapeutic III.

Intracellular GSH/GST antioxidants system change as an earlier biomarker for toxicity evaluation of iron oxide nanoparticles.

Glutathione (GSH) and glutathione-S-transferases (GSTs) are two frontlines of cellular defense against both acute and chronic toxicity of xenobiotics-induced oxidative stress. The contribution of GSH and GST enzymes to signaling pathways and the regulation of GSH homeostasis play a central role in the detoxification of numerous environmental toxins and impurities. Iron oxide nanoparticles stemmed from traffic exhaust, steel manufacturing, or welding as a potential environmental pollution can lead to adverse respiratory outcomes and aggravate the risk of chronic health conditions via persistent oxidative stress. In this work, two kinds of acute exposure experiments of iron oxide (Fe2O3 and Fe3O4) nanoparticles in cells and in vivo were conducted to evaluate the GSH levels and GST activity. Our current research presented Fe3O4 nanoparticles at lower concentrations (≤100 µg/ml) seem to be more toxic to the human bronchial epithelial cells as their consumption of GSH and decrease of GST activity. The catalysis activity of Fe3O4 nanoparticles per se may contribute to the intracellular GSH consumption along with inhibition of glutathione-S-transferase class mu 1 and P (GSTM1 and GSTP1) active site and expression decrease of GSTM1 and GSTP1. Accordingly, the GSH consumption and decrease in GST activity directed to the further lipid peroxidation regarded as an earlier marker for toxicity evaluation of iron oxide nanoparticles, and relevant intervention may be effective for prevention of respiratory exposure induced damage from iron oxide nanoparticles.

Occupational exposure to carbon black nanoparticles increases inflammatory vascular disease risk: an implication of an ex vivo biosensor assay.

BACKGROUND: Among manufactured or engineered nanoparticles, carbon black (CB) has largest production worldwide and is also an occupational respiratory hazard commonly seen in rubber industry. Few studies have assessed the risk for cardiovascular disease in carbon black exposed populations. An endothelial biosensor assay was used to quantify the capacity of sera from 82 carbon black packers (CBP) and 106 non-CBPs to induce endothelial cell activation ex vivo. The mediation effect of circulatory proinflammatory factors on the association between carbon black exposure and endothelial cell activation was assessed and further validated using in vitro intervention experiments. RESULTS: The average elemental carbon level inside carbon black bagging facilities was 657.0 µg/m3, which was 164-fold higher than that seen in reference areas (4.0 µg/m3). A global index was extracted from mRNA expression of seven candidate biosensor genes using principal component analysis and used to quantify the magnitude of endothelial cell activation. This global index was found to be significantly altered in CBPs compared to non-CBPs (P < 0.0001), however this difference did not vary by smoking status (P = 0.74). Individual gene analyses identified that de novo expression of key adhesion molecules (e.g., ICAM and VCAM) and chemotactic factors (e.g., CCL2, CCL5, and CXCL8) responsible for the recruitment of leukocytes was dramatically induced in CBPs with CXCL8 showing the highest fold of induction (relative quantification = 9.1, P < 0.0001). The combination of mediation analyses and in vitro functional validation confirmed TNF-α, IL-1ß, and IL-6 as important circulatory factors mediating the effects of carbon black exposure on endothelial cell activation responses. CONCLUSIONS: Inflammatory mediators in sera from CBPs may bridge carbon black exposure and endothelial cell activation response assessed ex vivo. CBPs may have elevated risk for cardiovascular diseases when comorbidity exists. Our study may serve as a benchmark for understanding health effects of engineered carbon based nanoparticles with environmental and occupational health relevance.

Electrospinning Induced Orientation of Protein Fibrils.

Amyloid-like fibrils are prepared from protein in the lab by controlled heat treatments, yet these must be further assembled to match the desirable mechanical and structural properties of biological fibers. Here, ß-lactoglobulin fibrils were incorporated into poly(ethylene oxide) fibers of 40-180 nm diameter by electrospinning. Protein fibrils presented as short segments dispersed within electrospun fibers, with no change in fibril diameter after electrospinning. Imaging analysis revealed fibrils were aligned within 20° relative to the fiber long axis, and alignment was further confirmed by polarized FTIR and anisotropic SAXS/WAXS scattering patterns. The elastic modulus of fibers increased with protein fibril content from 0.8 to 2 GPa, which is superior to reported values of silk, collagen, and gelatin. The present setup allows for manufacture of large quantities of polymeric fibers containing protein fibrils with varied diameter and mechanical strength, endowing great potential for a variety of applications.

High-content analysis of particulate matters-induced oxidative stress and organelle dysfunction in vitro.

Oxidative stress is usually considered to be a common mechanism by which particulate matter (PM) exposure induces adverse effects. However, the further biological events such as organelle dysfunction following oxidative stress remain to be explored. In this study, we applied high-content screening (HCS) technique to investigate the toxicological effects of carbon black (CB), diesel exhaust particle (DEP) and PM2.5 on oxidative stress and organelle function in human bronchial epithelial cell (16HBE), human embryo lung fibroblast cell (HELF) and human umbilical vein endothelial cell (HUVEC) which were used to represent distinct regions of the lung, and compared the toxicity impacts of different PMs and the sensitiveness of cell lines. We found three types of PMs induced mitochondrial dysfunction in three cell lines and lysosomal alkalinization in HUVEC while only CB triggered endoplasmic reticulum (ER) stress in 16HBE and HUVEC, and oxidative stress might mediate these processes. Moreover, CB basically exhibited more potent toxicity compared with DEP and PM2.5, which might be attributed to its less oxygen content. Finally, the finding that PMs-induced toxicity impacts exhibited a cell-type dependent manner might provide some information to help to understand the sensitivity of different tissue in the lung.

High-speed X-ray visualization of dynamic crack initiation and propagation in bone.

The initiation and propagation of physiological cracks in porcine cortical and cancellous bone under high rate loading were visualized using high-speed synchrotron X-ray phase-contrast imaging (PCI) to characterize their fracture behaviors under dynamic loading conditions. A modified Kolsky compression bar was used to apply dynamic three-point flexural loadings on notched specimens and images of the fracture processes were recorded using a synchronized high-speed synchrotron X-ray imaging set-up. Three-dimensional synchrotron X-ray tomography was conducted to examine the initial microstructure of the bone before high-rate experiments. The experimental results showed that the locations of fracture initiations were not significantly different between the two types of bone. However, the crack velocities in cortical bone were higher than in cancellous bone. Crack deflections at osteonal cement lines, a prime toughening mechanism in bone at low rates, were observed in the cortical bone under dynamic loading in this study. Fracture toughening mechanisms, such as uncracked ligament bridging and bridging in crack wake were also observed for the two types of bone. The results also revealed that the fracture toughness of cortical bone was higher than cancellous bone. The crack was deflected to some extent at osteon cement line in cortical bone instead of comparatively penetrating straight through the microstructures in cancellous bone. STATEMENT OF SIGNIFICANCE: Fracture toughness is with great importance to study for crack risk prediction in bone. For those cracks in bone, most of them are associated with impact events, such as sport accidents. Consequently, we visualized, in real-time, the entire processes of dynamic fractures in notched cortical bone and cancellous bone specimens using synchrotron X-ray phase contrast imaging. The onset location of crack initiation was found independent on the bone type. We also found that, although the extent was diminished, crack deflections at osteon cement lines, a major toughening mechanism in transversely orientated cortical bone at quasi-static rate, were still played a role in resisting cracking in dynamically loaded specimen. These finding help researchers to understand the dynamic fracture behaviors in bone.

Gd-Metallofullerenol nanoparticles cause intracellular accumulation of PDGFR-α and morphology alteration of fibroblasts.

Gadolinium-metallofullerenols (Gd@C82(OH)22) are a promising agent for cancer therapy and have shown beneficial effects in regulating the tumor microenvironment with low toxicity. However, the underlying mechanism by which Gd@C82(OH)22 interacts with fibroblasts remains unclear. In order to explore the critical role that activated fibroblasts play in tumorigenesis and fibrosis, we investigated the regulatory effect of Gd@C82(OH)22 in fibroblast activation and oncogenic transformation, and found that the PDGFR-α is an essential molecule in modulating the morphology and functional changes in fibroblasts after Gd@C82(OH)22 treatment. Apart from increasing the PDGFR-α protein level, Gd@C82(OH)22 nanoparticles also significantly increased the protein level of Rab5, which is required for regulating PDGFR-α endosomal recycling. The Rab5-mediated recycling of PDGFR-α maybe attributed to the Gd@C82(OH)22 regulated inhibition of fibroblast activation. Overall, our work demonstrated that Gd@C82(OH)22 nanoparticles can attenuate the PDGF-stimulated phosphorylation of PDGFR-α in fibroblasts and suppress the fibroblast activation by interrupting endosomal recycling. These findings may be contributed to the collagen accumulation for encaging cancer.

Role of sodium-hydrogen exchanger isoform 1 in regulating hepatocyte apoptosis induced by hyperammonaemia / Papel de la isoforma 1 del intercambiador iónico de sodio/hidrógeno en la regulación de la apoptosis de hepatocitos inducida por hiperamoniaquemia

Background: The "secondary injury" theory of liver failure indicated that hyperammonaemia due to liver failure causes further deterioration of hepatocytes. Our previous studies have demonstrated that high blood ammonia levels may lead to hepatocyte apoptosis, as NH4Cl loading caused metabolic acidosis and an increase in sodium-hydrogen exchanger isoform 1 (NHE1). In this study, we established a hyperammonia hepatocyte model to determine the role of NHE1 in the regulation of hepatocyte apoptosis induced by NH4Cl. Materials and methods: In current studies, intracellular pH (pHi) and NHE1 activity were analyzed using the pHi-sensitive dye BCECF-AM. The results showed that intracellular pH dropped and NHE1 activity increased in hepatocytes under NH4Cl treatment. As expected, decreased pHi induced by NH4Cl was associated with increased apoptosis, low cell proliferation and ATP depletion, which was exacerbated by exposure to the NHE1 inhibitor cariporide. We also found that NH4Cl treatment stimulated PI3K and Akt phosphorylation and this effect was considerably reduced by NHE1 inhibition. Conclusion: This study highlighted the significant role of NHE1 in the regulation of cell apoptosis induced by hyperammonaemia

Antecedentes: La teoría de la «lesión secundaria» de la insuficiencia hepática mostró que la hiperamoniaquemia provocada por la insuficiencia hepática causa mayor deterioro de los hepatocitos. Nuestros anteriores estudios previos han demostrado que los niveles altos de amoníaco en sangre pueden conducir a la apoptosis de los hepatocitos. Como la carga de NH4Cl provocó acidosis metabólica y un aumento de la isoforma 1 del intercambiador de sodio/hidrógeno (NHE1). En este estudio, establecimos un modelo de hepatocitos de hiperamonia para establecer el papel de NHE1 en la regulación de la apoptosis de hepatocitos inducida por NH4Cl. Materiales y métodos: En los estudios actuales, el pH intracelular (pHi) y la actividad del NHE1 se analizaron con el colorante BCECF-AM, sensible al pHi. Los resultados mostraron que el pH intracelular disminuyó y la actividad del NHE1 aumentó en hepatocitos con tratamiento del NH4Cl. Como se esperaba, la disminución del pHi inducido por NH4Cl se relacionó con un aumento de la apoptosis, baja proliferación celular y reducción del ATP, que se exacerbó por la exposición a cariporide, inhibidor del NHE1. También encontramos que el tratamiento del NH4Cl estimuló la fosforilación de PI3K y Akt, y este efecto se redujo considerablemente por la inhibición del NHE1. Conclusión: Este trabajo ha destacado el importante papel del NHE1 en la regulación de la apoptosis celular inducida por hiperamoniaquemia

Role of sodium-hydrogen exchanger isoform 1 in regulating hepatocyte apoptosis induced by hyperammonaemia.

BACKGROUND: The "secondary injury" theory of liver failure indicated that hyperammonaemia due to liver failure causes further deterioration of hepatocytes. Our previous studies have demonstrated that high blood ammonia levels may lead to hepatocyte apoptosis, as NH4Cl loading caused metabolic acidosis and an increase in sodium-hydrogen exchanger isoform 1 (NHE1). In this study, we established a hyperammonia hepatocyte model to determine the role of NHE1 in the regulation of hepatocyte apoptosis induced by NH4Cl. MATERIALS AND METHODS: In current studies, intracellular pH (pHi) and NHE1 activity were analyzed using the pHi-sensitive dye BCECF-AM. The results showed that intracellular pH dropped and NHE1 activity increased in hepatocytes under NH4Cl treatment. As expected, decreased pHi induced by NH4Cl was associated with increased apoptosis, low cell proliferation and ATP depletion, which was exacerbated by exposure to the NHE1 inhibitor cariporide. We also found that NH4Cl treatment stimulated PI3K and Akt phosphorylation and this effect was considerably reduced by NHE1 inhibition. CONCLUSION: This study highlighted the significant role of NHE1 in the regulation of cell apoptosis induced by hyperammonaemia.

Ghrelin protects human umbilical vein endothelial cells against advanced glycation end products-induced apoptosis via NO/cGMP signaling.

OBJECTIVES: The aim of this study was to investigate the intracellular mechanism involved in the anti-apoptotic effect of ghrelin on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were pretreated with ghrelin before exposure to 200 µg/ml advanced glycation end products (AGEs)-BSA for 48 h. Cell viability and apoptosis were determined by MTT assay and Annexin V/PI staining. Intracellular cGMP levels evaluation and cGMP analogs were employed to explore possible mechanisms. RESULTS: The inhibitory effect on AGEs induced HUVECs apoptosis could be exerted by ghrelin and co-incubation with growth hormone secretagogue receptor (GHSR)-1a antagonist [D-Lys(3)]-GHRP-6 abolished this inhibition. Decreased cGMP level in AGEs induced HUVECs apoptosis was restored by ghrelin pretreatment and abolished by [D-Lys(3)]-GHRP-6 co-incubation. cGMP analogs (8 Br-cGMP and DB-cGMP) pretreatment also exhibited inhibitory effect on AGEs induced HUVECs apoptosis. CONCLUSIONS: Our results demonstrated that ghrelin produces a protective effect on HUVECs through GHS-R1a and cGMP/NO signaling pathway mediates the effect of ghrelin. These observations suggest a novel intracellular mechanism in the process of AGEs induced HUVECs apoptosis.