Long-term clinical outcomes of extracorporeal shockwave lithotripsy and endoscopic retrograde cholangiopancreatography for pancreatic duct stone treatment in patients with chronic pancreatitis.

BACKGROUND AND AIMS: Extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferred therapeutic approaches for painful chronic pancreatitis (CP) with pancreatic stones. This study aimed to report the short- and long-term outcomes following P-ESWL and ERCP in a large cohort with CP. METHODS: Patients with painful CP and pancreatic stones >5 mm in size, who underwent P-ESWL and subsequent ERCP between March 2011 and June 2018, were included in this retrospective-prospective mixed observational study. The total stone clearance rates were recorded. All patients were followed up until the end of March 2024, with the visual analogue scale (VAS) for pain, pain type, quality-of-life scores and other relevant information recorded. RESULTS: A total of 2071 patients underwent P-ESWL, and 93.1% of them subsequently underwent ERCP during the study period. Patients were followed up for an average of 11.8 years from the onset of CP and 6.7 years from the first P-ESWL procedure. Complete stone clearance was achieved in 73.7% of the patients. At the end of the follow-up period, 70.1% of the patients achieved complete pain remission. Significant pain type conversion and lower VAS scores were observed in the patients after treatment. Quality-of-life scores and body mass indices increased after P-ESWL and ERCP. CONCLUSIONS: P-ESWL and ERCP are effective and minimally invasive treatments for pancreatic stones in patients with painful CP. Most patients achieved complete pain relief, and pain-type conversion was common after treatment. (ClinicalTrials.gov: NCT05916547).

Construction of composite self-assembly coating based on chitosan for enhancing the flame-retardant and antibacterial performances of cotton fabric.

In this work, the step-by-step dip-coating (SBS) method was used to effectively improve the drawback of LBL by reducing the construction of a multilayer polyelectrolyte. Bio-based flame retardants, phytic acid (PA), and chitosan (CS) were further self-assembly on the surface of cotton fabric treated by epichlorohydrin-modified aramid nanofibers (AEP), ionic liquid (IL), and Cu ion. The pure cotton fabric was immersed in each dipping liquid only once, improving fire safety and antibacterial performance. The treated cotton self-extinguished with a 59 mm char length in the vertical flammability test, and the limiting oxygen index (LOI) value increased from 18.5 % to 38.5 %. The result of the cone calorimeter test (CCT) revealed that the fire hazard of flame-retardant cotton noteworthy declined (e.g., ~44.1 % and 55.4 % decline in peak heat release rate (pHRR) and total heat release rate (THR)). Conspicuously, the treated cotton exhibited a remarkably inhibiting effect on E. coli and S. aureus activity. The cotton fabric after flame-retardant finishing exhibited excellent fire safety and antibacterial performance.

ACTIVATION OF KLOTHO/SIRT1 SIGNALING PATHWAY ATTENUATES MYOCARDIAL ISCHEMIA REPERFUSION INJURY IN DIABETIC RATS.

ABSTRACT: Diabetes and myocardial ischemia reperfusion (MIR) injury are characterized by oxidative stress, inflammation, autophagy disorders, and cardiac contractile dysfunction. Klotho and SIRT1 regulate the level of oxidative stress to participate in the regulation of many physiological functions such as cell survival, aging, apoptosis, autophagy, mitochondrial biogenesis, and inflammation. We hypothesized that the activation of Klotho/SIRT1 signaling pathway could attenuate MIR in diabetic rats. Type 1 diabetes and MIR injury model were established to examine this hypothesis in vivo . Primary rat cardiomyocytes and H9c2 cells were exposed to high glucose conditions and hypoxia/reoxygenation (H/R) insult in vitro . Hemodynamic parameters of heart function, myocardial infarct size, oxidative stress, markers of MIR injury or cell viability, and the mRNA and protein expression of Klotho and SIRT1 were measured. There was lower expression of Klotho and SIRT1 in diabetic MIR hearts than in nondiabetic rats, as well as significantly increased oxidative stress levels and decreased autophagy levels. Recombinant Klotho (rKlotho) protein and the SIRT1 agonist SRT1720 could significantly attenuate MIR injury in diabetes by activating Klotho/SIRT1 signaling pathway to reduce oxidative stress and restore autophagy levels. These findings suggest that the Klotho/SIRT1 pathway plays an important role in MIR injury in diabetic rats, and rKlotho protein and agonist SRT1720 have therapeutic potential for alleviating diabetic myocardial IR injury by activating Klotho/SIRT1 to reduce oxidative stress and restore autophagy levels.

Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases.

Protein posttranslational modifications are important factors that mediate the fine regulation of signaling molecules. O-linked ß-N-acetylglucosamine-modification (O-GlcNAcylation) is a monosaccharide modification on N-acetylglucosamine linked to the hydroxyl terminus of serine and threonine of proteins. O-GlcNAcylation is responsive to cellular stress as a reversible and posttranslational modification of nuclear, mitochondrial and cytoplasmic proteins. Mitochondrial proteins are the main targets of O-GlcNAcylation and O-GlcNAcylation is a key regulator of mitochondrial homeostasis by directly regulating the mitochondrial proteome or protein activity and function. Disruption of O-GlcNAcylation is closely related to mitochondrial dysfunction. More importantly, the O-GlcNAcylation of cardiac proteins has been proven to be protective or harmful to cardiac function. Mitochondrial homeostasis is crucial for cardiac contractile function and myocardial cell metabolism, and the imbalance of mitochondrial homeostasis plays a crucial role in the pathogenesis of cardiovascular diseases (CVDs). In this review, we will focus on the interactions between protein O-GlcNAcylation and mitochondrial homeostasis and provide insights on the role of mitochondrial protein O-GlcNAcylation in CVDs.

Urbanization, economic agglomeration and economic growth.

Are Chinese cities too agglomerated, and are production factors continuing to flow to cities?In recent years, research on this issue has attracted more and more attention from academics, for the research on this issue, academics generally believe that urbanization has a positive role in promoting economic growth, but whether urbanization will bring economic agglomeration and what is the role of economic agglomeration on the development of the economy? The research on this issue is still insufficient, therefore, Based on the panel data of 27 provinces from 2006 to 2020, it is generally believed that urbanization has a positive role in promoting economic growth. This paper adds economic agglomeration factors and uses a spatial econometric model to test the spillover effect of urbanization growth. The main conclusions are as follows: First, urbanization and economic agglomeration have a positive effect on economic growth, and there is a spatial spillover effect. Secondly, the advancement of urbanization is closely associated with economic growth, particularly in relation to the development of economic agglomeration. When economic agglomeration is based on a single-center model, it tends to impede urbanization and economic progress. In contrast, an economic agglomeration model with multiple centers has the potential to stimulate urbanization and further enhance economic growth. Thirdly, it is worth noting that the influence of urbanization on economic growth varies across different regions. Factors such as geographical location, resource availability, and local economic conditions contribute to this regional variation.

Epitaxy-Directed Self-Assembly of Copolymers and Polymer Blends.

Directed self-assembly of materials into patterned structures is of great importance since the performance of them depends remarkably on their multiscale hierarchical structures. Therefore, purposeful structural regulation at different length scales through crystallization engineering provides an opportunity to modify the properties of polymeric materials. Here, an epitaxy-directed self-assembly strategy for regulating the pattern structures including phase structure as well as crystal modification and orientation of each component for both copolymers and polymer blends is reported. Owing to the specific crystallography registration between the depositing crystalline polymers and the underlying crystalline substrate, not only order phase structure with controlled size at nanometer scale but also the crystal structure and chain orientation of each component within the separated phases for both copolymers and polymer blend systems can be precisely regulated.

A biomimetic design for efficient petrochemical spill disposal: CoFe-PBA modified superhydrophobic melamine sponge with mechanical/chemical durability and low fire risk.

Due to frequent petrochemical spills, environmental pollution and the threat of secondary marine fires have arisen, necessitating an urgent need for petrochemical spill treatment strategies with high-performance oil-water separation capabilities. To address the challenges of poor durability, instability in hydrophobic conditions, and difficulty in absorbing high-viscosity crude oil associated with hydrophobic absorbent materials, the authors of this study took inspiration from the unique micro and nanostructures of springtails' water-repellent skin. We engineered a superhydrophobic melamine sponge using interfacial assembly techniques designated as Si@PBA@PDA@MS. This material demonstrated improved mechanical and chemical durability, enhanced photothermal performance, and reduced fire risk. The metal-organic framework (MOF)-derived cobalt-iron Prussian blue analog (CoFe-PBA) was firmly anchored to the sponge framework by the chelation of cobalt ions using polydopamine (PDA). The results demonstrated that Si@PBA@PDA@MS demonstrated excellent superhydrophobicity (WCA=163.5°) and oil absorption capacity (53.4-97.5 g/g), maintaining high durability even after 20 cycles of absorption-squeezing. Additionally, it could still exhibit excellent mechanical properties, hydrophobic stability, and absorption performance across a wide temperature range (0-100 °C), pH range (1-14), and high compression strength (ε = 80%), with excellent mechanical/chemical durability. Furthermore, Si@PBA@PDA@MS demonstrated remarkable photothermal performance and low fire risk, offering efficient, safe, and sustainable practical value for effective petrochemical spill treatment.

The spectral resolution of DOM in urban rivers affected by different non-point source intensities using self-organizing maps.

UV-Vis, three-dimensional excitation-emission matrix fluorescence spectroscopy (EEMs) and a self-organizing map (SOM) were used to study changes in the composition and constituent concentrations of dissolved organic matter (DOM) in the water column of two urban rivers with different non-point source inputs during spring and summer. The level of humification and the relative molecular mass of DOM were remarkably higher in the summer than in the spring (P < 0.01) in both rivers. The SOM model showed that the fluorescence intensity of the spring component was lower than in summer in water bodies with higher levels of non-point source inputs, while the opposite was true for water bodies with lower levels of non-point source inputs. Principal component analysis (PCA) showed that nutrients like nitrogen and phosphorus promoted autogenous processes in these water bodies. Seasonal variations and differing intensities of non-point source inputs had remarkable effects on urban river waters (R2 = 0.775, P < 0.001). Non-point source inputs increased the concentrations of humus-like fractions and promoted autogenesis in the water bodies.

A High-Efficient DOPO-Based Flame Retardant as a Co-Curing Agent for Simultaneously Enhancing the Fire Safety and Mechanical Properties of Epoxy Resin.

Simultaneously enhancing the fire safety and mechanical properties of epoxy resin (EP) remains a persistent challenge. Herein, a high-efficient phosphaphenanthrene-based flame retardant (FNP) is synthesized using 3,5-diamino-1,2,4-triazole, 4-formylbenzoic acid, and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide. Due to the presence of active amine groups, FNP is employed as a co-curing agent for fabricating EP composites with outstanding fire safety and mechanical properties. EP containing 8 wt% FNP (EP/8FNP) achieves a vertical burning (UL-94) V-0 rating with a limiting oxygen index of 31%. Meanwhile, FNP declines the peak heat release rate, total heat release, and total smoke release of EP/8FNP by 41.1%, 31.8%, and 16.0%, respectively, compared to those of unmodified EP. The increased fire safety of EP/FNP composites is because FNP promotes the formation of an intumescent, compact, and cross-linking char layer for EP/FNP composites, and releases P-containing substances and noncombustible gases in the gas phase during combustion. In addition, EP/8FNP exhibits 20.3% and 5.4% increase in the flexural strength and modulus compared with those of pure EP. Furthermore, FNP enhances the glass transition temperature of EP/FNP composites from 141.6 °C for pure EP to 147.3 °C for EP/8FNP. Therefore, this work is conducive to the future development of fabricating fire-safe EP composites with enhanced mechanical properties.

A self-organizing map approach to the analysis of lake DOM fluorescence for differentiation of organic matter sources.

The sources and properties of dissolved organic matter (DOM) in two lakes with different non-point source inputs were investigated by combining conventional three-dimensional fluorescence spectroscopy methods with a self-organizing map (SOM). To assess the DOM humification level, the representative neurons 1, 11, 25, and 36 were assessed. The SOM model showed that the DOM humification level of the Gaotang Lake (GT) which has a mainly agricultural non-point source input was significantly higher than that of the Yaogao Reservoir (YG) which has a mainly terrestrial source input (P < 0.01). The GT DOM mainly came from factors such as agricultural-related farm compost and decaying plants, while the YG DOM originated from human activities around the lake. The source characteristics of the YG DOM are obvious, with a high level of biological activity. Five representative areas in the fluorescence regional integral (FRI) were compared. The comparison showed that during the flat water period, the GT water column showed more terrestrial characteristics, even though the humus-like fractions in the DOM of both lakes were derived from microbial decomposition. Principal component analysis (PCA) showed that the agricultural lake water DOM (GT) was dominated by humus components, while the urban lake water DOM (YG) was dominated by authigenic sources.

Organic Phosphoric Acid Doped Polyaniline-Coupled g-C3 N4 for Enhancing Fire Safety of Intumescent Flame-Retardant Epoxy Resin.

Two kinds of polyaniline coupled graphitized carbon nitride nanosheets doped with different organic phosphoric acids (CP@PA, with phytic acid; CP@NP, with amino trimethyl phosphonic acid) are developed by in-situ polymerization. According to the analysis of the section morphology and element distribution of epoxy resin (EP) composites, although CP@PA and CP@NP show completely different morphology, they can significantly enhance the dispersion of graphitized carbon nitride nanosheets in EP. Moreover, the different oxidation states of phosphorus contained in the CP@PA and CP@NP lead to varying effects on the fire safety of EP. The flame retardancy Index (FRI) is a dimensionless index to evaluate the performance of flame retardants. When used as a flame retardant, CP@NP (FRI = 3.22) is better than CP@PA (FRI = 1.29) in flame retardant, especially in suppressing thermal hazards. As a synergist of intumescent flame retardants (IFR), CP@PA (FRI = 26.12) is most effective in improving the comprehensive fire safety property of EP and achieves an "Excellent" rating. Therefore, two different flame-retardant mechanisms of CP@PA and CP@NP are summarized by analyzing the combustion behavior and changes of condensed phase. In summary, this research may be helpful to the design of nano synergies for IFR systems.

Co-curing preparation of flame retardant and smoke-suppressive epoxy resin with a novel phosphorus-containing ionic liquid.

Phosphorus-containing ionic liquid derivatives have been proven to be effective flame retardants for epoxy resin (EP). Flame retardants can accelerate the curing process and improve flame retardancy and smoke suppression of EP composites, which is challenging. In this paper, a novel phosphorus-containing ionic liquid (TPP-PF6) was synthesized and used both as a co-curing agent with 4,4'-diaminodiphenylmethane (DDM) and as a highly effective flame retardant for EP. It has been found that TPP-PF6 was conducive to improve the char formation of EP to inhibit the smoke release at high temperatures. For EP/TPP-PF6 composites, the flame-retardant performance was enhanced rapidly with the increase of TPP-PF6. With only 2 wt% of TPP-PF6, EP/2.0TPP-PF6 reached a UL-94 V-0 rating and a limiting oxygen index of 30.3%. The peak heat release rate, total heat release, and total smoke production values of EP/2.0TPP-PF6 were reduced by 36.32%, 45.81%, and 15.1% compared with those of pure EP, respectively. The thermal degradation products and flame retardant mechanism in gas and condensed phases were studied. It was found that TPP-PF6 had flame retardant effect in the barrier effect of the condensed phase and the quenching effect of the gas phase. This work explores the high-efficiency flame retardant and smoke-suppressive structures with co-curing properties for EP, thus promoting the wide application of EP materials.

Evaluation of Applicability of Minimum Required Compressive Strength for Cold Weather Concreting Based on Winter Meteorological Factors.

In this paper, we evaluated the applicability of the minimum required compressive strength for cold weather concreting based on winter meteorological factors. In this study, a compressive strength test, dynamic elastic modulus test, hydration degree test, underwater weighing test, and freeze-thaw test were performed to investigate the effect of compressive strength development at early ages on frost resistance of concrete. In particular, the ASTM equivalent number of cycles (CyASTM-sp) of various locations was estimated based on winter meteorological factors. The results of experiments showed that the frost resistance of concrete at early ages increases with increased compressive strength. The relative dynamic modulus of elasticity of concrete of 5.0 MPa showed that it can be maintained above 90% within 18 freeze-thaw cycles. In addition, the CyASTM-sp results showed that a compressive strength of 5.0 MPa can protect concrete from early age frost damage in all investigated locations, indicating that a compressive strength of 5.0 MPa is the minimum required for safe and reliable cold weather concreting. However, for concrete structures subjected to repeated freeze-thaw cycles, it is necessary to select a higher compressive strength value according to the construction condition.

miR-451 protects against ischemic stroke by targeting Phd3.

Ischemic stroke still remains a therapeutic challenge due to its complex pathogenesis and implications. By screening biomarkers in the peripheral blood of ischemic stroke patients, miR-451 was identified as a differentially expressed miRNA along the disease course of ischemic stroke. To investigate the role of miR-451, middle cerebral artery occlusion (MCAO) was performed as an ischemic stroke model in mice. Intracerebroventricular administration of miR-451 mimic in the MCAO mice significantly decreased infarct size, while miR-451 inhibitor significantly increased infarct size. To understand the molecular mechanism of the protective effect of miR-451, Phd3 (also Egln3) was validated as a new miR-451 target. Either fewer or more Phd3-positive cells were observed in brain sections from mice receiving miR-451 mimic or inhibitor, respectively. In addition, the levels of p53 (a known Phd3 target) were significantly downregulated when the levels of Phd3 were reduced, suggesting its participation in reducing apoptosis after the miR-451 administration. Indeed, reduced apoptosis upon miR-451 mimic administration was detected by TUNEL staining. In conclusion, this study demonstrated a new protective role of miR-451 in cerebral ischemia and identified Phd3 as a novel miR-451 target, linking the mechanism to the involvement of p53 in the regulation of apoptosis during the pathogenesis of ischemic stroke.

ΜicroRNA-122 protects against ischemic stroke by targeting Maf1.

The protection of brain tissue against damage and the reduction of infarct size is crucial for improving patient prognosis following ischemic stroke. Therefore, the present study aimed to investigate the regulatory effect of microRNA (miR)-122 and its target gene repressor of RNA polymerase III transcription MAF1 homolog (Maf1) on the infarct area in ischemic stroke. Reverse transcription-quantitative PCR (RT-qPCR) was performed to determine miR-122 expression levels in an ischemic stroke [middle cerebral artery occlusion (MCAO)] mouse model. Nissl staining was conducted to measure the infarct area of the MCAO mouse model. Moreover, RT-qPCR was performed to investigate the relationship between the expression of Maf1 and miR-122 in the MCAO mouse model. Dual-luciferase reporter assay in vitro and miR-122 mimic or inhibitor treatment in vivo were conducted to verify that miR-122 targeted and inhibited Maf1 expression. The results suggested that miR-122 was upregulated in the brain tissue of MCAO model mice. miR-122 overexpression effectively reduced the size of the infarct area in comparison with a control and miR-122 knockdown in brain tissue resulted in the opposite effect. Moreover, Maf1 was confirmed to be a direct target of miR-122. The results of a dual-luciferase reporter assay indicated that miR-122 bound to the 3'-untranslated region of Maf1. Maf1 expression decreased after stroke model induction in comparison with that in sham animals, and Maf1 expression was negatively associated with the expression of miR-122. In addition, miR-122 knockdown increased Maf1 expression levels, whereas miR-122 overexpression decreased Maf1 expression levels in comparison with a control. In conclusion, the results suggested that miR-122 improved the outcome of acute ischemic stroke by reducing the expression of Maf1.

Acetaldehyde Induces Neurotoxicity In Vitro via Oxidative Stress- and Ca2+ Imbalance-Mediated Endoplasmic Reticulum Stress.

Excessive drinking can damage brain tissue and cause cognitive dysfunction. Studies have found that the early stage of neurodegenerative disease is closely related to heavy drinking. Acetaldehyde (ADE) is the main toxic metabolite of alcohol. However, the exact mechanisms of ADE-induced neurotoxicity are not fully clear. In this article, we studied the cytotoxic effect of ADE in HT22 cells and primary cultured cortical neuronal cells. We found that ADE exhibited cytotoxicities against HT22 cells and primary cultured cortical neuronal cells in dose-dependent manners. Furthermore, ADE induced apoptosis of HT22 cells by upregulating the expression of caspase family proapoptotic proteins. Moreover, ADE treatment could significantly increase the intracellular Ca2+ and reactive oxygen species (ROS) levels and activate endoplasmic reticulum stress (ERS) in HT22 cells. ADE upregulated ERS-related CHOP expression dose-dependently in primary cultured cortical neuronal cells. In addition, inhibition of ROS with antioxidant N-acetyl-L-cysteine (NAC) reduced the accumulation of ROS and reversed ADE-induced increase of ERS-related protein and apoptosis-related protein levels. Mitigation of ERS with ERS inhibitor 4-PBA obviously suppressed ADE-induced apoptosis and the expression of ERS-related proteins. Therefore, ADE induces neurotoxicity of HT22 cells via oxidative stress- and Ca2+ imbalance-mediated ERS.

Titanium dioxide nanoparticles induce mouse hippocampal neuron apoptosis via oxidative stress- and calcium imbalance-mediated endoplasmic reticulum stress.

The purpose of this study was to explore the potential neurotoxicity and the underlying mechanism of titanium dioxide nanoparticles (TiO2-NPs) to mouse hippocampal neuron HT22 cells. We found that TiO2-NPs had concentration-dependent and time-dependent cytotoxicities to HT22 cells by the MTT assay. Propidium iodide (PI) staining with FACScan flow cytometry proved that TiO2-NPs dose-dependently increased the apoptosis rate in HT22 cells, and the apoptotic features were observed by Hochest 33258 and AO/EB staining. The levels of calcium (Ca2+) and reactive oxygen species (ROS) were significantly increased in TiO2-NPs-treated cells. Further studies by western blot and real-time QPCR proved that the protein and mRNA levels of GRP78, IRE-1α, ATF6, CHOP and caspase-12 were up-regulated after TiO2-NPs treatment, which indicates that TiO2-NPs-induced cytotoxicity is related to endoplasmic reticulum stress (ERS). Apoptosis-related protein cleaved caspase-3 and pro-apoptotic protein Bax expression levels were up-regulated, and the anti-apoptotic protein Bcl-2 expression level was down-regulated in TiO2-NPs-treated cells. The antioxidant N-acetyl-L-cysteine (NAC) can significantly reduce TiO2-NPs-induced ERS characterized by the down-regulation of GRP78 and cleaved caspase-12 levels, which indicates that oxidative stress is participated in TiO2-NPs-induced ERS. Our study suggests that TiO2-NPs-induced apoptosis in HT22 cells is through oxidative stress- and calcium imbalance-mediated ERS.

Alcohol aggravates ketamine-induced behavioral, morphological and neurochemical alterations in adolescent rats: The involvement of CREB-related pathways.

Currently, an increasing proportion of adolescent ketamine users simultaneously consume alcohol. However, the potential behavioural and neurological alterations induced by such a drug combination and the underlying mechanisms have not been systematically examined. Therefore, in the present study, the behavioural and morphological changes and the underlying mechanisms were studied in adolescent rats after repeated alcohol and/or ketamine treatment. This study provided the first evidence that co-administration of alcohol (2 and 4 g/kg, i.g.) in adolescent rats significantly potentiated the neurotoxic properties of repeated ketamine (30 mg/kg, i.p.) treatments over 14 days, manifesting as increased locomotor activity, stereotypic behaviour, ataxia and morphological changes. This potentiation was associated with the enhancement by alcohol of ketamine-induced glutamate (Glu) and dopamine (DA) release in the cortex and hippocampus. Further mechanistic study demonstrated that alcohol potentiated ketamine-induced neurotoxicity through down-regulation of Akt (a serine/threonine kinase or protein kinase, PKB), protein kinase A (PKA), calmodulin-dependent kinase IV (CaMK-IV)-mediated cyclic AMP-responsive element binding protein (CREB) pathways and induction of neuronal apoptosis in the cortex and hippocampus of the adolescent rats. As this study provides strong evidence that repeated alcohol and ketamine co-exposure may cause serious neurotoxicity, attention needs to be drawn to the potential risk of this consumption behaviour, especially for adolescents.

Silver nanoparticles induce SH-SY5Y cell apoptosis via endoplasmic reticulum- and mitochondrial pathways that lengthen endoplasmic reticulum-mitochondria contact sites and alter inositol-3-phosphate receptor function.

Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response. Prolonged exposure of cells to AgNPs damaged calcium (Ca2+) homeostasis, increased the length of contact sites between the ER and mitochondria, altered IP3R function by the increased levels of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the ER and enhanced mitochondrial Ca2+ uptake. Finally, Ca2+ overload and disrupted homeostasis in the mitochondria triggered apoptotic cell death. Our results suggest that caution should be exercised in the use of AgNPs in humans.

Salidroside, a scavenger of ROS, enhances the radioprotective effect of Ex-RAD® via a p53-dependent apoptotic pathway.

Salidroside (Sal), the predominant component of a Chinese medicinal herb, Rhodiola rosea L., has become an attractive bioagent due to its significant anti-radiation, antioxidant and immune adjustment effects. We explored the radioprotective effect of Sal to ascertain whether it could enhance the anti-radiation effect of ON 01210.Na (Ex-RAD®) in vivo and in vitro, and elucidate its underlying mechanism. Our data demonstrated that Sal inhibited radiation-induced apoptosis, scavenged reactive oxygen species (ROS), and decreased the DNA damage of human umbilical vein endothelial cells (HUVECs). Sal downregulated the expression of Bax and p53 and increased the ratio of Bcl-2/Bax, which indicated that Sal inhibited the radiation-induced apoptosis through p53-dependent pathways. The radioprotection of the Sal pretreatment was also evidenced by an increasing survival rate of the mice, maintaining antioxidant enzyme levels in the liver, and accelerating hematopoietic recovery. The results suggest that Sal exhibits an excellent radioprotective effect with powerful antioxidant activity in vitro and in vivo. Sal enhanced the radioprotective effect of Ex-RAD by improving the antioxidant effect, the scavenging of ROS, by accelerating hematopoietic recovery and DNA repair as well as by regulating apoptotic and repair signaling pathways. Combined modality treatments were more effective than single-agent treatments, demonstrating the value of multiple-agent radioprotectants.