Bone progeria diminished the therapeutic effects of bone marrow mesenchymal stem cells on retinal degeneration.

Senescence is closely related to the occurrence of retinal degeneration. Recent studies have shown that bone marrow mesenchymal stem cells (BMMSCs) have significant therapeutic effects on retinal degeneration, While BMMSCs suffer from functional decline in bone aging. Whether senescence affects BMMSCs therapy on retinal degeneration remains unknown. Here, we applied the previously established bone progeria animal model, the senescence-accelerated mice-prone 6 (SAMP6) strain, and surprisingly discovered that SAMP6 mice demonstrated retinal degeneration at 6 months old. Furthermore, BMMSCs derived from SAMP6 mice failed to prevent MNU-induced retinal degeneration in vivo. As expected, BMMSCs from SAMP6 mice exhibited impairment in the differentiation capacities, compared to those from the age-matched senescence-accelerated mice-resistant 1 (SAMR1) strain. Moreover, BMMSCs from SAMR1 mice counteracted MNU-induced retinal degeneration, with increased expression of the retina survival hallmark, N-myc downstream regulated gene 2 (NDRG2). Taken together, these findings reveal that bone progeria diminished the therapeutic effects of BMMSC on retinal degeneration.

Effects of resveratrol on the levels of ATP, 5-HT and GAP-43 in the hippocampus of mice exposed to chronic unpredictable mild stress.

Growing evidence suggested that energy deficiency might be involved in the pathophysiological mechanism of depression. Energy deficiency, mainly results from mitochondrial damage, can lead to the dysfunction of synaptic neurotransmission, and further cause depressive-like behavior. The antidepressant effect of resveratrol had been widely demonstrated in previous studies; however, the underlying mechanism remains poorly understood. The present study aimed to investigate whether the antidepressant effects of resveratrol involved in the energy levels and neurotransmission in the hippocampus. We found that resveratrol and fluoxetine significantly attenuated depressive-like behaviors induced by chronic unpredictable mild stress (CUMS), which evidenced by the increased sucrose preference and the reduced immobility time in a forced swimming test. In addition, resveratrol increased hippocampal ATP levels, decreased Na+-K+-ATPase and pyruvate levels, and upregulated the levels of mitochondrial DNA (mtDNA), mRNA expression of sirtuin (SIRT)1 and peroxisome proliferator-activated receptor γ coactivator (PGC)1α. Furthermore, resveratrol and fluoxetine increased serotonin (5-HT) levels and downregulated the mRNA expression of 5-HT transporter (SERT) in the hippocampus. The decreased protein expression of growth-associated protein (GAP)-43 induced by CUMS was also ameliorated by resveratrol and fluoxetine. These findings demonstrated the antidepressant effects of resveratrol and suggested that resveratrol was able to promote mitochondrial biogenesis, enhance ATP and 5-HT levels, as well as upregulate GAP-43 expression in the hippocampus.

Depressive-like behaviors are induced by chronic liver injury in male and female mice.

Depression is a highly prevalent mental disease and increasingly become a global public health problem. Recent studies have shown that the dysfunction of liver was associated with depression. However, the previous studies have not been fully explained the relationship between depression and liver injury. The present study was aimed to investigate whether chronic liver injury could induce depressive-like behavior. Chronic liver injury was induced by intraperitoneal injection of carbon (CCl4), D-galactosamine (D-GalN) and thioacetamide (TAA), respectively. And the results showed that the serum activities of ALT in CCl4, D-GalN and TAA groups were significantly increased in both male and female mice compared with the control group, while the activities of AST increased only in CCl4 group. Meanwhile, H&E staining showed that CCl4, D-GalN and TAA induced hepatocytes injury in both male and female mice. Moreover, the sucrose preference was significantly decreased and the immobility time in forced swimming test and tail suspension test were significantly prolonged in CCl4 and D-GalN group compared with control group. Our findings demonstrated that chronic liver injury induced by CCl4 and D-GalN could induce depressive-like behaviors in mice.

Transcriptomic analysis reveals the mechanism of sulfasalazine-induced liver injury in mice.

Liver injury is one of the main toxic effect of sulfasalazine (SASP). However, the toxicological mechanism of SASP-induced liver injury remains unclear. In the present study, the liver injury was induced by orally treatment with SASP for 4 weeks in mice. The hepatic mRNA profiles were detected by RNA sequencing and the differentially expressed genes (DEGs) were analyzed by bioinformatics methods. The elevated serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TBIL), combined with the hepatic histopathological features verified that liver injury was successfully caused by SASP. Transcriptomic results showed that 187 genes (fold change > 1.5 and P < 0.05) were differentially expressed, of which 106 genes were up-regulated and 81 genes were down-regulated in SASP-treated group. Moreover, the further analysis showed that these 187 differentially expressed genes (DEGs) were enriched in 123 GO terms, which mainly including oxidation-reduction process, oxidoreductase activity and epoxygenase P450 pathway. KEGG pathway analysis showed 30 pathways including chemical carcinogenesis, retinol metabolism, arachidonic acid metabolism, linoleic acid metabolism and glutathione metabolism. Among these 187 DEGs, the top 22 hub genes were screened from network of protein-protein interaction (PPI) and verified by qRT-PCR. The results showed that the mRNA levels of hepatic drug-metabolizing enzymes, including cyp2b50, cyp2c50, cyp2c39, cyp2c38, cyp2c29, cyp2c54, cyp2c55, cyp2a5, gsta1, gsta2, gstt2, gstm2 and ephx1, were significantly up-regulated, while egfr and egr1 were down-regulated in SASP-treated group. Moreover, the mRNA levels of egfr and cyp2c55 exhibited a dose-dependent changes in SASP groups. Western blotting verified that the changes of protein levels of EGFR and CYP2C55 were consistent with mRNA levels. Considering that egfr has the highest score in PPI degree and cyp2c55 has the largest fold change in qPCR analysis, our present results suggested that the toxicological mechanisms of SASP-induced liver injury might be related to multi-biological processes and pathways, and egfr and cyp2c55 may play important roles in SASP-induced liver injury. The present study would be helpful for better understanding the hepatotoxic mechanism of SASP. However, the precise mechanism still needs further research.

Selective Separation of Acetic and Hexanoic Acids across Polymer Inclusion Membrane with Ionic Liquids as Carrier.

This paper first reports on the selective separation of volatile fatty acids (VFAs) (acetic and hexanoic acids) using polymer inclusion membranes (PIMs) containing quaternary ammonium and phosphonium ionic liquids (ILs) as the carrier. The affecting parameters such as IL content, VFA concentration, and the initial pH of the feed solution as well as the type and concentration of the stripping solution were investigated. PIMs performed a much higher selective separation performance toward hexanoic acid. The optimal PIM composed of 60 wt% quaternary ammonium IL with the permeability coefficients for acetic and hexanoic acid of 0.72 and 4.38 µm s-1, respectively, was determined. The purity of hexanoic acid obtained in the stripping solution increased with an increase in the VFA concentration of the feed solution and decreasing HCl concentration of the stripping solution. The use of Na2CO3 as the stripping solution and the involvement of the electrodialysis process could dramatically enhance the transport efficiency of both VFAs, but the separation efficiency decreased sharply. Furthermore, a coordinating mechanism containing hydrogen bonding and ion exchange for VFA transport was demonstrated. The highest purity of hexanoic acid (89.3%) in the stripping solution demonstrated that this PIM technology has good prospects for the separation and recovery of VFAs from aqueous solutions.

NDRG2 suppression as a molecular hallmark of photoreceptor-specific cell death in the mouse retina.

Photoreceptor cell death is recognized as the key pathogenesis of retinal degeneration, but the molecular basis underlying photoreceptor-specific cell loss in retinal damaging conditions is virtually unknown. The N-myc downstream regulated gene (NDRG) family has recently been reported to regulate cell viability, in particular NDRG1 has been uncovered expression in photoreceptor cells. Accordingly, we herein examined the potential roles of NDRGs in mediating photoreceptor-specific cell loss in retinal damages. By using mouse models of retinal degeneration and the 661 W photoreceptor cell line, we showed that photoreceptor cells are indeed highly sensitive to light exposure and the related oxidative stress, and that photoreceptor cells are even selectively diminished by phototoxins of the alkylating agent N-Methyl-N-nitrosourea (MNU). Unexpectedly, we discovered that of all the NDRG family members, NDRG2, but not the originally hypothesized NDRG1 or other NDRG subtypes, was selectively expressed and specifically responded to retinal damaging conditions in photoreceptor cells. Furthermore, functional experiments proved that NDRG2 was essential for photoreceptor cell viability, which could be attributed to NDRG2 control of the photo-oxidative stress, and that it was the suppression of NDRG2 which led to photoreceptor cell loss in damaging conditions. More importantly, NDRG2 preservation contributed to photoreceptor-specific cell maintenance and retinal protection both in vitro and in vivo. Our findings revealed a previously unrecognized role of NDRG2 in mediating photoreceptor cell homeostasis and established for the first time the molecular hallmark of photoreceptor-specific cell death as NDRG2 suppression, shedding light on improved understanding and therapy of retinal degeneration.

Paeoniflorin Ameliorates Fructose-Induced Insulin Resistance and Hepatic Steatosis by Activating LKB1/AMPK and AKT Pathways.

The present study aimed to evaluate the effects of paeoniflorin on insulin resistance and hepatic steatosis induced by fructose. Male Sprague-Dawley rats were fed 20% fructose drink for eight weeks. The insulin sensitivity, serum lipid profiles, and hepatic lipids contents were measured. The results showed that paeoniflorin significantly decreased serum insulin and glucagon levels, improved insulin sensitivity and serum lipids profiles, and alleviated hepatic steatosis in fructose-fed rats. Moreover, paeoniflorin enhanced the phosphorylation level of AMP-activated protein kinase (AMPK) and protein kinase B (PKB/AKT) and inhibited the phosphorylation of acetyl coenzyme A carboxylase (ACC)1 in liver. Paeoniflorin also increased the hepatic carnitine palmitoyltransferase (CPT)-1 mRNA and protein expression and decreased the mRNA expression of sterol regulatory element-binding protein (SREBP)1c, stearyl coenzyme A decarboxylase (SCD)-1 and fatty acid synthetase (FAS). Furthermore, we found that paeoniflorin significantly increased the heptatic protein expression of tumor suppressor serine/threonine kinase (LKB)1 but not Ca2+/CaM-dependent protein kinase kinase (CaMKK)ß. These results suggest that the protective effects of paeoniflorin might be involved in the activation of LKB1/AMPK and insulin signaling, which resulted in the inhibition of lipogenesis, as well as the activation of ß-oxidation and glycogenesis, thus ameliorated the insulin resistance and hepatic steatosis. The present study may provide evidence for the beneficial effects of paeoniflorin in the treatment of insulin resistance and non-alcoholic fatty liver.

[Characteristics of Enteromorpha prolifera Biochars and Their Adsorption Performance and Mechanisms for Cr(â ¥)].

This study aims to understand the recycling process of Enteromorpha prolifera by using the slow pyrolysis technology to prepare biochars under different temperatures and by characterizing the physicochemical properties of biochars. The results showed that a relatively high level pyrolysis of Enteromorpha prolifera could be reached when the temperature was up to 400℃. The yield rate and the ash content of biochars were negatively correlated with the pyrolysis temperature, while the carbon content was positively correlated. The specific surface area of Enteromorpha prolifera biochars was in the range of 44.54-317.82 m2·g-1. The biochar surface was in the shape of a honeycomb and rich in oxygen-containing functional groups, such as hydroxyl (-OH) and carboxyl (-COOH) groups. The adsorption experiments revealed that the adsorption of Cr(Ⅵ) onto Enteromorpha prolifera biochars followed the pseudo-second-order kinetics equation and Langmuir isotherm, indicating that the adsorption process was controlled by the fast reaction process and governed by monomolecular and chemical adsorption. The optimal pH for Cr(Ⅵ) adsorption onto Enteromorpha prolifera biochars was 2 and their adsorption capabilities were in the order of BC400 > BC700 > BC600 > BC500 > BC300 (the adsorption capacity of BC400 was 4.79 mg·g-1). The adsorption mechanism included the electrostatic interactions between biochar and anions (HCrO-4 and Cr2O2-7) and the complexation of oxygen-containing functional groups.

Hypouricemic effect of flaccidoside II in rodents.

To investigate the effect of flaccidoside II on the serum uric acid levels in hyperuricemic rodents. Both mice and rats were injected intraperitoneally with potassium oxonate to induce hyperuricemia. Different dosages of flaccidoside II were orally administrated to hyperuricemic and normal rodents for 7 days, respectively. Liver xanthine oxidase (XOD) activities in hyperuricemic mice were determined using the colorimetric method. Acute toxicity of flaccidoside II was also evaluated in mice. Allopurinol, as a positive control, was administered under the same treatment scheme. The results showed that flaccidoside II (32, 16 and 8 mg/kg) could significantly lower serum uric acid levels in hyperuricemic mice. Flaccidoside II (24, 12 and 6 mg/kg) could also markedly lower serum uric acid levels in hyperuricemic rats. However, unlike allopurinol, oral administration of flaccidoside II did not produce any observable hypouricemic effect in normal animals. Flaccidoside II at the dose of 32 mg/kg significantly suppressed XOD activities in the liver of hyperuricemic mice, while at doses of 16 and 8 mg/kg flaccidoside II did not show a significant effect on XOD activities. In addition, flaccidoside II (300 mg/kg) has no or less toxicity than allopurinol in mice. These findings demonstrate that flaccidoside II exhibits anti-hyperuricemic activity in hyperuricemic animals.

Curcumin attenuates chronic ethanol-induced liver injury by inhibition of oxidative stress via mitogen-activated protein kinase/nuclear factor E2-related factor 2 pathway in mice.

OBJECTIVE: This study aimed to investigate the protective effect of curcumin on chronic ethanol-induced liver injury in mice and to explore its underlying mechanisms. MATERIALS AND METHODS: Ethanol-exposed Balb/c mice were simultaneously treated with curcumin for 6 weeks. Liver injury was evaluated by biochemical and histopathological examination. Lipid peroxidation and anti-oxidant activities were measured by spectrophotometric method. Anti-oxidative genes expression such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD) were determined by real-time polymerase chain reaction. The nuclear factor E2-related factor 2 (Nrf2) and the phosphorylation states of specific proteins central to intracellular signaling cascades were measured by western blotting. RESULTS: Curcumin treatment protected liver from chronic ethanol-induced injury through reducing serum alanine aminotransferase and aspartate aminotransferase activities, improving liver histological architecture, and reversing lipid disorders indicated by decrease of triglyceride, total cholesterol and low-density lipoprotein-cholesterol levels and increase of High-density lipoprotein-cholesterol levels. Meanwhile, curcumin administration attenuated oxidative stress via up-regulating SOD and glutathione peroxidase activities, leading to a reduction of lipid hydroperoxide production. In addition, curcumin increased Nrf2 activation and anti-oxidative genes expressions such as NQO1, HO-1, and SOD through inducing extracellular signal-regulated kinase (ERK) and p38 phosphorylation. CONCLUSION: Our data suggested that curcumin protected the liver from chronic-ethanol induced injury through attenuating oxidative stress, at least partially, through ERK/p38/Nrf2-mediated anti-oxidant signaling pathways.

Dynamic magnetism of an iron(II)-chlorido spin chain and its hexametallic segment.

An air-stable iron(ii) chain compound [Fe(phen)(Cl)2]n (, phen = 1,10-phenanthroline) was prepared and exhibits intrachain ferromagnetic interactions as well as competing interchain antiferromagnetic interactions that are mediated by π-π stacking of the phen ligands, resulting in metamagnetic behaviour. The interchain interactions can be altered by changing the external magnetic field, and disparate magnetic dynamics was thus observed from zero to the critical field of 1500 Oe. Zero-field cooled (ZFC) and field-cooled (FC) magnetization and heat capacity measurements indicate that long-range antiferromagnetic ordering occurs at lower fields, and this ordering disappears when the external field is larger than 1500 Oe. The low-frequency ac susceptibility data are consistent with the exponential increase of the temperature-dependent dc data, indicating a Glauber-type dynamics under the field of 1500 Oe. Thus, is considered as a metamagnetic single-chain magnet. For further analysis, a discrete hexametallic segment of the chain, [Fe6(phen)6(Cl)12] (), was also isolated and was shown to possess a high-spin ground state and display slow magnetic relaxations like single-molecule magnets. Magnetic analysis using CONDON suggests weak ferromagnetic interactions between the metal centres. The polymeric compound can be viewed as being constructed using the hexametallic unit which is of a low energy barrier, suggesting the significance of intrachain ferromagnetic interactions in enhancing the spin-reversal energy barrier of the short chains.

Restraining the motion of a ligand for modulating the structural phase transition in two isomorphic polar coordination polymers.

A structural phase transition induced by ligand motion was found in a new polar coordination polymer: [Cu(NCS)2(4-APy)2]n (4-APy = 4-aminopyridine). Restraining such motion in an isomorphic compound [Cu(NCS)2(4-MeAPy)2]n (4-MeAPy = 4-methylaminopyridine) results in distinct phase transition behaviour. These findings provide a new clue for modulating phase transition behaviour in known materials.

Above-room-temperature ferroelastic phase transition in a perovskite-like compound [N(CH3)4][Cd(N3)3].

A new perovskite-like compound [N(CH3)4][Cd(N3)3] is reported here, which undergoes a series of reversible phase transitions including an above-room-temperature ferroelastic phase transition. An order-disorder mechanism is found in these structural transitions owing to the sway of the rod-like N3(-) bridges as well as the rotation of the tetrahedron-like [N(CH3)4](+) guests.

Magnetic variation induced by structural transformation from coordination chains to layers upon dehydration.

The reaction of CoBr(2), 1,2-di(4H-1,2,4-triazol-4-yl)diazene (bta) and KSCN yielded a one-dimensional coordination polymer [Co(SCN)(2)(bta)(H(2)O)(2)] with water molecules coordinated to the metal ions. After dehydration at 100 °C, the compound transformed into a layered coordination polymer [Co(SCN)(2)(bta)], whose structure was determined by powder X-ray diffraction based on the single-crystal structure of another layered coordination polymer [Cd(SCN)(2)(bta)]. Interestingly, a magnetic variation from a simple paramagnet to an antiferromagnetic ordered phase of a single-chain-magnet that exhibits both metamagnetic behaviour and slow magnetic relaxation was observed upon the dehydration process.

Chemical/physical pressure tunable spin-transition temperature and hysteresis in a two-step spin crossover porous coordination framework.

A two-dimensional (2D) square-grid type porous coordination polymer [Fe(bdpt)(2)]·guest (1·g, Hbdpt = 3-(5-bromo-2-pyridyl)-5-(4-pyridyl)-1,2,4-triazole) with isolated small cavities was designed and constructed as a spin-crossover (SCO) material based on octahedral Fe(II)N(6) units and an all-nitrogen ligand. Three guest-inclusion forms were successfully prepared for 1·g (1·EtOH for g = ethanol, 1·MeOH for g = methanol, 1 for g = Null), in which the guest molecules interact with the framework as hydrogen-bonding donors. Magnetic susceptibility measurements showed that 1·g exhibited two-step SCO behavior with different transition temperatures (1·EtOH < 1·MeOH < 1) and hysteresis widths (1·EtOH > 1·MeOH > 1 ≈ 0). Such guest modulation of two-step spin crossover temperature and hysteresis without changing two-step state in a porous coordination framework is unprecedented. X-ray single-crystal structural analyses revealed that all two-step SCO processes were accompanied with interesting symmetry-breaking phase transitions from space group of P2(1)/n for all high-spin Fe(II), to P1 for ordered half high-spin and half low-spin Fe(II), and back to P2(1)/n for all low-spin Fe(II) again by lowering temperature. The different SCO behaviors of 1·g were elucidated by the steric mechanism and guest-host hydrogen-bonding interactions. The SCO behavior of 1·g can be also controlled by external physical pressure.

A one-dimensional coordination polymer exhibiting simultaneous spin-crossover and semiconductor behaviour.

A rare organosulfur one-dimensional coordination polymer, [Co(C(9)H(6)NS)(2)], was synthesized by the reaction between the 8-mercaptoquinoline and cobalt acetate salts in EtOH, which shows strong magnetic coupling and the presence of spin-glassy and spin-crossover phenomena with simultaneous semiconductor behaviour.

Hepatotoxicity and gene expression down-regulation of CYP isozymes caused by renal ischemia/reperfusion in the rat.

Renal ischemia/reperfusion (I/R) occurs in many clinical scenarios, including trauma, elective surgery, and transplantation. Events initiated by this process can lead to inflammation in the kidneys, culminating in local injury as well as distant organ dysfunction. The objectives of this study were to investigate the changes in the functions of the liver and the regulation of gene expression of cytochrome P450 (CYP) isozymes after renal I/R. Hepatoxocity was assessed by serum alanine aminotransferase (sALT), serum aspartate aminotransferase (sAST) and liver glutathione-S-transferase (GST) activities, liver glutathione (GSH) level, and histopathological examination. Hepatic cytochrome P4503A1 (CYP3A1) and cytochrome P4502E1 (CYP2E1) activities were measured by erythromycin N-demethylase (ERD) and aniline hydroxylase (ANH) activities, respectively. CYP3A1 and CYP2E1 mRNA expression was determined by RT-PCR. Results showed that activities of sALT and sAST were significantly increased, while hepatic CYP3A1and CYP2E1 activities as well as their respective mRNA levels were significantly decreased after renal I/R. Moreover, hepatic tissue congestion, degeneration, and local necrosis were observed in rats after 1, 4, and 8h renal reperfusion following 2h renal ischemia. In conclusion, the present study suggests that renal I/R can cause hepatotoxicity and gene expression down-regulation of CYP isozymes in rats.