A Novel Antihepatitis Drug, Bicyclol, Prevents Liver Carcinogenesis in Diethylnitrosamine-Initiated and Phenobarbital-Promoted Mice Tumor Model

Bicyclol, an antihepatitis drug developed by Chinese scientists, has been shown to prevent the malignant transformation induced by 3-methylcholanthrene and 12-O-tetradecanoylphorbol-13-acetate in WB-F344 rat liver epithelial cells. This study provides further evidence on its role as a chemopreventive agent in experimental mice with diethylnitrosamine- (DEN-) initiated and phenobarbital- (PB-) promoted liver carcinoma. Liver tissue and serum were collected. In the two-stage model of hepatocarcinogenesis in mice, oral administration of bicyclol (100, 200 mg/kg) before DEN injection showed significant reduction in the incidence of hepatocellular foci, nodules, or carcinoma. Histopathological examination revealed that there was no hepatocellular carcinoma (HCC) and hepatoma formation in the mice pretreated with bicyclol (200 mg/kg) at week 20, while the mice treated with DEN/PB developed 33.3% HCC and 55.6% hepatoma. Furthermore, the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and α-fetal protein (AFP) in serum significantly increased in the DEN/PB model group in comparison with the control group. Pretreatment with bicyclol showed a marked reduction in the above condition. Bicyclol also decreased the expression of AFP and proliferating cell nuclear antigen level in the liver tissue and attenuated the decrease in body weight. In this study, we also found that 10 weeks after stopping the administration of PB and drugs, the control and bicyclol-treated (200 mg/kg) animals showed no HCC and hepatoma formation at the time of termination whereas DEN/PB-induced mice developed 100% hepatoma and 50% HCC. These results further indicate that bicyclol has the chemopreventive potential for liver carcinogenesis induced by carcinogens

Squamosamide derivative FLZ protects dopaminergic neurons against inflammation-mediated neurodegeneration through the inhibition of NADPH oxidase activity

<p>Abstract</p> <p>Background</p> <p>Inflammation plays an important role in the pathogenesis of Parkinson's disease (PD) through over-activation of microglia, which consequently causes the excessive production of proinflammatory and neurotoxic factors, and impacts surrounding neurons and eventually induces neurodegeneration. Hence, prevention of microglial over-activation has been shown to be a prime target for the development of therapeutic agents for inflammation-mediated neurodegenerative diseases.</p> <p>Methods</p> <p>For <it>in vitro </it>studies, mesencephalic neuron-glia cultures and reconstituted cultures were used to investigate the molecular mechanism by which FLZ, a squamosamide derivative, mediates anti-inflammatory and neuroprotective effects in both lipopolysaccharide-(LPS)- and 1-methyl-4-phenylpyridinium-(MPP⁺)-mediated models of PD. For <it>in vivo </it>studies, a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-(MPTP-) induced PD mouse model was used.</p> <p>Results</p> <p>FLZ showed potent efficacy in protecting dopaminergic (DA) neurons against LPS-induced neurotoxicity, as shown in rat and mouse primary mesencephalic neuronal-glial cultures by DA uptake and tyrosine hydroxylase (TH) immunohistochemical results. The neuroprotective effect of FLZ was attributed to a reduction in LPS-induced microglial production of proinflammatory factors such as superoxide, tumor necrosis factor-α (TNF-α), nitric oxide (NO) and prostaglandin E₂(PGE₂). Mechanistic studies revealed that the anti-inflammatory properties of FLZ were mediated through inhibition of NADPH oxidase (PHOX), the key microglial superoxide-producing enzyme. A critical role for PHOX in FLZ-elicited neuroprotection was further supported by the findings that 1) FLZ's protective effect was reduced in cultures from PHOX^-/-mice, and 2) FLZ inhibited LPS-induced translocation of the cytosolic subunit of p47^PHOXto the membrane and thus inhibited the activation of PHOX. The neuroprotective effect of FLZ demonstrated in primary neuronal-glial cultures was further substantiated by an <it>in vivo </it>study, which showed that FLZ significantly protected against MPTP-induced DA neuronal loss, microglial activation and behavioral changes.</p> <p>Conclusion</p> <p>Taken together, our results clearly demonstrate that FLZ is effective in protecting against LPS- and MPTP-induced neurotoxicity, and the mechanism of this protection appears to be due, at least in part, to inhibition of PHOX activity and to prevention of microglial activation.</p

Protective effect of schisanhenol against alloxan-induced inhibition of glucose-stimulated insulin release

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Anticonvulsant activity of B2, an adenosine analog, on chemical convulsant-induced seizures.

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is a N(6)-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP), pentylenetetrazol (PTZ), picrotoxin, kainite acid (KA), or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A1 and A2A receptors. Furthermore, DPCPX, a selective A1 receptor antagonist, but not SCH58261, a selective A2A receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A1 receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy

Facile synthesis of Co-Fe-B-P nanochains as an efficient bifunctional electrocatalyst for overall water-splitting

Design of cost-effective bifunctional electrocatalysts for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is vital for developing hydrogen energy for the future. Herein, a cost-effective phosphorus-doped Co-Fe-B material with chain-like structure (denoted as Co₁-Fe₁-B-P) is reported as an efficient and novel bifunctional electrocatalyst for the OER and HER, and was produced via a facile water-bath synthesis and subsequent phosphorization. For the OER, the as-prepared Co₁-Fe₁-B-P nanochains require an extremely low overpotential of about 225 mV at 10 mA cm⁻² and possess a small Tafel slope of 40 mV dec⁻¹ in alkaline media. Impressively, the HER properties of Co₁-Fe₁-B-P nanochains are superior to those of P-free Co-Fe-B in terms of overpotential at 10 mA cm⁻² (173 mV vs. 239 mV) and kinetic Tafel slope (96 mV dec⁻¹ vs. 105 mV dec⁻¹). The synergetic effect between Co-Fe-B and doped-P is mainly responsible for the satisfactory bifunctional performance, while the one-dimensional (1D) chain-like structure endows Co₁-Fe₁-B-P with abundant catalytically active sites that enhance the atom utilization efficiency. Moreover, the developed Co₁-Fe₁-B-P nanochains can be simultaneously utilized as both the cathode and anode for overall water-splitting, which requires a cell voltage of only 1.68 V to deliver 10 mA cm⁻². This work provides a feasible and promising protocol to realize metal borides as efficient electrocatalysts in energy-related applications.This work was supported by the Taishan Scholar Program of Shandong Province, China (ts201712045), the Key Research and Development Program of Shandong Province (2018GGX104001), the Natural Science Foundation of Shandong Province of China (ZR2017MB054 and ZR201807060818) and the Doctoral Fund of QUST (0100229001 and 010022873)

3D Robust Carbon Aerogels Immobilized with Pd₃Pb Nanoparticles for Oxygen Reduction Catalysis

Development of desired electrocatalysts with high activity, excellent stability, and high selectivity for oxygen reduction reaction (ORR) is of significant importance for fuel cells. Herein, a high-efficiency electrocatalyst for the ORR is reported which utilizes a cross-linked carbon aerogel of reduced oxide graphene (rGO), and carbon nanotubes (CNTs) functioned as a three-dimensionally (3D) scaffold for anchoring ordered Pd₃Pb nanoparticles (Pd₃Pb/rGO-CNTs). The Pd₃Pb/rGO-CNTs were synthesized by a facile and scalable route, mainly depending on the formation of a poly­(vinyl alcohol) cross-linked GO-CNTs double-network hydrogel that allows for the efficient capture of highly active Pd₃Pb particles after pyrolysis. The resulting composite exhibits remarkable ORR performances in terms of high half-wave potential, excellent stability, and methanol tolerance ability, resulting from the synergistic effect of ordered structure of Pd₃Pb phase and 3D interconnected double-network of rGO-CNTs aerogels. The ordered Pd₃Pb intermetallic compounds mainly work as the active centers for the ORR, while rGO-CNTs aerogels not only prevent Pd₃Pb nanoparticles from aggregation but also provide open and accessible pores for fast transportation of reactants to the active centers

Boosting oxygen reduction catalysis with n-doped carbon coated Co9S8 microtubes

Herein, nitrogen-doped carbon coated hollow Co9S8 microtubes (Co9S8@N–C microtubes) are prepared through a facile solvothermal procedure, followed by dopamine polymerization process together with a post-pyrolysis which present excellent electrocatalytic activity for oxygen reduction reaction (ORR). The Co9S8 within the hollow Co9S8@N–C microtubes presents a well-defined single-crystal structure with dominated (022) plane. To obtain desired electrocatalyst, the annealing temperature and the thickness of carbon layer tuned by changing the dopamine concentration are optimized systematically. The electrochemical results demonstrate that the coordination of the N-doped carbon layer, exposed (022) plane, and hollow architecture of Co9S8 microtubes calcined at 700 °C affords outstanding ORR performance to Co9S8@N–C microtubes. The moderate thickness of the carbon layer is crucial for improving ORR activity of Co9S8@N–C microtubes, while increasing or decreasing the thickness would result in activity decrease. More importantly, the N-doped carbon layer can protect inner Co9S8 from undergoing aggregation and dissolution effectively during the ORR, resulting in excellent electrocatalytic stability

Oxygen Vacancy-Rich In-Doped CoO/CoP Heterostructure as an Effective Air Cathode for Rechargeable Zn-Air Batteries

An efficient and low-cost electrocatalyst for reversible oxygen electrocatalysis is crucial for improving the performance of rechargeable metal-air batteries. Herein, a novel oxygen vacancy-rich 2D porous In-doped CoO/CoP heterostructure (In-CoO/CoP FNS) is designed and developed by a facile free radicals-induced strategy as an effective bifunctional electrocatalyst for rechargeable Zn-air batteries. The electron spin resonance and X-ray absorption near edge spectroscopy provide clear evidence that abundant oxygen vacancies are formed in the interface of In-CoO/CoP FNS. Owing to abundant oxygen vacancies, porous heterostructure, and multiple components, In-CoO/CoP FNS exhibits excellent oxygen reduction reaction activity with a positive half-wave potential of 0.81 V and superior oxygen evolution reaction activity with a low overpotential of 365 mV at 10 mA cm(-2). Moreover, a home-made Zn-air battery with In-CoO/CoP FNS as an air cathode delivers a large power density of 139.4 mW cm(-2), a high energy density of 938 Wh kg(Zn)(-1), and can be steadily cycled over 130 h at 10 mA cm(-2), demonstrating great application potential in rechargeable metal-air batteries

Robust N-doped carbon aerogels strongly coupled with iron – cobalt particles as efficient bifunctional catalysts for rechargeable Zn – air batteries

The rational design of highly-active and stable reversible oxygen electrocatalysts for both the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) plays a key role in rechargeable metal–air batteries, yet remains a great challenge. Herein, a novel dual-crosslinked hydrogel strategy is proposed to synthesize a new type of carbon aerogel that anchors the iron–cobalt (FeCo) particles as a bifunctional oxygen catalyst. The proposed hydrogel composed of an organic/inorganic network can be easily obtained by initiating sol–gel polymerization of cyanometalates, chitosan and graphene oxide. After pyrolysis, FeCo nanocrystals can be in situ uniformly immobilized within the N-doped “dual-network” carbon aerogels (FeCo/N-DNC) with a robust 3D porous framework. When used as an electrocatalyst, the newly developed FeCo/N-DNC aerogels exhibit a positive onset potential (0.89 V) and half-wave potential (0.81 V) for the ORR and a low overpotential (0.39 V) at 10 mA cm−2 for the OER, while presenting excellent electrochemical stability after being tested for 10 000 s. More importantly, the FeCo/N-DNC driven Zn–air battery reveals a smaller charge/discharge voltage gap, higher power/energy density and better cycling stability than the costlier Pt/C + RuO2 mixture catalyst. Our findings provide a facile and feasible synthetic strategy for obtaining highly active and stable electrocatalysts