Ginsenoside Rb1 protects dopaminergic neurons from inflammatory injury induced by intranigral lipopolysaccharide injection

Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson’s disease.Ginsenoside Rbl,the most active ingredient of ginseng,reportedly exerts neuroprotective effects by suppressing inflammation in vitro.The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rbl in a lipopolysaccharide-induced rat Parkinson’s disease model.Rats were divided into four groups.In the control group,sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days.In the ginsenoside Rbl group,ginsenoside Rb1(20 mg/kg)was intraperitoneally injected for 14 consecutive days after sham surgery.In the lipopolysaccharide group,a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson’s disease model.Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days.In the ginsenoside Rbl +lipopolysaccharide group,lipopolysaccharide was unilaterally microinjected into the rat substantial nigra.Subsequently,ginsenoside Rbl was intraperitoneally injected for 14 consecutive days.To investigate the therapeutic effects of ginsenoside Rbl,behavioral tests were performed on day 15 after lipopolysaccharide injection.We found that ginsenoside Rbl treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group.To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rbl,contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography.Compared with the lipopolysaccharide group,ginsenoside Rbl obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites in the striatum.To further explore the neuroprotective effect of ginsenoside Rbl against lipopolysaccharide-induced neurotoxicity,immunohistochemistry and western blot assay of tyrosine hydroxylase were performed to evaluate dopaminergic neuron degeneration in the substantial nigra par compacta.The results showed that lipopolysaccharide injection caused a large loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra and a significant decrease in overall tyrosine hydroxylase expression.However,ginsenoside Rb1 noticeably reversed these changes.To investigate whether the neuroprotective effect of ginsenoside Rbl was associated with inhibition of lipopolysaccharide-induced microglial activation,we examined expression of the microglia marker Iba-1.Our results confirmed that lipopolysaccharide injection induced a significant increase in Iba-1 expression in the substantia nigra;however,ginsenoside Rbl effectively suppressed lipopolysaccharide-induced microglial overactivation.To elucidate the inhibitory mechanism of ginsenoside Rb1,we examined expression levels of inflammatory mediators(tumor necrosis factor-a,interleukin-1β,inducible nitric oxide synthase,and cyclooxygenase 2)and phosphorylation of nuclear factor kappa B signaling-related proteins(IκB,IKK)in the substantia nigra with enzyme-linked immunosorbent and western blot assays.Our results revealed that compared with the control group,phosphorylation and expression of inflammatory mediators IκB and IKK in the substantia nigra of lipopolysaccharide group rats were significantly increased;whereas,ginsenoside Rbl obviously reduced lipopolysaccharide-induced changes on the lesioned side of the substantial nigra par compacta.These findings confirm that ginsenoside Rbl can inhibit inflammation induced by lipopolysaccharide injection into the substantia nigra and protect dopaminergic neurons,which may be related to its inhibition of the nuclear factor kappa B signaling pathway.This study was approved by the Experimental Animal Ethics Committee of Shandong University of China in April 2016(approval No.KYLL-2016-0148).

Differential hepatic features presenting in Wilson disease-associated cirrhosis and hepatitis B-associated cirrhosis

BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses,alcoholism, and metabolic disorders, such as Wilson disease(WD). There are no clear markers or clinical features that define cirrhosis originating from these disparate origins. We hypothesized that cirrhosis is not one disease and cirrhosis of different etiology may have differential clinical hepatic features.AIM To delineate the liver features between WD-associated cirrhosis and hepatitis Bassociated cirrhosis in the Chinese population.METHODS In this observational study, we reviewed the medical data of consecutive inpatients who had WD-associated cirrhosis or hepatitis B-associated cirrhosis from January 2010 to August 2018, and excluded patients who had carcinoma,severe heart or pulmonary diseases, or other liver diseases. According to the etiology of cirrhosis, patients were divided into two groups: WD-associated cirrhosis group(60 patients) and hepatitis B-associated cirrhosis group(56 patients). The liver fibrosis degree, liver function indices, and portal hypertension features of these patients were compared between the two groups.RESULTS No inter-group differences were observed in the diagnostic liver fibrosis markers,however, clinical features clearly defined the origin of cirrhosis. WD-associated cirrhosis patients(16-29 years) had lower levels of alanine transaminase,aspartate transaminase, and bilirubin, lower prothrombin time, lower incidence of hepatic encephalopathy, and lower portal vein diameter(P < 0.05), compared to cirrhosis resulting from hepatitis B in older patients(45-62 years). Importantly,they had decreased risks of progression from Child-Pugh grade A to B(odds ratio = 0.046, 95% confidence interval: 0.006-0.387, P = 0.005) and of ascites(odds ratio = 0.08, 95% confidence interval: 0.01-0.48, P = 0.005). Conversely, WDassociated cirrhosis patients had a higher risk of splenomegaly(odds ratio = 4.15,95% confidence interval: 1.38-12.45, P = 0.011).CONCLUSION WD-associated cirrhosis presents a higher risk of splenomegaly associated with leukopenia and thrombocytopenia, although revealing milder liver dysfunction and portal hypertension symptoms, which recommends WD patients to be monitored for associated complications.

Comment on 'Efficacy and adverse events of cold vs hot polypectomy: A meta-analysis'

This is a comment on a meta-analysis of published studies comparing cold vs hot polypectomy. We believe that the conclusion of this meta-analysis that "cold polypectomy is a time-saving procedure for removing small polyps with markedly similar curability and safety to hot polypectomy" needs more rigorous evidence.

Fabrication and analysis of TIG welding-brazing butt joints of in-situ TiB2/7050 composite and TA2

Lightweight hybrid structures of Al MMCs and titanium alloy dissimilar materials have great prospect in the defence industry application. So, it is necessary to join Al MMCs with Ti metal to achieve this structural design. In this work, in-situ Ti B_(2)/7050 composite and TA2 were firstly attempted to join by TIG welding-brazing technique. The result was that the intact welding-brazing butt joint was successfully fabricated. The joint presents dual characteristics, being a brazing on TA2 side and a welding on Ti B_(2)/7050 side. At brazing joint side, ER4043 filler metal effectively wets on TA2 under TIG heating condition,and a continuous interfacial reaction layer with 1 e3 mm is formed at welded metal/TA2 interface. The whole interfacial reaction layers are composed of Ti(Al Si)3 intermetallic compounds(IMCs), but their morphologies at the different regions present obvious distinguishes. The microhardness of the reaction layers is as much as 141 e190 HV. At welding joints side, the fusion zone appears the equixaed crystal structure, and the grain sizes are much smaller than those of welded metal, which is attributed to the effect of Ti B2 particulates from the melted Ti B_(2)/7050 on acceleration formation and inhibiting growth for the new crystal nucleus. The tensile test results show that average tensile strength of the optimal welding-brazing joint is able to achieve 138 MPa. The failure of the tensile joint occurs by quasi-cleavage pattern, and the cracks initiate from the IMCs layer at the groove surface of TA2 and propagate into the welded metal.

A review and perspective on molybdenum-based electrocatalysts for hydrogen evolution reaction

Water electrolysis has been considered as a sustainable way for producing renewable energy of hydrogen.However,this process requires a low-cost and high-efficient hydrogen evolution reaction(HER)catalyst to improve the overall reaction efficiency.Molybdenum(Mo)-based electrocatalysts are regarded as the promising candidates to replace the benchmark but expensive Ptbased HER catalysts,due to their high activity and stability in a wide pH range.In this review,we present a comprehensive and critical summary on the recent progress in the Mo-based electrodes for HER,including molybdenum alloys,molybdenum sulfides,molybdenum selenides,molybdenum carbides,molybdenum phosphides,molybdenum borides,molybdenum nitrides,and molybdenum oxides.Particular attention is mainly focused on the synthetic methods of Mo-based materials,the strategies for increasing the catalytic activity,and the relationship between structure/composition and electrocatalytic performance.Finally,the future development and perspectives of Mo-based electrocatalysts toward high HER performance are proposed.