Biochanin A impedes STAT3 activation by upregulating p38δ MAPK phosphorylation in IL-6-stimulated macrophages

Inflammation Research - IL-6-induced STAT3 activation is associated with various chronic inflammatory diseases. In this study, we investigated the anti-STAT3 mechanism of the dietary polyphenol,...     

PCR-RFLP analysis indicates that recombination might be a common occurrence among the cassava infecting begomoviruses in India

Cassava mosaic disease (CMD) is caused in India by two bipartite begomoviruses, Indian cassava mosaic virus (ICMV), and Sri Lankan cassava mosaic virus (SLCMV). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used as a rapid means of investigating the molecular diversity of ICMV and SLCMV in 38 samples of CMD-affected cassava plants under field conditions in new areas of cassava cultivation, along with traditional areas in southern India. A very large proportion of the samples showed SLCMV, based on a discriminatory PCR between SLCMV and ICMV, reported earlier. PCR-RFLP analysis of three regions of viral DNA indicated that in most samples, although the AC1 and the AV1 resembled SLCMV, as expected, the intergenic regions (binding site for host replication machinery) resembled ICMV more closely, indicating recombination events between ICMV and SLCMV. Results also indicate that the AC1 is more conserved within SLCMV compared to the AV1 gene.     

Sequencing and computational analysis of complete genome sequences of <Emphasis Type="Italic">Citrus yellow mosaic badna virus</Emphasis> from acid lime and pummelo

Citrus yellow mosaic badna virus (CMBV), a member of the Family Caulimoviridae, Genus Badnavirus, is the causative agent of Citrus mosaic disease in India. Although the virus has been detected in several citrus species, only two full-length genomes, one each from Sweet orange and Rangpur lime, are available in publicly accessible databases. In order to obtain a better understanding of the genetic variability of the virus in other citrus mosaic-affected citrus species, we performed the cloning and sequence analysis of complete genomes of CMBV from two additional citrus species, Acid lime and Pummelo. We show that CMBV genomes from the two hosts share high homology with previously reported CMBV sequences and hence conclude that the new isolates represent variants of the virus present in these species. Based on in silico sequence analysis, we predict the possible function of the protein encoded by one of the five ORFs. The nucleotide sequences reported in this paper have been submitted to the NCBI GenBank nucleotide sequence database and have been assigned the accession numbers EU489744 and EU489745.     

Agroinfection of cloned Sri Lankan cassava mosaic virus DNA to <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis>, <Emphasis Type="Italic">Nicotiana tabacum</Emphasis> and cassava

Sri Lankan cassava mosaic virus (SLCMV) is a bipartite begomovirus infecting cassava in India and Sri Lanka. We have used Agrobacterium-mediated inoculation (agroinoculation) of cloned SLCMV DNA to inoculate additional hosts, Nicotiana tabacum and Arabidopsis. Although SLCMV infection in these hosts caused stunting, leaf deformation and developmental abnormalities, accumulation levels of viral DNA in the infected plants suggested that this virus was poorly adapted to them. In the natural host, cassava, agroinoculation produced infection at a low frequency. The monopartite nature of SLCMV, reported earlier in N. benthamiana, was maintained in the new hosts as well as in cassava.     

Contribution of β-phenethylamine, a component of chocolate and wine, to dopaminergic neurodegeneration： implications for the pathogenesis of Parkinson＇s disease

While the cause of dopaminergic neuronal cell death in Parkinson＇s disease（PD）is not yet understood,many endogenous molecules have been implicated in its pathogenesis.β-phenethylamine（β-PEA）,a component of various food items including chocolate and wine,is an endogenous molecule produced from phenylalanine in the brain.It has been reported recently that long-term administration ofβ-PEA in rodents causes neurochemical and behavioral alterations similar to that produced by parkinsonian neurotoxins.The toxicity ofβ-PEA has been linked to the production of hydroxyl radical（.OH）and the generation of oxidative stress in dopaminergic areas of the brain,and this may be mediated by inhibition of mitochondrial complex-I.Another significant observation is that administration ofβ-PEA to rodents reduces striatal dopamine content and induces movement disorders similar to those of parkinsonian rodents.However,no reports are available on the extent of dopaminergic neuronal cell death after administration ofβ-PEA.Based on the literature,we set out to establishβ-PEA as an endogenous molecule that potentially contributes to the progressive development of PD.The sequence of molecular events that could be responsible for dopaminergic neuronal cell death in PD by consumption ofβ-PEA-containing foods is proposed here.Thus,long-term over-consumption of food items containingβ-PEA could be a neurological risk factor having significant pathological consequences.     

Impact of thromboprophylaxis guidelines on clinical outcomes following total hip and total knee replacement

Background

The American College of Chest Physicians (ACCP) guidelines recommends thromboprophylaxis for total hip replacement (THR) and total knee replacement (TKR) patients. We examined alignment with ACCP thromboprophylaxis guidelines among THR/TKR patients, and compared symptomatic venous thromboembolism (VTE), bleeding event rates and risk factors for VTE between patients receiving ACCP-recommended thromboprophylaxis (‘ACCP’) and those who did not (‘non-ACCP’).

Methods

This retrospective observational study used a large US health plan claims database that was linked to an inpatient database containing detailed inpatient medication use and a database containing date-of-death information. Patients who had THR/TKR surgery between April 01, 2004 and December 31, 2006 were included. Comparisons of VTE and bleeding events between ACCP and non-ACCP patients were analyzed using chi-squared tests and multivariate logistic regression.

Results

Of 3,497 linked patients, 1,395 (40%) received ACCP recommended thromboprophylaxis. Of the patients who received non-ACCP recommended prophylaxis the majority (81%) received shorter than the recommended minimum 10 day prophylaxis and 118 (5.6%) of patients received no prophylaxis. Overall, non-ACCP patients were almost twice as likely to experience an incident DVT (3.76% versus 2.01%, p = 0.003) and more than eight times as likely to experience an incident PE (1.19% versus 0.14%, p = 0.001) relative to ACCP patients; there were no statistically significant difference in bleeding rates. Multivariate logistic regression indicated that the odds of a VTE event were significantly lower for ACCP patients (DVT: OR = 0.54; p = 0.006; PE: OR = 0.12; p = 0.004).

Conclusions

This study offers a unique perspective on ‘real-world’ thromboprophylaxis patterns and associated outcomes in THR and TKR patients in the US. It suggests that only 40% of THR/TKR patients receive ACCP-recommended thromboprophylaxis and that not receiving ACCP thromboprophylaxis is an independent risk factor for both DVT and PE.     

Attenuation of Aluminum Chloride-Induced Neuroinflammation and Caspase Activation Through the AKT/GSK-3β Pathway by Hesperidin in Wistar Rats

Hesperidin, a flavanoglycone abundantly present in citrus fruits, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties. Previous reports from our laboratory indicated the neuroprotective effect of hesperidin against aluminum chloride (AlCl₃)-induced memory loss, acetylcholine esterase hyperactivity, oxidative stress, and enhanced expression of amyloid β protein biosynthesis-related markers. However, their role on AlCl₃-induced inflammation, caspase activation, Tau pathology, altered Akt/GSK 3β signaling pathway, and Aβ clearance marker has not yet been fully elucidated. Intraperitonial injection of AlCl₃ (100 mg/kg body weight) for 60 days significantly elevated the expressions of insulin-degrading enzyme (IDE), cyclin-dependent kinase 5 (CDK 5), and phosphoTau (pTau); inflammatory markers such as glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), NF-kB, cyclooxygenase-2 (COX-2), interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS); and apoptotic markers including cytosolic cytochrome c (cyto c), caspase-3, caspase-8, and caspase-9, and lowered expressions of mitochondrial cyto c, phospho-Akt (pAkt) and phospho-glycogen synthase kinase-3β (pGSK-3β) in the hippocampus and cortex. Co-administration of hesperidin to AlCl₃ rats for 60 days significantly ameliorated the aluminum-induced pathological changes. The behavioral studies also supported the above findings. Our results imply that treatment with hesperidin might be a potent option for treating the symptoms of cognitive impairment in Alzheimer’s disease by targeting its most prominent hallmarks.     

Effectiveness of a mindfulness-based cognitive therapy program as an adjunct to pharmacotherapy in patients with panic disorder

Mindfulness-based cognitive therapy (MBCT) has been studied to treat patients with depressive or anxiety disorders. The aim of this study was to examine whether MBCT is effective as an adjunct to pharmacotherapy in the treatment of patients with panic disorder. Twenty-three patients with panic disorder were included in a MBCT program for a period of 8 weeks. The Hamilton Anxiety Rating Scale (HAM-A), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Anxiety Sensitivity Index-Revised (ASI-R), Albany Panic and Phobia Questionnaire (APPQ), and Panic Disorder Severity Scale (PDSS) were used to assess the patients during the MBCT program. Both HAM-A and PDSS scores were significantly decreased at the 2nd, 4th and 8th weeks compared to baseline in the patients with panic disorder (HAM-A, p < 0.01; PDSS, p < 0.01). Also, BAI, APPQ and ASI-R were improved significantly after MBCT program (BAI, p < 0.01; APPQ, p < 0.01; ASI-R, p < 0.01). In addition, all subscale scores of ASI-R decreased significantly. MBCT could be effective as an adjunct to pharmacotherapy in patients with panic disorder. However, randomized controlled trials are needed.     

Melatonin inhibits 6-hydroxydopamine production in the brain to protect against experimental parkinsonism in rodents

Abstract:  We tested the hypothesis that melatonin regulates formation of 6-hydroxydopamine (6-OHDA) in the brain and thereby protects animals from dopaminergic neurotoxicity and the development of parkinsonism in animals. Employing a ferrous-ascorbate-dopamine (FAD) hydroxyl radical (^•OH) generating system, in the present study we demonstrate a dose-dependent attenuation of 6-OHDA generation by melatonin in vitro. Intra-median forebrain bundle infusion of FAD caused significant depletion of striatal dopamine (DA), which was blocked by melatonin. Per-oral administration of l -3,4-dihydroxyphenylalanine (l -DOPA) for 7 days caused a dose-dependent increase in the formation of 6-OHDA in the mouse striatum, which was increased synergistically by the systemic administration of the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the 7th day of l -DOPA treatment. Melatonin treatment significantly attenuated both the l -DOPA and MPTP-induced increases in the levels of striatal 6-OHDA, and protected against striatal DA depletion caused by the neurotoxin. These observations suggest a novel mode of melatonin-induced dopaminergic neuroprotection in two models of Parkinson's disease, and suggest the possible therapeutic use of this well-known antioxidant indoleamine neurohormone in parkinsonism.