Eriocaulon buergerianum extract protects PC12 cells and neurons in zebrafish against 6-hydroxydopamine-induced damage

<p>Abstract</p> <p>Background</p> <p><it>Ericaulon buergerianum </it>(<it>Gujingcao</it>) is an ophthalmic, anti-inflammatory and antimicrobial Chinese medicinal herb. This study aims to investigate the neuroprotective effects of <it>Ericaulon buergerianum </it>ethanol extract (EBE) and to elucidate its underlying action mechanism.</p> <p>Methods</p> <p>The viability of dopaminergic (DA) neuron in zebrafish was examined by anti-tyrosine hydroxylase (TH) immunostaining. The locomotor activity of zebrafish was assessed with a digital video tracking system. The viability and cellular damage of the PC12 cells were determined by MTT and LDH assays respectively. The nuclear morphological changes in apoptotic cells were evaluated with DNA staining by Hoechst 33342 dye. Intracellular nitric oxide (NO) was quantified by DAF-FM diacetate staining. The expression of inducible nitric oxide synthase (iNOS) was determined by Western blot.</p> <p>Results</p> <p>EBE inhibited the 6-OHDA-induced decrease in total distance of movement in zebrafish. Pretreatments of EBE (25, 50, 100 and 200 μg/ml) increased the viability of 6-OHDA-damaged PC12 cells in a dose dependent manner. Protection against 6-OHDA-induced nuclear fragmentation and accumulation of apoptotic bodies was also observed in EBE pretreated cells. Anti-oxidative (inhibition of NO production and iNOS expression in PC12 cells <it>in vitro</it>) activities of EBE are related to its neuroprotective effects in 6-OHDA-induced DA neuron damage.</p> <p>Conclusion</p> <p>EBE exhibited significant neuroprotective activities in zebrafish, including recovery of dopaminergic neuron loss caused by 6-OHDA in a dose-dependent manner <it>in vivo</it>, inhibition of 6-OHDA-induced decrease of total distance in movement in zebrafish. The iNOS-NO pathway may be involved.</p

Hong Kong Renal Registry Report 2012

SummaryThis report examined the characteristics and trends of dialysis and renal transplant patients among the resident population of Hong Kong who were managed by hospitals or dialysis centers of the Hospital Authority, and accounted for approximately 95% of all patients receiving renal replacement therapies (RRTs) in the territory. Patients receiving RRTs solely in the private sector were not included in this report. Data trends from 1996 to 2011 are presented. In 2011, 1115 new patients were accepted into RRT programs, and the incident rate was 157 patients per million populations (pmp). An increasing trend was noted. The incident rate was 95.1 pmp at the commencement of the annual report in 1996. The point prevalence on December 31, 2012 was 8197 with a prevalence rate of 1152.5 pmp. Overall, there were 3573 patients (43.6%) on peritoneal dialysis (PD) and 1246 patients (15.2%) on hemodialysis (HD), and 3378 patients (41.2%) were living with a functioning renal transplant. The PD/HD ratio was 74.2:25.8. The “PD First” policy was continued. The overall mortality rate among RRT patients was 9.95 patients per 100 patient-years exposed. There was a decreasing trend in mortality among PD patients. Infection and cardiovascular complications were the most common causes of death. Renal transplant was the modality with the best survival rates. The 5 years cumulative patient survival rate for patients on transplant treatment was 89.6%, whereas the corresponding patient survival rates for PD and HD patients were 50.7% and 55.7%, respectively. More than 70% of RRT patients with reports on rehabilitation were active and had normal daily activities

An International Collaborative Consensus Statement on En Bloc Resection of Bladder Tumour Incorporating Two Systematic Reviews, a Two-round Delphi Survey and a Consensus Meeting

Funding/Support and role of the sponsor: This study was supported by the General Research Fund/Early Career Scheme of the Research Grants Council, Hong Kong, China (reference no. 24116518).Peer reviewedPostprin

The histone H3K36 demethylase Rph1/KDM4 regulates the expression of the photoreactivation gene PHR1

The dynamics of histone methylation have emerged as an important issue since the identification of histone demethylases. We studied the regulatory function of Rph1/KDM4 (lysine demethylase), a histone H3K36 demethylase, on transcription in Saccharomyces cerevisiae. Overexpression of Rph1 reduced the expression of PHR1 and increased UV sensitivity. The catalytically deficient mutant (H235A) of Rph1 diminished the repressive transcriptional effect on PHR1 expression, which indicates that histone demethylase activity contributes to transcriptional repression. Chromatin immunoprecipitation analysis demonstrated that Rph1 was associated at the upstream repression sequence of PHR1 through zinc-finger domains and was dissociated after UV irradiation. Notably, overexpression of Rph1 and H3K36A mutant reduced histone acetylation at the URS, which implies a crosstalk between histone demethylation and acetylation at the PHR1 promoter. In addition, the crucial checkpoint protein Rad53 acted as an upstream regulator of Rph1 and dominated the phosphorylation of Rph1 that was required for efficient PHR1 expression and the dissociation of Rph1. The release of Rph1 from chromatin also required the phosphorylation at S652. Our study demonstrates that the histone demethylase Rph1 is associated with a specific chromatin locus and modulates histone modifications to repress a DNA damage responsive gene under control of damage checkpoint signaling

CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia

Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL

Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong

We report a multicenter study of Chinese children in Hong Kong with systemic lupus erythematosus (SLE) nephritis. Children were included if: they fulfilled the ACR criteria, had significant proteinuria or casturia, were Chinese and younger than 19 years and had been diagnosed with SLE between January 1990 and December 2003. Investigators in each center retrieved data on clinical features, biopsy reports, treatment and outcome of these patients. There were 128 patients (eight boys, 120 girls; mean age: 11.9+/-2.8 years). About 50% presented with multisystem illness and 40% with nephritic/nephrotic symptoms. Negative anti-dsDNA antibodies were found in 6% of the patients. Renal biopsy revealed WHO Class II, III, IV and V nephritis in 13 (10%), 22 (17%), 69 (54%) and 13 (10%) patients, respectively. The clinical severity of the nephritis did not accurately predict renal biopsy findings. The follow-up period ranged from 1 to 16.5 years (mean+/-SD: 5.76+/-3.61 years). During the study five patients died (two from lupus flare, one from cardiomyopathy, two from infections). Four patients had endstage renal failure (ESRF) (one died during a lupus flare). All deaths and end-stage renal failure occurred in the Class IV nephritis group. Chronic organ damage was infrequent in the survivors. The actuarial patient survival rates at 5, 10 and 15 years of age were 95.3, 91.8, and 91.8%, respectively. For Class IV nephritis patients, the survival rates without ESRF at 5, 10, and 15 years were 91.5, 82.3 and 76%, respectively. The survival and chronic morbidity rates of the Chinese SLE children in the present study are comparable to those of other published studies.postprin

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Measurement of differential cross sections and W + /W − cross-section ratios for W boson production in association with jets at √s =8 TeV with the ATLAS detector

This paper presents a measurement of the W boson production cross section and the W + /W − cross-section ratio, both in association with jets, in proton--proton collisions at s √ =8 TeV with the ATLAS experiment at the Large Hadron Collider. The measurement is performed in final states containing one electron and missing transverse momentum using data corresponding to an integrated luminosity of 20.2 fb −1 . Differential cross sections for events with one or two jets are presented for a range of observables, including jet transverse momenta and rapidities, the scalar sum of transverse momenta of the visible particles and the missing transverse momentum in the event, and the transverse momentum of the W boson. For a subset of the observables, the differential cross sections of positively and negatively charged W bosons are measured separately. In the cross-section ratio of W + /W − the dominant systematic uncertainties cancel out, improving the measurement precision by up to a factor of nine. The observables and ratios selected for this paper provide valuable input for the up quark, down quark, and gluon parton distribution functions of the proto