Different Strategies for the Treatment of Age-Related Macular Degeneration in China: An Economic Evaluation

Purpose. To assess the cost-effectiveness of bevacizumab compared to ranibizumab, verteporfin photodynamic therapy (PDT), and usual care for the treatment of age-related macular degeneration (AMD) in China. Methods. A Markov model was developed according to patient visual acuity (VA) in the better-seeing eye (Snellen scale). Four cohorts of patients were treated with one of the following therapies: bevacizumab, ranibizumab, PDT, or usual care. Clinical data related to treatments were obtained from published randomized clinical trials. Direct medical costs and resource utilization in the Chinese health care setting were taken into account. Health and economic outcomes were evaluated over a lifetime horizon. Sensitivity analyses were performed. Results. Treatment with ranibizumab provided the greatest gains in quality-adjusted life-years (QALYs). The cost per marginal QALY gained with bevacizumab over usual care was $1,258,$3,803, and $2,066 for the predominantly classic, minimally classic, and occult lesions, respectively. One-way sensitivity analysis showed considerably influential factors, such as utility values and effectiveness data. Probabilistic sensitivity analysis indicated that, compared to usual care, PDT and ranibizumab most cases would be cost-effective in the bevacizumab arm at a threshold of$7,480/QALY. Conclusion. Bevacizumab can be a cost-effective option for the treatment of AMD in the Chinese setting

New Anti-inflammatory Cyclopeptides From a Sponge-Derived Fungus Aspergillus violaceofuscus

Three new cyclic peptides including a cyclic tetrapeptide (1), an aspochracin-type cyclic tripeptide sclerotiotide L (2) and a diketopiperazine dimer (3), have been isolated from the ethyl acetate extract of a marine sponge-derived fungus Aspergillus violaceofuscus. The structures of all compounds were unambiguously elucidated on the basis of HRESIMS, 1D and 2D NMR spectroscopic data, MS/MS experiments and chemical methods. Compounds 1 and 3 showed anti-inflammatory activity against IL-10 expression of the LPS-induced THP-1 cells with inhibitory rates of 84.3 and 78.1% respectively at concentration of 10 μM

The Peptide LLTRAGL Derived from <i>Rapana venosa</i> Exerts Protective Effect against Inflammatory Bowel Disease in Zebrafish Model by Regulating Multi-Pathways

Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease with unknown pathogenesis which has been gradually considered a public health challenge worldwide. Peptides derived from Rapana venosa have been shown to have an anti-inflammatory effect. In this study, peptide LLTRAGL derived from Rapana venosa was prepared by a solid phase synthesis technique. The protective effects of LLTRAGL were studied in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced zebrafish colitis model. The underlying mechanisms of LLTRAGL were predicted and validated by transcriptome, real-time quantitative PCR assays and molecular docking. The results showed that LLTRAGL reduced the number of macrophages migrating to the intestine, enhanced the frequency and rate of intestinal peristalsis and improved intestinal inflammatory damage. Furthermore, transcriptome analysis indicated the key pathways (NOD-like receptor signal pathway and necroptosis pathway) that link the underlying protective effects of LLTRAGL’s molecular mechanisms. In addition, the related genes in these pathways exhibited different expressions after TNBS treatment. Finally, molecular docking techniques further verified the RNA-sequencing results. In summary, LLTRAGL exerted protective effects in the model of TNBS-induced colitis zebrafish. Our findings provide valuable information for the future application of LLTRAGL in IBD

New generation Shelf flux models

The ecological condition of the Continental Shelf is of great concern for many countries. The understanding of the integrated effects that result in the present and future situation requires answers on many research topics, such as flow modelling, including turbulence and large eddy simulation, transport processes, chemistry, ecology, etc. This paper focuses on 'high performance computing issues' for flux modelling. Flux modelling of contaminants, nutrients and ecosystem parameters in general in the Continental Shelf is essential to improve the understanding of this important ecosystem. From a computational point of view, flux modelling is a 'grand challenge'; its computational demands are so huge that the present state-of-the-art does not yield numerical models of desired accuracy. Several assumptions and simplifications are needed to arrive at 'manageable' numerical models whose run times are acceptably low. In an attempt to relieve the computational burden on flux modelling, a significant amount of research at the institutes participating in the NOWESP project has been and still is directed towards high performance computing techniques. In the quest for faster models several approaches are used: * parallelization of (sequential) codes on parallel/vector computers of shared memory type; * parallelization of (sequential) codes on parallel computers with distributed memory; * development of numerical techniques that (are expected to) lead to better efficiency and robustness of flux models. Developments of the latter kind usually take into account the use of a parallel machine but it also includes the implementation of sophisticated iterative solution techniques for solving systems of equations. This may already pay off on sequential machines. In this paper we assess the progress made in recent years on high performance flux modelling. In the spirit of the learning-by-doing process adopted in the NOWESP project, this assessment is followed by some recommendations for future research to further overcome the lack of computational power that is needed for full scale flux models

Active compounds from Calendula officinalis flowers act via PI3K and ERK signaling pathways to offer neuroprotective effects against Parkinson's disease

Calendula officinalis flowers, associated with diverse biological effects, could be utilized as functional food ingredients to play a crucial role in human health. In this study, we examined the anti-PD activity of C. officinalis flower extracts and investigated their bioactive compounds and molecular mechanisms based on LC–MS/MS assay, bioinformatic exploration and in vitro treatment of SH-SY5Y cells. C. officinalis extracts exhibited significant positive effects on the length and fluorescence density of the dopaminergic neuron region in zebrafish larvae. At 10 μg/mL, the extract restored the length to 96.54% and fluorescence density to 87.77% of the control values, which was equivalent to the effect of a positive drug, indicating the extract's powerful potential to alleviate PD symptoms. Five active compounds, including chlorogenic acid, 3,4-dicaffeoylquinic acid (DA), rutin, isorhamnetin 3-O-glucoside (IG) and calenduloside E (CE) were identified in extracts by LC-QTOF-MS/MS. Hsp90α, PI3K and ERK were revealed as core targets of DA, IG and CE in relation to anti-PD activity. The compounds docked deeply within the pocket region of Hsp90α protein, and their binding energies (∆Gb) were −6.93 kcal/mol (DA), −6.51 kcal/mol (IG) and −3.03 kcal/mol (CE), respectively. Subsequently, they concurrently activated the PI3K/Akt signaling pathway and inhibited the ERK signaling pathway, thereby preventing neuronal death and alleviating neuronal degeneration. These compounds from C. officinalis could be potent nutraceutical agents with protective properties that may shield dopaminergic neurons against the damage caused by PD. Our findings provide a basis for utilizing the C. officinalis flowers in functional foods

Ranibizumab versus Bevacizumab for Ophthalmic Diseases Related to Neovascularisation: A Meta-Analysis of Randomised Controlled Trials

<div><p>Background</p><p>Bevacizumab is believed to be as effective and safe as ranibizumab for ophthalmic diseases; however, its magnitude of effectiveness and safety profile remain controversial. Thus, a meta-analysis and systematic review appears necessary.</p><p>Methods</p><p>PubMed and EMBASE were systematically searched with no restrictions. All relevant citations comparing ranibizumab and bevacizumab were considered for inclusion. Pooled effect estimates were obtained using a fixed- and random-effects meta-analysis.</p><p>Results</p><p>Nine independent randomised-controlled clinical trials (RCTs) involving 2,289 participants were identified. Compared with bevacizumab, the overall combined weighted mean difference (WMD) of the mean change in visual acuity for ranibizumab was 0.52 letters (95% CI −0.11–1.14). The odds ratios (ORs) of gaining ≥15, gaining 5–14, losing 5–14 and losing ≤15 letters were 1.10 (95% CI 0.90–1.33), 0.93 (95% CI 0.77–1.11), 0.89 (95% CI 0.65–1.22) and 0.95 (95% CI 0.73–1.25), respectively. The risk of serious systemic events increased by 17% (95% CI 6%–27%, p = 0.0042) for bevacizumab treatment in comparison with ranibizumab. No statistically significant differences between the two treatments were found for the nonfatal arterial thrombotic events, ocular serious adverse, death from vascular and all causes events.</p><p>Conclusions</p><p>Bevacizumab is not inferior to ranibizumab as a treatment for achieving visual acuity. The use of bevacizumab was associated with an increased risk of developing serious systemic events. Weighing the costs and health outcomes is necessary when selecting between bevacizumab and ranibizumab for ophthalmic diseases. Due to the limitations of the available data, further research is needed.</p></div