Need for multiple biomarkers to adjust parameters of closed-loop deep brain stimulation for Parkinson's disease

Closed-loop deep brain stimulation（DBS）：DBS has been established as a surgical therapy for movement disorders and select neuropsychiatric disorders.Various efforts to improve the clinical outcomes of the procedure have been previously made.Several factors affect the DBS clinical outcomes such as lead position,programming technique,

The immune regulation of PD-1/PDL-1 axis, a potential biomarker in multiple sclerosis

Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of new biomarkers of disease and potential therapeutic targets. In chronic infection or in cancer, the immune system response is faulty and maintained in a condition defined as T-cell exhaustion induced by expression of co-inhibitory receptors. The PD-1/PDL-1 pathway is demonstrated to be the main one responsible for promoting T-cell exhaustion, and immunotherapies targeting PD-1 or PDL-1 have shown beneficial clinical outcomes in several tumours and chronic diseases. Contrarily, transcriptional T-cell exhaustion signature and high expression of co-inhibitor receptor PD-1 are associated with favourable prognosis in multiple sclerosis and other autoimmune diseases. Several studies have clearly demonstrated PD-1 has a dual role in immune self-tolerance: to constrain autoreactive T cells in anergic condition and to protect the tissue from the damage caused by the activation of endogenous autoreactive T cells. Consequently, immune checkpoint inhibitor therapies that target inhibitory receptors in cancer cause an exacerbation of autoimmune diseases. This review describes the roles of the PD-1/ PDL-1 pathway in cancer and autoimmune diseases, especially in multiple sclerosis, and how manipulating PD-1 can be a therapeutic approach in multiple sclerosis.

Evaluation of joint toxicity of heavy metals and herbicide mixtures in soils to earthworms(Eisenia fetida)

It is widely acknowledged that a simplified and robust approach to evaluating thecombined effects of chemical mixtures is critical for ecological risk assessment(ERA)of contaminated soil.The earthworm(Eisenia fetida)was used as a model to study the combined effects of polymetallic contamination and the herbicide siduron in field soil using a microcosm experiment.The responses of multiple biomarkers,including the activities of catalase(CAT),superoxide dismutase(SOD),glutathione reductase(GR)and acetylcholine esterase(AChE),the concentrations of glycogen,soluble protein(SP),malonaldehyde(MDA),and metallothionein(MT),and the neutral red uptake test(NRU),were investigated.Multivariate analysis,Principal Component Analysis(PCA)and Spearman’s Rank Correlations analysis(BVSTEP)revealed that the activities of AChE and CAT and the NRU content were the prognostic biomarkers capturing the minimum data set of all the variables.Internal Cd(tissue Cd)in earthworms was closely related to the health status of worms under combined contamination of heavy metals and siduron.The integrated effect(E mix)calculated based on the activities of AChE and CAT and NRU content using the stress index method had significantly linear regression with internal Cd(p<0.01).E mix(10),E mix(20),and E mix(50)were then calculated,at 1.27,1.63 and 2.71 mg/kg dry weight,respectively.It could be concluded that a bioassaybased approach incorporating multivariate analysis and internal dose was pragmatic and applicable to evaluating combined effects of chemical mixtures in soils under the guidance of the top-down evaluation concept of combined toxicity.