ResearchPad - 43 Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Late‐Onset Immunotherapy Toxicity and Delayed Autoantibody Changes: Checkpoint Inhibitor–Induced Raynaud's‐Like Phenomenon]]> Autoantibody analysis may provide insight into the mechanism, nature, and timing of immune‐related adverse events. This case report describes a case of immune checkpoint inhibitor‐induced late‐onset Raynaud's‐like phenomenon in a patient receiving combination immunotherapy.

<![CDATA[Higher-order assembly of Sorting Nexin 16 controls tubulation and distribution of neuronal endosomes]]>

Endosomal maturation and distribution, driven by membrane remodeling, are critical for receptor traffic and signaling. Using both in vitro and in vivo approaches, Wang et al. reveal an unexpected coiled-coil–mediated membrane remodeling activity of SNX16 that controls neuronal endosomal tubulation, distribution, and receptor traffic.

<![CDATA[Synaptic neurexin-1 assembles into dynamically regulated active zone nanoclusters]]>

Using super-resolution microscopy, Trotter et al. illuminate an unexpected nanoscale organization of excitatory synapses in which neurexins are assembled in the presynaptic active zone into dynamic nanoclusters that are regulated by ADAM10-mediated ectodomain cleavage.

<![CDATA[Identification of circulating MOG-specific B cells in patients with MOG antibodies]]>


To identify circulating myelin oligodendrocyte glycoprotein (MOG)-specific B cells in the blood of patients with MOG antibodies (Abs) and to determine whether circulating MOG-specific B cells are linked to levels and epitope specificity of serum anti-MOG-Abs.


We compared peripheral blood from 21 patients with MOG-Abs and 26 controls for the presence of MOG-specific B cells. We differentiated blood-derived B cells in vitro in separate culture wells to Ab-producing cells via engagement of Toll-like receptors 7 and 8. We quantified the anti-MOG reactivity with a live cell–based assay by flow cytometry. We determined the recognition of MOG epitopes with a panel of mutated variants of MOG.


MOG-Ab–positive patients had a higher frequency of MOG-specific B cells in blood than controls, but MOG-specific B cells were only detected in about 60% of these patients. MOG-specific B cells in blood showed no correlation with anti-MOG Ab levels in serum, neither in the whole group nor in the untreated patients. Epitope analysis of MOG-Abs secreted from MOG-specific B cells cultured in different wells revealed an intraindividual heterogeneity of the anti-MOG autoimmunity.


This study shows that patients with MOG-Abs greatly differ in the abundance of circulating MOG-specific B cells, which are not linked to levels of MOG-Abs in serum suggesting different sources of MOG-Abs. Identification of MOG-specific B cells in blood could be of future relevance for selecting patients with MOG-Abs for B cell–directed therapy.

<![CDATA[Shaoyao-Gancao Decoction alleviated hyperandrogenism in a letrozole-induced rat model of polycystic ovary syndrome by inhibition of NF-κB activation]]>

Shaoyao-Gancao Decoction (SGD) has been widely used for the treatment of gynopathy. The present study aimed to evaluate the therapeutic effect and potential mechanism of SGD on hyperandrogenism in polycystic ovary syndrome (PCOS) rats. In the present work, SGD was orally administrated to the PCOS rats at the dose of 12.5, 25, and 50 g/kg/d for 14 consecutive days. UPLC–MS/MS was performed to identify the main chemical components of SGD. Body weight, ovarian weight, cystic dilating follicles, and serum levels of steroid hormones were tested to evaluate the therapeutic effect of SGD. In order to further clarify the underlying mechanism, we also measured mRNA and the protein levels of NF-κB, NF-κB p65, P-NF-κB p65, and IκB by RT-qPCR and Western blotting techniques. Our results showed that SGD treatment significantly alleviated hyperandrogenism in PCOS rats as evidenced by reduced serum levels of T and increased E2 and FSH levels. In addition, SGD effectively reduced the phosphorylation of NF-κB p65 and increased the expression of IκB. Results of the present study demonstrated that SGD could ameliorate hyperandrogenism in PCOS rats, and the potential mechanism may relate to the NF-κB pathway.

<![CDATA[Rare copy number variants in the genome of Chinese female children and adolescents with Turner syndrome]]>

Turner syndrome (TS) is a congenital disease caused by complete or partial loss of one X chromosome. Low bone mineral status is a major phenotypic characteristic of TS that can not be fully explained by X chromosome loss, suggesting other autosomal-linked mutations may also exist. Therefore, the present study aimed to detect potential genetic mutations in TS through examination of copy number variation (CNV). Seventeen patients with TS and 15 healthy volunteer girls were recruited. Array-based comparative genomic hybridization (a-CGH) was performed on whole blood genomic DNA (gDMA) from the 17 TS patients and 15 healthy volunteer girls to identify potential CNVs. The abnormal CNV of one identified gene (CARD11) was verified by quantitative PCR. All cases diagnosed had TS based on genotype examination and physical characteristics, including short stature and premature ovarian failure. Three rare CNVs, located individually at 7p22.3, 7p22.2, and Xp22.33, where six genes (TTYH3, AMZ1, GNA12, BC038729, CARD11, and SHOX (stature homeobox)) are located, were found in TS patients. Quantitative PCR confirmed the CNV of CARD11 in the genome of TS patients. Our results indicate that CARD11 gene is one of the mutated genes involved in TS disease. However, this CNV is rare and its contribution to TS phenotype requires further study.

<![CDATA[Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain]]>

Neuroblasts born postnatally in the ventricular–subventricular zone migrate long distances via the rostral migratory stream (RMS) to the olfactory bulb. Nakamuta et al. show that DOCK7 drives tangential migration of neuroblasts in the RMS by controlling both leading process extension and somal translocation through Rac-dependent and myosin phosphatase–RhoA–interacting protein-dependent pathways, respectively.

<![CDATA[Regulation and dysregulation of axon infrastructure by myelinating glia]]>

Pan and Chan discuss the role of myelinating glia in axonal development and the impact of demyelination on axon degeneration.

<![CDATA[Failure of alemtuzumab as a rescue in a NMOSD patient treated with rituximab]]> ]]> <![CDATA[International consensus diagnostic criteria for neuromyelitis optica spectrum disorders]]>

Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.

<![CDATA[The role of gut microbiota in the effects of maternal obesity during pregnancy on offspring metabolism]]>

Obesity is considered a global epidemic. Specifically, obesity during pregnancy programs an increased risk of the offspring developing metabolic disorders in addition to the adverse effects on the mother per se. Large numbers of human and animal studies have demonstrated that the gut microbiota plays a pivotal role in obesity and metabolic diseases. Similarly, maternal obesity during pregnancy is associated with alterations in the composition and diversity of the intestine microbial community. Recently, the microbiota in the placenta, amniotic fluid, and meconium in healthy gestations has been investigated, and the results supported the “in utero colonization hypothesis” and challenged the traditional “sterile womb” that has been acknowledged worldwide for more than a century. Thus, the offspring microbiota, which is crucial for the immune and metabolic function and further health in the offspring, might be established prior to birth. As a detrimental intrauterine environment, maternal obesity influences the microbial colonization and increases the risk of metabolic diseases in offspring. This review discusses the role of the microbiota in the impact of maternal obesity during pregnancy on offspring metabolism and further analyzes related probiotic or prebiotic interventions to prevent and treat obesity and metabolic diseases.

<![CDATA[Aquaporin-4 IgG autoimmune syndrome and immunoreactivity associated with thyroid cancer]]> ]]>