Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide.Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system， peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

Peer reviewed article authored by (Zhang YY, Fan YC, Wang M, Wang D, Li XH). Read article or submit your manuscript for publishing.

Studies found that elevated levels of cytokines such as interleukin- (IL-) 1β, IL-6, and tumor necrosis factor-α (TNF-α) are closely associated with the pathogenesis of depression. Obesity providing a low-grade inflammation state was proposed to be implicated in susceptibility to depression in obesity. However, the alterations of cytokines and the TLR4-NF-κB signal in the brain of normal-weight and obese mice under stress have not been fully elucidated. This study used chronic unpredictable mild stress (CUMS) to induce a depressive-like behavior in an animal model and examine depressive-like behaviors, memory changes, and serum corticosterone levels, as well as the expressions of cytokines and NF-κB in the frontal cortex and hippocampus. We aimed to observe the role of neuroinflammation in susceptibility to depression in obesity under CUMS. In addition, we investigated the protective effect of inhibiting the TLR4-NF-κB signal. Our results demonstrated that CUMS induced depressive-like behavior and spatial memory damage, higher level of serum corticosterone, and overexpression of cytokines and NF-κB in the frontal cortex and hippocampus in both C57BL/6 and ob/ob mice. ob/ob mice displayed serious behavioral disorder and higher levels of IL-1β, IL-6, TNF-α, and NF-κB. Our results concluded that a hyperactive TLR4-NF-κB signal and higher level of cytokines are involved in susceptibility to depression in stressed obese mice.

Background: Studies have shown that psychosocial stress is involved in Alzheimer’s disease (AD) pathogenesis; it induces M1 microglia polarization and production of pro-inflammatory cytokines, leading to neurotoxic outcomes and decreased β-amyloid (Aβ) clearance. Icariin has been proven to be an effective anti-inflammatory agent and to activate peroxisome proliferator-activated receptors gamma (PPARγ) which induces the M2 phenotype in the microglia. However, whether restraint/isolation stress reduces the clearance ability of microglia by priming and polarizing microglia to the M1 phenotype, and the effects of icariin in attenuating the inflammatory response and relieving the pathological changes of AD are still unclear. Methods: APP/PS1 mice (male, aged 3 months) were randomly divided into a control group, a restraint/isolation stress group, and a restraint/isolation stress + icariin group. The restraint/isolation stress group was subjected to a paradigm to build a depressive animal model. Sucrose preference, open field, elevated plus maze, and Y maze test were used to assess the stress paradigm. Morris water maze test was performed to evaluate spatial reference learning and memory. Enzyme-linked immunosorbent assay and immunohistochemistry were used to identify the microglia phenotype and Aβ accumulation. Western blotting was used to detect the expression of PPARγ in the hippocampus and prefrontal cortex (PFC). Results: Restraint/isolation stress induced significant depressive-like behaviors in APP/PS1 mice at 4 months of age and memory impairment at 10 months of age, while 6 months of icariin administration relieved the memory damage. Restraint/isolation stressed mice had elevated pro-inflammatory cytokines, decreased anti-inflammatory cytokines, increased Aβ plaque accumulation and more M1 phenotype microglia in the hippocampus and PFC at 10 months of age, while 6 months of icariin administration relieved these changes. Moreover, restraint/isolation stressed mice had down-regulated PPARγ expression in the hippocampus and PFC at 10 months of age, while 6 months of icariin administration reversed the alteration, especially in the hippocampus. Conclusion: Restraint/isolation stress induced depressive-like behaviors and spatial memory damage, over-expression of M1 microglia markers and more severe Aβ accumulation by suppressing PPARγ in APP/PS1 mice. Icariin can be considered a new treatment option as it induces the switch of the microglia phenotype by activating PPARγ.

Objective: The homeostasis of the immune system is influenced by the gut microbiota. Previous studies have reported dysbiosis in the gut microbiota of myasthenia gravis (MG) patients. To investigate potential alterations in gut microbiota and metabolites in newly diagnosed and untreated MG patients, we conducted a case-control study.Methods: Fecal samples were collected from 11 newly diagnosed and untreated MG patients as well as 11 age-and sex-matched healthy controls. These samples underwent analysis for gut microbiota using 16S ribosomal RNA (rRNA) gene sequencing, while fecal metabolome was analyzed using liquid chromatography-electrospray tandem mass spectrometry system (LC-ESI-MS/MS).Results: The microbial community richness (observed species) and diversity (Shannon and Simpson indices) were significantly lower in the MG group compared to the control group. Microbiota composition analysis revealed significant differences between the MG and control groups at phylum, family, and genus levels. Linear discriminant analysis effect size (LEfSe) analysis showed a substantial decrease in abundance of the genus Faecalibacterium within the MG group. Fecal metabolome analysis identified three up-regulated metabolites involved in amino acid metabolism (taurine, creatinine, L-carnitine), one up-regulated metabolite involved in lipid metabolism (oleic acid), with correlation analysis indicating a positive association between Faecalibacterium abundance and creatinine levels.Conclusion: Our findings suggest that dysbiosis already exists in newly diagnosed and untreated MG patients, implying that dysbiosis within the gut microbiota may be an initiating factor contributing to MG pathogenesis. Furthermore, F. prausnitzii may hold promise as a probiotic for treating MG.

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disorder that also involves neuroinflammation in addition to many other features. Icariin (ICA) as one of the active ingredients of Chinese herbal medicine has the immunomodulating function. This study aimed to investigate the immunotherapeutic potential of ICA on AD. Methods: APP/PS1 mice and wild type C57BL/6 mice were subjected to orally ICA administration (60 mg/kg/d) for 8 months. Then, the ethological and biochemical experiments, such as Morris water maze assay, Aβ ELISA, blood T cell flow cytometry, and plasma and brain cytokines array, were conducted to evaluate the effects of ICA administration. Results: ICA significantly improved spatial learning and memory retention in APP/PS1 mice. Long-term application of ICA could also reduce hippocampus Aβ deposition, modulate the differentiation of CD4+ T cells, and modulate the release of inflammatory cytokines in plasma and brain tissue. Conclusion: ICA shows the neuroprotective effects via modulating the CD4⁺ T lymphocyte-related immuno-inflammatory responses in APP/PS1 mice and may be a promising drug against AD progression.