Guillain-Barre syndrome (GBS) is a potentially life-threatening postinfectious disease characterized by rapidly progressive, symmetrical weakness of the extremities About 25% of patients develop respiratory insufficiency and many show signs of autonomic dysfunction Diagnosis can usually be made on clinical grounds, but lumbar puncture and electrophysiological studies can help to substantiate the diagnosis and to differentiate demyelinating from axonal subtypes of GBS Molecular mimicry of pathogen-borne antigens, leading to generation of crossreactive antibodies that also target gangliosides, is part of the pathogenesis of GBS; the subtype and severity of the syndrome are partly determined by the nature of the antecedent infection and specificity of such antibodies Intravenous immunoglobulin and plasma exchange are proven effective treatments but many patients have considerable residual deficits Discrimination of patients with treatment-related fluctuations from those with acute-onset chronic inflammatory demyelinating polyneuropathy is important, as these conditions may require different treatments Novel prognostic models can accurately predict outcome and the need for artificial ventilation, which could aid the selection of patients with a poor prognosis for more-individualized care This Review summarizes the clinical features of and diagnostic criteria for GBS, and discusses its pathogenesis, treatment and prognosis

Guillain–Barré syndrome: pathogenesis, diagnosis, treatment and prognosis

The role of JAK/STAT signaling pathway and its inhibitors in diseases.

Objective Recent evidence suggesting an important role of gut-derived inflammation in brain disorders has opened up new directions to explore the possible role of the gut-brain axis in neurodegenerative diseases. Given the prominence of dysbiosis and colonic dysfunction in patients with Parkinson’s disease (PD), we propose that toll-like receptor 4 (TLR4)-mediated intestinal dysfunction could contribute to intestinal and central inflammation in PD-related neurodegeneration. Design To test this hypothesis we performed studies in both human tissue and a murine model of PD. Inflammation, immune activation and microbiota composition were measured in colonic samples from subjects with PD and healthy controls subjects and rotenone or vehicle-treated mice. To further assess the role of the TLR4 signalling in PD-induced neuroinflammation, we used TLR4-knockout (KO) mice in conjunction with oral rotenone administration to model PD. Results Patients with PD have intestinal barrier disruption, enhanced markers of microbial translocation and higher pro-inflammatory gene profiles in the colonic biopsy samples compared with controls. In this regard, we found increased expression of the bacterial endotoxin-specific ligand TLR4, CD3+ T cells, cytokine expression in colonic biopsies, dysbiosis characterised by a decrease abundance of SCFA-producing colonic bacteria in subjects with PD. Rotenone treatment in TLR4-KO mice revealed less intestinal inflammation, intestinal and motor dysfunction, neuroinflammation and neurodegeneration, relative to rotenone-treated wild-type animals despite the presence of dysbiotic microbiota in TLR4-KO mice. Conclusion Taken together, these studies suggest that TLR4-mediated inflammation plays an important role in intestinal and/or brain inflammation, which may be one of the key factors leading to neurodegeneration in PD.

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Role of TLR4 in the gut-brain axis in Parkinson’s disease: a translational study from men to mice

Parkinson's disease (PD) is a chronic and progressive disorder characterized neuropathologically by loss of dopamine neurons in the substantia nigra, intracellular proteinaceous inclusions, reduction of dopaminergic terminals in the striatum, and increased neuroinflammatory cells. The consequent reduction of dopamine in the basal ganglia results in the classical parkinsonian motor phenotype. A growing body of evidence suggest that neuroinflammation mediated by microglia, the resident macrophage-like immune cells in the brain, play a contributory role in PD pathogenesis. Microglia participate in both physiological and pathological conditions. In the former, microglia restore the integrity of the central nervous system and, in the latter, they promote disease progression. Microglia acquire different activation states to modulate these cellular functions. Upon activation to the M1 phenotype, microglia elaborate pro-inflammatory cytokines and neurotoxic molecules promoting inflammation and cytotoxic responses. In contrast, when adopting the M2 phenotype microglia secrete anti-inflammatory gene products and trophic factors that promote repair, regeneration, and restore homeostasis. Relatively little is known about the different microglial activation states in PD and a better understanding is essential for developing putative neuroprotective agents. Targeting microglial activation states by suppressing their deleterious pro-inflammatory neurotoxicity and/or simultaneously enhancing their beneficial anti-inflammatory protective functions appear as a valid therapeutic approach for PD treatment. In this review, we summarize microglial functions and, their dual neurotoxic and neuroprotective role in PD. We also review molecules that modulate microglial activation states as a therapeutic option for PD treatment.

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Targeting Microglial Activation States as a Therapeutic Avenue in Parkinson’s Disease

Therapy resistance is a characteristic of cancer cells that significantly reduces the effectiveness of drugs. Despite the popularity of cisplatin (CP) as a chemotherapeutic agent, which is widely used in the treatment of various types of cancer, resistance of cancer cells to CP chemotherapy has been extensively observed. Among various reported mechanism(s), the epithelial–mesenchymal transition (EMT) process can significantly contribute to chemoresistance by converting the motionless epithelial cells into mobile mesenchymal cells and altering cell–cell adhesion as well as the cellular extracellular matrix, leading to invasion of tumor cells. By analyzing the impact of the different molecular pathways such as microRNAs, long non-coding RNAs, nuclear factor-κB (NF-ĸB), phosphoinositide 3-kinase-related protein kinase (PI3K)/Akt, mammalian target rapamycin (mTOR), and Wnt, which play an important role in resistance exhibited to CP therapy, we first give an introduction about the EMT mechanism and its role in drug resistance. We then focus specifically on the molecular pathways involved in drug resistance and the pharmacological strategies that can be used to mitigate this resistance. Overall, we highlight the various targeted signaling pathways that could be considered in future studies to pave the way for the inhibition of EMT-mediated resistance displayed by tumor cells in response to CP exposure.

https://www.mdpi.com/1422-0067/21/11/4002/pdf

Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance.

Baicalein increases cisplatin sensitivity of A549 lung adenocarcinoma cells via PI3K/Akt/NF-κB pathway

Emerging evidence suggests that the peripheral immune system has an active role in the progression of Parkinson's disease (PD). The finding of T‑helper (Th; CD4+) cells infiltrating into the substantia nigra in PD patients demonstrated that Th cells are involved in PD. However, the association between peripheral T‑helper cell sub‑sets (Th1, Th2, Treg and Th17) and the sub‑set balance (Th1/Th2 and Th17/Treg) and PD has remained elusive. In the present study, sixty PD patients of the First Affiliated Hospital of Bengbu Medical College as well as 40 age‑ and environment‑matched healthy individuals were enrolled. The fraction of CD4+ T cells in the peripheral blood was assessed by automated hematology analysis and its sub‑sets (Thl, Th2, Thl7, Treg) were quantified by flow cytometry. The results showed that in the PD group, the proportion of Th1 and Th17 cells was increased, while that of Th2 and Treg cells was decreased. Compared with the control group, the Th1/Th2 and Th17/Treg ratios were significantly enhanced, and shifted towards Th1 and Th17, respectively. Furthermore, this Th1‑type response (Th1/Th2 balance shifting towards Th1) were associated with motor function scores determined by Unified Parkinson's Disease Rating Scale III (UPDRS‑III) scores. However, no correlation was found between the change in the Th17/Treg cell balance (Th17/Treg balance shifting towards Th1) and UPDRS‑III scores. These data supported that chronic immune stimulation, specifically CD4+‑cell sub‑set imbalance, is linked to PD pathobiology and disease severity. CD4+‑cell sub‑sets and their imbalance may therefore represent novel biomarkers or therapeutic targets for PD.

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Clinical correlation of peripheral CD4+‑cell sub‑sets, their imbalance and Parkinson's disease

Constipation is frequently reported in Parkinson's disease (PD). We evaluated the characteristics of patients with PD and constipation and explored the role of T cell subsets in PD-associated constipation. One hundred and two patients with PD treated at the First Affiliated Hospital of Bengbu Medical College were enrolled in this study between January 2012 and October 2013. All patients completed KESS questionnaires and constipation was rated. The proportions of peripheral blood Thl7 and Treg cells were assessed by flow cytometry in 45 patients. Colonoscopies were performed in six patients. Thirty-one patients with PD reported slow-transit constipation (STC), 15 rectal evacuation disorder (RED) and 33 mixed constipation (Mixed). STC most frequently occurred before onset of PD motor symptoms, while Mixed occurred before or after motor symptoms, and RED occurred most frequently after motor symptoms. CD4+ T cell infiltration in the colonic mucosa was observed in patients with PD and constipation. The frequency of Th17 and Treg cells in patients with PD and constipation was significantly higher than in those without constipation (P 0.05). Constipation reported before the onset of PD motor symptoms was most often STC or Mixed, and PD constipation may be associated with immune activation in the colonic mucosa.

Clinical characteristics and peripheral T cell subsets in Parkinson’s disease patients with constipation

Fc receptor like 3 in Chinese patients of Han nationality with Guillain-Barré syndrome.

Currently available treatments for Parkinson's disease (PD) do not delay or prevent disease development and progression. DL-3-n-butylphthalide (NBP), isolated from Apium graveolens seeds, alleviates oxidative damage and mitochondrial dysfunction. It has been revealed to reduce the loss of dopamine neurons in pre-clinical PD models, and has been approved for the treatment of ischemic stroke patients. The purpose of the present study was to examine whether NBP has the capacity provide a benefit for PD patients and to slow disease progression. A randomized, controlled trial was performed between September 2014 and December 2016. Pairs of patients matched by age, gender and off-medication Unified PD Rating Scale motor subscale (UPDRS-III) scores, were randomly assigned to an NBP treatment group and a control group. All patients continued their originally prescribed medication regimen and those in the NBP group were administered NBP at 200 mg three times daily for 24 weeks. Primary outcome measures were changes in UPDRS-III, including tremor score and non-tremor score, the Pittsburgh sleep quality index (PSQI) and the PD 39-items questionnaire (PDQ) scores. Assessments were completed by blinded evaluators at baseline and 12, 24 and 48 weeks after randomization. All patients were monitored for adverse events (AEs). A total of 103 patients were enrolled in the present study. The NBP group exhibited significantly greater improvements in the non-tremor, PSQI and PDQ-39 scores than the control group, which generally exhibited no improvement. NBP-associated AEs were uncommon and primarily consisted of mild gastrointestinal symptoms. In conclusion, over the 6-month treatment period, NBP was safe and effective for improving the symptoms and impairing the progression of patients with PD (Trial registry number, ChiCTR1800018892).

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Xiaolin Liu

Papers

Baicalein increases cisplatin sensitivity of A549 lung adenocarcinoma cells via PI3K/Akt/NF-κB pathway

Clinical correlation of peripheral CD4+‑cell sub‑sets, their imbalance and Parkinson's disease

Clinical characteristics and peripheral T cell subsets in Parkinson’s disease patients with constipation

Fc receptor like 3 in Chinese patients of Han nationality with Guillain-Barré syndrome.

DL‑3‑n‑butylphthalide therapy for Parkinson's disease: A randomized controlled trial