ABSTRACT
Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) is a chronic, recurrent, antibody-mediated, inflammatory demyelinating disease of the central nervous system, characterized by optic neuritis and transverse myelitis. The binding of NMO-IgG with astrocytic aquaporin-4 (AQP4) functions directly in the pathogenesis of >60% of NMOSD patients, and causes astrocyte loss, secondary inflammatory infiltration, demyelination, and neuron death, potentially leading to paralysis and blindness. Current treatment options, including immunosuppressive agents, plasma exchange, and B-cell depletion, are based on small retrospective case series and open-label studies. It is noteworthy that monoclonal antibody (mAb) therapy is a better option for autoimmune diseases due to its high efficacy and tolerability. Although the pathophysiological mechanisms of NMOSD remain unknown, increasingly, therapeutic studies have focused on mAbs, which target B cell depletion, complement and inflammation cascade inactivation, blood-brain-barrier protection, and blockade of NMO-IgG-AQP4 binding. Here, we review the targets, characteristics, mechanisms of action, development, and potential efficacy of mAb trials in NMOSD, including preclinical and experimental investigations.
ABSTRACT
Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) is a chronic, recurrent, antibody-mediated, inflammatory demyelinating disease of the central nervous system, characterized by optic neuritis and transverse myelitis. The binding of NMO-IgG with astrocytic aquaporin-4 (AQP4) functions directly in the pathogenesis of >60% of NMOSD patients, and causes astrocyte loss, secondary inflammatory infiltration, demyelination, and neuron death, potentially leading to paralysis and blindness. Current treatment options, including immunosuppressive agents, plasma exchange, and B-cell depletion, are based on small retrospective case series and open-label studies. It is noteworthy that monoclonal antibody (mAb) therapy is a better option for autoimmune diseases due to its high efficacy and tolerability. Although the pathophysiological mechanisms of NMOSD remain unknown, increasingly, therapeutic studies have focused on mAbs, which target B cell depletion, complement and inflammation cascade inactivation, blood-brain-barrier protection, and blockade of NMO-IgG-AQP4 binding. Here, we review the targets, characteristics, mechanisms of action, development, and potential efficacy of mAb trials in NMOSD, including preclinical and experimental investigations.
ABSTRACT
Immunoglobulin G against myelin oligodendrocyte glycoprotein (MOG-IgG) is detectable in neuromyelitis optica spectrum disorder (NMOSD) without aquaporin-4 IgG (AQP4-IgG), but its pathogenicity remains unclear. In this study, we explored the pathogenic mechanisms of MOG-IgG in vitro and in vivo and compared them with those of AQP4-IgG. MOG-IgG-positive serum induced complement activation and cell death in human embryonic kidney (HEK)-293T cells transfected with human MOG. In C57BL/6 mice and Sprague-Dawley rats, MOG-IgG only caused lesions in the presence of complement. Interestingly, AQP4-IgG induced astroglial damage, while MOG-IgG mainly caused myelin loss. MOG-IgG also induced astrocyte damage in mouse brains in the presence of complement. Importantly, we also observed ultrastructural changes induced by MOG-IgG and AQP4-IgG. These findings suggest that MOG-IgG directly mediates cell death by activating complement in vitro and producing NMOSD-like lesions in vivo. AQP4-IgG directly targets astrocytes, while MOG-IgG mainly damages oligodendrocytes.
ABSTRACT
Leukemia inhibitory factor (LIF) contributes to the neuroprotection by neural stem cells (NSCs) after ischemic stroke. Our aim was to explore whether LIF-transfected NSCs (LIF-NSCs) can ameliorate brain injury and promote neuroprotection in a rat model of cerebral ischemia. To accomplish this goal, we transfected NSCs with a lentivirus carrying the LIF gene to stably overexpress LIF. The LIF-NSCs reduced caspase 3 activation under conditions of oxygen-glucose deprivation in vitro. Transient cerebral ischemia was induced in rats by 2 h of middle cerebral artery occlusion (MCAo), and LIF-NSCs were intravenously injected at 6 h post-ischemia. LIF-NSC treatment reduced the infarction volume and improved neurological recovery. Moreover, LIF-NSCs improved glial cell regeneration and ameliorated white matter injury in the MCAo rats. The NSCs acted as carriers and increased the expression of LIF in the lesions to protect against cerebral infarction, suggesting that LIF-NSCs could be a potential treatment for cerebral infarction.
ABSTRACT
Chronic liver diseases can further develop to liver fibrosis and cirrhosis. Currently, there is no effective treatment except liver orthotopic transplantation at this point. The extreme shortage of liver organ source forced people to find alternative treatment strategies. Mesenchymal stem cells ( MSCs) have the abilities of immunomodulatory, hepatocyte differentiation, promotion of liver cells regeneration in situ and inhibiting the activation of hepatic stellate cells. Therefore, MSCs transplantation provides a very broad prospect for cell therapy. It is important to provide preclinical evaluation of the efficacy and safety before the application of cell therapy in clinical trials. The progress of various animal models of human liver diseasees and significance of using MSCs to treat liver diseases in preclincal studies based on these animal models were reviewed in this paper.
ABSTRACT
<p><b>OBJECTIVE</b>To explore genetic mutations and clinical features of a pedigree affected with dopa-responsive dystonia.</p><p><b>METHODS</b>PCR and Sanger sequencing were applied to detect mutations of the GCH1 gene among 7 members from the pedigree.</p><p><b>RESULTS</b>The family was detected to have a known heterozygous mutation of the GCH1 gene (c.550C>T). For the 7 members from the pedigree, the age of onset has ranged from 13 to 60 years. The mother of the proband has carried the same mutation but was still healthy at 80. The symptoms of the other three patients were in slow progression, with diurnal fluctuation which can be improved with sleeping, dystonias of lower limbs, and tremor of both hands. Treatment with small dose of levodopa has resulted in significant improvement of clinical symptoms. By database analysis, the c.550C>T mutation was predicted as probably pathological.</p><p><b>CONCLUSION</b>The c.550C>T mutation probably underlies the disease in this pedigree. The clinical phenotypes of family members may be variable for their ages of onset. Some may even be symptom free.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Base Sequence , DNA Mutational Analysis , Dystonic Disorders , Genetics , GTP Cyclohydrolase , Genetics , Heterozygote , Molecular Sequence Data , Mutation , Pedigree , PhenotypeABSTRACT
[ABSTRACT]OBJECTIVETo explore the clinical characteristics of benign paroxysmal positionalvertigo(BPPV) after sudden hearing loss and to observe the curative effect. METHODS36 patients with BPPV after sudden hearing loss were observed.And their therapeutic findings were compared with that of the 50 patients with primary BPPV and 40 patients of sudden hearing loss without vertigo. RESULTSBPPV after sudden hearing loss occurred in the hearing loss ears, of which 27 cases were posterior semicircular canal lithiasis and 3 cases were horizontal semicircular canal lithiasis. The 36 patients with BPPV after sudden hearing loss and 40 patients with primary BPPV were cured after several times of reposition maneuver treatment.The efficiency of 40 patients of sudden hearing loss without vertigo was higher than that of 36 patients with BPPV after sudden hearing loss.CONCLUSIONBPPV after the sudden hearing loss mainly occurs in the posterior semicircular canal. The therapeutic efficacy of canalith repositioning maneuver for the secondary BPPV was similar to that of the primary BPPV.The therapeutic efficacy of sudden hearing loss without vertigo was superior to sudden hearing loss with BPPV.
ABSTRACT
Objective To investigate the value of otolith-repositioning maneuver combined with medical treatment on benign paroxysmal positional vertigo in the elderly patients.Methods 176 elderly people who suffered from benign paroxysmal positional vertigo were randomly divided into observation group and control group (n=88,each).All patients were treated with basal medicine treatment and compulsive position for 21 days,and patients in the observation group were treated with otolith repositioning maneuver added on the basis.The clinical efficacy and adverse reactions were observed and compared between the two groups after treatment.Results The curative rate and effective rate were higher in observation group than in control group at 2,3 weeks after treatment [50.0％ (44/88) vs.11.4％ (10/88),70.5％ (62/88) vs.47.7％ (42/88),77.3％ (68/88) vs.29.5％ (26/88),93.2％ (82/88) vs.86.4％ (76/88),x2 =37.32,73.32,37.32,53.43,respectively,all P＜0.05].Dizziness combined with nausea and vomiting,and walking instability were both found in the two groups,which had no statistical difference (x2 =3.25,P＞0.05).Patients in observation group developed arrhythmia and Tumarkin otolith crisis after treatment.The transfer rate of surgery was lower in observation group than in control group (x2 =45.43,P＜0.01).Conclusions Otolith-repositioning maneuver combined with medical treatment have good clinical effect and safety on benign paroxysmal positional vertigo in the elderly.
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Objective To observe the effects of lycopene on fibrinolytic activity and nitric oxide in atherosclerosis rabbits. Methods 30 New Zealand rabbits were randomly divided into three groups. They were individually housed in metal cages. Throughout the experimental period, they were given restricted amounts of food. Control group was fed with normal diet,model group was fed with 1% cholesterol,10% lard and 89% normal diet, lycopene group was fed with 1% cholesterol,10% lard and normal diet plus 6% lycopene.At the time of the first day and the 8th week, blood samples were drawn from ear edge vein of rabbits. The activity and content of plashaa tissue type plasminogen activator(t-PA)and plasminogen activator inhibitor(PAI-1)were detected. The levels of serum Nitric oxide (NO)were determined.At the end of the study, the plaque areas were measured. SPSS 10.0 software was used to evaluate the differences among the three groups. Results Compared with control group, atherosclerosis rabbits had lower content and activity of t-PA, higher content and activity of PAI-1 and lower content of NO. Compared with model group, lycopene group had no significant difference about the content and activity of tPA and PAI-1.But lycopen increased the levels of serum NO, significantly diminished the area of lipid plaque. Conclusions The experimental results suggested that lycopene had antiatherogenic effects. The possible mechanisms might be that lycopene could decrease lipid peroxidation injure, maintain the concentration of NO and protect vascular endothelium. The antiatherogenic effects of lycopene had no correlation with the fibrinolytic activity.