ABSTRACT
OBJECTIVE@#To investigate the protective effects of total saponins from Panax japonicus (TSPJ) against high-fat dietinduced testicular Sertoli cell junction damage in mice.@*METHODS@#Forty male C57BL/6J mice were randomized into normal diet group, high-fat diet group, and low-dose (25 mg/kg) and high-dose (75 mg/kg) TSPJ treatment groups (n=10). The mice in the normal diet group were fed a normal diet, while the mice in the other groups were fed a high-fat diet. After TSPJ treatment via intragastric administration for 5 months, the testes and epididymis of the mice were collected for measurement of weight, testicular and epididymal indices and sperm parameters. HE staining was used for histological evaluation of the testicular tissues and measurement of seminiferous tubule diameter and seminiferous epithelium height. The expression levels of ZO-1, occludin, claudin11, N-cadherin, E-cadherin and β-catenin in Sertoli cells were detected with Western blot, and the localization and expression levels of ZO-1 and β-catenin in the testicular tissues were detected with immunofluorescence assay. The protein expressions of LC3B, p-AKT and p-mTOR in testicular Sertoli cells were detected using double immunofluorescence assay.@*RESULTS@#Treatment with TSPJ significantly improved high-fat diet-induced testicular dysfunction by reducing body weight (P < 0.001), increasing testicular and epididymal indices (P < 0.05), and improving sperm concentration and sperm viability (P < 0.05). TSPJ ameliorated testicular pathologies and increased seminiferous epithelium height of the mice with high-fat diet feeding (P < 0.05) without affecting the seminiferous tubule diameter. TSPJ significantly increased the expression levels of ZO-1, occludin, N-cadherin, E-cadherin and β-catenin (P < 0.05) but did not affect claudin11 expression in the testicular tissues. Immunofluorescence assay showed that TSPJ significantly increased ZO-1 and β-catenin expression in the testicular tissues (P < 0.001), downregulated LC3B expression and upregulated p-AKT and p-mTOR expressions in testicular Sertoli cells.@*CONCLUSION@#TSPJ alleviates high-fat diet-induced damages of testicular Sertoli cell junctions and spermatogenesis possibly by activating the AKT/mTOR signaling pathway and inhibiting autophagy of testicular Sertoli cells.
Subject(s)
Male , Animals , Mice , Mice, Inbred C57BL , Testis , Sertoli Cells , beta Catenin , Diet, High-Fat , Occludin , Proto-Oncogene Proteins c-akt , Seeds , Cadherins , Intercellular JunctionsABSTRACT
Background@#and Purpose Patients presenting with clinical characteristics that are strongly suggestive of neuromyelitis optica spectrum disorders (NMOSD) have a high risk of developing definite NMOSD in the future. Little is known about the clinical course, treatment, and prognosis of these patients with likely NMOSD at disease onset. @*Methods@#This study prospectively recruited and visited 24 patients with the limited form of NMOSD (LF-NMOSD) at disease onset from November 2012 to June 2021. Their demographics, clinical course, longitudinal aquaporin-4 immunoglobulin G (AQP4-IgG) serology, MRI, therapeutic management, and outcome data were collected and analyzed. @*Results@#The onset age of the cohort was 38.1±12.0 years (mean±standard deviation). The median disease duration was 73.5 months (interquartile range=44.3–117.0 months), and the follow-up period was 54.2±23.8 months. At the end of the last visit, the final diagnosis was categorized into AQP4-IgG-seronegative NMOSD (n=16, 66.7%), AQP4-IgG-seropositive NMOSD (n=7, 29.2%), or multiple sclerosis (n=1, 4.2%). Seven of the 24 patients (29.2%) experienced conversion to AQP4-IgG seropositivity, and the interval from onset to this serological conversion was 37.9±21.9 months. Isolated/mixed area postrema syndrome (APS) was the predominant onset phenotype (37.5%). The patients with isolated/mixed APS onset showed a predilection for conversion to AQP4-IgG seropositivity. All patients experienced a multiphasic disease course, with immunosuppressive therapy reducing the incidence rates of clinical relapse and residual functional disability. @*Conclusions@#Definite NMOSD may be preceded by LF-NMOSD, particularly isolated/ mixed APS. Intensive long-term follow-up and attack-prevention immunotherapeutic management is recommended in patients with LF-NMOSD.
ABSTRACT
Objective To investigate the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Methods We collected and analyzed the clinical and laboratory data and obtained the clinical characteristics of diagnosis and treatment from fifteen patients with positive GFAP antibody tested by cerebrospinal fluid and diagnosed autoimmune GFAP astrocytopathy by the multi-centers. Results The mean age of the first onset of autoimmune GFAP astrocytopathy was 39.73 years old (range 4-65 years), with no significant gender difference. In terms of clinical manifestations, we found the whole brain symptoms including abnormal mental behavior, disturbance of consciousness, epileptic attack accounting for more than 50, , meningitis accounting for 66.7%, myelitis (53.3%), limb tremor (53.3%), vision loss (33.3%); systemic symptoms including fever(100%) and fatigue(86.7%). 46.7% of patients were initially diagnosed with tuberculous meningoencephalitis and were treated with diagnostic antituberculous therapy. The MRI showed 46.7% of patients showed brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle. Conclusions Autoimmune GFAP astrocytopathy are acute or subacute dieases and the main clinical features include encephalitis, meningitis, myelitis and optic neuritis. They are likely to be misdiagnosed as tuberculous meningoencephalitis and can manifest progressive loss of consciousness in early phase, which is even life threatening.
ABSTRACT
Objective To investigate the characteristics of ocular movement disorders in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), and explore the clinical application of videonystagmograph (VNG) exami?nation in the diagnosis and differential diagnosis of MS. Methods Sixteen MS ,10 NMO and 30 control ( sudden deafness ) patients were enrolled prospectively. Ocular movement disorders including saccades, gaze fixation, smooth pursuits, opto?kinetic nystagmus and spontaneous nystagmus were evaluated by using VNG. Results The positive rate of ocular motility disorders in MS patients detected by VGN was 68.75%. The incidences of abnormalities in saccades, smooth pursuits and optokinetic nystagmus were significantly higher in MS than in control groups (P= 0.000, 0.001 and 0.001, respectively). The positive rate of ocular motility disorders in NMO patients detected by VGN was 80.00%. The incidences of abnormal?ities in saccades, gaze fixation, smooth pursuits and optokinetic nystagmus were significantly higher in NMO than control groups (P=0.000, 0.012, 0.000 and 0.002, respectively). The positive rate of ocular motility disorders was not significant? ly different in MS and MS patients (68.5%vs. 80%,P>0.05). Compared with bedside physical examination, VNG showed a notable higher sensitivity in the detection of ocular motility disorders(68.75% vs. 37.50%). Furthermore, VNG disor?ders might indicate brain lesions undetected by MRI. Conclusion This small sample research indicates that VNG is a valuable tool in the detection of ocular motility disorders as well as brain lesions in MS and NMO patients. However, its role in the differential diagnosis between MS and NMO is not confirmed.