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Objective: To analyze the phenotypes, genotypes, and the relationship of phenotypes and genotypes for Chinese patients with Bardet-Biedl syndrome (BBS). Methods: The Chinese Wanfang and Weipu data, and PubMed were searched up to December 2022. Patients with detailed clinical feature data were involved in the analysis. Results: A total of 153 Chinese patients, including 87 males, 53 females, and 12 unknown, were enrolled. Their ages ranged from 1.2 to 44 years old with a mean of 16.70 ± 9.90 years old. Among these patients, 80 (52.29%) were reported by ophthalmologists, and only 24 (15.68%) reported by pediatricians. Most patients (132/137, 96.35%) had visual problems; 131/153 (85.62%) had polydactyly; 124/132 (93.93%) were overweight or obese; 63/114 (55.26%) had renal abnormalities; kidney dysfunction was found in 33 (21.57%); 83/104 (79.81%) had hypogonadism and/or genital hypoplasia; and 111/136 (81.62%) had mental retardation. In this series, genetic analysis was performed in 90 (58.82%) patients, including 22 BBS7 (24.71%), 20 BBS2 (22.73%), and 10 BBS10 (11.24%) patients. Moreover, 11 fetuses were diagnosed prenatally in the last 4 years except for one patient in 2004 year. It was noted that BBS7 had higher penetrance. BBS2 had higher hearing impairment and lower renal abnormality penetrance. BBS10 also had lower renal abnormality penetrance as well. Conclusion: Misdiagnosis or miss diagnosis of BBS may be common in China. In patients with polydactyly, visual impairment, obesity, renal abnormalities, hypogonadism, and mental retardation, or in fetuses with polydactyly and/or renal abnormalities, BBS should be considered in the differential diagnosis. Other deformities should be evaluated carefully and genetic analysis should be performed as early as possible.
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Objective:To observe theclinical efficacy of modified Banxia Baizhu Tianmatang combined with acupuncture on migraine with wind phlegm disturbance syndrome, and the regulatory effect on neurovasoactive peptide and vascular endothelial activator. Method:Two hundred and fifty patients were randomly divided into control group (75 cases) and observation group (75 cases). Patients in Two group got acupuncture for 6 times, 1 time/day, after a day of rest, they got placebogranules of Banxia Baizhu Tianmatang, 10 g/time, 2 times/day. Patients in observation group got Banxia Baizhu Tianmatang, 1 dose/day, and also the same acupuncture with the therapyof control group. And the treatment lasted for 4 weeks. At the half, 1<sup>st</sup>, 2<sup>nd</sup>, 6<sup>th</sup>, 12<sup>th</sup>, 24<sup>th</sup>, and 48<sup>th</sup> hour after treatment, VAS were scored, rate of pain relief within 6, 12, and 24 hours, disappearance rate and recurrence rate of pain within 72 hours, migraine attack times, headache duration and headache degree before 4 weeks of treatment, during the treatment and after the treatment were recorded. Before and after treatment, accompanying symptoms, wind phlegm disturbance syndrome, headache impact test version-6 (HIT-6) and the migraine disability assessment questionnaire (MIDAS) were scored. And levels of calcitonin gene-related peptide (CGRP), nitric oxide (NO), endothelin-1 (ET-1), pituitary adenylate cyclase activating peptide (PACAP), S100B protein, substance P(SP), von Willebrand factor (vWF) and fibrinogen (FIB) were detected. And safety was evaluated. Result:VAS in two groups decreased at different time points (<italic>P<</italic>0.01), and VAS in observation group at 6<sup>th</sup>, 12<sup>th</sup>, 24<sup>th </sup>and 48<sup>th</sup> hour after treatment were lower than those in control group (<italic>P<</italic>0.01). The rate of pain relief in observation group at 6<sup>th</sup> and 12<sup>th</sup> hours after treatment and the disappearance rate of pain at 72<sup>th</sup> hour were 67.14%(47/70), 87.14% (61/70) and 92.86% (65/70), which were higher than 50.00% (34/68), 70.59% (48/68) and 79.41% (54/68) in control group. The recurrence rate of pain in observation group was 21.43% (15/70), which was lower than 39.71% (27/68) in control group (<italic>P<</italic>0.05). During the treatment and drug withdrawal, times of migraine attack, headache duration and headache degree were all less than those in control group (<italic>P<</italic>0.01). Scores of accompanying symptoms, wind phlegm disturbance syndrome, HIT-6 and MIDAS were all lower than those in control group (<italic>P<</italic>0.01). The clinical effect was better than that in control group (<italic>Z</italic>=2.106, <italic>P<</italic>0.05). Levels of CGRP, PACAP, S100B protein, SP, ET-1, vWF and FIB were lower than those in control group, while level of NO was higher than control group (<italic>P<</italic>0.01). Conclusion:Modified Banxia Baizhu Tianmatang combined with acupuncture had a better instant analgesic effect, with a significant effect on continuing analgesia and reducing headache recurrence. It can also alleviate migraine symptoms and accompanying symptoms, andreduce the impact of migraine on daily life and the degree of disability. Its mechanism may be related to the regulation of neurovasoactive peptides and vascular endothelial substances. It is worth for further study.
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Accumulating data have revealed that abnormal activity of the mTOR (mammalian target of rapamycin) pathway plays an important role in epileptogenesis triggered by various factors. We previously reported that pretreatment with perifosine, an inhibitor of Akt (also called protein kinase B), abolishes the rapamycin-induced paradoxical increase of S6 phosphorylation in a rat model induced by kainic acid (KA). Since Akt is an upstream target in the mTOR signaling pathway, we set out to determine whether perifosine has a preventive effect on epileptogenesis. Here, we explored the effect of perifosine on the model of temporal epilepsy induced by KA in rats and found that pretreatment with perifosine had no effect on the severity or duration of the KA-induced status epilepticus. However, perifosine almost completely inhibited the activation of p-Akt and p-S6 both acutely and chronically following the KA-induced status epilepticus. Perifosine pretreatment suppressed the KA-induced neuronal death and mossy fiber sprouting. The frequency of spontaneous seizures was markedly decreased in rats pretreated with perifosine. Accordingly, rats pretreated with perifosine showed mild impairment in cognitive functions. Collectively, this study provides novel evidence in a KA seizure model that perifosine may be a potential drug for use in anti-epileptogenic therapy.
Subject(s)
Animals , Male , Rats , Anticonvulsants , Pharmacology , Brain , Pathology , Convulsants , Toxicity , Disease Models, Animal , Epilepsy, Temporal Lobe , Pathology , Kainic Acid , Toxicity , Neurons , Pathology , Phosphorylcholine , Pharmacology , Protein Kinase Inhibitors , Pharmacology , Proto-Oncogene Proteins c-akt , Rats, Sprague-Dawley , Status Epilepticus , PathologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of licorice flavonoid (LF) on kainic acid (KA)-induced seizure in mice and its mechanism.</p><p><b>METHODS</b>Male adult ICR mice were injected with 25 mg/kg KA to induce temporal lobe seizure. LF was administrated 7 d before seizure induction (pre-treatment) or 24 h after seizure induction (post-treatment) for 7 d. Acute seizure latency, seizure stage and duration were observed and compared between LF- and vehicle-treated mice. From d2 on, mice with status epilepticus were video-monitored for spontaneous seizures, 10 h/d for 6 w. Immunohistochemical analysis of BrdU and Timm staining was conducted to detect the neurogenesis and mossy fiber sprouting, respectively.</p><p><b>RESULTS</b>No significant difference was observed in acute seizure latency, seizure stage and duration between LF-and vehicle-treated mice. KA-induced acute seizure resulted in spontaneous seizure in mice, and the seizure frequency was increased with time. Pre- and post-treatment with LF decreased seizure frequency from w3 after modeling [(0.58±0.15)/d, (0.38±0.38)/d vs (1.23±0.23)/d, P <0.05]. Furthermore, KA-induced seizure resulted in robust neurogenesis and mossy fiber sprouting, while treatment with LF both pre- and post- KA injection significantly inhibited neurogenesis (15.6±2.6, 17.1±3.1 vs 28.9±3.5, P <0.05) and mossy fiber sprouting (1.33±0.31, 1.56±0.42 vs 3.0±0.37, P <0.05).</p><p><b>CONCLUSION</b>LF has no significant anti-seizure effect. However, it can decrease epileptogenesis through inhibition of neurogenesis and mossy fiber sprouting.</p>
Subject(s)
Animals , Male , Mice , Disease Models, Animal , Flavonoids , Pharmacology , Glycyrrhiza , Chemistry , Kainic Acid , Mice, Inbred ICR , Mossy Fibers, Hippocampal , Neurogenesis , Seizures , Drug Therapy , Status Epilepticus , Drug TherapyABSTRACT
<p><b>OBJECTIVE</b>To construct and identify lentiviral vector containing human ILK-shRNA and mda7 gene.</p><p><b>METHODS</b>Based on the human ILK gene sequences, RNAi target sequences were designed and cloned into the lentiviral vector pSicoR-eGFP by restriction endonuclease HpaI and XhoI double digestion and T4 DNA ligase ligation. Based on the human mda7 gene sequences, PCR primers were designed to clone the full-length mda7, and were cloned into the lentiviral vector pLVX-Puro. After the candidate clones were identified by DNA sequencing, the recombinant plasmid and the three packaging plasmids were co-transfected into the human embryonic kidney 293T cells by lipofectamine 2000 to produce the lentiviral particles. Human prostate cancer PC-3 cells were infected with the constructed lentiviral vector. The ILK and mda7 expression levels in PC-3 cells were quantified by qPCR and Western blot, respectively. The effect of ILK and mda7 on proliferation and migration of PC-3 cells were assessed by MTT method and Transwell assay, respectively.</p><p><b>RESULTS</b>ILK-pSicoR-eGFP and mda7-pLVX-Puro lentiviral vectors were successfully constructed. Strong green fluorescence was observed in the 293T cells under the fluorescent microscope after co-transfection of 293T cells with 4 plasmids of lentiviral vector. The transfection efficiency of the collected virus exceeded 90% in the 293T cells and the PC-3 cells were infected with the lentiviral particles with high efficiency. The A and B lentiviral vector inhibited the expression of ILK at both the mRNA and protein levels in PC-3 cells significantly. The mda7-pLVX-Puro lentiviral vector increased the expression of mda7 in PC-3 cells, and the ability was maintained for one month. Within 96 h, ILK and mad7 significantly inhibited the proliferation and migration of PC-3 cells (Ps<0.05).</p><p><b>CONCLUSION</b>The lentiviral vectors of ILK knockdown and mda7 over-expression have been successfully constructed and identified. The recombinant lentivirus can efficiently infect human prostate cancer PC-3 cells, in which ILK expression is inhibited and mda7 is over-expressed.</p>