ABSTRACT
Although 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups: receiving 5-ALA-PDT (group A), laser irradiation (group B), and mock procedures but without any treatment (group C), respectively. The growth, histology, microvessel density (MVD), and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced (P<0.05), MVD was significantly decreased (P<0.001), and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.
ABSTRACT
Alzheimer's Disease (AD) is a chronic neurodegenerative disease that usually takes many years from preclinical phase to prodromal phase characterized by mild symptoms before the onset of dementia. Once diagnosed with AD, the brain is already severely damaged and the disease will process quickly to the most severe stages since there is no medications that reverse the neuronal injuries in the brain. Thus, simple, inexpensive, and widely available methods for detecting potential AD patients during their preclinical phases are urgently needed. In such case, olfactory testing may offer a chance for early diagnosis of AD. However, there are limitations in these olfactory tests due to the complexity of the brain areas it extends to and the frequently olfactory fatigue occurred in the behavioral olfactory tests. Great efforts have been done epidemiologically to investigate the correlation between olfactory functions and possibility of developing AD. Different patterns of olfactory dysfunction have been found in AD at early stages and even mild cognitive impairment (MIC), but the cause of the dysfunction remained unclear. Various kinds of AD animal models have been used in the field to clarify the existence of olfactory dysfunctions and thus study the underling mechanism of the dysfunction. In this review we discuss (1) the function of Tau physiologically and pathologically; (2) the genetic background and biological characteristics of the most commonly used Tau transgenic mice; (3) the structural and molecule basis of olfaction; (4) the possible relationship between Tau pathology and olfactory dysfunction. Finally, we suggest that the tau transgenic mouse models may be helpful in studying the possible mechanisms of the dysfunction.
Subject(s)
Animals , Mice , Alzheimer Disease , Disease Models, Animal , Mice, Transgenic , Olfaction Disorders , tau ProteinsABSTRACT
Although 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups: receiving 5-ALA-PDT (group A), laser irradiation (group B), and mock procedures but without any treatment (group C), respectively. The growth, histology, microvessel density (MVD), and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced (P<0.05), MVD was significantly decreased (P<0.001), and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.
Subject(s)
Animals , Rats , Aminolevulinic Acid , Pharmacology , Therapeutic Uses , Brain Neoplasms , Drug Therapy , Pathology , Cell Line, Tumor , Glioma , Drug Therapy , Pathology , Microvessels , Photochemotherapy , Photosensitizing Agents , Pharmacology , Therapeutic Uses , Rats, Wistar , Xenograft Model Antitumor AssaysABSTRACT
Objective To find out the iodine nutritional status and thyroid function of pregnant and lactating women in the urban areas of Wuwei City of Gansu Province,and to provide a scientific basis for iodine supplementation.Methods Blood and urine samples of pregnant (52 persons) and lactating women (59 persons) were collected in 2009.Urinary iodine content was measured with arsenic cerium catalytic spectrophotometric.Serum free three triiodothyronine(FT3),free thyroid hormone(FT4),triiodo thyronine(TT3),serum total thyroxine (TT4) and thyroid-stimulating hormone (TSH) were detected with direct chemiluminescence immunoassay.Results The medians urinary iodine of pregnant and lactating women were 274.68,217.88 μg/L.The rates of low urinary iodine (pregnant women below 150 μg/L,lactating women lower than 100 μg/L) were 9.62％ (5/52) and 6.78％ (4/59).Serum TT3,TT4 levels in pregnant women[(2.48 ± 0.59),(132.18 ± 33.36)nmoL/L] were higher than that in the lactating women[(2.16 ± 0.49),(108.79 ± 28.36)nmol/L,t =-3.123,-3.971,all P ＜ 0.05].Thyroid dysfunction incidence rates of pregnant and lactating women were 17.31％ (9/52) and 8.47％ (5/59).Thyroid dysfunction was mostly subclinical hypothyroidism.Conclusions Overall iodine nutrition of pregnant and lactating women is in good condition,some individuals have the trend of hypothyroidism.It is necessary to carry out routine monitoring of urinary iodine and thyroid function.
ABSTRACT
Objective To evaluate the effect of health education on the target population of iodine deficiency disorders (IDD) in Linxia Hui autonomous prefecture.Methods During 2006-2010,IDD health education was carried out in the target population of Linxia Hui autonomous prefecture,and IDD knowledge of 5th grade pupil and 20-50 years old child-bearing women were surveyed by stratified sampling and questionnaire survey methods to evaluate the effect of health education.Results After health education,IDD knowledge passing rate rose from 55.6％ (548/986) and 18.0％(118/657) to 90.0％(1103/1225) and 86.2％(687/797) among pupils and women,respectively.The awareness rates of iodine deficiency in causing goiter,mental retardation and birth born silly children,and the key role of iodized salt in controling IDD were increased from 79.2％ (781/986),76.5％ (754/986),51.7％ (510/986) and 82.3％ (811/986) to 88.8％ (1088/1225),85.6％ (1049/1225),68.7％ (842/1225) and 90.0％ (1103/1225) among pupils,and from 48.6％ (319/657),28.3％ (186/657),15.4％ (101/657) and 39.6％ (260/657) to 86.2％ (687/797),70.0％ (558/797),46.3％ (369/797) and 87.3％ (696/797) among women,and all the difference were significant,respectively.Belief rate held by students that health education can prevent iodine deficiency disorders was 87.3％ (1069/1225),and 52.9％ (648/1225) of the students told their parents about IDD.The rate of consciously purchase of qualified iodized salt was 87.1％ (694/797) after health education among women of childbearing age,and the consumption rate of iodized salt was 64.6％(515/797).More than 90％ of the people in relevant departments knew iodine deficiency disorders related knowledge,in particular,had a clear understanding of intellectual hazards caused by iodine deficiency,and actively supported and participated in health education in the prevention and control of iodine deficiency disorders.Conclusions Comprehensive health education measures taken through schools and religious organizations has promoted a shift in the behavior,beliefs and attitudes of its consciously purchase and consumption of iodized salt,and integrated knowledge,attitude and practice (KAP).It is a good model of health education through religious organizations in ethnic minority areas.It has promoted the health education feasibility and accessibility,and the effect is more durable.
ABSTRACT
Objective To assess the improvement of intelligence quotient through an Universal Salt Iodization Supply Program,among children.Methods 3518 and 1611 children were selected from primary schools in Linxia Hui Autonomous Prefecture of Gansu in 2006 and 2010respectively.Intelligence quotient (IQ) were measured by the revised Chinese Combined Raven Test C2 (CRT-C2).Results In 2006,the average IQ of children aged 8-10 was 85.1,including 16.7％ of them with IQ≤69.The average IQ was between 80-90 in different counties and cities,with significant differences (P＜0.05).The average IQs were 92.0,90.6 and 81.8 among 8,9 and 10 years old children respectively with 10 year old' s low than those 8 and 9 year olds (P＜0.05).The average IQs of boys and girls were 84.5 and 85.6,but with no significant difference (P ＞0.05).The average IQ of children aged 8-10 in 2010 was 97.2 and 12 points higher than in 2006 (P＜0.05),but 8 IQ points (P＜0.05) less than the average level 105 from the overall of Gansu province.4.7％ of the children having an IQ≤69.IQ of children from Linxia city and Yongjing county,were up to the theoretical level of 100,with an average IQ at around 95 in other counties.The average IQs between counties or cities showed significant differences.The IQ of 8,9 year olds and 10 year olds did not present significant difference (P＞0.05),but in boys (98.8) and in girls (95.9) the difference was significant (P＜0.05).Conclusion The average IQ was close to the theoretical level (100) with the gradual implementation of universal salt iodization program,showing that the iodized salt did play a key role on children's intelligence.However,the average IQ was still lower than the average level of the whole Gansu province in 2010.
ABSTRACT
<p><b>OBJECTIVE</b>To establish the triple-transgenic mouse model and study their biological characteristics by molecular biology, behavior and pathology.</p><p><b>METHODS</b>Hybrid the Tau and amyloid precursor protein (APP)/presenilins (PS1) transgenic mouse, the genotype of offspring mice were identified by PCR. Transcribed target genes were detected by RT-PCR. The protein expression of exogenous genes was detected by Western-blot. The pathological change of neurofibrillary tangles and senile plaque were observed by Bielschowsky silver staining and ABC immunohistochemical method. The changes time of learning and memory were observed by Morris water maze.</p><p><b>RESULTS</b>APP, PS1 and Tau genes were transcript in Tau/APP/PS1 mice. In 6 to 8 months old Tau/APP/PS1 mice, the neurofibrillary tangles and senile plaque could be found in cortex and hippocampus. In 6 months old Tau/APP/PS1 mice, the learning and memory abilities were worse.</p><p><b>CONCLUSION</b>With the behavior change and pathological changes in Tau and beta-amyloid protein (AP), the Tau/APP/PS1 triple-transgenic mice can be used as a further study animal model of AD's pathogenesis and the target of drug treatment.</p>
Subject(s)
Animals , Male , Mice , Alzheimer Disease , Pathology , Amyloid beta-Protein Precursor , Genetics , Brain , Pathology , Disease Models, Animal , Learning , Memory , Mice, Transgenic , Neurofibrillary Tangles , Pathology , Plaque, Amyloid , Pathology , Presenilin-1 , Genetics , tau Proteins , GeneticsABSTRACT
Objective To analyze monitoring results of iodized salt and distribution characteristics of problem areas with non-iodized salt in Gansu province during 2001 - 2009 and to provide a basis to develop countermeasures to iodine deficiency disorders. Methods According to the criterion of "The National Scheme of Iodized Salt Surveillance", two levels of monitoring were carried out on production and wholesale-level(during 2001 -2007) and household-level(during 2001 - 2009). Salt iodine was determined by direct titration method (GB/T13025.7-1999), and Sichuan salt or special salt was determined with an arbitration method. Criteria for qualified iodized salt was (35 ± 15)mg/kg(20 - 50 mg/kg), and for non-iodized salt was ＜ 5 mg/kg. Results During 2001 - 2007, a total of 4900 salt samples at production and wholesale-levels were examined, with a qualification rate of 97.80% (4792/4900). Non-iodized salt rates were all below 5% in Gansu province, consumption rate of qualified iodized salt was higher than 90% after 2003. During 2001 - 2009, cities(states) with non-iodized salt problems appeared 23 times, with Linxia accounting for 39.1%(9/23), Wuwei accounting for 21.7%(5/23). During 2001 -2009, counties(districts) with non-iodized salt problem appeared 123 times, including 68 times of ethnic minorities and state poverty counties, accounting for 55.3%(68/123). During 2001 - 2005 and 2006 - 2009, ethnic minorities and state poverty counties were accounting for 49.4%(44/89) and 70.6%(24/34) in counties with non-iodized salt problem. Conclusions The quality of iodized-salt at production and wholesale level is satisfactory in Gansu province, household consumption rate of qualified iodized salt have reached national standard for eliminating iodine deficiency disorders. But ethnic minorities and state poverty counties are main regions with non-iodized salt problem,these areas will be the key areas of prevention of iodine deficiency disorders in Gansu province in the future.
ABSTRACT
<p><b>BACKGROUND</b>Pancreatic beta-cell apoptosis induced by lipotoxicity, to a large extent, contributes to the progression of type 2 diabetes. To investigate the mechanism of free fatty acid induced apoptosis, we aimed to study the effects of palmitic acid (PA) on the apoptosis and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression in βTC3 cells as well as the possible role of nuclear factor-κB (NF-κB) in this process.</p><p><b>METHODS</b>Hoechst 33258 was used to detect βTC3 cell apoptosis, which was induced by PA stimulation for 12 hours. PGC-1α expression was analyzed by reverse transcription polymerase chain reaction, IκB kinase β (IKKβ), IκBα, NF-κB-inducing kinase (NIK) and Rel-B expressions were analyzed by Western blotting. MG132 was employed to block the endogenous IκBα degradation before PA administration, and then its effect on PA-inducing cell apoptosis and PGC-1α mRNA expression was analyzed.</p><p><b>RESULTS</b>Significant increased cell apoptosis was found at the concentration of 0.5 mmol/L and 1.0 mmol/L PA administration. PA (0.5 mmol/L) could extensively reduced the expression of PGC-1α mRNA. After exposing βTC3 cells to 0.5 mmol/L PA for different time periods (0, 4, 6, 8, 10 and 12 hours), IKKβ protein expression increased while IκBα, NIK and Rel-B protein expression declined in a time-dependent manner. Pretreatment with MG132 to inhibit the degradation of IκBα, partially prevented the down-regulation of PGC-1α mRNA expression after 12-hour PA treatment in accordance with the decrease of PA induced apoptosis.</p><p><b>CONCLUSIONS</b>NF-κB canonical pathway was activated in PA-mediated βTC3 cell apoptosis, whereas non-canonical pathway was inhibited. Reduced PGC-1α expression by PA in βTC3 cells could involve the activation of canonical NF-κB pathway, so as to deteriorate the PA induced apoptosis.</p>
Subject(s)
Humans , Apoptosis , Cell Line , Heat-Shock Proteins , Genetics , Metabolism , Insulin-Secreting Cells , Metabolism , Leupeptins , Pharmacology , NF-kappa B , Genetics , Metabolism , Palmitic Acid , Pharmacology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Transcription Factors , Genetics , MetabolismABSTRACT
Nicotine enhances the function of learning and memory, but the underlying mechanism still remains unclear. Hippocampal long-term potentiation (LTP) is assumed to be a cellular mechanism of learning and memory. Our previous experiments showed that with the single pulses evoking 80% of the maximal population spike (PS) amplitude, nicotine (10 μmol/L) induced LTP-like response in the hippocampal CA1 region. In the present study, the nicotinic acetylcholine receptor (nAChR) subtypes and relevant neurotransmitter releases involved in LTP-like response induced by nicotine were investigated by extracellularly recording the PS in the pyramidal cell layer in the hippocampal CA1 region in vitro. LTP-like response induced by nicotine was blocked by mecamylamine (1 μmol/L) or κ-bungarotoxin (0.1 μmol/L), but not by dihydro-β-erythtroidine (DHβE, 10 μmol/L). Moreover, it was inhibited by propranolol (10 μmol/L), but not by phentolamine (10 μmol/L) or atropine (10 μmol/L). The results suggest that noradrenaline release secondary to the activation of κ-bungarotoxin-sensitive nAChRs participates in LTP-like response induced by nicotine in the hippocampal CA1 region.