Pathological Changes in APP/PS-1 Transgenic Mouse Models of Alzheimer's Disease Treated with Ganoderma Lucidum Preparation / 中国医学科学院学报

Objective To explore the efficacy of ganoderma lucidum preparation(Ling Zhi) in treating APP/PS-1 transgenic mouse models of Alzheimer's disease(AD).Methods APP/PS-1 transgenic mice of 4 months were randomly divided into model group,ganoderma lucidum treatment groups,including high [2250 mg/(kg·d)] and middle [750 mg/(kg·d)] dose groups,i.e.LZ-H and LZ-M groups,and the positive control group(treated with donepezil hydrochloride [2 mg/(kg·d)]).In addition,C57BL/6J wild mice were selected as normal group.The animals were administered for 4 months.Histopathological examinations including hematoxylin-eosin(HE) staining,immunohistochemistry,special staining,and electron microscopy were applied,and then the pathological morphology and structures in different groups were compared. Results The senile plaques and neurofibrillar tangles in the cerebrum and cerebellum were dissolved or disappeared in LZ-H and LZ-M groups.Decrease of amyloid angiopathy was found in LZ-H and LZ-M groups.The immature neurons appeared more in hippocampus and dentate nucleus of LZ-H and LZ-M groups than those in AD model and donepezil hydrochloride groups(hippcampus:F=1.738,P=0.016;dentate nucleus:F=1.924,P=0.026),and these immature neurons differentiated to be neurons.More Purkinje cells loss occurred in AD model mice than that in LZ-H and LZ-M groups(F=9.46,P=0.007;F=9.46,P=0.010).The LZ-H and LZ-M groups had more new neuron stem cells grown up in cerebellum.Electromicroscopic examination showed the hippocampal neurons in LZ-H and LZ-M group were integrated,the nuclear membrane was intact,and the mitochondria in the cytoplasm,endoplasmic reticulum,Golgi bodies,microtubules,and synapses were also complete.The microglial cell showed no abnormality.No toxicity appeared in the pathological specimens of mice treated with ganoderma lucidum preparation.Conclusion The ganoderma lucidum preparation can dissolve and decline or dismiss the senile plaques and neurofibrillar tangles in the brain of AD mice and also reduce the amyloid angiopathy.

Increase of TNFα-stimulated osteoarthritic chondrocytes apoptosis and decrease of matrix metalloproteinases 9 by NF-κB inhibition / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-κB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9).</p><p><b>METHODS</b>Annexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFα-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants.</p><p><b>RESULTS</b>It was confirmed by both flow cytometry and western blotting that chondrocytes from OA patients have an apoptotic background. Use of CAPE in combination with 10 ng/mL of TNFα for 24 h facilitated the apoptosis. MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9), and the physiologic calcium concentration (2.5 mmol/L) could delay the autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh supernatant increased significantly in response to stimulation by 10 ng/mL of TNFα for 24 h. The stimulatory effect of TNFα just on proMMP-9 was counteracted significantly by CAPE.</p><p><b>CONCLUSION</b>NF-κB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFα (a pro-apoptotic factor). Therefore, therapeutic NF-κB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.</p>

Comparative proteomic analysis of rat juvenile and adult dura / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been widely observed that infants and young children can reossify large calvarial defects when they are younger than 2 years of age; afterwards, they lose this regenerative potential. Previous studies have implicated that the dura mater serves as a key regulator of calvarial regeneration. However, the molecular mechanism of calvarial reossification remains elusive.</p><p><b>METHODS</b>In order to identify the proteins that may participate in this process, we performed a proteome-wide comparison of the protein expression levels of immature and mature dura using 2D electrophoresis and MALDI-TOF mass spectrometry. The Western blotting was used to verify the results of the 2D electrophoresis/MALDI-TOF mass spectrometry.</p><p><b>RESULTS</b>Eleven proteins were found to express with significant differences in the immature and the mature dura. Among them, the emergence of vimentin, tropomyosin, beta-actin and gamma-actin were further confirmed by the Western blotting analysis.</p><p><b>CONCLUSION</b>The proteins and proteomic profiles provide a better understanding of the molecular mechanism of calvarial regeneration.</p>

Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C-->T mutation of low-density lipoprotein receptor gene / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Familial hypercholesterolemia (FH), caused by low density lipoprotein (LDL) receptor (LDL-R) gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited molecular data concerning FH are available in China. The present study described the clinical profiles and cell biological defects of a Chinese FH kindred with novel LDL-R gene mutation.</p><p><b>METHODS</b>The patient's LDL-R gene coding region was sequenced. The patient's lymphocytes were isolated and the LDL-R expression, binding and up-take functions were observed by immunohistochemistry staining and flow cytometry detection. The patient's heart and the major large vessels were detected by vessel ultrasound examination and myocardial perfusion imaging (MPI).</p><p><b>RESULTS</b>The patient's LDL-R expression, LDL binding and up-take functions were significantly lower than normal control (39%, 63% and 76% respectively). A novel homozygous 1439 C-->T mutation of the LDL-R gene was detected in the patient and his family. ECG showed atypical angina pectoris. Echocardiogram showed stenosis of the coronary artery and calcification of the aortic valve and its root. Blood vessel ultrasound examination showed the thickness of large vessel intima, and the vessel lumen was narrowed by 71%. MPI showed ischemic changes.</p><p><b>CONCLUSIONS</b>The LDL-R synthesis dysfunction of FH patients leads to arterial stenosis and calcification, which are the major phenotype of the clinical disorder. The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China.</p>

Structure and function of apolipoprotein and prevention and therapy of virus diseases / 中国医学科学院学报

Apolipoprotein, an important component of the lipoproteins, modulates the activity of enzyme, introduces the binding of cell receptor and lipoproteins, and keeps the structural stability of lipoproteins. The amphipathic helices structure in apolipoproteins is the structural basis that it binds and transports lipids. A certain envelope glycoprotein (gp) in the outer membrane of HIV also has been found to be with such amphipathic helices structure. Recent studies have shown that the liposome consisted of apolipoproteins and phospholipids may defend against HCV, HIV, and herpes simplex virus, and even neutralize the endotoxin released by bacteria. The liposome made up of apolipoproteins and phospholipid has became a potential carrier for anti-tumor and anti-virus drugs.

Structure analysis of apolipoprotein B 3' variable number of tandem repeats / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the distribution, frequency and structure of variable number of tandem repeats (VNTR) in 3' region of apoB gene in Chinese population.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood obtained under consent from randomly-chosen 522 individuals who came to the hospital for physical examination, and used to screen for polymorphisms of 3' VNTR of the apoB gene by employing polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), gradient polyacrylamide gel electrophoresis, cloning and sequencing.</p><p><b>RESULTS</b>Sixteen types of alleles of apoB 3oVNTR were identified, among which heterozygotes were more than homozygotes. The biggest allele is HVE58, and the smallest one is HVE22. HVE34 had the highest frequency (40.4%), followed by HVE32 (34.7%). This showed significant difference from the allelic distribution of other populations (Caucasian and Swedish). Through sequencing of 60 alleles, a new isomer (Y-A=ATAATTAAATATTT) and four new types of alleles were found.</p><p><b>CONCLUSION</b>The Chinese population we studied had a higher frequency of small alleles and showed a difference in allelic structure and frequency distribution from European and American in this populations.</p>

Correlation between APOA gene polymorphism and intracranial aneurysm / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the correlation between a pentanucleotide repeats (PNR) polymorphism of APOA and the genesis of intracranial aneurysm.</p><p><b>METHODS</b>Fifty-eight patients with intracranial aneurysms diagnosed by angiography and 58 healthy controls were enrolled in our study. The gene polymorphism of APOA PNR were detected by polymerase chain reaction (PCR) and non-denatured polyacrylamide gels electropherosis (PAGE).</p><p><b>RESULTS</b>Eight kinds of gene types and 6 kinds of alleles were found in these two groups. There were two sites of sequence variance in the 5' control region of APOA gene, which were significantly different between the patients and controls.</p><p><b>CONCLUSION</b>Correlation may exist between intracranial aneurysm and APOA gene.</p>

Role of histamine in airway remodeling of asthmatic guinea pig / 生理学报

To investigate the role of histamine in airway remodeling, 50 healthy guinea pigs were divided into 5 groups: control group: nebulized inhalation of distilled water for 8 weeks; asthma model group: nebulized inhalation of ovalbumin (OVA) for 8 weeks after sensitization; continued asthma model group: nebulized inhalation of OVA for 14 weeks after sensitization; histamine group: nebulized inhalation of OVA for 14 weeks after sensitization and histamine was added in the last 6 weeks; antagonist group: nebulized inhalation of OVA for 14 weeks after sensitization and histamine receptor antagonists were added in the last 6 weeks. For each group, the concentration of histamine, sodium ion (Na(+)), chlorine ion (Cl(-)), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), pH, actual bicarbonate (AB), standard bicarbonate (SB) in serum, and thickness of airway mucosa, base membrane and smooth muscle were measured and compared with each other. The results showed that: (1) the concentration of histamine in serum and the thickness of airway increased, the following order was, the control group, the asthma model group, the continued asthma model group and histamine group (P<0.01); and the concentration of histamine in serum and the thickness of airway of antagonist group was lower than that of the continued asthma model group (P<0.05, 0.01). (2) PaO2 of the asthma model group was lower than that of the normal control group (P<0.01); PaO2, pH, AB, SB decreased, the following order was, the asthma model group, the continued asthma model group and the histamine group (P<0.01); and PaO2, pH, AB, SB of the antagonist group was higher than that of the continued asthma model group (P<0.01); but for PaCO2, the order was converse (P<0.01); For the concentration of Na(+) and Cl(-) in serum, there was no difference among these groups. It is concluded that: (1) Histamine is one of the mediators in the airway remodeling of asthma. (2) Histamine receptor antagonists may play a role in preventing and treating airway remodeling. (3) There is a negative correlation between the PaO2, pH and the wall thickness of the airway (P<0.01), while a positive correlation between the PaCO2, anion gap (AG) and the wall thickness of the airway (P<0.01).

Polymorphisms in the apolipoprotein A5 gene and apolipoprotein C3 gene in patients with coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between the -1131T/C and 56C/G polymorphism in the APOA5 gene as well as the -482C/T in the APOC3 gene and susceptibility to coronary artery disease (CAD) in a Chinese Han population.</p><p><b>METHODS</b>Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polyacrylamide gel electrophoresis (PAGE) methods, we analyzed the genotypes in 312 CAD patients diagnosed by angiography and 317 healthy controls. The levels of serum lipid profiles were also studied by biochemical methods.</p><p><b>RESULTS</b>The frequency of the APOA5 -1131 C allele in CAD patients was significantly higher than that of the control group (39.9% vs. 33.3%, P = 0.02). Compared with the wild type TT, CC homozygotes had a significantly increased CAD risk (OR = 1.93 and OR = 1.80 using unadjusted and adjusted logistic regression models, respectively). This association still existed after adjustment for the APOC3-482 variant. The APOA5-1131C allele also showed a correlation with increasing plasma TG levels (P < 0.01).</p><p><b>CONCLUSIONS</b>The APOA5-1131T/C polymorphism but not APOC3-482C/T might contribute to an increased risk of CAD among Chinese accompanied by an elevation of serum TG levels; this effect was found to be independent of the APOC3-482C/T variant.</p>

Natural gas and indoor air pollution: a comparison with coal gas and liquefied petroleum gas / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The study was designed to compare the combustion products of coal gas, liquefied petroleum gas and natural gas in relation to indoor air pollution.</p><p><b>METHODS</b>Regular pollutants including B(a)P were monitored and 1-hydroxy pyrene were tested in urine of the enrolled subjects. Radon concentrations and their changes in four seasons were also monitored in the city natural gas from its source plant and transfer stations to final users. To analyze organic components of coal gas, liquefied petroleum gas and natural gas, a high-flow sampling device specially designed was used to collect their combustion products, and semi-volatile organic compounds contained in the particles were detected by gas chromatograph-mass spectrograph (GC/MS).</p><p><b>RESULTS</b>Findings in the study showed that the regular indoor air pollutants particles and CO were all above the standard in winter when heating facilities were operated in the city, but they were lowest in kitchens using natural gas; furthermore, although NO2 and CO2 were slightly higher in natural gas, B(a)P concentration was lower in this group and 1-hydroxy pyrene was lowest in urine of the subjects exposed to natural gas. Organic compounds were more complicated in coal gas and liquefied petroleum gas than in natural gas. The concentration of radon in natural gas accounted for less than 1% of its effective dose contributing to indoor air pollution in Beijing households.</p><p><b>CONCLUSION</b>Compared to traditional fuels, gases are deemed as clean ones, and natural gas is shown to be cleaner than the other two gases.</p>

Study on the relationship between smoking, alcohol intake and hyperlipidemia in fishermen / 中华流行病学杂志

<p><b>OBJECTIVE</b>To identify the relationship between smoking, alcohol intake and hyperlipidemia in fishermen.</p><p><b>METHODS</b>115 fishermen were randomly recruited and divided into case and control groups according to the result of blood lipoprotein. A questionnaire was used to record general information and the history of smoking and alcohol intake. Statistics were gathered to compare the difference of lipoprotein and apolipoprotein level between exposure and control groups and to calculate the OR value of smoking and alcohol intake.</p><p><b>RESULTS</b>The OR of smoking was 3.417 (95% CI: 1.132 - 10.308), with significant dosage-effect relationship between smoking index and hyperlipidemia. The serum low density lipoprotein-cholesterol (LDL-C) and apolipoprotein (apo) B levels in smoking group was higher than that of control group. The OR value of alcohol intake at early age (early than 20) were 3.275 (95% CI: 1.249 - 8.580) and 4.016 (95% CI: 1.475 - 10.952) respectively. The LDL-C, apoB, the serum total cholesterol (TC)/high density lipoprotein-cholesterol (HDL-C) levels in alcohol abuse group were higher than that of control group.</p><p><b>CONCLUSION</b>Smoking and alcohol abuse were important risk factors of hyperlipidemia, through changing the level of LDL-C and apoB. There was synergistic action between smoking and alcohol abuse in the development of hyperlipidemia.</p>

Analysis of lecithin-cholesterol acyltransferase cDNA and protein sequence from tree shrew / 中国医学科学院学报

<p><b>OBJECTIVE</b>To acquire cDNA sequence of lecithin-cholesterol acyltransferase (LCAT) from tree shrew and analyze the sequence structure.</p><p><b>METHODS</b>The first strand cDNA was acquired by reverse transcription using mRNA from tree shrew liver as template. By the method of SMART RACE PCR, tree shrew LCAT cDNA was acquired and deduced its amino acids sequence. The sequence and structure of tree shrew LCAT cDNA and amino acid were analyzed and predicted by the molecular software.</p><p><b>RESULTS</b>Tree shrew LCAT cDNA is composed of 1,340 bp, including 2 bp 5' untranslated region (5' UTR), 1,320 bp open reading frame (ORF) which encodes protein precursor of 440 amino acids (24 amino acids signal peptide and 416 amino acids mature peptide), and 18 bp 3' untranslated region (3'UTR). The stop codon is TAA and there is a poly (A) signal sequence AATAAA and a 25 bp poly (A) tail. Tree shrew LCAT cDNA sequence has been accepted by GenBank as a new gene, accession number AF272861 and its homology with human and baboon was 90% and 89%, respectively.</p><p><b>CONCLUSION</b>The sequence of LCAT cDNA in tree shrew has high identity with that of human and other experimental animal species.</p>