Dihydroquercetin alleviates dopamine neuron loss via regulating TREM2 activation.

BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder, marked by the degeneration of dopamine (DA) neurons in the substantia nigra (SN). Current evidence strongly suggests that neuroinflammation, primarily mediated by microglia, contributes to PD pathogenesis. Triggering receptor expressed on myeloid cells 2 (TREM2) might serve as a promising therapeutic target for PD due to its ability to suppress neuroinflammation. Dihydroquercetin (DHQ) is an important natural dihydroflavone and confers apparent anti-inflammatory, antioxidant and anti-fibrotic effects. Recently, DHQ-mediated neuroprotection was exhibited. However, the specific mechanisms of its neuroprotective effects remain incompletely elucidated. METHODS: In this study, rat models were utilized to induce damage to DA neurons using lipopolysaccharide (LPS) and 6-hydroxydopamine (6-OHDA) to assess the impacts of DHQ on the loss of DA neurons. Furthermore, DA neuronal MN9D cells and microglial BV2 cells were employed to investigate the function of TREM2 in DHQ-mediated DA neuroprotection. Finally, TREM2 knockout mice were used to investigate whether the neuroprotective effects mediated by DHQ through a mechanism dependent on TREM2. RESULTS: The main findings demonstrated that DHQ effectively protected DA neurons against neurotoxicity induced by LPS and 6-OHDA and inhibited microglia-elicited neuroinflammation. Meanwhile, DHQ promoted microglial TREM2 signaling activation. Notably, DHQ failed to reduce inflammatory cytokines release and further present neuroprotection from DA neurotoxicity upon TREM2 silencing. Similarly, DHQ didn't exert DA neuroprotection in TREM2 knockout mice. CONCLUSIONS: These findings suggest that DHQ exerted DA neuroprotection by regulating microglia TREM2 activation.

lncRNA260 siRNA Accelerates M2 Macrophage Polarization and Alleviates Oxidative Stress via Inhibiting IL28RA Gene Alternative Splicing.

The macrophage transformation of inflammatory M1 to anti-inflammatory M2 could be promoted by activating PI3K/AKT signaling pathway. In our previous study, it was found that downregulation of lncRNA260 could ameliorate hypoxic cardiomyocyte injury by regulating IL28RA through the activation of PI3K/AKT signaling pathways. It was suggested that lncRNA260 siRNA could promote the macrophages toward M2 polarization by regulating IL28RA. In this study, lncRNA260 siRNA was used to observe its effect on the polarization of murine bone marrow-derived macrophages (BMDM) and investigate its related mechanisms. lncRNA 260 specific siRNA were designed and synthesized which were transfected into murine BMDM with liposomes. The experiment was divided into three groups: Hypoxia group, Hypoxia+lncRNA 260-specific siRNA transfection group, and Normoxia group. The CD206-APC/CD11b-FITC or CD206-FITC/CD107b (Mac-3) double positive proportions were used to compare the M2 polarization proportions in the hypoxia process by using the immunofluorescence staining method. The p-AKT, Arg 1, PI3KCG, IL28RAV1, and IL28RAV2 protein expression changes were observed by using the western blot method. Compared with the Normoxia group, the M2 proportions were significantly decreased in the Hypoxia group (P < 0.05). Compared with the hypoxia group, the M2 proportions were significantly increased in the Hypoxia+lncRNA260 siRNA transfection group (P < 0.05). In the Hypoxia group, the ratios of Arg 1/ß-Actin, p-AKT/ß-Actin, PI3KCG/ß-Actin, and IL28RAV1/ß-Actin were significantly lower than those in the Normoxia group (P < 0.05). After transfection with lncRNA260 siRNA, the ratios of Arg1/ß-Actin, p-AKT/ß-Actin, PI3KCG/ß-Actin, and IL28RAV1/ß-Actin were significantly higher than those in the Hypoxia group (P < 0.05). Compared with the Normoxia group, the IL28RAV2/ß-Actin in the Hypoxia group was significantly increased (P < 0.05). After transfection with lncRNA260 siRNA, the ratio of IL28RAV2/ß-Actin was significantly decreased than that in the Hypoxia group (P < 0.05). lncRNA260 siRNA could promote the M2 polarization of the hypoxia macrophages by reducing the IL28RAV2 alternative splicing variant, which might be related to the activation of the JAK-STAT and PI3K/AKT signaling pathways. It will provide a new strategy for the anti-inflammation, antioxidative stress therapy, and cardiac remodeling after AMI.

Role of Nrf2 in Parkinson's Disease: Toward New Perspectives.

Parkinson's disease (PD) is one of the most common and chronic degenerative diseases in the central nervous system. The main pathology of PD formation is the progressive loss of dopaminergic neurons in substantia nigra and the formation of α-synuclein-rich Lewy bodies. The pathogenesis of PD is not caused by any single independent factor. The diversity of these independent factors of PD, such as iron accumulation, oxidative stress, neuroinflammation, mitochondrial dysfunction, age, environment, and heredity, makes the research progress of PD slow. Nrf2 has been well-known to be closely associated with the pathogenesis of PD and could regulate these induced factors development. Nrf2 activation could protect dopaminergic neurons and slow down the progression of PD. This review summarized the role of Nrf2 pathway on the pathogenesis of PD. Regulation of Nrf2 pathway might be one of the promising strategies to prevent and treat PD.

Neuroprotective effect of aldose reductase knockout in a mouse model of spinal cord injury involves NF-κB pathway.

The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and the infiltration of macrophages. Activated microglia/macrophages have either detrimental or beneficial effects on neural regeneration based on their functional polarized M1/M2 subsets. Aldose reductase (AR) has recently been shown to be a key component of the innate immune response. However, the mechanisms involved in AR and innate immune response remain unclear. In this study, wild-type (WT) or AR-deficiency (KO) mice were subjected to SCI by a spinal crush injury model. AR KO mice showed better locomotor recovery and smaller injury lesion areas after spinal cord crushing compared with WT mice. Here, we first demonstrated that AR deficiency repressed the expression level of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS) in vitro via the activation of autophagy. AR deficiency caused 4-hydroxy-2-(E)-nonenal (4-HNE) accumulation in LPS-induced macrophages. We also found that exogenous addition of low concentrations of 4-HNE in LPS-induced macrophages had the effect of promoting further activation of NF-κB pathway, whereas high concentrations of 4-HNE had inhibitory effects. Together, these results indicated that autophagy as a mechanism underlying AR and 4-HNE in LPS-induced macrophages.

PCSK9 Gene E670G Polymorphism and Coronary Artery Disease: An Updated Meta-Analysis of 5,484 Subjects.

Objective: Research has shown a possible relationship between the E670G polymorphism of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and an increased risk of coronary artery disease (CAD). However, there is no clear consensus on the subject because of conflicting results in the literature. The current meta-analysis was performed to better elucidate the potential relationship between the PCSK9 gene E670G polymorphism and CAD. Methods: There were 5,484 subjects from 13 individual studies who were included in the current meta-analysis. The fixed- or random-effects models were used to evaluate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Results: The current meta-analysis found a significant association between PCSK9 gene E670G polymorphism and CAD under allelic (OR = 1.79, 95% CI = 1.42-2.27, P = 1.00 × 10-6), dominant (OR = 2.16, 95% CI = 1.61-2.89, P = 2.22 × 10-7), heterozygous (OR = 2.02, 95% CI = 1.55-2.64, P = 2.47 × 10-7), and additive genetic models (OR = 1.92, 95% CI = 1.49-2.49, P = 6.70 × 10-7). Conclusions: PCSK9 gene E670G polymorphism was associated with an elevated risk of CAD, especially in the Chinese population. More specifically, carriers of the G allele carriers of the PCSK9 gene may be predisposed to developing CAD.

GHRL Gene Leu72Met Polymorphism and Type 2 Diabetes Mellitus: A Meta-Analysis Involving 8,194 Participants.

Background: Although many studies indicate a positive correlation between GHRL gene Leu72Met polymorphism and an increased susceptibility to type 2 diabetes mellitus (T2DM), inconsistencies between independent studies still remain. Objective: Considering the inconsistencies between them, we have performed the current meta-analysis study. The objective of this study is to better examine the correlation of the GHRL gene Leu72Met polymorphism and T2DM. Methods: The current meta-analysis, involving 8,194 participants from 11 independent studies, was performed. A fixed effect model was used to evaluate the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs). Results: A significant association was found between T2DM and GHRL gene Leu72Met polymorphism under recessive (OR: 1.33, 95% CI: 1.01-1.76, P = 0.04), and homozygous genetic models (OR: 1.34, 95% CI: 1.01-1.78, P = 0.04) in the whole population. The correlation was more distinct in our subgroup analysis of the Chinese population under recessive (OR: 1.52, 95% CI: 1.07-2.15, P = 0.02), dominant (OR: 1.70, 95% CI: 1.38-2.10, P < 0.00001), additive (OR: 1.16, 95% CI: 1.02-1.33, P = 0.02), and homozygous genetic models (OR: 1.54, 95% CI: 1.07-2.20, P = 0.02). Conclusions: In short, GHRL gene Leu72Met polymorphism was significantly correlated with increased T2DM risk, particularly in the Chinese population. Individuals carrying the Met72 allele of GHRL Leu72Met gene polymorphism, particularly those of Chinese ancestry, may be more susceptible to developing T2DM disease.

Solute Carrier Family 30 Member 8 Gene 807C/T Polymorphism and Type 2 Diabetes Mellitus in the Chinese Population: A Meta-Analysis Including 6,942 Subjects.

BACKGROUND: Although solute carrier family 30 (zinc transporter) member 8 (SLC30A8) gene 807C/T polymorphism is associated with an increased risk of type 2 diabetes mellitus (T2DM) risk, there remains some inconsistency between individual studies. OBJECTIVE: The aim of the study is to explore the relationship between SLC30A8 gene 807C/T polymorphism and T2DM in the Chinese population. METHODS: The current meta-analysis compiles and analyzes the data of 6,942 participants from 10 independent studies. Either a fixed or random-effects model was adopted to evaluate the pooled odds ratio (ORs) and the corresponding 95% confidence interval (95% CI). RESULTS: A significant association between SLC30A8 gene 807C/T polymorphism and T2DM was found in the Chinese population under allelic (OR: 0.85, 95% CI: 0.80-0.91, P = 7.42 × 10-7), recessive (OR: 0.52, 95% CI: 0.38-0.72, P = 8.49 × 10-5), dominant (OR: 2.40, 95% CI: 1.68-3.41, P = 1.30 × 10-6), homozygous (OR: 0.52, 95% CI: 0.40-0.67, P = 2.90 × 10-7), heterozygous (OR: 0.79, 95% CI: 0.71-0.88, P = 1.63 × 10-5), and additive genetic models (OR: 0.73, 95% CI: 0.64-0.83, P = 7.05 × 10-7). CONCLUSION: SLC30A8 gene 807C/T polymorphism was significantly associated with an increased T2DM risk in the Chinese population. Therefore, individuals of Chinese descent with the C allele of SLC30A8 gene 807C/T polymorphism may be more susceptible to developing T2DM, while individuals with the T allele may be protected against T2DM.

Protective effects of PI3KCG gene on acute myocardial infarction.

BACKGROUND: To study the protective effects of recombinant phosphatidylinositol 3-kinase p110 gamma (rPLV-PI3KCG) lentiviral vector in Sprague-Dawley (SD) rats with acute myocardial infarction (AMI). METHOD: The AMI rat models were established by ligaturing left anterior descending coronary artery. The rPLV-PI3KCG or empty lentiviral vectors were injected at the edge of the infarct zone. The experiment was divided randomly into four groups (n=8): (I) Sham group; (II) AMI group; (III) AMI + empty vector injection group (AMI + E group); and (IV) AMI + PLV-PI3KCG injection group (AMI + PLV-PI3KCG group). The ultrasonic cardiogram (UCG) was used to compare the structural or functional changes among the four groups after operation for 10 days. Meanwhile, the rats were sacrificed and HE staining was used to compare the myocardial tissue changes among the four groups. The immunofluorescence and western blots were performed to compare the angiogenesis in the infarct region and explore the mechanism of the protective effects of PI3KCG gene on AMI rats. RESULTS: Compared with AMI group and AMI + E group, in the AMI + PLV-PI3KCG group, left ventricular end diastolic diameter (LVEDd) was decreased, left ventricular ejection fraction (LVEF%) was significantly increased, and vascular endothelial growth factor (VEGF) expression was significantly increased in the infarct region (P<0.05); PI3KCG, pAkt/Akt, HIF-1a, and Bcl-2/Bax protein expressions were significantly increased (P<0.05). CONCLUSIONS: The rPLV-PI3KCG injection could improve the cardiac function, relieve the cardiac injury after the AMI operation. PI3KCG gene could play the protection role in the AMI process possibly by activating PI3K/Akt signal pathway, inhibiting apoptosis and promoting angiogenesis.

ADRB3 Gene Trp64Arg Polymorphism and Essential Hypertension: A Meta-Analysis Including 9,555 Subjects.

Background: Presence of the ß3-Adrenergic receptor (ADRB3) gene Trp64Arg (T64A) polymorphism may be associated with an increased susceptibility for essential hypertension (EH). A clear consensus, however, has yet to be reached. Objective and methods: To further elucidate the relationship between the ADRB3 gene Trp64Arg polymorphism and EH, a meta-analysis of 9,555 subjects aggregated from 16 individual studies was performed. The combined odds ratios (ORs) and their corresponding 95% confidence intervals (CI) were evaluated using either a random or fixed effect model. Results: We found a marginally significant association between ADRB3 gene Trp64Arg polymorphism and EH in the whole population under the additive genetic model (OR: 1.200, 95% CI: 1.00-1.43, P = 0.049). Association within the Chinese subgroup, however, was significant under allelic (OR: 1.150, 95% CI: 1.002-1.320, P = 0.046), dominant (OR: 1.213, 95% CI: 1.005-1.464, P = 0.044), heterozygous (OR: 1.430, 95% CI:1.040-1.970, P = 0.03), and additive genetic models (OR: 1.280, 95% CI: 1.030-1.580, P = 0.02). A significant association was also found in the Caucasian subgroup under allelic (OR: 1.850, 95% CI: 1. 260-2.720, P = 0.002), dominant (OR: 2.004, 95% CI: 1.316-3.052, P = 0.001), heterozygous (OR: 2.220, 95% CI: 1.450-3.400, P = 0.0002), and additive genetic models (OR: 2.000, 95% CI: 1. 330-3.010, P = 0.0009). Conclusions: The presence of the ADRB3 gene Trp64Arg polymorphism is positively associated with EH, especially in the Chinese and Caucasian population. The Arg allele carriers of ADRB3 gene Trp64Arg polymorphism may be at an increased risk for developing EH.

ALDH2 gene G487A polymorphism and coronary artery disease: a meta-analysis including 5644 participants.

Several studies indicate the mitochondrial Aldehyde Dehydrogenase-2 (ALDH2) gene G487A polymorphism may be correlated with coronary artery disease (CAD) susceptibility, but a clear consensus has yet to be reached. To elucidate the relationship between the ALDH2 gene G487A polymorphism and CAD within the Chinese population, a meta-analysis of 5644 subjects from nine individual studies was performed. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals were assessed using random or fixed-effect models depending the heterogeneity existence or not. Our meta-analysis found a significant association between ALDH2 gene G487A polymorphism and CAD in the Chinese population under allele (OR: 1.830, 95% CI: 1.560-2.140, P = 1.36 × 10-13 ), recessive (OR: 1.920, 95% CI: 1.530-2.390, P = 1.20 × 10-8 ), dominant (OR: 1.593, 95% CI: 1.336-1.900, P = 2.22 × 10-7 ), homozygous (OR: 2.280, 95% CI: 1.810-2.870, P = 3.17 × 10-12 ) and heterozygous genetic models (OR: 3.330, 95% CI: 2.070-5.370, P = 7.81 × 10-7 ). The positive correlation between the ALDH2 gene G487A polymorphism and CAD makes the mutation a strong candidate as a genetic risk marker for CAD. Through further analysis, we also found that A allele carriers of ALDH2 gene G487A polymorphism may be particularly susceptible to CAD.

Small Ubiquitin-Like Modifier 4 (SUMO4) Gene M55V Polymorphism and Type 2 Diabetes Mellitus: A Meta-analysis Including 6,823 Subjects.

BACKGROUND: Many studies suggest that the small ubiquitin-like modifier 4 (SUMO4) M55V gene polymorphism (rs237025) may be associated with an increased risk of type 2 diabetes mellitus (T2DM). However, due to other conflicting results, a clear consensus is lacking in the matter. OBJECTIVE AND METHODS: A meta-analysis consisting of 6,823 subjects from 10 studies was conducted to elucidate relationship between the SUMO4 M55V gene polymorphism and T2DM. Depending on the heterogeneity of the data, either a fixed or random-effects model would be used to assess the combined odds ratio (ORs) and their corresponding 95% confidence interval (CI). RESULTS: SUMO4 gene M55V polymorphism was significantly associated with T2DM in the whole population under allelic (OR: 1.18, 95% CI: 1.10-1.28, P = 1.63 × 10-5), recessive (OR: 1.59, 95% CI: 1.14-2.23, P = 0.006), dominant (OR: 0.815, 95% CI: 0.737-0.901, P = 6.89 × 10-5), homozygous (OR: 1.415, 95% CI: 1.170-1.710, P = 0.0003), heterozygous (OR: 1.191, 95% CI: 1.072-1.323, P = 0.001), and additive genetic models (OR: 1.184, 95% CI: 1.097-1.279, P = 1.63 × 10-5). In our subgroup analysis, a significant association was found again in the Chinese population, but not in Japanese or Iranian population. CONCLUSION: SUMO4 gene M55V polymorphism may correlate with increased T2DM risk. Chinese carriers of the V allele of the SUMO4 gene M55V polymorphism may be predisposed to developing T2DM.

LEPR gene Gln223Arg polymorphism and type 2 diabetes mellitus: a meta-analysis of 3,367 subjects.

BACKGROUND: The Leptin receptor (LEPR) Gln223Arg gene polymorphism has been associated with an increased susceptibility to Type 2 diabetes mellitus (T2DM). Results from various studies, however, are inconsistent. OBJECTIVE AND METHODS: To better elucidate the association of LEPR Gln223Arg gene polymorphism with T2DM in the Chinese population, a meta-analysis of 3,367 subjects from seven independent studies was performed. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) were evaluated by the fixed-effects model. RESULTS: A significant relationship between LEPR Gln223Arg gene polymorphism and T2DM in the Chinese population was found under allele (OR: 1.432, 95% CI: 1.211-1.694, P=2.67×10-5), dominant (OR: 1.466, 95% CI: 1.215-1.769, P=6.33×10-5), recessive (OR: 0.539, 95% CI: 0.303-0.960, P=0.036), heterozygous (OR: 0.700, 95% CI: 0.577-0.849, P=3.06×10-4), and homozygous (OR: 0.472, 95% CI: 0.265-0.839, P=0.011) genetic models. CONCLUSIONS: LEPR Gln223Arg gene polymorphism was associated with an increased risk of T2DM in the Chinese population. Therefore, Chinese carriers of the G allele of LEPR Gln223Arg gene polymorphism may be more susceptible to T2DM than the general population.

LncRNA260-specific siRNA targeting IL28RA gene inhibit cardiomyocytes hypoxic/reoxygenation injury.

BACKGROUND: The interleukin 28 receptor alpha (IL28RA) gene was indicated to be associated with apoptosis. However, it was not clear whether long non-coding RNA 260 (lncRNA 260)-specific siRNA targeting IL28RA gene could inhibit hypoxic reoxygenation (H/R) cardiomyocytes injury or not. To explore the mechanisms underlying the protective effects of lncRNA260-specific siRNA-mediated inhibition of IL28RA from H/R injury in cardiomyocytes, the current research was performed. METHODS: The primary neonatal rat cardiomyocytes were transfected with three different pairs of siRNA specific to lncRNA260 targeting IL28RA gene and then were undergone with the conditions simulating H/R injury. RESULTS: All three groups of cardiomyocytes treated with lncRNA260-specific siRNA experienced significantly decreased levels of lactate dehydrogenase activity and apoptosis rate relative to the non-treatment and negative control groups (P<0.05), also expressed reduced levels of IL28RA, and increased levels of PI3KCG and Bcl-2/Bax (P<0.05). CONCLUSIONS: The lncRNA260-specific siRNA may reduce cardiomyocyte apoptosis associated with H/R injury by decreasing levels of the IL28RA gene product and thus activating the PI3K/AKT signaling pathway.

AR C-106T gene polymorphism and diabetic nephropathy in the Eastern Asians with T2DM: A meta-analysis including 2120 subjects.

BACKGROUND: Aldose reductase (AR) gene C-106T polymorphism may be associated with diabetic nephropathy (DN) susceptibility, but the results of individual studies remain controversial. OBJECTIVE AND METHODS: To explore the relationship between AR gene C-106T gene polymorphism and DN in the Eastern Asians with type 2 diabetes mellitus (T2DM) population, we conducted a meta-analysis of 2120 participants from 5 studies. Pooled odds ratio (ORs) and the corresponding 95% confidence interval (95% CI) were evaluated by either a fixed or random-effects models. RESULTS: AR C-106T gene polymorphism was significantly associated with DN in the Eastern Asians population with T2DM under allelic (OR: 1.81, 95% CI: 1.30-2.52, P=0.0005), recessive (OR: 1.88, 95% CI: 1.20-2.97, P=0.006), dominant (OR: 9.22, 95% CI: 2.73-31.12, P=0.0003), homozygous (OR:2.27, 95% CI: 1.43-3.61, P=0.0005), heterozygous (OR: 5.75, 95% CI: 1.96-16.81, P=0.001), and additive genetic models (OR: 2.27, 95% CI: 1.48-3.48, P=0.0002). CONCLUSIONS: In the Eastern Asians with T2DM, the AR gene C-106T gene polymorphism is correlated with an increased risk of DN. The Eastern Asians with the T allele of AR gene C-106T gene polymorphism might be susceptible to DN.

EPCR Gene Ser219Gly Polymorphism and Venous Thromboembolism: A Meta-Analysis of 9,494 Subjects.

Background: Although endothelial cell protein C receptor (EPCR) gene Ser219Gly polymorphism has been associated with venous thromboembolism (VTE) susceptibility, no clear consensus has yet been reached. Objective and methods: A meta-analysis of 9,494 subjects from 13 individual studies was conducted to better elucidate the potential relationship between the EPCR gene Ser219Gly polymorphism and VTE. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were evaluated by using fixed or random effect models. Results: The current meta-analysis suggested that there was a significant association between EPCR gene Ser219Gly polymorphism and VTE under allelic (OR: 1.42, 95% CI: 1.21-1.66, P = 1.30 × 10-5), recessive (OR: 2.02, 95% CI: 1.44-2.85, P = 5.35 × 10-5), homozygous (OR: 2.24, 95% CI: 1.59-3.16, P = 3.66 × 10-6), and additive genetic models (OR: 1.63, 95% CI: 1.30-2.04, P = 2.24 × 10-5). Conclusions:EPCR gene Ser219Gly polymorphism was associated with an elevated risk of VTE and the Gly residue carriers of the EPCR gene might be predisposed to VTE.

LPL gene Pvu II polymorphism and hypertriglyceridemia: a meta-analysis involving 1,640 subjects.

BACKGROUND/AIMS: Although lipoprotein lipase (LPL) gene Pvu II polymorphism has been associated with an increased risk of hypertriglyceridemia (HT), there is no clear consensus within the scientific community. METHODS: A meta-analysis of 1,640 subjects from six individual studies was conducted to better elucidate the potential relationship between the LPL gene Pvu II polymorphism and HT within the Chinese population. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were evaluated by using fixed effect models. RESULTS: Our analysis indicated a significant association between LPL gene Pvu II polymorphism and HT within the Chinese population under allelic (OR, 1.550; 95% CI, 1.320 to 1.830; p = 1.158 × 10-7), recessive (OR, 0.540; 95% CI, 0.390 to 0.750; p = 0.0002), dominant (OR, 1.889; 95% CI, 1.501 to 2.377; p = 5.960 × 10-8), homozygous (OR, 2.167; 95% CI, 1.531 to 3.067; p = 1.242 × 10-5), heterozygous (OR, 1.810; 95% CI, 1.419 to 2.309; p = 1.842 × 10-6), and additive genetic models (OR, 1.553; 95% CI, 1.320 to 1.828; p = 1.158 × 10-7). CONCLUSIONS: Because LPL gene Pvu II restriction fragment length polymorphism polymorphism was associated with an elevated risk of HT, the P+ allele carriers of the LPL gene might be predisposed to HT.

TGF-ß1 Gene -509C/T Polymorphism and Coronary Artery Disease: An Updated Meta-Analysis Involving 11,701 Subjects.

Background: The transforming growth factor-ß1 (TGF-ß1) gene -509C/T polymorphism has been suggested to be associated with increased coronary artery disease (CAD) risk. However, the individual studies results are still inconsistent. Objective and methods: To investigate the relationship between TGF-ß1 gene -509C/T polymorphism and CAD, a meta-analysis involving 11,701 participants from 8 individual studies was conducted. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals were evaluated by using random or fixed effect models. Results: A significant association between TGF-ß1 gene -509C/T polymorphism and CAD was detected in the total population under allelic (OR: 1.130, 95% CI: 1.060-1.200, P = 0.0001), recessive (OR: 1.390, 95% CI: 1.100-1.750, P = 0.006), dominant (OR: 0.857, 95% CI: 0.785-0.935, P = 2.507 × 10-4), homozygous (OR: 1.258, 95% CI: 1.098-1.442, P = 0.001), heterozygous (OR: 1.147, 95% CI: 1.046-1.257, P = 0.003), and additive genetic models (OR: 1.131, 95% CI: 1.063-1.204, P = 5.442 × 10-5). In the subgroup analysis, there was a significant association between them in Chinese population under all of the genetic models (P < 0.05), except under the heterozygous genetic model (P > 0.05). In the Caucasian subgroup, a significant association between them was also detected under all of the genetic models (P < 0.05), except under the recessive genetic model (P > 0.05). Conclusions:TGF-ß1 gene -509C/T polymorphism was significantly associated with increased CAD risk. The people with T allele of TGF-ß1 gene -509C/T polymorphism might be predisposed to CAD.

Matrix metalloproteinase-9 Gene-1562C>T Gene Polymorphism and Coronary Artery Disease in the Chinese Han Population: A Meta-Analysis of 5468 Subjects.

BACKGROUND: Multiple studies indicate that the matrix metalloproteinase-9 (MMP-9)-1562C>T gene polymorphism may be associated with an increased risk of coronary artery disease (CAD) in the Chinese Han population. However, a clear consensus has yet to be established. OBJECTIVE AND METHODS: A meta-analysis of 5468 subjects from 10 separate studies was performed to explore the possible relationship between the MMP-9-1562C>T gene polymorphism and CAD within the Chinese Han population. Pooled odds ratio (ORs) for the association and the corresponding 95% confidence intervals (CIs) were evaluated by a random or fixed-effect model. RESULTS: Our analysis confirms the association between the MMP-9-1562C>T gene polymorphism and an increased risk of CAD within the Chinese Han population under allelic (OR: 1.60, 95% CI: 1.25-2.04, P = 0.0002), recessive (OR: 3.05, 95% CI: 1.67-5.56, P = 0.0003), dominant (OR: 2.23, 95% CI: 1.49-3.35, P = 0.0001), homozygous (OR: 3.41, 95% CI: 1.87-6.23, P < 0.0001), heterozygous (OR: 2.03, 95% CI: 1.40-2.93, P = 0.0002), and additive genetic models (OR: 1.78, 95% CI: 1.33-2.39, P < 0.0001). CONCLUSIONS: In the Chinese Han population, the MMP-9-1562C>T gene polymorphism is correlated with an increased risk of CAD. Therefore, Han Chinese carriers of the -1562T allele may be at an increased risk of CAD.

Panorama of DNA hairpin folding observed via diffusion-decelerated fluorescence correlation spectroscopy.

Based on a confocal microscopy platform, we extended the FCS time window by three orders of magnitude to the s timescale by attaching a polystyrene microsphere. We simultaneously monitored the relaxations of multiple intermediates involved in DNA hairpin folding, thus offering a much more detailed view of the kinetics of hairpin folding experimentally.

[Construction and primary application of two HBV-HLA-A*2402-peptide tetramers].

AIM: To construct two soluble HLA-A*2402-peptide tetramers and detect the HBV-specific cytotoxic T lymphocytes (CTLs) with the constructed HLA-A*2402-peptide tetramers. METHODS: After proteins HLA-A*2402-BSP and beta2m were made an effective prokanyotical expression, the purified proteins were refolded into HLA-A*2402-beta2m-peptide complexes in the presence of two antigenic peptides (Hepatitis B virus Pol756-764 or Core117-125) with dilution method. Then the complexes were biotinylated by BirA enzyme and purified by gel-filtration chromatography. The tetramers were generated by mixing the complex with PE-Streptavidin in the molar ratio of 5:1. FCM can and cell quest software were used to analyze the stained PBMCs. RESULTS: Two biotinylated HBV-HLA-A*2402-peptide complexes were identified by Western blot and they were shown to have natural conformation by Dot-ELISA and ELISA. CONCLUSION: The constructed HLA-A*2402-peptide tetramers can detect the HBV-specific CTLs in the patients with self-limited acute HBV infection.