Malvidin attenuates trauma-induced heterotopic ossification of tendon in rats by targeting Rheb for degradation via the ubiquitin-proteasome pathway.

The pathogenesis of trauma-induced heterotopic ossification (HO) in the tendon remains unclear, posing a challenging hurdle in treatment. Recognizing inflammation as the root cause of HO, anti-inflammatory agents hold promise for its management. Malvidin (MA), possessing anti-inflammatory properties, emerges as a potential agent to impede HO progression. This study aimed to investigate the effect of MA in treating trauma-induced HO and unravel its underlying mechanisms. Herein, the effectiveness of MA in preventing HO formation was assessed through local injection in a rat model. The potential mechanism underlying MA's treatment was investigated in the tendon-resident progenitor cells of tendon-derived stem cells (TDSCs), exploring its pathway in HO formation. The findings demonstrated that MA effectively hindered the osteogenic differentiation of TDSCs by inhibiting the mTORC1 signalling pathway, consequently impeding the progression of trauma-induced HO of Achilles tendon in rats. Specifically, MA facilitated the degradation of Rheb through the K48-linked ubiquitination-proteasome pathway by modulating USP4 and intercepted the interaction between Rheb and the mTORC1 complex, thus inhibiting the mTORC1 signalling pathway. Hence, MA presents itself as a promising candidate for treating trauma-induced HO in the Achilles tendon, acting by targeting Rheb for degradation through the ubiquitin-proteasome pathway.

Multicomponent Analysis of Liuwei Dihuang Pills by a Single Marker Quantification Method and Chemometric Discrimination of Fingerprints.

An effective and comprehensive quality evaluation method for Liuwei Dihuang pills (LDP) was established by the simultaneous determination of 8 active components in LDP by the quantitative analysis of multicomponents by single marker (QAMS) method and high-performance liquid chromatography (HPLC) fingerprint combined with chemometrics. These 8 active components were determined by QAMS and the external standard method (ESM), and the quantitative results of the two methods were compared to validate the accuracy and feasibility of the QAMS method. 8 active components showed good linear relationships within their ranges, whose average recoveries were 99.7∼102.3%. No significant difference was found (P > 0.05) in the quantitative results determined by QAMS and ESM. Furthermore, the fingerprint of LDP was also established, with 11 common peaks identified, and the similarity of the fingerprints of 21 batches of LDP was greater than 0.95. The 21 batches of LDP were basically divided into 3 groups by hierarchical cluster analysis (HCA) and principal component analysis (PCA), and 3 differential markers were screened out by orthogonal partial least squares discriminant analysis (OPLS-DA). The established QAMS method is accurate, economical, fast, and convenient and can simultaneously determine the content of 8 active components in LDP. HPLC fingerprint combined with chemometric analysis more comprehensively evaluated the quality consistency of different batches of LDP and analyzed the markers that cause quality differences between batches. It can provide a scientific basis and reference of quality consistency evaluation for the manufacturers and drug regulatory departments of the preparation.

Circ_0006873 suppresses the osteogenic differentiation of human-derived mesenchymal stem cells through mediating miR-20a/SMURF2 axis in vitro.

The clinical application of human-derived mesenchymal stem cells (hMSCs) in osteoporosis (OP) treatment is promising. We aimed to uncover the role of circular RNA 0006873 (circ_0006873) in OP progression using hMSCs. The levels of circ_0006873, pantothenate kinase 2 (PANK2) messenger RNA (mRNA), microRNA-20a (miR-20a), SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) mRNA and the mRNA levels of osteogenesis-related markers were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of osteogenesis-related markers and SMURF2 was detected by Western blot assay. Alkaline phosphatase (ALP) staining and activity were determined using an ALP staining Kit and an ALP Colorimetric Assay Kit. Circ_0006873 was highly expressed in the serum samples and bone tissue samples of OP patients compared with control cases. Circ_0006873 overexpression down-regulated the expression of osteogenesis-related markers and reduced ALP staining and activity. Circ_0006873 down-regulated miR-20a level through its interaction with miR-20a in hMSCs. Circ_0006873 suppressed osteogenic differentiation through targeting miR-20a. SMURF2 was a molecular target of miR-20a, and miR-20a promoted osteogenic differentiation through targeting SMURF2. Circ_0006873 suppressed the osteogenic differentiation of hMSCs by upregulating SMURF2 level via sponging miR-20a in vitro.

Farrerol alleviates collagenase-induced tendinopathy by inhibiting ferroptosis in rats.

Tendinopathy is mainly characterized by local pain, functional limitation and decreased athletic ability, which seriously affects the quality of life of patients and the career of athletes. Farrerol (FA), one of the main active compounds extracted from Rhododendron and plants in the Rhododendron family, has a wide range of pharmacological activities, such as immunomodulatory, anti-inflammatory and antiviral effects. However, the effect of FA on tendinopathy is unclear. Here, we investigated the pharmacological effect and mechanism of FA in tendon injury through collagenase-induced tendinopathy in vivo and RSL3-induced tenocytes injury in vitro. The results showed that FA alleviated the infiltration of inflammatory cells, promoted tenogenesis and improved mechanical properties of the Achilles tendon in rats. In addition, ferroptosis inducer RSL3 inhibits the tenogenesis in vitro and in vivo, which accelerates the progression of tendinopathy. Moreover, FA effectively inhibited iron accumulation and alleviated ferroptosis in the Achilles tendon. Using in vitro experiments, we found that FA antagonized ferroptosis by reducing lipid peroxidation and iron accumulation in tenocytes. Finally, we found that glutathione peroxidase 4 silencing could block the protective effect of FA on ferroptosis of tenocytes. Therefore, the results of this study suggest that FA can relieve collagenase-induced tendinopathy by inhibiting ferroptosis, and reveal that FA may be a potentially effective drug for the treatment of tendinopathy in the future.

Genetic Association of ERCC6 rs2228526 Polymorphism with the Risk of Cancer: Evidence from a Meta-Analysis.

At present, several studies have assessed the association between ERCC6 rs2228526 polymorphism and the risk of cancer. However, the association remained controversial. To provide a more accurate estimate on the association, we performed a meta-analysis search of case-control studies on the associations of ERCC6 rs2228526 with susceptibility to cancer. PubMed, Embase, Google Scholar, Wanfang database, and Chinese National Knowledge Infrastructure databases (CNKI) China Biological Medicine Database (CBM) (up to August 2021) were searched to identify eligible studies. The effect summary odds ratio (OR) with 95% confidence intervals (CI) was applied to assay the association between the ERCC6 rs2228526 polymorphism and the risk of cancer. 14 studies included 15 case-control studies which contained 5,856 cases, and 6,387 controls were finally determined as qualified studies for this meta-analysis. Overall, based on current studies, we found significant association between ERCC6 rs2228526 polymorphism and the risk of cancer in four genetic models [the allele model G vs. A: 1.10, (1.03-1.17); the homozygous model GG vs. AA: 1.27, (1.07-1.51); heterozygote model GA vs. AA: 1.08, (1.00-1.17); the dominant model GG + GA vs. AA: 1.10, (1.02-1.19); the recessive model GG vs. GA + AA: 1.22, (1.03-1.45)]. In the stratified analysis based on ethnicity, we found significant association in two genetic models in Asians. Further, significant genetic cancer susceptibility was found under PB control on subgroup analysis by source of control. In addition, no significant association was found in lung cancer and bladder cancer patients in subgroup analyses based on cancer style. This study suggests that the ERCC6 rs2228526 polymorphism may be associated with increased cancer risk.

Untargeted metabolomics reveals the effect of rearing systems on bone quality parameters in chickens.

The objective of this study was to investigate the effects of rearing systems on the bone quality parameters in chickens using a metabolomics strategy. A total of 419 male one-day-old chicks were randomly allocated to two groups, a floor rearing group (FRG, n = 173) and a cage rearing group (CRG, n = 246). At 6, 8, 10, and 12 weeks of age, all chickens were radiographed by a digital X-ray machine, and body weight was recorded. At 12 weeks of age, 12 birds were selected from each group to obtain tibia and femur, and bone quality parameters of bone mineral density (BMD), mineral content (BMC), breaking strength (BBS), stiffness, Young's modulus (YM), ash content, calcium content, and phosphorus content were determined. An untargeted metabolomics assay was performed to identify changes in the serum metabolic profile (n = 8 birds/group). The results showed that cage-reared chickens had wider tibiae and greater body weight compared with floor-reared chickens. There were no significant differences in BMC or BBS between the two groups (p > 0.05), but BMD, ash content, calcium content, and phosphorus content of the tibia and femur of FRG were significantly higher than those of CRG (p < 0.05). Greater stiffness and YM of the femur were also observed in birds raised in the FRG compared with those raised in the CRG (p < 0.05). Taken together, the results suggest that rearing systems affected bone quality parameters. Furthermore, 148 and 149 differential metabolites were identified in positive and negative ion modes by LC-MS/MS analysis, among which 257 metabolites were significantly correlated with 16 bone quality parameters, including leucine, myristoleic acid, glycocholic acid, and N-phenylacetamide. KEGG analysis indicated that 15 metabolic pathways, including six pathways of amino acid metabolism, two pathways of lipid metabolism, and two pathways of carbohydrate metabolism, were responsible for bone quality. Overall, the present study demonstrated the effect of rearing systems on bone quality parameters, and identified several metabolites and metabolic pathways associated with bone quality parameters.

Green and Short Preparation of CeO2 Nanoparticles with Large Specific Surface Area by Spray Pyrolysis.

Green and short preparation of CeO2 nanoparticles with large specific surface area from rare earth extraction (CeCl3) was successfully achieved by spray pyrolysis (SP). In this method, a precursor solution is first prepared by mixing CeCl3, C6H8O, and H2O in the requisite quantities. Subsequently, the precursor consisting of a mixture of CeO2 and C was obtained by SP method by using the precursor solution. Finally, the calcination at 500 °C~800 °C in air for two hours to transform the precursor to CeO2 nanoparticles. Thermodynamic analysis and experimental studies were performed to determine the optimal SP temperature and citric acid amount. The results indicated that the maximum specific surface area (59.72 m2/g) of CeO2 nanoparticles were obtained when the SP temperature was 650 °C and the molar ratio of citric acid to CeCl3 was 1.5.

Concentrations of polycyclic aromatic hydrocarbons in street dust from bus stops in Qingyang city: Estimates of lifetime cancer risk and sources of exposure for daily commuters in Northwest China.

Lifetime cancer risk and exposure of daily commuters to polycyclic aromatic hydrocarbons (PAHs) in cities of Northwest China were determined from a study of street dust samples obtained from bus stops in Qingyang city. The sum of 16 priority PAHs (Σ16 PAHs) concentrations in the dust samples ranged from 0.8 to 18.3 mg kg-1 (mean 3.0 mg kg-1) and the distribution of individual, carcinogenic, combustion specific, low (2-3 rings) and high molecular weight (4-6 rings) PAHs was determined. The benzo[a]pyrene toxic equivalents of Σ16 PAHs ranged from 0.01 to 12.2 mg kg-1 (mean 0.8 mg kg-1). Incremental lifetime cancer risk from exposure to PAHs in dust at bus stops in Qingyang city was estimated at 1.9 × 10-6 for adults and 3.5 × 10-6 for children (confidence limit ≥ 95%). Emission source analysis of PAHs in bus stop dust showed that they were mainly derived from residential coal, oil and biomass combustion, e.g. from boilers, traffic vehicles, and Kang heaters. Higher concentrations of PAHs were obtained at bus stops near transport hubs, commercial districts, and administrative institutions.

Neuroprotective Effects of Deuterium-Depleted Water (DDW) Against H2O2-Induced Oxidative Stress in Differentiated PC12 Cells Through the PI3K/Akt Signaling Pathway.

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Induction of endogenous antioxidants to act against oxidative stress-mediated neuronal damage seems to be a reasonable strategy for delaying the progression of such diseases. In this study, we investigated the neuroprotective effect of deuterium-depleted water (DDW) against H2O2-induced oxidative stress in differentiated PC12 cells and the possible signaling pathways involved. The differentiated PC12 cell line was pretreated with DDW containing different concentrations (50-100 ppm) of deuterium and then treated with H2O2 to induce oxidative stress and neurotoxicity. We assessed cell survival, reactive oxygen species (ROS) generation, TUNEL assay, catalase (CAT), copper and zinc-containing superoxide dismutase (CuZn-SOD) and superoxide dismutase (SOD) activity and performed Western blot analysis to investigate the neuroprotective effect of DDW. The results indicated that DDW could attenuate H2O2-induced apoptosis, reduce ROS formation, and increase CAT, CuZn-SOD and SOD activity in H2O2-treated PC12 cells. Western blot analysis revealed that DDW treatment significantly increased the expression of p-Akt, Bcl-2 and GSK-3ß. However, the protective effect of DDW on cell survival and the DDW-mediated increases in p-Akt, Bcl-2 and GSK-3ß were abolished by pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002. In summary, DDW may protect differentiated PC12 cells against H2O2-induced oxidative stress through the PI3K/Akt signaling pathway.

Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term Starvation.

The blood-brain barrier (BBB) is essential for the exchange of nutrient and ions to maintain the homeostasis of central nervous system (CNS). BBB dysfunction is commonly associated with the disruption of endothelial tight junctions and excess permeability, which results in various CNS diseases. Therefore, maintaining the structural integrity and proper function of the BBB is essential for the homeostasis and physiological function of the CNS. Here, we showed that serum starvation disrupted the function of endothelial barrier as evidenced by decreased trans-endothelial electrical resistance, increased permeability, and redistribution of tight junction proteins such as Claudin-5 (Cldn5). Further analyses revealed that autophagy was activated and protected the integrity of endothelial barrier by scavenging ROS and inhibiting the redistribution of Cldn5 under starvation, as evidenced by accumulation of autophagic vacuoles and increased expression of LC3II/I, ATG5 and LAMP1. In addition, autophagosome was observed to package and eliminate the aggregated Cldn5 in cytosol as detected by immunoelectron microscopy (IEM) and stimulated emission depletion (STED) microscope. Moreover, Akt-mTOR-p70S6K pathway was found to be involved in the protective autophagy induced by starvation. Our data demonstrated that autophagy played an essential role in maintaining the integrity of endothelial barrier by regulating the localization of Cldn5 under starvation.

Physicochemical properties and toxic elements in bus stop dusts from Qingyang, NW China.

To appraise the content and pollution level of cadmium (Cd), arsenic (As), mercury (Hg), nickel (Ni) and lead (Pb) in bus stop dusts, representative samples (n = 53) were collected from the city of Qingyang in Gansu province, NW China. The Cd, As, Hg, Ni, and Pb contents and physicochemical properties (particle size, organic matter, pH and magnetic properties) of the bus stop dusts were investigated. Pollution levels were evaluated by the Nemero synthesis pollution index (NSPI) and geoaccumulation index (Igeo). The results indicate that the magnetic susceptibilities of the bus stop dusts were higher than those in the local soils. Cd, As, Ni, and Pb contents ranged from 0.4 to 3.1, 7.1 to 16.3, 12.7 to 151.3, and 20.1 to 96.2 mg kg-1, with average values of 1.2, 10.1, 22.2, and 44.9 mg kg-1, while Hg content ranged from 4.5 to 1357.7 µg kg-1 with an average of 214.0 µg kg-1. The mean contents of Cd, As, Hg, Ni, and Pb were 12.0, 0.8, 10.0, 0.6, and 2.4 times the local soil background value, respectively. Cd, Hg and Pb in approximately 96%, 62% and 19% of the bus stop dusts were above the "moderately polluted" level in terms of Igeo. As and Ni were defined as "practically unpolluted" in all of the bus stop dusts. The NSPI values of all of the bus stop dust samples exceeded 3, which reveals overall serious contamination of harmful elements.

Application of bone transgenic zebrafish in anti-osteoporosis chemical screening.

BACKGROUND: The zebrafish (Danio rerio) has recently been shown to be an ideal model to study bone disease including osteoporosis. The zebrafish osteoporosis model could be induced by glucocorticoid treatment with chemical staining for reflecting the level of bone mineralization. However, this methodology was unstable. Here, we developed a novel methodology to directly evaluate the bone mass and density. METHODS: We generated and used the bone of transgenic zebrafish Tg (ola.sp7:nlsGFP) to evaluate the bone mass and density by measuring the areal extent and the integrated optical density (IOD) of enhanced green fluorescent protein (eGFP). This methodology was further compared with the traditional chemically stained method showing the bone mineralization. Furthermore, genes related to zebrafish osteoporosis were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: Our results of new methods were consistent with those from chemically stained fish, following glucocorticoid-induction or epimedium flavonoid (FE)-rescue treatments. qRT-PCR analyses on mRNA levels revealed that glucocorticoid induces osteoporosis by downregulating the expression of osteoblast-related factors osterix, osteocalcin, and osteopontin, and upregulating the expression of osteoclast-related factor tartrate-resistant acid phosphatase. In FE-rescued fish, the expression of osteogenic factors osterix, osteocalcin, and osteopontin were increased. CONCLUSION: Compared to the traditional chemical staining methods, the new osteoporosis model using Tg(ola.sp7:nlsGFP) is more convenient and efficient for studying osteoporosis in vivo, and especially for high-throughput anti-osteoporosis drug screening.

Health Risks and Contamination Levels of Heavy Metals in Dusts from Parks and Squares of an Industrial City in Semi-Arid Area of China.

The contamination characteristics and health risk of barium (Ba), cobalt (Co), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), vanadium (V), zinc (Zn), arsenic (As), mercury (Hg), and cadmium (Cd) in samples of dust gathered from squares and parks of Baotou city, an industrial city situated in a semi-arid location of the northwest China were investigated. The contents of Ba, Co, Cr, Cu, Mn, Ni, V, Pb, and Zn in the collected dust samples were determined using X-ray fluorescence spectrometry, while the contents of As and Hg in the dust were investigated by use of the ICP-MS. Further, cadmium was quantified through the atomic absorption spectrometry. Levels of contamination of heavy metals analyzed in the dust samples were evaluated using the Geo-Accumulation index (Igeo) as well as through a Pollution Load Index (PLI). Their health risks to children and adults were evaluated based on the US EPA model of health risk. The findings portrayed that the mean concentrations of Ba, Co Cr, Cu, Pb, V, Cd, and Hg were elevated as compared with their local soil background values. Mean values of Igeo illustrate the order of Co > Cr> Cd > Hg > Pb > Cu > Ba > V > Ni > Mn > Zn > As. It was evident that dusts from the parks and squares were "unpolluted" to "moderately polluted". Assessment of health risk depicts that ingestion is the foremost route of exposure in regard to the heavy metals, then the dermal adsorption follows. Hg exposure from dust might also set impending health threats to children. Besides, the cancer risks of Co, Cr, Ni, Cd, and As are considered to be within the presently tolerable range.

Lack of association between MTHFR A1298C variant and Alzheimer's disease: evidence from a systematic review and cumulative meta-analysis.

OBJECTIVES: Previous studies have investigated the association between MTHFR A1298C (rs1801131) polymorphism and susceptibility to Alzheimer's disease (AD). Nevertheless, an ultimate conclusion remains obscure. We then executed this meta-analysis to estimate this association more precisely. METHODS: Related studies were systematically searched on PubMed, Embase, China National Knowledge Infrastructure, Google scholar, and AlzGene databases. The association was evaluated by reviewing the odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Publication bias, sensitivity analysis, and cumulative meta-analysis were performed to help draw a more definite conclusion. RESULTS: Ten eligible studies were finally enrolled in this meta-analysis. Lack of association between MTHFR A1298C polymorphism and AD risk was observed in five genetic models (allelic: OR = 1.17, 95% CI: 0.88-1.56; homozygous: OR = 1.15, 95% CI: 0.87-1.53; heterozygous: OR = 1.19, 95% CI: 0.76-1.86; dominant: OR = 1.23, 95% CI: 0.81-1.87; recessive: OR = 1.16, 95% CI: 0.89-1.52). The result of cumulative meta-analysis sorted by publication year was also detected a dynamic tendency of no correlation between MTHFR A1298C polymorphism and AD. CONCLUSION: This meta-analysis reveals that MTHFR A1298C polymorphism may not be associated with AD risk.

Evidence for the Participation of Acid-Sensing Ion Channels (ASICs) in the Antinociceptive Effect of Curcumin in a Formalin-Induced Orofacial Inflammatory Model.

Curcumin, a major bioactive component of turmeric, has diverse therapeutic effects such as anti-inflammatory, antioxidant, anticancer, and antinociceptive activities. The acid-sensing ion channels (ASICs), which can be activated by acute drops in the extracellular pH, play an important role in nociception. However, very little is known about the interaction between ASICs and curcumin in nociception of inflammation. In our study, we investigated whether the antinociceptive effects of curcumin are mediated via ASICs using an orofacial nociceptive model and in vitro western blotting, immunofluorescence, whole-cell patch-clamp recordings in the trigeminal system. Intraperitoneally administered curcumin at a dose of 50 mg/kg can reduce hyperalgesia in both the phases of a formalin-induced orofacial nociceptive model. Curcumin reduced the amplitude of ASICs currents in a dose-dependent manner in trigeminal ganglion (TG) neurons, and curcumin also reduced the protein quantity but did not change the distribution of ASICs in TG. Thus, our results indicate that curcumin can reduce formalin-induced ASICs activation and thus inhibit ASICs-mediated inflammatory pain hypersensitivity.

Protective effect of Anoectochilus roxburghii polysaccharide against CCl4-induced oxidative liver damage in mice.

This study investigated the isolation and characterization of Anoectochilus roxburghii polysaccharides (ARP), and further evaluated whether ARP possessed hepatoprotective activities against CCl4-induced oxidative liver damage in mice. ARP is comprised of glucose and galactose in a 1.9:1 molar ratio, and the molecular weight is 19.5kDa. ARP displayed significant scavenging effects against hydroxyl radical, superoxide anion radical, DPPH radical and a strong reducing power. In vivo experiment demonstrated ARP (150mg/kg) administrated to mice for 7days prior to carbon tetrachloride treatment, attenuated the elevated expression levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG) in serum and inhibited the formation of hepatic malondialdehyde (MDA). ARP pretreatment also increased antioxidant enzyme activities such as glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) in the liver of CCl4-induced mice. Furthermore, hepatic histopathological changes induced by CCl4 were significantly normalized by ARP pretreatment. These findings demonstrated that ARP possessed hepatoprotective effect against acute CCl4-induced liver damage by reducing lipid oxidation.

Genetic Association of CHAT rs3810950 and rs2177369 Polymorphisms with the Risk of Alzheimer's Disease: A Meta-Analysis.

Choline acetyltransferase (CHAT) rs3810950 and rs2177369 polymorphisms have been implicated in susceptibility to Alzheimer's disease (AD). Due to the inconsistent results from previous studies, a meta-analysis was performed to estimate the association between these polymorphisms and AD risk more precisely. Pooled results of our meta-analysis indicated CHAT rs2177369 polymorphism was correlated with decreasing AD risk in one of five genetic models (dominant: OR = 0.77, 95% CI: 0.62-0.96), while rs3810950 mutant was associated with AD development in three models (allelic: OR = 1.18, 95% CI: 1.01-1.37, homozygous: OR = 1.63, 95% CI: 1.09-2.42, and recessive: OR = 1.65, 95% CI: 1.20-2.26). In subgroup analysis by ethnicity, the association between CHAT rs3810950 polymorphism and AD risk was just found in the recessive model (OR = 1.47, 95% CI: 1.05-2.07) among Caucasians, while four genetic models (allelic: OR = 1.23, 95% CI: 1.01-1.48; homozygous: OR = 2.24, 95% CI: 1.48-3.39; dominant: OR = 1.21, 95% CI: 1.06-1.40; and recessive: OR = 2.18, 95% CI: 1.45-3.29) assumed this association in Asians. In conclusion, our meta-analysis indicated CHAT rs2177369 polymorphism might play a protective role in AD, while rs3810950 variant was a risk factor for AD but its single heterozygous mutations might not influence susceptibility to AD.

Genetic association of TLR4 Asp299Gly, TLR4 Thr399Ile, and CD14 C-159T polymorphisms with the risk of severe RSV infection: a meta-analysis.

Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization in infants worldwide. It is recognized by Toll-like receptor 4 (TLR 4) and cluster of differentiation 14 (CD14) in the innate immune response. Previous case-control studies reported the influence of TLR4 Asp299Gly, TLR4 Thr399Ile, and CD14 C-159T polymorphisms on the risk of severe RSV infection. However, a decisive conclusion has not been achieved. Therefore, we performed this meta-analysis to examine the association between these three polymorphisms and the development of RSV bronchiolitis. A systematic literature search was performed using the PubMed, EMbase, Google Scholar Search, China National Knowledge Infrastructure, China Biological Medicine, and Wanfang Databases. The data were extracted and pooled odds ratios with 95% confidence intervals were calculated under six genetic models. A total of six studies with 1009 cases and 1348 controls, three studies with 473 cases and 481 controls, or four studies with 325 cases and 650 controls relating to each of the three polymorphisms were included in this meta-analysis. The analyzed data indicated that all of these polymorphisms were not associated with the risk of severe RSV infection. This is the first meta-analysis to investigate the relationship of TLR4 Asp299Gly, TLR4 Thr399Ile, and CD14 C-159T polymorphisms with the risk of severe RSV infection. Although the results of this retrospective analysis indicated a lack of the association, more extensive multicentric studies with large sample sizes are necessary to provide a more reliable estimation of the association between these three polymorphisms and RSV bronchiolitis susceptibility.

Quantitative assessment of the association between interleukin-10 promoter gene polymorphisms and nasopharyngeal carcinoma susceptibility.

INTRODUCTION: Previous studies about the possible link between genetic polymorphisms of interleukin-10 (IL-10) and nasopharyngeal carcinoma (NPC) risk offer controversial results, and the sample sizes recruited in these trials were relatively modest. To further determine this association, a comprehensive analysis was performed in the present study. EVIDENCE ACQUISITION: Eligible studies were selected from PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), China Biological Medicine Database and Wanfang Database. A total of 623 cases and 1,018 controls for the IL-10 -1082G/A polymorphism, 463 cases and 862 controls for the IL-10 -819T/C polymorphism, and 463 cases and 862 controls for the IL-10 -592A/C polymorphism were finally included in this meta-analysis. EVIDENCE SYNTHESIS: Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association by fixed-effects or random-effects models according to heterogeneity. In the present analysis, a strong relationship between the -1082G/A polymorphism in IL-10 promoter and NPC susceptibility was found in all genetic models [allele, 0.65 (0.45-0.94), P=0.02; co-dominant, 0.15 (0.06-0.38), P<0.0001;, dominant 14.37 (2.86-72.09), P=0.001; and recessive fashions, 0.56 (0.45-0.71), P<0.0001)]. However, NPC risk was linked to -592A/C or -819T/C polymorphism in IL-10 promoter only in the co-dominant model in both genetic situations [for -819T/C, 0.36 (0.17-0.78), P=0.01; for -592A/C, 0.39 (0.19-0.80), P=0.01]. CONCLUSIONS: Our study has shown that the IL-10 -1082G/A polymorphism might be associated with increased risk of NPC under all genetic models. However, NPC risk is linked to -592A/C or -819T/C polymorphism in IL-10 promoter only in the co-dominant model in both genetic situations.

Lung morphometry changes in prevention of airway remodeling by protocatechuic aldehyde in asthmatic mice.

Airway remodeling can lead to irreversible airflow obstruction and persistent airway hyper-responsiveness, which is the pathological basis of refractory asthma. To investigate the preventive effect of protocatechuic aldehyde on airway remodeling in asthmatic mice by lung morphometry methods. BALB/c mice were used to establish model of airway remodeling by ovalbumin (OVA) inhalation. Bronchoalveolar lavage fluid (BALF) were collected for eosinophils (EOS) count and detection of interleukin 4 (IL-4), interleukin-13 (IL-13) and interferon (IFN-γ) content. The left lung pathological sections were performed HE, AB-PAS and Masson staining. The epithelial lamina thickness of the left main bronchus (Re), the smooth muscle layer thickness (Rm), the number of goblet cells and goblet cell area percentage (%Ac) and gas side of the road and vascular collagen deposition (%Aco, %Avc) situation were measured. Protocatechuic aldehyde gavage made the reduction of BALF EOS count. IL-4 and IL-13 levels also decreased, while the IFN-γ level increased. The left main bronchus Re, Rm, goblet cell count, Ac% and Aco% and Avc% reduced. Protocatechuic aldehyde can significantly control airway inflammation and prevent airway remodeling.