[Clinical features and spinal lesions in patients with chronic prostatitis/chronic pelvic pain syndrome].

Objective: To analyze the clinical features and spinal lesions related to micturitionin of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) patients. Methods: Patients with CP/CPPS were enrolled to this study at the outpatient department of Tongji Hospital between January and June 2019. The data of clinical features was collected and analyzed, including lower urinary tract symptoms(LUTS), bowel syndrome and pain over different parts of body, as well as lower urinary tract dysfunction, spinal lesions and pelvic organ morphological changes demonstrated by MRI. The potential role of spinal lesions in the development of CP/CPPS syndrome was investigated. Results: A total of 126 CP/CPPS patients were included, with an age［M（Q1，Q3）］of 41(31,53) years and a course of disease of 2(1,20) years. Among them, 126 (100.0%) were complicated with LUTS, 72(57.1%) with bowel dysfunction and 88(69.8%) with pain. MRI showed the cervical central disc herniation(126 cases, 100.0%), the ischemic changing in the cervical area of visceral efferant pathway(82 cases, 65.1%), the lumbar central disc herniation(65 cases, 51.6%), and the sacral nerve cysts(97 cases, 77.0%) are commonly seen. In addition, the morphological changes in the visceral organs containing smooth muscle were demonstrated, including thickened bladder wall(91 cases, 72.2%), distended seminal vesicles(70 cases, 55.6%) and distended sigmoid colon/rectum(59 cases, 46.8%). Conclusions: CP/CPPS patients were characterized by the co-existence of LUTS, bowel dysfunction and somatic pain in one individual. The presence of multi-organ symptoms, combined with the high prevalence of spinal lesions associated with micturition reflex, suggesting the potential role of the spinal lesions in the development of CP/CPPS.

[Single center experience of transcatheter aortic valve replacement with a simplified operative protocol].

Objective: To summarize the single center experience of transcatheter aortic valve replacement (TAVR) with a simplified operative protocol. Methods: Consecutive patients who underwent transfemoral TAVR (TF-TAVR) from July 2020 to December 2020 in Fuwai Hospital were retrospectively analyzed. We compared the baseline characteristic, procedure information, 30-day follow-up outcomes of the patients who underwent TF-TAVR without the simplified operative protocol (routine group) or with the simplified operative protocol (simplified protocol group). Results: 93 patients were collected, 42 patients belonging to routine group, 51 patients belonging to simplified protocol group. In simplified protocol group, there were 51 patients planned to use ultrasound-guided femoral access puncture, procedure was successful in all 51 patients (100%). There were 49 patients planned to use the radial artery as the secondary access, procedure was successful in 45 patients (92%). There were 48 patients planned to use the strategy of avoidance of urinary catheter, this strategy was achieved in 35 patients (73%). There were 12 patients planned to use the left ventricular guidewire to pace, procedure was successful in 11 patients (92%). There were no differences in baseline characteristics, major clinical endpoints and 30-day follow-up outcomes between the two groups. Meanwhile, the procedure time ((62.5±17.9)min vs. (78.3±16.7)min, P<0.001), operation room time ((133.7±25.1)min vs. (159.2±42.6)min, P<0.001), X-ray exposure time ((17.2±6.5)min vs. (20.2±7.7)min, P=0.027) were significantly shorten in simplified protocol group compared with the routine group. Conclusion: Our study results indicate that the simplified operative protocol of TF-TAVR is as effective and safe as the routine operative protocol, meanwhile using the simplified operative protocol can significantly increase the operative efficiency of TF-TAVR.

[Expression of SQSTM1 in papillary thyroid carcinoma and its influence on invasion, migration and proliferation of papillary thyroid cancer cells].

Objective: To investigate the expression of SQSTM1 in thyroid papillary carcinoma and its influence on the invasion and migration of thyroid papillary carcinoma cells TPC-1. Methods: From April to June 2019, cancer tissues and adjacent tissues of 21 cases with thyroid papillary carcinoma in the First Affiliated Hospital of Zhengzhou University were collected, and the expression of SQSTM1 was detected by RT-qPCR. SQSTM1 knockdown cell line SQSTM1-KD-TPC-1 was constructed in TPC-1 cells by lentivirus transfection. RT-qPCR was used to detect SQSTM1 expression in TPC-1 cells and SQSTM1-KD-TPC-1 cells. The changes of invasion and migration before and after SQSTM1 knockdown in TPC-1 cells were detected by transwell test. The proliferation of TPC-1 and SQSTM1-KD-TPC-1 cells were detected by MTT and clone formation test. RT-qPCR was used to detect the gene expression of proliferation related proteins. Results: The expression of SQSTM1 in papillary thyroid carcinoma tissues was significantly higher than that in normal adjacent tissues, and 76.2%(16/21) of the petients showed high mRNA expression. Knock down SQSTM1 significantly inhibited the ability of tumor proliferation, invasion and migration, and the expression of proliferation-related proteins were significantly decreased (P<0.01), indicating that SQSTM1 was involved in the regulation of proliferation related pathway mechanism. Conclusion: SQSTM1 significantly promotes invasion, migration and proliferation in thyroid papillary cancer cells TPC-1 and may be a potential gene therapy target.

[The inhibitory effect of CtBP-interacting protein on the oxidative damage of cerebral endothelia cells].

Objective: To explore the effect of CtBP-Interacting protein (CtIP) on oxidative damage of cerebral endothelia cells and its mechanism. Method: Cerebral endothelia cells were stimulated by TBHP to induce oxidative damage. The cell line of CtIP gene were prepared by over-expression and interfering lentivirus technology. Cell damage was detected by immunofluorescence assay of cysteinyl aspartate specific proteinase-3 (Caspase-3). The expression of CtIP and Caspase-3 protein was detected by Western blotting, and the related genes of CtIP signaling pathway were detected by Realtime RT-PCR. Result: The results of immunofluorescence and Western blotting showed that overexpression of CtIP inhibited the Caspase-3 expression reducing to 1/3 level compared with normal cultured cerebral endothelia cells. Interfering with CtIP expression resulted in the Caspase-3 expression increased significantly to 4/5 level compared with normal cultured cerebral endothelia cells and cerebral endothelia cells were damaged more severely. Realtime RT-PCR data showed that expression of CtIP significantly increased the expression of BRCA1 and ZBRK1 genes, but inhibited the expression of p21 gene. Conclusion: It is confirmed that CtIP gene has the significantly inhibitory effect on injured cerebral endothelia cells, and the regulatory relationship between CtIP gene and BRCA1, ZBRK1 and p21 genes in the process of injury are determined.

Efficient nitrogen-vacancy centers' fluorescence excitation and collection from micrometer-sized diamond by a tapered optical fiber in endoscope-type configuration.

Using an optical fiber to both excite the nitrogen-vacancy (NV) center in diamond and collect its fluorescence is essential to build NV-based endoscope-type sensor. Such endoscope-type sensor can reach inaccessible fields for traditional NV-based sensors built by bulky optical components and extend the application areas. Since single NV's fluorescence is weak and can easily be buried in fluorescence from optical fiber core's oxide defects excited by the green laser, fixing a micrometer size diamond containing high-density NVs rather than a nanodiamond containing single NV or several NVs on the apex of an optical fiber to build an endoscope-type sensor is more implementable. Unfortunately, due to small numerical aperture (NA), most of the optical fibers have a low fluorescence collection efficiency, which limits the sensitivity and spatial resolution of the NV-based endoscope-type sensor. Here, using a tapered optical fiber (TOF) tip, we significantly improve the efficiency of the laser excitation and fluorescence collection of the NV ensembles in diamond. This could potentially enhance the sensitivity and spatial resolution of the NV-based endoscope-type sensor. Numerical calculations show that the TOF tip delivers a high NA and has a high NV excitation and fluorescence collection efficiency. Experiments demonstrate that such TOF tip can obtain up to over 7-fold excitation efficiency and over 15-fold fluorescence collection efficiency of that from a flat-ended fiber (non-TOF) tip.

Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping.

The incidence of Staphylococcus aureus bacteremia (SAB) is significantly higher in African American (AA) than in European-descended populations. We used admixture mapping (AM) to test the hypothesis that genomic variations with different frequencies in European and African ancestral genomes influence susceptibility to SAB in AAs. A total of 565 adult AAs (390 cases with SAB; 175 age-matched controls) were genotyped for AM analysis. A case-only admixture score and a mixed χ2(1df) score (MIX) to jointly evaluate both single-nucleotide polymorphism (SNP) and admixture association (P<5.00e-08) were computed using MIXSCORE. In addition, a permutation scheme was implemented to derive multiplicity adjusted P-values (genome-wide 0.05 significance threshold: P<9.46e-05). After empirical multiplicity adjustment, one region on chromosome 6 (52 SNPs, P=4.56e-05) in the HLA class II region was found to exhibit a genome-wide statistically significant increase in European ancestry. This region encodes genes involved in HLA-mediated immune response and these results provide additional evidence for genetic variation influencing HLA-mediated immunity, modulating susceptibility to SAB.

Colorimetric Sensing of Toxic Metal and Antibacterial Studies by Using Bioextract Synthesized Silver Nanoparticles.

Here, we report the simple and cost effective colorimetric technique for the determination of toxic metals (Hg2+) in aqueous sample by using bioextract silver nanoparticles (AgNPs). The indigenous AgNPs were synthesised by green and ecologically friendly style using extract of fig (Ficus carica) leaf. The synthesized AgNPs were confirmed by UV-vis spectroscopy, FT-IR spectroscopy, and scanning electron microscopy methods. The synthesis of AgNPs was observed by its colour changing from light yellow to dark brownish. The existence of furanocoumarins bioactive materials in the fig leaf extract, which act as bio-reducing and capping agent, help in the formation of stabilized silver nanoparticles. In addition, the bacterial activity of the synthesized silver nanoparticles was tested against gram-negative (Klebsiella oxytocam, Pseudomonas aeruginosam, Shigella flexneri and Proteus mirabilis), gram-positive (Staphylococcus aureus and Micrococcus luteus) and one Candida (Candida albicans) human pathogen and the results showed moderate activity.

Effects of curcumin plus Soy oligosaccharides on intestinal flora of rats with ulcerative colitis.

To explore the therapeutic effect of curcumin (Cur) and soybean oligosaccharides (SBOS) on ulcerative colitis (UC) through testing the intestinal flora and ulcerative colitis (UC). 80 male SD rats were selected divided into four groups with 20 rats in each group: normal group, sulfasalazine (SASP) group, model group and group of curcumin plus soy oligosaccharide. All animals were treated for 4 weeks. In the fifth week rats were decapitated. Macroscopic damage scores of colonic mucosa were calculated. A 4mL blood sample was taken to detect the contents of serum tumor necrosis factor -α (TNF-α) and interleukin 8 (IL-8) by the double antibody sandwich ABC-ELISA method (enzyme-linked immunosorbent assay). Colonic tissues with the most obvious lesions were obtained using a surgical scissor. A routine hematoxylin-eosin (HE) staining method was used to stain pathological specimens and images of staining results were obtained. Histological injury scores of colonic mucosa were calculated. Ulcerative colitis model rats had the highest macroscopic damage scores and histological injury scores of colonic mucosa. After treatment the contents of TNF-α and IL-8 decreased significantly in the group of curcumin plus soy oligosaccharide compared with the model group with statistical significance (P <0.01) while the contents were close to those in the SASP group. There was no statistical significance (P> 0.05). The treatment could decrease TNF-α and IL- 8 expression and reduce colonic mucosa inflammation and tissue damage.

In vitro cell culture system optimization of keratinocytes from oral lichen planus (OLP) patients.

OBJECTIVES: The aim of this study was to optimize the culture system of keratinocytes obtained from patients with oral lichen planus (OLP) and verify whether this model could simulate the local inflammatory environment of OLP. MATERIALS AND METHODS: Keratinocytes were isolated from 48 patients with OLP and cultured in vitro. The ultrastructure of OLP keratinocytes was observed via electron microscopy. The expression of pancytokeratin and vimentin was determined by immunohistochemistry, and the proliferation of OLP keratinocytes was measured by CCK-8 assay. Immunofluorescence staining was used to detect TLR4 and NF-κB p65 expression, and the levels of IL-1ß, IL-6, and TNF-α in the supernatant were measured by ELISA. RESULTS: When seeded in plates precoated with recombinant human type-1 collagen, keratinocytes isolated from patients who received systemic antifungal treatment and were younger than 40 years were more successful to be cultured in vitro. Characteristic pancytokeratin was expressed in almost all OLP keratinocytes. Compared with normal oral keratinocytes, OLP keratinocytes demonstrated higher levels of TLR4/NF-κB p65 and inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. CONCLUSIONS: We successfully optimized the culture system of OLP keratinocytes,which mimicked the local inflammatory environment of OLP and may be used as a cell model of OLP.

[Influence of growing experience on non-heterosexual orientation among male college students in Nanjing].

Objective: To analyze the influence of growing experience on non-heterosexual orientation among male college students. Methods: From October to November in 2015, a total of 2 535 male students from 96 classes in 14 colleges/departments were recruited from two colleges that participated in the experimental work of AIDS prevention by cluster random sampling method. A structured questionnaire was administered in this study, including general demographic information, growing experience and Kinsey scale (to evaluate sexual orientation). Out of 2 500 questionnaires distributed in this study, 2 332 effective copies were withdrew, with the effective rate at 93.3%. Chi square test was used to analyze the differences of non-heterosexual orientation among the individuals with different social demographic characteristics. Multivariate logistic regression model was used to analyze the influencing factors of non-heterosexual orientation. Results: Among the 2 332 individuals, the proportion of self-reported non-heterosexual was 6.2% (144).The proportions of male students who identify as non-heterosexual from freshman to junior year were 5.2%(63/1216),6.9%(65/941),11.7%(13/111) and 4.7%(3/64), respectively (χ(2)=9.06,P=0.029). Compared with the individuals of very good relationship with parents, those with bad relationship (OR=3.3, 95%CI: 1.7-6.5) and general relationship (OR=1.7, 95%CI: 1.0-2.9) with parents had a higher risk of non-heterosexual orientation, respectively. Those encountered sexual assault had a higher risk of non-heterosexual orientation than those without encountered sexual assault (OR=5.9, 95%CI: 3.2-10.9). Conclusions: This study reported a high proportion of self-reported non-heterosexual among college male students in Nanjing, and highlighted the importance of targeting students with poor parental relationships and who subjected to sexually abused.

Genetic associations with viral respiratory illnesses and asthma control in children.

BACKGROUND: Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. OBJECTIVE: We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season. METHODS: The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma (COAST) birth cohort study. RESULTS: A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study. CONCLUSIONS: We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma.

Vitamin D prevents articular cartilage erosion by regulating collagen II turnover through TGF-ß1 in ovariectomized rats.

OBJECTIVE: To explore the effect of vitamin D on turnover of articular cartilage with ovariectomy (OVX) induced OA, and to investigate transforming growth factor-ß1 (TGF-ß1) as a possible underlying mechanism mediated by 1α,25(OH)2D3. DESIGN: Sixty-six rats were randomly allocated into seven groups: sham plus control diet (SHAM+CTL), OVX+CTL diet, sham plus vitamin D-deficient (VDD) diet, OVX+VDD diet, and three groups of ovariectomized rats treated with different doses of 1α,25(OH)2D3. The cartilage erosion and the levels of serum 17ß-estradiol, 1α,25(OH)2D3 and C-telopeptide of type II collagen (CTX-II) were measured. TGF-ß1, type II Collagen (CII), matrix metalloproteinases (MMP)-9,-13 in articular cartilage were assessed by immunohistochemistry. TGF-ß1 and CTX-II expression were measured in articular cartilage chondrocytes treated with/without tumor necrosis factor (TNF-α), 1α,25(OH)2D3, and TGF-ß receptor inhibitor (SB505124) in vitro. RESULTS: Cartilage erosion due to OVX was significantly reduced in a dose-dependent manner by 1α,25(OH)2D3 supplementation, and exacerbated by VDD. The expressions of TGF-ß1 and CII in articular cartilage were suppressed by OVX and VDD, and rescued by 1α,25(OH)2D3 supplementation. The expression of MMP-9,-13 in articular cartilage increased with OVX and VDD, and decreased with 1α,25(OH)2D3 supplementation. In vitro experiments showed that 1α,25(OH)2D3 increased the TGF-ß1 expression of TNF-α stimulated chondrocytes in a dose-dependent manner. 1α,25(OH)2D3 significantly counteracted the increased CTX-II release due to TNF-α stimulation, and this effect was significantly suppressed by SB505124. CONCLUSION: VDD aggravated cartilage erosion, and 1α,25(OH)2D3 supplementation showed protective effects in OVX-induced OA partly through the TGF-ß1 pathway.

Emission efficiency enhanced by reducing the concentration of residual carbon impurities in InGaN/GaN multiple quantum well light emitting diodes.

A series of samples with varying growth pressure are grown and their optical and structural properties are investigated. It is found that the residual carbon concentration decreases when the reactor pressure increases from 80 to 450 Torr during the InGaN/GaN multiple quantum well growth. It results in an enhanced peak intensity of electroluminescence because carbon impurities can induce deep energy levels and act as non-radiative recombination centers in InGaN layers.

A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs.

UNLABELLED: The ultimate goal of osteoporosis treatment is prevention of fragile fracture. Local treatment targeting specific bone may decrease the incidence of osteoporotic fractures. We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous injection augmented vertebrae in ovariectomized minipigs. INTRODUCTION: The greatest hazard associated with osteoporosis is local fragility fractures. An adjunct, local treatment might be helpful to decrease the incidence of osteoporotic fracture. Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low. Directly delivering simvastatin to the specific bone that is prone to fractures may reinforce the target bone and reduce the incidence of fragility fractures. METHODS: We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel, conducted scanning electron microscopy, rheological, and drug release analyses to evaluate the delivery system; injected it into the lumbar vertebrae of ovariectomized minipigs via minimally invasive CT-guided percutaneous vertebral injection. Three months later, BMD, microstructures, mineral apposition rates, and strength were determined by DXA, micro-CT, histology, and biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by immunohistochemistry and Western blots. RESULTS: Poloxamer 407 is an effective controlled delivery system for intraosseous-injected simvastatin. A single injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD, bone microstructure, and strength; the bone volume fraction and trabecular thickness increased nearly 150 %, bone strength almost doubled compared with controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and osteocalcin. CONCLUSIONS: CT-guided percutaneous vertebral injection of a single simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in ovariectomized minipigs. The underlying mechanism appears to involve the higher expression of VEGF and BMP-2.

A taxonomic review of white grubs and leaf chafers (Coleoptera: Scarabaeidae: Melolonthinae) recorded from forestry and agricultural crops in Sub-Saharan Africa.

Integrated pest management (IPM) is difficult to implement when one knows little about the pest complex or species causing the damage in an agricultural system. To implement IPM on Sub-Saharan African melolonthine pests access to taxon specific knowledge (their identity) and what is known (their biology) of potential pest species is a crucial step. What is known about Sub-Saharan African melolonthine white grubs and chafers has not yet been amalgamated, and this review thus synthesizes all available literature for the Region. The comprehensive nature of the review highlights pest taxon trends within African melolonthines. To facilitate the retrieval of this information for IPM purposes, all relevant taxonomic and biological information is provided for the taxa covered including an on-line supplementary annotated-checklist of taxon, crop, locality and reference(s). Based on the literature reviewed, recommendations are made to promote effective and efficient management of African melolonthine scarab pests. An on-line supplementary appendix provides a list of specialists, useful internet resources, keys, catalogues and sampling methods for the larvae and adults of melolonthine scarab beetles for subsequent morphological or molecular work.

Active vitamin D3, 1,25-(OH)2D3, protects against macrovasculopathy in a rat model of type 2 diabetes mellitus.

To investigate the protective effect of the active form of vitamin D3, 1,25-(OH)2D3, on macrovasculopathy in rats with type 2 diabetes mellitus (T2DM), 8-week-old male Sprague-Dawley rats were randomly divided into control group, T2DM group, and treatment group. The T2DM model was established after 6 weeks by administering an intraperitoneal injection of streptozotocin (30 mg/kg). 1,25-(OH)2D3 was administered by gavage to rats in the treatment group, and an equal volume of peanut oil was administered to rats in the T2DM group. Fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterols were measured in all rats. The morphology of the thoracic aorta was examined, and the expression of tumor necrosis factor alpha (TNF-α), endothelin (ET), endothelial nitric oxide synthase (eNOS), CD54, and CD106 in the thoracic aorta was determined by immunohistochemistry. The expression of FPG, TG, TC, and LDL-C in rats from the T2DM and treatment groups was significantly elevated compared with rats from the control group (P < 0.05). Compared with that in control group, the expression of TNF-α, ET, eNOS, and CD106 was significantly upregulated in the T2DM group and the treatment group, while the expression of CD54 was increased only in the T2DM group (P < 0.05). Moreover, the levels of TNF-α, CD54, and CD106 in rats from the treatment group were lower than those in the T2DM group (P < 0.05). These data suggest that 1,25-(OH)2D3 may protect the macrovessels from injury in T2DM rats by inhibiting the expression of TNF-α, CD54, and CD106.

Effect of weaning age on cortisol release in piglets.

The effect of weaning age on the adrenal cortex, which plays a vital role in the stress response, is currently unknown. Therefore, plasma adrenocorticotropic hormone (ACTH) and cortisol levels, weights and relative weights of adrenal glands, and steroidogenesis-related protein and enzyme expression levels in piglets weaned on different days were determined. Piglets weaned at 35 days had significantly lower ACTH levels than those weaned at 14 or 21 days, and cortisol levels of piglets weaned at 21, 28, and 35 days were significantly lower than those of piglets weaned on day 14. Adrenal gland weights of piglets weaned at 28 and 35 days and relative adrenal gland weights of piglets weaned at 35 days were significantly lower than those of piglets weaned at 14 days. However, no significant difference was detected in the expression of melanocortin-type 2 receptor mRNA, which is associated with weaning age. Steroidogenic acute-regulatory (StAR) mRNA and cholesterol side-chain cleavage cytochrome P450 mRNA expression levels in piglets weaned at 28 and 35 days were significantly lower than in those weaned at 14 or 21 days, and P450 11ß mRNA expression levels in piglets weaned at 28 and 35 days were significantly lower than in those weaned at 14 days. Therefore, early-weaned piglets exhibited increased adrenal gland weights and StAR and steroidogenic enzyme expression, all of which contributed to high cortisol levels. The high plasma ACTH and cortisol levels in early-weaned piglets indicate that these animals would be greatly affected by stress.

Injection of Toll-like receptor 4 siRNA into the ventrolateral periaqueductal gray attenuates withdrawal syndrome in morphine-dependent rats.

We assessed the role of the Toll-like receptor 4 (TLR4) gene in the ventrolateral periaqueductal gray (vlPAG) region of morphine-dependent rats on attenuating withdrawal syndrome, and regulating glutamic acid decarboxylase (GAD67), glutamic acid (Glu), and gamma-aminobutyric acid (GABA). After siRNA-mediated downregulation of TLR4, changes were observed in withdrawal behavior and downstream signaling molecules. Rats were injected into the vlPAG with TLR4 siRNA, followed by intraperitoneal injection of morphine for 5 consecutive days, and then naloxone, and the behavioral indices of morphine withdrawal were observed. 'Wet-dog' shakes, teeth chattering, and the total scores of withdrawal reactions were reduced. TLR4 expression and Glu levels were reduced, whereas GAD67 and GABA levels were increased. Overall, these findings indicate that modifying TLR4 gene expression in the vlPAG stimulates expression of the downstream signaling molecule, GAD67, which decreases Glu levels and increases GABA levels. This mechanism may explain the inhibition of withdrawal syndrome in morphine-dependent rats.

A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.

BACKGROUND: Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. OBJECTIVE: We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. METHODS: We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N = 610 adults) and the Hutterites (N = 601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N = 450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N = 8858) consortium. RESULTS: We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P = 1.6 × 10(-7) ) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P = 8.9 × 10(-7) ) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. CONCLUSIONS AND CLINICAL RELEVANCE: This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.