[Effects of Microplastic High-density Polyethylene on Cotton Growth, Occurrence of Fusarium wilt, and Rhizosphere Soil Bacterial Community].

Plastic mulch, especially polyethylene mulch, is widely used in agricultural production in China, but the microplastics formed by its degradation gradually have accumulated in soil, causing a series of environmental problems. At present, there have been many reports on the environmental biological effects of microplastics in farmland soil, but studies on the effects of microplastics on crop growth, disease occurrence, and rhizosphere soil bacterial communities are still lacking. In the previous study, it was found that 1% high-density polyethylene (HDPE, 500 mesh) could increase the incidence rate of cotton Fusarium wilt (33.3%) and inhibit growth, but this phenomenon was not found after soil sterilization. It was speculated that HDPE could affect the growth and occurrence of Fusarium wilt by regulating the soil microbial community. Therefore, high-throughput sequencing technology, combined with network and FAPROTAX function analysis, were used to investigate the effects of HDPE on the bacterial community structure, interaction network, and soil function in cotton rhizosphere in order to analyze the mechanism of HDPE. NovaSeq sequencing showed that the bacterial community of HDPE-treated cotton rhizosphere soil was composed of 54 phyla and 472 genera; the number of phyla and genera was higher than that in untreated soil. The α and ß diversity and ANOSIM/Adonis analyses showed that HDPE significantly reduced the richness of the bacterial community and changed the composition of the community structure. Based on a T-test species difference analysis, HDPE significantly reduced the relative abundance of bacteria with biological control, pollutant degradation, and antifungal drug synthesis (such as Kribbella, Massiliam, Hailiangium, and Ramlibacter).The change in the bacterial community will lead to the change in soil bacterial function. Further analysis of FAPROTAX function revealed that HDPE weakened some biochemical functions of bacteria in the cotton rhizosphere soil, such as aerobic chemoheterotrophy, fermentation, and nitrate reduction. The correlation network at the genus level showed that HDPE treatment weakened the interaction between rhizosphere bacteria, reduced the number of positive correlation connections, increased the number of negative correlation connections, simplified network structure, and changed the key flora. The above results showed that HDPE could reduce the cotton growth and the occurrence of Fusarium wilt by changing the bacterial community, interaction, and functional metabolism in rhizosphere soil, which can provide guidance for evaluating the ecological risk of polyethylene microplastics and the remediation of contaminated soil.

Discovery of Novel 3,11-Bispeptide Ester Arenobufagin Derivatives with Potential in Vivo Antitumor Activity and Reduced Cardiotoxicity.

Arenobufagin, one of the bufadienolides isolated from traditional Chinese medicine Chan'su, exhibits potent antitumor activity. However, serious toxicity and small therapeutic window limits its drug development. In the present study, to our knowledge, novel 3,11-bispeptide ester arenobufagin derivatives have been firstly designed and synthesized on the base of our previous discovery of active 3-monopeptide ester derivative. The in vitro antiproliferative activity evaluation revealed that the moiety at C3 and C11 hydroxy had an important influence on cytotoxic activity and selectivity. Compound ZM350 notably inhibited tumor growth by 58.8 % at a dose 10 mg/kg in an A549 nude mice xenograft model. Therefore, compound ZM350 also presented a concentration-dependent apoptosis induction and low inhibitory effect against both hERG potassium channel and Cav1.2 calcium channel. Our study suggests that novel 3,11-bispeptide ester derivatives will be a potential benefit to further antitumor agent development of arenobufagin.

Identification of genetic variants of the IL-22 gene in association with an altered risk of COPD susceptibility.

The incidence of chronic obstructive pulmonary disease (COPD) is related to the interaction between environmental exposure and genetic factors. Far more than 15% of smokers eventually develop COPD. In addition to smoking, genetic susceptibility may be another factor in the development of COPD. IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis. Here, we conducted a case-control study to evaluate the association between IL-22 tag-single nucleotide polymorphisms (SNPs) and COPD risk. Four tag-SNPs (rs2227478, rs2227481, rs2227484 and rs2227485) were identified according to linkage disequilibrium (LD) analysis in 30 healthy controls. A total of 513 COPD cases and 504 controls were recruited to perform an association study between these four tag-SNPs and COPD risk. We found that the "C" allele of rs2227478T>C and the "T" allele of rs2227481C>T were obviously related to decreased COPD susceptibility. Genetic model analysis showed that rs2227478T>C and rs2227481C>T were significantly associated with a decreased risk of COPD under dominant models after adjusting for the above factors. In the recessive model, rs2227485T>C was obviously associated with decreased COPD risk. Our data showed that only rs2227485T>C was associated with a decreased COPD risk after Bonferroni correction. The eQTL analysis showed that rs2227485T>C was significantly associated with IL-22 expression. The pGL4-rs2227485-C gene reporter had a higher promoter activity than pGL4-rs2227485-T. In our study, rs2227485T>C, located in the promoter region of IL-22, was associated with a decreased risk of COPD and increased IL-22 promoter activity, suggesting that this variant might modulate COPD susceptibility.

[The Role of Platelet Exosomes in Atherogenic Thrombosis --Review].

Exosomes are subtypes of extracellur vesicles containing a variety of cell-specific proteins, lipids and nucleic acids released during cell activation or apoptosis, and play the role of intercellur communication mediators in different physiological and pathological processes. With the development of research in recent years, the role of platelet-derived exosomes in cardiovascular diseases has attracted extensive attention. This paper reviews the role of platelet-derived exosomes in atherosclerotic thrombosis and the potential role of platelet-derived exosomes as biomarkers for the diagnosis and treatment of atherosclerotic thrombotic disease and the problems to be solved.

Gut Microbial Characteristics of Adult Patients With Epilepsy.

OBJECTIVE: To characterize the intestinal flora of patients with epilepsy and its correlation with epilepsy. METHODS: Patients with ages > 18 years were consecutively enrolled from the outpatient department, Affiliated Hospital of Guizhou Medical University from January 2018 to December 2019. A total of 71 subjects were recruited, including epilepsy patients (n = 41) as an observation group and patient family members (n = 30) as a control group. Fresh stool specimens of all the subjects were collected. The 16S ribosomal RNA sequencing was analyzed to determine changes in intestinal flora composition and its correlation with epilepsy. Subgroup analysis was then conducted. All patients with epilepsy were divided into an urban group (n = 21) and a rural group (n = 20) according to the region, and bioinformatics analyses were repeated between subgroups. RESULTS: LEfSe analysis showed that Fusobacterium, Megasphaera, Alloprevotella, and Sutterella had relatively increased abundance in the epilepsy group at the genus level. Correlation analysis suggested that Fusobacterium sp. (r = 0.584, P < 0.01), Fusobacterium mortiferum (r = 0.560, P < 0.01), Ruminococcus gnavus (r = 0.541, P < 0.01), and Bacteroides fragilis (r = 0.506, P < 0.01) were significantly positively correlated with the occurrence of epilepsy (r ≥ 0.5, P < 0.05). PICRUSt function prediction analysis showed that there were significant differences in 16 pathways between the groups at level 3. Comparing the rural group with the urban group, Proteobacteria increased at the phylum level and Escherichia coli, Fusobacterium varium, Prevotella stercorea, and Prevotellaceae bacterium DJF VR15 increased at the species level in the rural group. CONCLUSION: There were significant differences in the composition and functional pathways of gut flora between epilepsy patients and patient family members. The Fusobacterium may become a potential biomarker for the diagnosis of epilepsy.

A case report of brain abscess caused by Nocardia farcinica.

BACKGROUND: Brain abscess due to the Nocardia genus is rarely reported and it is usually found in immunocompromised patients. Treatment of Nocardia brain abscess is troublesome and requires consideration of the severity of the underlying systemic disease. The difficulties in identifying the bacterium and the frequent delay in initiating adequate therapy often influence the prognosis of patients. CASE PRESENTATION: Here, we report a rare case of brain abscess caused by Nocardia farcinica. The patient's medical history was complicated: he was hospitalized several times, but no pathogens were found. At last, bacteria were found in the culture of brain abscess puncture fluid; the colony was identified as Nocardia farcinica by mass spectrometry. Targeted antibiotic treatment was implemented, brain abscess tended to alleviate, but the patient eventually developed fungal pneumonia and died of acute respiratory distress syndrome (ARDS). CONCLUSION: Brain abscess caused by Nocardia farcinica can appear in non-immunocompromised individuals. Early diagnosis, reasonable surgical intervention, and targeted antibiotic treatment are critical for Nocardia brain abscess treatment. In the treatment of Nocardia brain abscess, attention should paid be to the changes in patients' immunity and infection with other pathogens, especially fungi, avoided.

Luteolin inhibits the proliferation, adhesion, migration and invasion of choroidal melanoma cells in vitro.

Choroidal melanoma is a devastating disease that causes visual loss and a high mortality rate due to metastasis. Luteolin, a potential anticancer compound, is widely found in natural plants. The aim of this study was to evaluate the antiproliferative, antiadhesive, antimigratory and anti-invasive effects of luteolin on choroidal melanoma cells in vitro and to explore its potential mechanism. Cell counting kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) assays, Cell adhesion, migration, and invasion assays were performed to examine the inhibitory effects of luteolin on cell cell viability, proliferation, adhesion, migration and invasion capacities, respectively. Considering the correlation between Matrix metalloenzymes and tumor metastasis, Enzyme-linked immunosorbent assays (ELISAs) were used to assess matrix metalloproteases MMP-2 and MMP-9 secretion. Western blotting was performed to detect p-PI3K P85, Akt, and p-Akt protein expression. The cytoskeletal proteins vimentin were observed with cell immunofluorescence staining. Luteolin can inhibit OCM-1 cell proliferation, migration, invasion and adhesion and C918 cell proliferation, migration, and invasion through the PI3K/Akt signaling pathway. Therefore, Luteolin may have potential as a therapeutic medication for Choroidal melanoma.

LncRNA MIAT Promotes Inflammation and Oxidative Stress in Sepsis-Induced Cardiac Injury by Targeting miR-330-5p/TRAF6/NF-κB Axis.

Sepsis is a whole-body inflammation and main cause of death in intensive care units worldwide. We aimed to investigate the roles of lncRNA MIAT and miR-330-5p in modulating inflammatory responses and oxidative stress in lipopolysachariden (LPS)-induced septic cardiomyopathy. Serum and heart tissue were collected from in vivo septic mice model, ELISA and qRT-PCR were used to measure the expression of pro-inflammation cytokines, MIAT and miR-330-5p, respectively. The knockdown of MIAT and overexpression of miR-330-5p were conducted to assess their effects on regulating inflammation response and intracellular oxidative stress in LPS-stimulated HL-1 cells. The reactive oxygen (ROS) level, mitochondrial membrane potential (MMP), GSH/GSSH ratio, and lipid peroxidation assessment (MDA) were used to evaluate the intracellular oxidative stress. Dual-luciferase reporter assay was performed to identify the association between MIAT and miR-330-5p, TRAF6 and miR-330-5p, respectively. In septic mice, the expression of MIAT and pro-inflammation cytokines was elevated while the expression of miR-330-5p decreased. Knockdown of MIAT or overexpression of miR-330-5p restrained inflammation and oxidative stress induced by LPS in vitro; MIAT directly targeted miR-330-5p to regulate NF-κB signaling, and miR-330-5p targeted against TRAF6 to suppress the activation of NF-κB signaling. We determined that lncRNA MIAT directly binds to miR-330-5p to activate TRAF6/NF-κB signaling axis and further promotes inflammation response as well as oxidative stress in LPS-induced septic cardiomyopathy. This finding suggests the potential therapeutic role of lncRNA MIAT and miR-330-5p in LPS-induced myocardial injury.

Spinal Clear Cell Meningiomas: Clinical Features and Factors Predicting Recurrence.

OBJECTIVE: As a World Health Organization grade II tumor of the nervous system, clear cell meningioma (CCM) is an uncommon histologic variant of meningioma. Spinal CCMs are even rarer, with <100 spinal CCMs reported in the English literature. We present this study to characterize clinical manifestations of spinal CCMs and determine the factors predicting recurrence. METHODS: A literature search was performed for relevant case reports and series in PubMed and Embase until September 1, 2019. These articles were reviewed to identify clinical features, treatment modalities, and prognosis of patients with spinal CCMs. RESULTS: Eighty-four spinal CCMs were analyzed. Of these patients, 36 (42.9%) were young (age ≤18 years), and the mean age at resection was 24 years. Fifty-three patients (63.1%) were female and 31 (36.9%) were male. Most of the tumors (56/84, 66.7%) were located in the lumbar region. In 31 patients (36.9%) >2 segments in the craniocaudal direction were involved (number of involved segments ≥3 levels). Gross tumor resection was performed in 77 patients (91.7%). Twenty patients (23.8%) showed radiographic evidence of recurrence during follow-up. Recurrence-free survival at 1, 5, and 10 years after resection of spinal CCM was 87%, 71%, and 47%, respectively. Multivariate analysis showed that age ≤18 years (hazard ratio [HR], 3.64; P = 0.024), subtotal resection (HR, 3.43; P = 0.031), and segments involving ≥3 levels (HR, 5.66; P = 0.002) were associated with increased recurrence. CONCLUSIONS: Spinal CCMs have their own unique clinical features compared with conventional spinal meningiomas and intracranial CCMs. Spinal CCMs have a predilection to affect younger patients, are prone to appear in the lumbar region, and have a high recurrence rate. Age ≤18 years, subtotal resection, and involvement of long segments (≥3 levels) are positive predictors of recurrence.

Septic shock caused by Rhizobium radiobacter in an elderly woman: A case report.

RATIONALE: Rhizobium radiobacter is a Gram-negative pathogen present in soil and plants. Cases of R radiobacter infection in immunocompromised hosts have been sporadically reported. However, septic shock caused by R radiobacter is rarely seen. PATIENT CONCERNS: Here, we describe an elderly patient with a rapid progression of watery diarrhea, anorexia, fever, weakness, oliguria, and shock. Blood results showed increased total white blood cell count and C-reactive protein. Arterial blood gas results showed hypoxia and elevated lactate level. The Sequential Organ Failure Assessment score was 11. Blood culture at admission showed Gram-negative bacteria, which were later confirmed as R radiobacter. DIAGNOSIS: Septic shock caused by R Radiobacter. INTERVENTIONS: The patient was treated with intravenous cefoperazone/sulbactam and sequential oral levofloxacin. OUTCOMES: The patient recovered completely. CONCLUSION: R radiobacter may be considered as a potential opportunistic pathogen that may cause severe sepsis in elderly patients, especially those with multiple underlying diseases.

[miR-362 regulates the proliferation and apoptosis of porcine immature Sertoli cells through targeting the ZNF644 gene].

In testicular tissue, immature Sertoli cell proliferation ability determines the size of mature Sertoli cell populations, which further regulates the spermatogenesis in the adult male animals. Studies have demonstrated that microRNAs (miRNAs) participate in the regulation of the immature Sertoli cell proliferation and apoptosis, but the functions of most identified miRNAs remain unclear. In this study, based on previous RNA-seq results, we analyzed the regulatory role (s) of miR-362 in proliferation and apoptosis of porcine immature Sertoli cells. The ZFN644 gene was predicted to be a target gene of miR-362 using bioinformatics methods. The expression levels of miR-362 and ZNF644 gene were measured using qRT-PCR assay in developing porcine testicular tissues and in immature Sertoli cells transfected with either miR-362 mimic or miR-362 inhibitor. The dual luciferase reporter assay was used to determine the regulatory relationship between miR-362 and ZNF644. The results showed that a putative target site of miR-362 was located in the 3'UTR of ZNF644. The expression of miR-362 was significantly and negatively correlated with ZNF644 expression in the developing porcine testicular tissues. Co-transfection of miR-362 and psiCHECK2-ZNF644-WT 3'UTR luciferase vector significantly suppressed luciferase activity. The ZNF644 gene expression level was significantly regulated by miR-362, demonstrating that miR-362 targets ZNF644 gene and inhibits its expression in porcine immature Sertoli cells. Flow cytometry, CCK8, and EdU assays were used to measure the effects of over-expression of miR-362 or knockdown of ZNF644 on porcine immature Sertoli cell proliferation; Annexin V-FITC/PI staining assays and qRT-PCR technology were used to test the apoptosis and the expression levels of cell survival-related genes, respectively. Over-expression of miR-362 and knockdown of ZNF644 arrested the porcine immature Sertoli cells in G1 and G2 phases of the cell cycle, respectively, and inhibited proliferation, enhanced apoptosis in the porcine immature Sertoli cells, and significantly regulated the expression levels of cell survival-related genes. Taken together, these data indicate that miR-362 inhibits proliferation and promotes apoptosis in porcine immature Sertoli cells by targeting the ZNF644 gene, thereby providing the scientific basis for further study on the function(s) of miR-362 in the porcine spermatogenesis.

Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway.

Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α-induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1ß, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and inhibition of these signaling molecules significantly repressed CSE-induced HIF-1α expression. It indicated that STS inhibits CSE-induced HIF-1α expression likely by blocking MAPK signaling. Furthermore, STS also promoted HIF-1α protein degradation in CSE-stimulated macrophages. Taken together, these results suggest that STS prevents COPD development possibly through the inhibition of HIF-1α signaling, and may be a novel strategy for the treatment of COPD.

[Variations in growth response and cadmium accumulation of different gender Morus alba seedlings to combined treatments of Cd and acid rain]. / ä¸åŒæ€§åˆ«æ¡‘æ ‘å¹¼è‹—å¯¹é•‰ä¸Žé ¸é›¨å¤åˆå¤„ç†çš„ç”Ÿé•¿å“åº”åŠé•‰ç§¯ç´¯å·®å¼‚.

To investigate sex-specific adaptive responses and cadmium accumulation of Morus alba seedlings, we analyzed growth parameters, photosynthetic capacity and chlorophyll fluorescence parameters, and Cd accumulation and allocation of Qiangsang 1 (female) and Nongsang 14 (male) under different treatments [cadmium (Cd, 100 mg·kg-1), acid rain (AR, pH 3.0) and their combinations (Cd+AR)]. When exposed to Cd stress alone, females showed higher cadmium content in root, stem and leaf than males. The root, stem and total biomass, and maximum net photosynthetic rate (Amax) of males were significantly decreased, while those of females (except Amax) showed no significant changes. Cd had no effect on maximal photochemical efficiency (Fv/Fm), photochemical quenching coefficient (qP), non-photochemical quenching coefficient (qN) in both sexes. When exposed to Cd+AR stress, the total biomass and Amax of males and females decreased. Compared to Cd stress alone, the cadmium content in root and leaf of females significantly increased while those of males did not under Cd+AR. In addition, Cd+AR stress had no effect on Fv/Fm and qP, but significantly increased qN in both sexes. Our results suggested that females had greater tolerance than males when exposed to Cd stress alone in short term. Acid rain would decrease the tolerance of females to Cd stress, which might attribute to the enhanced absorption and accumulation of cadmium.

Two-stage study of lung cancer risk modification by a functional variant in the 3'-untranslated region of SMAD5 based on the bone morphogenetic protein pathway.

Increasing evidence supports a key role for the bone morphogenetic protein (BMP) signaling pathway in lung vasculogenesis and angiogenesis. Genetic variations in BMP genes have been found to be correlated with cancer risk. In particular, the mutation in the 3'-untranslated region of BMPs may significantly affect gene function, leading to cancer susceptibility. The aim of the present study was to determine whether genetic variations in the components of the BMP family are associated with lung cancer risk. A total of 314 tag single-nucleotide polymorphisms were identified in 18 genes, which are considered to either compose or regulate BMPs, and their association with lung cancer risk was evaluated in a two-stage case-control study with 4,680 cases and controls. A consistently significant association of SMAD5 rs12719482 with elevated lung cancer risk was observed in the three types of sources of populations (adjusted additive model in the combined population: Odds ratio=1.32, 95% confidence interval: 1.16-1.51). The lung cancer risk statistically significantly increased with the increasing number of variant alleles of SMAD5 rs12719482 in a dose-dependent pattern (P for trend=4.9×10-5). Consistent evidence was identified for a significant interaction between the rs12719482 and cigarette smoking, performed as either a continuous or discrete variable. These findings indicated that SMAD5 rs12719482 may be a possible candidate marker for susceptibility to lung cancer in the Chinese population.

Efficacy of favipiravir (T-705) in nonhuman primates infected with Ebola virus or Marburg virus.

Favipiravir is a broad-spectrum antiviral agent that has demonstrated efficacy against Ebola virus (EBOV) in rodents. However, there are no published reports of favipiravir efficacy for filovirus infection of nonhuman primates (NHPs). Here we evaluated the pharmacokinetic profile of favipiravir in NHPs, as well as in vivo efficacy against two filoviruses, EBOV and Marburg virus (MARV). While no survival benefit was observed in two studies employing once- or twice-daily oral dosing of favipiravir during EBOV infection of NHPs, an antiviral effect was observed in terms of extended time-to-death and reduced levels of viral RNA. However, oral dosing in biosafety level-4 (BSL-4) presents logistical and technical challenges, and repeated anesthesia events may potentially worsen survival outcome in animals. For the third study of treatment of MARV infection, we therefore made use of catheters, jackets, and tethers for intravenous (IV) dosing and blood collection, which minimized the requirement for repeated anesthesia events. When MARV infection was treated with IV favipiravir, five of six animals (83%) survived infection, while all untreated NHPs succumbed. An accompanying report presents the results of favipiravir treatment of EBOV infection in mice.

Chikungunya Arthritis Mechanisms in the Americas: A Cross-Sectional Analysis of Chikungunya Arthritis Patients Twenty-Two Months After Infection Demonstrating No Detectable Viral Persistence in Synovial Fluid.

OBJECTIVE: To determine if chikungunya virus persists in synovial fluid after infection, potentially acting as a causative mechanism of persistent arthritis. METHODS: We conducted a cross-sectional study of 38 Colombian participants with clinical chikungunya virus infection during the 2014-2015 epidemic who reported chronic arthritis and 10 location-matched controls without chikungunya virus or arthritis. Prior chikungunya virus infection status was serologically confirmed, and the presence of synovial fluid chikungunya virus, viral RNA, and viral proteins was determined by viral culture, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and mass spectrometry, respectively. Biomarkers were assessed by multiplex analysis. RESULTS: Patients with serologically confirmed chikungunya arthritis (33 of 38 [87%]) were predominantly female (82%) and African Colombian (55%) or white Colombian (33%), with moderate disease activity (mean ± SD Disease Activity Score in 28 joints 4.52 ± 0.77) a median of 22 months after infection (interquartile range 21-23 months). Initial symptoms of chikungunya virus infection included joint pain (97%), swelling (97%), stiffness (91%), and fever (91%). The most commonly affected joints were the knees (87%), elbows (76%), wrists (75%), ankles (56%), fingers (56%), and toes (56%). Synovial fluid samples from all patients with chikungunya arthritis were negative for chikungunya virus on qRT-PCR, showed no viral proteins on mass spectrometry, and cultures were negative. Case and control plasma cytokine and chemokine concentrations did not differ significantly. CONCLUSION: This is one of the largest observational studies involving analysis of the synovial fluid of chikungunya arthritis patients. Synovial fluid analysis revealed no detectable chikungunya virus. This finding suggests that chikungunya virus may cause arthritis through induction of potential host autoimmunity, suggesting a role for immunomodulating agents in the treatment of chikungunya arthritis, or that low-level viral persistence exists in synovial tissue only and is undetectable in synovial fluid.

The effects of CXCL10 polymorphisms on COPD susceptibility.

The polymorphisms of cytokine genes has been reported to modulate the individual's susceptibility to environmental stimuli in COPD development. C-X-C motif chemokine 10 (CXCL10) mediates recruitment inflammatory cells such as monocytes. Therefore, it may play a key role in COPD. Here, a case-control study was conducted to evaluate the association between CXCL10 tag-SNPs and COPD risk. Four tag-SNPs including rs4256246, rs4508917, rs56061981, and rs56316945 were identified based on the linkage disequilibrium (LD) analysis in 30 healthy controls. The associations between these four tag-SNPs and COPD risk were further evaluated in 480 COPD cases and 488 controls. We found that the "T" allele of rs56061981 was significantly associated with reducing risk of COPD, while "G" allele of rs56316945 was significantly associated with increasing risk of COPD. SNP rs56316945 was significantly associated with increasing risk of COPD under different models except recessive model after adjusting the sex, age, pack year, and biomass. SNP rs56061981 was significantly associated with decreasing COPD risk under different models except recessive model after adjusting the sex, age, pack year, and biomass. Stratified analysis of smoking status and biomass with SNPs supported rs56061981 may interact with biomass and smoking thus modulate COPD susceptibility and rs56216945 was apparently associated with the severity of pulmonary function of COPD patients. This study suggests that rs56061981 and rs56216945 in CXCL10 gene promoter contribute COPD susceptibility.

Genetic Variants in the Hedgehog Interacting Protein Gene Are Associated with the FEV1/FVC Ratio in Southern Han Chinese Subjects with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Convincing evidences have demonstrated the associations between HHIP and FAM13a polymorphisms and COPD in non-Asian populations. Here genetic variants in HHIP and FAM13a were investigated in Southern Han Chinese COPD. METHODS: A case-control study was conducted, including 989 cases and 999 controls. The associations between SNPs genotypes and COPD were performed by a logistic regression model; for SNPs and COPD-related phenotypes such as lung function, COPD severity, pack-year of smoking, and smoking status, a linear regression model was employed. Effects of risk alleles, genotypes, and haplotypes of the 3 significant SNPs in the HHIP gene on FEV1/FVC were also assessed in a linear regression model in COPD. RESULTS: The mean FEV1/FVC% value was 46.8 in combined COPD population. None of the 8 selected SNPs apparently related to COPD susceptibility. However, three SNPs (rs12509311, rs13118928, and rs182859) in HHIP were associated significantly with the FEV1/FVC% (Pmax = 4.1 × 10-4) in COPD adjusting for gender, age, and smoking pack-years. Moreover, statistical significance between risk alleles and the FEV1/FVC% (P = 2.3 × 10-4), risk genotypes, and the FEV1/FVC% (P = 3.5 × 10-4) was also observed in COPD. CONCLUSIONS: Genetic variants in HHIP were related with FEV1/FVC in COPD. Significant relationships between risk alleles and risk genotypes and FEV1/FVC in COPD were also identified.