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1.
Anticancer Res ; 40(5): 2995-3002, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366454

RESUMO

BACKGROUND/AIM: Expanded indications for patients with preoperatively suspected prostate cancer (PC) undergoing theranostic robotic-assisted laparoscopic radical prostatectomy (T-RARP) are reported. We aimed to build a nomogram of T-RARP to predict final pathologically proven PC. This study reviewed data of 153 patients that underwent T-RARP for suspected PC performed by the same surgeon. PATIENTS AND METHODS: Patients' preoperative demographic and clinical characteristics included age, prostate-specific antigen (PSA) level, PSA density (PSAD), history of acute urinary retention (AUR), abnormal digital rectal examination (DRE) of the prostate, and Prostate Imaging Reporting and Data System (PI-RADS) classification at 3-T multiparametric magnetic resonance imaging (MRI). Logistic regression with backward elimination was used to select potential risk factors. RESULTS: Based on Harrell's guidelines, we chose seven variables for our final model: Age, DRE corresponding with MRI, AUR, PSAD, prostate-specific antigen velocity (PSAV), PI-RADS, and biopsy pathology. A nomogram for prediction of adenocarcinoma was developed. The original C-index for the nomogram was 0.80 (95% confidence interval=0.74-0.89). The cut-off of the nomogram score for predicting PC was 50 (sensitivity=55.4%; specificity=91.9%). The receiver operating characteristic curve of the model analysis showed an area under the curve of 0.801. CONCLUSION: A nomogram was produced using age, DRE-corresponding MRI, AUR, PSAD, PSAV, PI-RADS, and biopsy pathology. A preoperative nomogram prediction of prostate adenocarcinoma can help the patient and his family understand the possibility of PC and assist them in their decision-making.

2.
Free Radic Biol Med ; 153: 187-201, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32320747

RESUMO

Exposure to cigarette smoke (CS) pollution has previously associated with dry eye symptoms but without detailed experimental data and elucidation of the mechanism. We aimed to evaluate the effects of CS on the ocular surfaces of mice and the extraction of DMSO lipid-soluble cigarette smoke particles (DCSP) on cultured human corneal epithelial cells (HCECs), and explore to elucidate the probable mechanism. C57BL mice were exposed to CS challenging. In vivo clinical evaluations, including corneal fluorescein staining, tear film break-up time, and confocal microscopic observations, were performed before exposure and post-exposure. At the end of the in vivo study, changes in corneal and conjunctival histology, corneal ultrastructure, and conjunctival goblet cell intensity were examined, expression of TUNLE and Ki67 in tissue were also detected. In vitro, cell confluence and caspase3/7 were assessed in DCSP treated HCECs. Production of TNF-α, IL-1ß and IL-6, activation of NF-κB and Ki67 were evaluated by means of ELISA and Western blot respectively in HCECs cultured with 0.6 µL/mL DCSP. We found that longer-term CS exposure induced dry eye symptoms in mice. Additionally, corneal and conjunctival epithelial damage occurred, the corneal ultrastructure changed, and the density of goblet cells decreased. Apoptosis and Ki67 increased in both the conjunctiva and the cornea of CS-exposed animals. Furthermore, although DCSP inhibited the proliferation of HCECs, expression of Ki67 increased and apoptosis was only induced significantly by 2.0 µL/mL DCSP. The release of IL-1ß and IL-6, activation of NF-κB were prompted by DCSP. The results indicated that CS is toxic to the ocular surface of mice and HCECs. Longer-term CS exposure in mice stimulates ocular surface changes that resemble those observed with dry eye. The mechanism may relate to inflammation and activation of NF-κB. In this study, we established a novel animal model to study dry eye, with the experimental data and elucidation of mechanism facilitating further research.

3.
J Am Heart Assoc ; 9(7): e014654, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32248764

RESUMO

Background Retinal arteriolar narrowing and venular widening has been widely suggested to be associated with subclinical changes in cardiac structure. The novel retinal vascular geometric indices might reflect more comprehensive information on microvasculature other than vascular caliber alone. However, the association between suboptimal retinal vascular geometry and cardiac structural alteration has not been studied. Methods and Results We recruited 50 participants without cardiovascular disease from the Cardiac Aging Study conducted between 2014 and 2016. We performed transthoracic echocardiography imaging to measure cardiac structure indices such as left ventricular internal diameter end diastole index, left ventricular internal diameter end systole index, left ventricular mass index, and left atrial volume index, and retinal imaging to measure retinal vascular geometric indices including branching angle, curvature tortuosity, and fractal dimension. We applied multiple linear regressions to examine associations between indices of cardiac structure and retinal vascular geometry, adjusting for age, sex, body mass index, mean blood pressure, and comorbidity. The average age of all participants was 62.54 years old and slightly more than half were male (27; 54%). Each unit increase in a set of cardiac structure indices was associated with larger retinal arteriolar branching angle (ß and 95% CI: for left ventricular internal diameter end systole index, 26.93°; 6.00-47.86; for left ventricular internal diameter end diastole index, 17.86°; 1.61-34.11; for left ventricular mass index, 0.39°; 0.10-0.67; for left atrial volume index, 0.91°; 0.24-1.58). Conclusions Adverse retinal arteriolar geometric morphology mirrored suboptimal cardiac structural alteration.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32224959

RESUMO

Screen media usage has become increasingly prevalent in daily life with children being exposed to screens at an early age. This is a growing public health concern with evidence linking screen exposure to detrimental health outcomes, whereas relationship between screen exposure and the presence of astigmatism among preschoolers remains unknown, thus we aimed to resolve this issue. During the 2017 survey of the Longhua Child Cohort Study, data of 29,595 preschoolers were collected via a caregiver-reported questionnaire regarding socio-demographics, screen exposure and refraction. Cox regression models were adopted to generate adjusted prevalence ratios (APR) and 95% confidence intervals (CI) to estimate the association between early screen exposure and astigmatism. 28,029 preschoolers were included in the final analysis. After adjustment for potential confounders, screen exposure during early life was significantly associated with the increased risk of astigmatism (APR and 95% CI: 2.25, 1.76-2.88), and the greatest risk was observed in the period from birth to 1-year (APR and 95% CI: 3.10, 2.41-3.98). The risk of astigmatism increased with both the total years of exposure and the average daily duration of screen exposure. Our findings suggested that preschoolers who were exposed to screens during early life might have an increased risk of astigmatism.

5.
Horm Metab Res ; 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299109

RESUMO

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited endocrine tumor syndrome caused by inactivating variants of the MEN1 gene. The aim of this study is to explore the clinical and genetic characteristics of four MEN1 patients. We isolated genomic deoxyribonucleic acid from lymphocytes, parathyroid, and thymic tumoral tissue specimens from the MEN1 patients. All exons of the MEN1 and CDNK1B genes and adjacent exon-intron sequences were amplified by polymerase chain reaction and subsequently sequenced. Further, the splice alterations were studied by sequencing the amplified RT-PCR products for MEN1 cDNA. We identified four heterozygous MEN1 germline variants: c.564delC, c.1268G>A, IVS5+5delG, and c.1546_1547insC. Both c.564delC and IVS5+5delG were novel variants. The impact of the MEN1 splice variant, IVS5+5delG, was evaluated using bioinformatics and in vitro analyses. The analyses indicated that this variant resulted in skipping of the neighboring exon and was disease-causing. Two novel somatic variants, c.249_252delGTCT and c.313_314insC, were found. Additionally, loss of heterozygosity (LOH) for the MEN1 locus (IVS5+5delG and c.564delC) was found in tumor tissue samples from the MEN1 patients, consistent with Knudson's two-hit mechanism. We identified four MEN1 germline variants and two novel somatic variants. Early recognition of the phenotype coupled with variant screening of the MEN1 gene is the key to diagnosing and treating MEN1 effectively at an early stage.

6.
Ecotoxicol Environ Saf ; 195: 110455, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32199215

RESUMO

Inhalation of neodymium oxide, a type of rare earth metal, can induce various respiratory diseases, such as lung tissue inflammation, but the associated mechanisms underlying this induction are still unclear. In this study, we explored the role and mechanisms of circular RNA in neodymium oxide-induced airway inflammation. Our study showed that treating human bronchial epithelial (16HBE) cells with neodymium oxide caused an inflammatory response by upregulating the expression of interleukin-8 (IL-8) and interleukin-1 beta (IL-1ß). Quantitative real-time polymerase chain reaction (qRT-PCR) analyses revealed significant downregulation of circRNA_0000638 in neodymium oxide-treated 16HBE cells. Data from functional analyses further showed that circ_0000638 inhibited inflammation induced by neodymium oxide in 16HBE cells. circ_0000638 targeted miR-498-5p and further increased the expression of NKRF (NF-κB repressing factor), which inhibited the activation of NF-κB (nuclear factor κB). Moreover, circ_0000638 reduced the expression of IL-8 and IL-1ß by inhibiting NF-κB activation in neodymium oxide-treated 16HBE cells. These results suggest that circ_0000638 can inhibit NF-κB activation by competitively binding to miR-498-5p, further downregulating the expression of IL-8 and IL-1ß in neodymium oxide-treated 16HBE cells.

7.
Accid Anal Prev ; 138: 105465, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32050109

RESUMO

Advance guide signs for exit ramps along urban expressways are increasingly critical, enhancing safety and mobility by improving the flow of vehicles exiting urban expressways. However, research has devoted scant attention to advance guide signs for exit ramps. This study aimed to identify and propose optimal design alternatives for exit ramp advance guide signs for different types of exit spacing. This study conducted a driving simulation experiment consisting of five design alternatives of advance guide signs and two exit ramp spacing variation. Eight indicators were measured. The repeated-measure analysis of variances (ANOVA) and the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) were performed for the influence analysis and efficiency evaluation of different schemes. Influence analysis results showed better design alternatives in five schemes of advance guide signs, enabling drivers to more easily locate destination exits and change lanes fewer times, in addition to reducing drivers' need to decelerate, and improving traffic flow in the key influence range of destination exit ramps. The percentage of drivers successfully locating the destination exits also increased with optimal design alternatives of advance guide signs. When the exit ramp spacing tightened, on the other hand, drivers had to make more lane changes and accelerate and decelerate more frequently in the key influence range. As a result, a lower percentage of drivers successfully located destination exits. Efficiency evaluation results were also obtained. In tight spacing, three advance guide signs are recommended to be placed at 1 km, 0.5 km and 0 km prior to the beginning of the tapered deceleration lane. If conditions are limited, at least two advance guide signs should be used. With greater spacing, four advance guide signs are recommended, located at 2 km, 1 km, 0.5 km, and 0 km prior to the beginning of the tapered deceleration lane. If road conditions are limited, three advance guide signs should be used.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32046062

RESUMO

This study aimed to explore the association between screen exposure in early life and preschool myopia. During the baseline survey of the Longhua Child Cohort Study (LCCS), data of 29,595 preschoolers were collected via a caregiver-reported questionnaire regarding children's socio-demographic characteristics, visual status, screen exposure and relevant parental information. Data of 26,433 preschoolers with normal eyesight or myopia were included in the analysis and cox regression modelling was employed to assess the associations. Results suggested the hypothesis that screen exposure in early life could be significantly and positively associated with preschool myopia, and in agreement with this hypothesis was the association being strengthened with the increasing daily exposure duration and total years of exposure; in the stratification analysis based on the presence of parental myopia, these associations still existed, and the strength of associations was stronger in preschoolers with myopic parents than those without. Moreover, a statistically significant association was only observed between initial screen exposure that occurred during 0-1-years old and myopia for preschoolers without myopic parents, while the significant associations were observed between initial screen exposure that occurred during 0-1, 1-2, 2-3, and after 3 years old and myopia for preschoolers who had myopic parents, with the strongest association found in the group of children initially exposed to electronic screens during 0-1 year old. Thus our findings indicated the hypothesis that screen exposure in early life might be associated with the occurrence of preschool myopia, and that the postnatal first year might be the sensitive period for the association. However, it is premature to conclude that early screen time leads to myopia with current data. Further longitudinal studies performed with cycloplegia are necessary to verify the hypothesis and shed light on the more urgent question whether early screen exposure contributes to the later myopia epidemic of school-aged children.

9.
J Cell Mol Med ; 24(7): 4023-4035, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32096914

RESUMO

As a main part of pigmentation disorders, skin depigmentation diseases such as vitiligo and achromic naevus are very common and get more attention now. The pathogenesis of depigmentation includes melanocyte dysfunction and loss, which are possibly caused by heredity, autoimmunity and oxidative stress. Among them, oxidative stress plays a key role; however, few clinical treatments can deal with oxidative stress. As reported, Cistanche deserticola polysaccharide (CDP) is an effective antioxidant; based on that, we evaluated its role in melanocyte and further revealed the mechanisms. In this study, we found that CDP could promote melanogenesis in human epidermal melanocytes (HEMs) and mouse melanoma B16F10 cells, it also induced pigmentation in zebrafish. Furthermore, CDP could activate mitogen-activated protein kinase (MAPK) signal pathway, then up-regulated the expression of microphthalmia-associated transcription factor (MITF) and downstream genes TYR, TRP1, TRP2 and RAB27A. Otherwise, we found that CDP could attenuate H2 O2 -induced cytotoxicity and apoptosis in melanocytes. Further evidence revealed that CDP could enhance NRF2/HO-1 antioxidant pathway and scavenge intracellular ROS. In summary, CDP can promote melanogenesis and prevent melanocytes from oxidative stress injury, suggesting that CDP helps maintain the normal status of melanocytes. Thus, CDP may be a novel drug for the treatment of depigmentation diseases.

10.
Immunol Invest ; : 1-13, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32079425

RESUMO

Background: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. Cyclophilin A (CypA), also known as PPIA, has been identified to play a vital role in the pathogenesis of cardiovascular or inflammatory diseases. However, no studies have examined the relationship between single-nucleotide polymorphisms (SNPs) in the peptidylprolyl isomerase A (PPIA) and the development of KD and KD with or without coronary artery lesions (CALs).Objective: The present study was conducted to evaluate whether PPIA SNPs are associated with susceptibility to KD or CALs in KD.Methods: Three PPIA SNPs were genotyped in 101 KD patients and 105 healthy controls from a Chinese population. The allele and genotype frequencies were compared between the case and control groups, as well as in KD patients with and without CALs.Results: The data revealed a significant difference in the genotype and allele frequencies of rs17860041 A/C between KD patients and normal controls. Compared to the rs17860041 CC genotype, the AC genotype demonstrated a consistently beneficial roles in reducing the KD incidence. Furthermore, the allele frequency of C in the KD group was higher than that in the control group (P < .05). Haplotype analysis for PPIA polymorphisms (rs10951772 A/G, rs17860041 A/C, and rs4720485 A/T) also confirmed this association in KD patients and normal controls.Conclusion: A PPIA promoter SNP (rs17860041 A/C) confers susceptibility to KD in Chinese children and was identified as an important marker of KD in this study.

11.
Virus Genes ; 56(2): 202-208, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31916138

RESUMO

Porcine endogenous retrovirus (PERV), which integrates as a provirus into the genome of pig cells, is an important biosafety issue in xenotransplantation. Screening and analyzing the presence and expression of PERV will provide essential parameters for assessing the biosafety of donor sources. In the present study, we investigated the prevalence of PERV in Diannan small-eared pigs, a unique closed colony that is distributed in southern Yunnan Province in southwestern China. PCR was performed to amplify env-A, env-B, env-C, pol, gag, and mtDNA in peripheral blood samples. The results revealed that PERV env-A, env-B, pol, and gag were detected in all individuals, but env-C was deficient in most pigs, suggesting that the main subtypes of PERVs in Diannan small-eared pigs are PERV-A and PERV-B. Furthermore, PERV pol and the porcine housekeeping gene GAPDH were detected by RT-PCR in all peripheral blood samples, indicating that PERV had transcriptional activity. Finally, the consensus sequences of PERV-A and PERV-B were amplified and digested with KpnI and MboI. Interestingly, a total of seven digestion patterns were obtained, which is less than that observed in other pig breeds. The PCR products were cloned into the pUCm-T vector and sequenced. The results showed that all of the inserts were highly homologous to either PERV-A or PERV-B, and the ratios of PERV-A and PERV-B were 21.1% and 78.9%, respectively. These data suggest that Diannan small-eared pigs may be a candidate donor source for xenotransplantation.

12.
J Diabetes Res ; 2020: 4739271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998806

RESUMO

Objective: To investigate the association of the serum adiponectin level with the intima media thickness of the dorsalis pedis artery (D-IMT) and macroangiopathy in type 2 diabetes (T2DM). Methods: We recruited 173 patients with T2DM, of whom 83 had macroangiopathy (MA group) and 90 did not have macroangiopathy (NM group), and 40 normal control subjects (NC group). We measured D-IMT using color B-mode Doppler ultrasonography. Serum adiponectin, blood glucose, lipids, and other clinical characteristics were analyzed. Participants were divided into three subgroups according to serum adiponectin level (high, moderate, and low). Results: Compared with the NM and NC groups, serum adiponectin levels were significantly decreased in the MA group after adjusting for sex and body mass index. Compared with the NM and NC groups, D-IMT was significantly increased in the MA group. Compared with the moderate- and high-adiponectin subgroups, D-IMT was significantly increased in the low-adiponectin subgroup. The prevalence of diabetic macroangiopathy increased gradually with decreasing adiponectin levels. After controlling for age, sex, smoking, and alcohol drinking, partial correlation analysis showed that adiponectin was negatively correlated with D-IMT. Elevated serum adiponectin was independently associated with a decreased risk for diabetic macroangiopathy by logistic regression analysis. Multiple linear regression analysis revealed that adiponectin was an independent factor of D-IMT. In receiver operating characteristic analyses, the area under the curve for traditional risk factors plus adiponectin for prediction of macroangiopathy was 0.984, while that of traditional risk factors alone was 0.972. Conclusions: Adiponectin is lower in patients with T2DM with macroangiopathy. We suggest that D-IMT could represent a noninvasive indicator of diabetic macroangiopathy. Decrease of adiponectin as an independent risk factor for both macroangiopathy and D-IMT among Chinese patients with T2DM suggests that adiponectin might have clinical utility in the prediction of diabetic macroangiopathy. This clinical trial is registered in the "Chinese Clinical Trial Registry." The registration number is ChiCTR-ROC-17011731.

13.
J Invest Dermatol ; 140(1): 152-163.e5, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31276678

RESUMO

The long noncoding RNA UCA1 was first discovered in bladder cancer and is known to regulate the proliferation and migration of melanoma. However, its role in melanogenesis is unclear. In this study, we aimed to explore the role and mechanism of UCA1 in melanogenesis. Our findings showed that the expression of UCA1 was negatively correlated with melanin content in melanocytes and pigmented nevus. Overexpression of UCA1 in melanocytes decreased melanin content and the expression of melanogenesis-related genes, whereas knockdown of UCA1 in melanocytes had the opposite effect. High-throughput sequencing revealed that microphthalmia-associated transcription factor (MITF), an important transcription factor affecting melanogenesis, was also negatively correlated with the expression of UCA1. Furthermore, the transcription factor CRE-binding protein (CREB), which promotes MITF expression, was negatively regulated by UCA1. The cAMP/protein kinase A (PKA), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) signaling pathways, which are upstream of the CREB/MITF/melanogenesis axis, were activated or inhibited in response to silencing or enhancing UCA1 expression, respectively. In addition, enhanced UCA1 expression downregulates the expression of melanogenesis-related genes induced by UVB in melanocytes. In conclusion, UCA1 may negatively regulate the CREB/MITF/melanogenesis axis through inhibiting the cAMP/PKA, ERK, and JNK signaling pathways in melanocytes. UCA1 may be a potential therapeutic target for the treatment of pigmented skin diseases.

14.
Mol Med Rep ; 21(1): 485-492, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746415

RESUMO

Individual differences in the response to fentanyl, which may be caused by different concentrations of the drug in the central nervous system, can complicate analgesic treatment. It has been reported that the organic anion transporting polypeptide (OATP) at the blood­brain barrier (BBB) in Sprague­Dawley rats may serve an important role in the transport of fentanyl across the BBB. However, whether human OATP can transport fentanyl has thus far not been reported. The present study aimed to establish a 293 cell line stably overexpressing OATP1A2, and to determine whether OATP1A2 is able to transport fentanyl across the plasma membrane. Initially, 293 cells were transfected with an OATP1A2­expressing plasmid (referred to as 293­OATP1A2 cells), and single colonies were selected and characterized following geneticin treatment. Subsequently, reverse transcription­quantitative polymerase chain reaction and western blot analyses were conducted to verify the transfection efficiency. Furthermore, treatment of 293­OATP1A2 cells with different concentrations of fexofenadine (FEX) and fentanyl was performed to investigate the transport function of OATP1A2 in 293 cells. FEX and fentanyl uptake experiments were also performed with naringenin, an inhibitor of OATP1A2. The results indicated that FEX and fentanyl uptake was significantly increased in 293­OATP1A2 cells compared with that in the control­transfected cells. The 293­OATP1A2­mediated uptake of FEX at concentration of 100 nM FEX was ~10­fold higher than that of 293­VC cells. The 293­OATP1A2­mediated uptake of fentanyl (100 nM) was 5.1­fold higher compared with that in 293­VC cells. In 293­OATP1A2 cells, the uptake of FEX without OATP1A2 inhibitor naringenin (100 µg/ml) was 2.8­fold higher compared with that in the presence of naringenin, and the uptake of fentanyl without naringenin was 7.3­fold higher compared with that in the presence of naringenin (100 µg/ml). In conclusion, 293 cells that overexpressed OATP1A2 were successfully constructed, and OATP1A2 was revealed to mediate fentanyl uptake in the cultured cells.

16.
Curr Neurovasc Res ; 17(1): 44-49, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31870265

RESUMO

BACKGROUND: Perihematomal edema (PHE) is a major threat leading to poor functional outcomes after intracerebral hemorrhage (ICH). TIMP-2 is considered to participate in the formation of PHE after ICH by antagonizing the damaging effects of MMP-2. In the early study, the polymorphisms of TIMP-2 rs8179090 have shown to influence the expression of TIMP-2. OBJECTIVE: To prove that the severity of PHE was different in ICH patients with different TIMP-2 rs8179090 genotypes. METHODS: In this prospective study, 130 hypertensive ICH patients were enrolled. The poly phisms of rs8179090 in TIMP-2 were determined. The hematoma volume and PHE volume were measured by computed tomography (CT) scan immediately after the onset of ICH, and were measured again one week and two weeks after the onset. Then, the comparison of TIMP-2 rs8179090 genotypes was made. RESULTS: TIMP-2-418 position (rs8179090) had two genotypes in the studied population, GC and GG. Patients with the GC genotype developed more severe PHE, with a higher incidence of delayed cerebral edema in cerebral hemorrhage than those with the GG genotype. CONCLUSION: We have found that the GC genotype group may develop more severe PHE, with an increased incidence of delayed cerebral edema in cerebral hemorrhage.

17.
J Autoimmun ; : 102372, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31810856

RESUMO

The genetic association of primary biliary cholangitis with major histocompatibility complex (MHC) has been widely confirmed among different ethnicities. To map specific MHC region variants associated with PBC in a Han Chinese cohort, we imputed HLA antigens and amino acids (AA) in 1126 PBC cases and 1770 healthy control subjects using a Han-MHC reference database. We demonstrate that HLA-DRB1 and/or HLA-DQB1 contributed the strongest signals, and that HLA-DPB1 was a separate independent locus. Regression analyses with classical HLA alleles indicate that HLA-DQB1*03:01 or HLA-DQß1-Pro55, HLA-DPB1*17:01 or HLA-DPß1-Asp84 and HLA-DRB1*08:03 could largely explain MHC association with PBC. Forward stepwise regression analyses with HLA amino acid variants localize the major signals to HLA-DRß1-Ala74, HLA-DQß1-Pro55 and HLA-DPß1-Asp84. Electrostatic potential calculations implicated AA variations at HLA-DQß1 position 55 and HLA-DPß1 position 84 as critical to peptide binding properties. Furthermore, although several critical Han Chinese AA variants differed from those shown in European populations, the predicted effects on antigen binding are likely to be very similar or identical and underlie the major component of MHC association with PBC.

18.
Insect Sci ; 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31840397

RESUMO

Metamorphosis is one of the most important physiological processes in insects. It is regulated by a serial of ecdysone cascade genes. Recently, lots of microRNAs (miRNAs) were investigated in insects; however, their function in metamorphosis is largely unknown. In the present study, the dynamics of a small RNA population was investigated by RNA sequencing from the midgut of a lepidopteran pest Spodoptera litura during larval-pupal metamorphosis. A total of 101 miRNAs were identified, and 75 miRNAs were differentially expressed during the metamorphic process. The relationship between these differentially expressed miRNAs and 12 ecdysone cascade genes was analyzed by four classical software programs, and a multiple-to-multiple regulatory network was found to exist between these miRNAs and their targets. Among them, miR-14-3p and its two targets (EcR and E75) were chosen for further validation. MiR-14-3p had higher expression level in the 6th instar larvae as compared with either the prepupae or pupae, which was opposite to that of both EcR and E75, two ecdysone cascade genes. Luciferase reporter assay confirmed that both EcR and E75 were regulated by miR-14-3p. Interestingly, the 3' untranslated regions are nearly identical to each other among different transcript variants of the ecdysone cascade genes, including EcR, USP, E75, E74, E78, E93, Hr3, Hr4, Hr39, Krh1 and Ftzf1. Thus, different transcript variants of one ecdysone cascade gene could be regulated by the same miRNA. The above data suggest that the ecdysone signaling pathway is under the tight control of miRNA. These findings expand our understanding of the mechanism of insect metamorphosis and may also provide a novel possibility for the control of pest insects in the future.

19.
Biotechnol Prog ; : e2953, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31846227

RESUMO

Triton X-100 has long been used either alone or in combination with solvent to inactivate enveloped viruses in biopharmaceutical manufacturing. However, European Chemicals Agency (ECHA) officially placed Triton X-100 on the Annex XIV authorization list in 2017 because 4-(1,1,3,3-tetramethylbutyl) phenol, a degradation product of Triton X-100, is of harmful endocrine disrupting activities. As a result, any use of Triton X-100 in the European Economic Area would require an ECHA issued authorization after the sunset date of January 4, 2021. In search of possible replacements for Triton X-100, we discovered that polysorbate 80 (PS80) in absence of any solvents was able to effectively inactive enveloped viruses such as xenotropic murine leukemia virus and pseudorabies virus with comparable efficacy as measured by log reduction factors. Interestingly, PS80 did not show any virucidal activities in phosphate buffered saline (PBS) while achieving robust virus inactivation in cell-free Chinese hamster ovary (CHO) bioreactor harvests. This intriguing observation led us to speculate that virus inactivation by PS80 involved components in the cell-free CHO bioreactor harvests that were absent in PBS. Specifically, we hypothesized that esterase and/or lipases in the cell-free bioreactor harvests hydrolyzed PS80 to yield oleic acid, a known potent virucidal agent, which in turn inactivated viruses. This theory was confirmed using purified recombinant lysosomal phospholipase A2 isomer (rLPLA2) in PBS. Subsequent characterization work has indicated that virus inactivation by PS80 is effective and robust within temperature and concentration ranges comparable to those of Triton X-100. Similar to Triton X-100, virus inactivation by PS80 is dually dependent on treatment time and temperature. Unlike Triton X-100, PS80 inactivation does not correlate with concentrations in a simple manner. Additionally, we have demonstrated that PS20 exhibits similar virus inactivation activities as PS80. Based on the findings described in the current work, we believe that PS80 is potentially a viable replacement for Triton X-100 and can be used in manufacturing processes for wide spectrum of biopharmaceuticals to achieve desirable virus clearance. Finally, the advantages and disadvantages of using PS80 for virus inactivation are discussed in the contexts of GMP manufacturing.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31623306

RESUMO

This study aimed to investigate the association between environmental exposure to tobacco smoke (ETS) during early life and astigmatism in Chinese preschool children. In this cross-sectional study, information concerning prenatal and postnatal ETS exposure at three stages of early life (during pregnancy, from birth to one year and from one to three years), visual problems of children and parents (including a confirmed diagnosis of astigmatism), socio-demographics and perinatal characteristics were obtained from 27,890 parent-reported questionnaires. Logistic regression analyses were undertaken to yield adjusted odds ratios (OR) for assessing their associations. After adjusting for the potential confounders, children were more likely to exhibit astigmatism when they were exposed to ETS during pregnancy + from one to three years [OR (95% CI) = 1.37 (1.02, 1.84)], or from birth to one year + from one to three years [OR (95% CI) = 1.36 (1.11, 1.66)], or during pregnancy + from birth to one year + from one to three years old [OR (95% CI) = 1.29 (1.16, 1.45)], compared to children without ETS exposure at any stage of early life. In Chinese preschool children, prenatal and postnatal astigmatism was associated with ETS exposure; the greater the ETS dose, the greater the astigmatism risk.


Assuntos
Astigmatismo/etiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Astigmatismo/epidemiologia , Astigmatismo/fisiopatologia , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos
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