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Background: Platelets play a significant role in the innate and adaptive processes of immunity and inflammation. Inflammatory bowel disease (IBD) is an autoimmune disease that is widely understood to be caused by a combination of genetic predisposition, aberrant immune responses, etc. Methods: To examine the relationships between genetically determined platelet indices and IBD, we conducted a Mendelian randomization (MR) study. Data associated with platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT) were used from the UK Biobank. The outcome data, including IBD, Crohn's disease (CD), ulcerative colitis (UC), were from the FinnGen database. The inverse variance-weighted (IVW), MR-Egger, weighted median methods were used for MR analyses. Results: The MR estimations from the IVW approach show a significant connection between PLT and IBD. Similarly, PCT and IBD have a relationship following the IVW and MR-Egger approaches. While PLT and PCT have strong relationships with CD, according to the findings of all three approaches respectively. Nevertheless, PDW was the only relevant indicator of UC. The only significant result was IVW's. Conclusion: Our findings suggest that the fluctuation of platelet indicators is of great significance in the development of IBD. PLT and PCT have a close association with IBD and CD, respectively; PDW only has a connection with UC. Platelets play an important role in the progression of IBD (UC, CD).
Subject(s)
Blood Platelets , Inflammatory Bowel Diseases , Mendelian Randomization Analysis , Humans , Blood Platelets/immunology , Inflammatory Bowel Diseases/blood , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/diagnosis , Platelet Count , Mean Platelet Volume , Genetic Predisposition to Disease , Crohn Disease/genetics , Crohn Disease/blood , Crohn Disease/immunology , Polymorphism, Single NucleotideABSTRACT
Objective: To analyze the phenotype and genotype of two pedigrees with inherited fibrinogen (Fg) deficiency caused by two heterozygous mutations. We also preliminarily probed the molecular pathogenesis. Methods: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and plasma fibrinogen activity (Fg∶C) of all family members (nine people across three generations and three people across two generations) were measured by the clotting method. Fibrinogen antigen (Fg:Ag) was measured by immunoturbidimetry. Direct DNA sequencing was performed to analyze all exons, flanking sequences, and mutated sites of FGA, FGB, and FGG for all members. Thrombin-catalyzed fibrinogen polymerization was performed. ClustalX 2.1 software was used to analyze the conservatism of the mutated sites. MutationTaster, PolyPhen-2, PROVEAN, SIFT, and LRT online bioinformatics software were applied to predict pathogenicity. Swiss PDB Viewer 4.0.1 was used to analyze the changes in protein spatial structure and molecular forces before and after mutation. Results: The Fg∶C of two probands decreased (1.28 g/L and 0.98 g/L, respectively). The Fg∶Ag of proband 1 was in the normal range of 2.20 g/L, while it was decreased to 1.01 g/L in proband 2. Through genetic analysis, we identified a heterozygous missense mutation (c.293C>A; p.BβAla98Asp) in exon 2 of proband 1 and a heterozygous nonsense mutation (c.1418C>G; p.BβSer473*) in exon 8 of proband 2. The conservatism analysis revealed that Ala98 and Ser473 presented different conservative states among homologous species. Online bioinformatics software predicted that p.BβAla98Asp and p.BβSer473* were pathogenic. Protein models demonstrated that the p.BβAla98Asp mutation influenced hydrogen bonds between amino acids, and the p.BβSer473* mutation resulted in protein truncation. Conclusion: The dysfibrinogenemia of proband 1 and the hypofibrinogenemia of proband 2 appeared to be related to the p.BβAla98Asp heterozygous missense mutation and the p.BβSer473* heterozygous nonsense mutation, respectively. This is the first ever report of these mutations.
Subject(s)
Humans , Afibrinogenemia/genetics , Codon, Nonsense , Pedigree , Phenotype , Fibrinogen/genetics , GenotypeABSTRACT
Juvenile polyps(JP),also known as retention polyps,are the most common type of colorectal polyps and the main cause of lower gastrointestinal bleeding in children,with rare incidence in adults.In recent years,with the development and application of electronic colonoscopy,the detection rate of colorectal JP has gradually increased.It is generally accepted that JP is a benign hamartomatous lesion of the intestine,while it can cause complications such as massive hemorrhage of the lower digestive tract,anemia,intussusception,and intestinal obstruction.Moreover,there are reports about the canceration of JP.Therefore,it is necessary to improve the understanding and achieve early diagnosis and treatment of this disease.This article reviews the research progress in the epidemiological characteristics,pathogenesis,clinical manifestations,diagnosis and treatment methods,and canceration risk of JP.
Subject(s)
Child , Adult , Humans , Colonoscopy/adverse effects , Rectal Neoplasms , Gastrointestinal HemorrhageABSTRACT
OBJECTIVES: To diagnose coronary artery stenosis by using the postmortem computed tomography angiography (PMCTA), and to explore the diagnostic value of PMCTA in sudden cardiac death. METHODS: Six death cases were selected, and the contrast medium iohexol was injected under high pressure through femoral artery approach with 5F pigtail catheter to obtain coronary image data and then the data was analyzed. The results of targeted coronary imaging and coronary artery calcium score (CaS) were compared with the results of conventional autopsy and histopathological examination. RESULTS: The autopsy and histopathological examination of cases with coronary artery stenosis obtained similar results in targeted coronary angiography, with a diagnostic concordance rate of 83.3%. Targeted coronary angiography could effectively show coronary artery diseases, and the CaS was consistent with the results of conventional autopsy and histopathological examination. CONCLUSIONS: Targeted coronary angiography can be used as an effective auxiliary method for conventional autopsy in cases of sudden cardiac death.
Subject(s)
Coronary Angiography , Coronary Artery Disease , Coronary Stenosis , Humans , Computed Tomography Angiography/methods , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Stenosis/diagnostic imaging , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/pathologyABSTRACT
Recently, the problem of water pollution, caused by antibiotics, is becoming more and more serious. Photocatalysis is one of the promising technologies for removing antibiotics from water. Herein, the In2.77S4/Ti3C2 composites were prepared by an in-situ hydrothermal growth method for photocatalytic degradation of tetracycline (TC). The as-developed composites were characterized by various methods. The UV-Vis DRS spectra reveals that the introduction of Ti3C2 makes the bandgap of the as-prepared composites smaller and the visible light absorption ability improved. The photocatalytic degradation efficiency of the as-prepared composite is enhanced under visible light illumination. It is shown as first increasing and then decreasing with increasing the content of Ti3C2 in the composite and reaches to the maximum of 89.3% in 90 min, which is higher than 75.1% of In2.77S4 and 6.7% of Ti3C2. The reason of improvement is the interface between In2.77S4 and Ti3C2 is tightly combined to form a heterojunction. Moreover, the photocurrent intensity of the as-obtained composite is improved, while its Nyquist arc radius is decreased. In addition, holes are the main active species and ·OH and ·O2 - play an auxiliary role during the degradation of TC.
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Red blood cell (RBC) transfusion is one of the most frequently performed clinical procedures and therapies to improve tissue oxygen delivery in hospitalized patients worldwide. Generally, the cross-match is the mandatory test in place to meet the clinical needs of RBC transfusion by examining donor-recipient compatibility with antigens and antibodies of blood groups. Blood groups are usually an individual's combination of antigens on the surface of RBCs, typically of the ABO blood group system and the RH blood group system. Accurate and reliable blood group typing is critical before blood transfusion. Serological testing is the routine method for blood group typing based on hemagglutination reactions with RBC antigens against specific antibodies. Nevertheless, emerging technologies for blood group testing may be alternative and supplemental approaches when serological methods cannot determine blood groups. Moreover, some new technologies, such as the evolving applications of blood group genotyping, can precisely identify variant antigens for clinical significance. Therefore, this review mainly presents a clinical overview and perspective of emerging technologies in blood group testing based on the literature. Collectively, this may highlight the most promising strategies and promote blood group typing development to ensure blood transfusion safety.
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Objective: To investigate the molecular pathogenesis and clinical features of unrelated 12 patients with inherited coagulation protein C (PC) deficiency in Chinese population. Methods: The PC activity (PC:A) and PC antigen (PC:Ag) were detected by chromogenic substrate and enzyme linked immunosorbent assay, respectively. The nine exons and flanking sequences of the protein C (PROC) gene were amplified by polymerase chain reaction with direct sequencing, and the suspected mutations were validated by reverse sequencing (clone sequencing for deletion mutations) . Results: The PC:A of the 12 probands decreased significantly, ranging from 18% to 55%, and the PC:Ag of the 10 probands decreased significantly. Eleven mutations were found, out of which four mutations [c.383G>A (p.Gly128Asp) , c.997G>A (p.Ala291Thr) , c.1318C>T (p.Arg398Cys) , and c.532G>C (p.Leu278Pro) ] were discovered for the first time. Six mutations were in the serine protease domain, four mutations were located in epidermal growth factor (EGF) -like domains, and one mutation was located in activation peptide. There were two deletion mutations (p.Met364Trp fsX15 and p.Lys192del) , and the rest were missense mutations. Mutations p.Phe181Val and p.Arg189Trp were identified in three unrelated families. All mutations may be inherited, and consanguineous marriages were reported in two families. Among the probands, nine cases had venous thrombosis, two cases had poor pregnancy manifestations, and one case had purpura. Conclusion: Patients with PC deficiency caused by PROC gene defects are prone to venous thrombosis, especially when there are other thrombotic factors present at the same time.
Subject(s)
Humans , Mutation , Mutation, Missense , Pedigree , Phenotype , Protein C/genetics , Protein C Deficiency/geneticsABSTRACT
In this paper, we investigated the impact of the linewidth of a QCW pulsed sodium laser on the brightness performance of a generating sodium laser guide star by using the numerical simulation tool PRS. We compared the field test results with the simulation results for two TIPC's 30W class sodium guide star lasers and found the results are in good agreement which proves the tool can be used for prediction. Then, we used the tool to study the influence of D2b repumping and different linewidths from 10MHz to 1GHz on the coupling efficiency and the photon return flux. For the TIPC's QCW pulsed solid-state laser, when the on-sky power density is 1 W/m2, the coupling efficiency is 79.6 (photons/s/W/(atoms/m2)) without D2b repumping, however, the value is up to 213.3 (photons/s/W/(atoms/m2)) with 15% D2b enabled and is increased by 168% than the value without D2b; when the power density reaches 10 W/m2, the coupling efficiencies without D2b and with 15% D2b are 66.6 and 233.6 (photons/s/W/(atoms/m2)), respectively. The results show that for the QCW pulsed laser, D2b repumping is necessary. With D2b enabled, if the spectral linewidth is too wide or too narrow, the photon return flux will be adversely affected. The return flux of 60MHz is 52.5% higher than that of 1GHz, while the return flux of 300MHz is 37.8% higher than that of 10 MHz when the laser power is 100W.
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BACKGROUND: Aggressive malignant primary orbital tumors are extremely rare in newborns. The current cases further clarify the clinical features of malignant primary orbital tumors in neonates. CASE SUMMARY: At the time of presentation at the Seventh Center of People's Liberation Army General (PLAG) Hospital, the children were 1-, 2- and 5-mo-old, respectively, and included 2 boys and 1 girl. All three cases had unilateral proptosis at birth, and underwent mass excision and histopathologic examination. A peripheral primary neuroectodermal tumor, an aggressive infantile fibromatosis and an embryonic rhabdomyosarcoma were diagnosed, respectively. The first case underwent routine chemotherapy following surgery but died within three months due to worsening condition as the tumor spread throughout the body. The other two children were treated by surgery, and at the follow-up visits 6 mo and 1 year after surgery, respectively, the wound was completed healed, and they had normal growth and development without radiotherapy or chemotherapy. A review of highly uncommon orbital tumors in newborns is also provided. CONCLUSION: Malignant primary tumors should be considered in the presence of unilateral proptosis in newborns.
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Postharvest strawberry is susceptible to gray mold disease caused by Botrytis cinerea, which seriously damage the storage capacity of fruits. Biological control has been implicated as an effective and safe method to suppress plant disease. The aim of this study is to evaluate the postharvest disease control ability of Bacillus cereus AR156 and explore the response of strawberry fruit to this biocontrol microorganism. Bacillus cereus AR156 treatment significantly suppressed gray mold disease and postponed the strawberry senescence during storage. The bacterium pretreatment remarkably enhanced the reactive oxygen-scavenging and defense-related activities of enzymes. The promotion on the expression of the encoding-genes was confirmed by quantitative real-time PCR (qRT-PCR) that significantly increased the expression of the marker genes of salicylic acid (SA) signaling pathway, such as PR1, PR2, and PR5, instead of that of the jasmonic acid (JA)/ethylene (ET) pathway, which was also shown. Moreover, through transcriptome profiling, about 6,781 differentially expressed genes (DEGS) in strawberry upon AR156 treatment were identified. The gene ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated that AR156 altered the transcription of numerous transcription factors and genes involved in the SA-related plant disease resistance, metabolism, and biosynthesis of benzoxazinoids and flavonoids. This study offered a non-antagonistic Bacillus as a method for postharvest strawberry storage and disease control, and further revealed that the biocontrol effects were arisen from the induction of host responses on the transcription level and subsequent resistance-related substance accumulation.
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BACKGROUND: The ophthalmic artery (OA) was first reconstructed using computer software. The structural differences of ophthalmic arteries in non-arteritic anterior ischemic optic neuropathy (NAION) and normal eyes, in addition to hemodynamic alterations, were assessed. METHODS: Thirty-one NAION eyes, 19 uninvolved eyes with NAION, and a control group of 26 healthy eyes were retrospectively included. Computed tomographic angiography data were recorded, and corresponding three-dimensional OA models were constructed. Initial OA and internal carotid artery (ICA) diameters and the angle between them were analyzed. Three different OA models were used to evaluate hemodynamic performance. The statistical relationships between the initial diameters of the OA and ICA and the angle between the OA and ICA were described. RESULTS: OA diameters in NAION eyes were significantly smaller than those in both uninvolved and healthy eyes (P<0.05). There was no significant difference between uninvolved and healthy eyes (P=0.31). The initial ICA diameter and the angle between the OA and ICA did not significantly differ among the three groups. In the three models, the blood flow velocity in the initial ophthalmic arteries of uninvolved eyes was higher than that in the NAION eyes. The mass flows of the right and left ophthalmic arteries, accounting for the ipsilateral ICA in the control model, were 0.57%. However, these values in uninvolved and NAION eyes were 1.36% and 0.25%, respectively. CONCLUSIONS: NAION is associated with a smaller initial OA diameter, which may be related to hypoperfusion. To our knowledge, this is the first pilot study to analyze hemodynamic alterations using OA models.
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BACKGROUND@#Shenque (CV8) acupoint is located on the navel and has been therapeutically used for more than 2000 years in Traditional Chinese Medicine (TCM). However, clinical research on the underlying therapeutic molecular mechanisms of the CV8 acupoint lags far behind. This study aimed to study the mechanisms of umbilical acupoint therapy by using stem cells.@*METHODS@#The morphological characteristics of CV8 acupoint were detected under a stereomicroscope using hematoxylin and eosin (H&E) staining. Oil Red, Masson, and immunohistochemical staining on multi-layered slices were used to identify the type of cells at the CV8 acupoint. Cell proliferation was measured by a cell counting kit-8 (CCK-8) method. Flow cytometry and immunohistochemistry were used for cell identification. Induced differentiation was used to compare the differentiation of cells derived from CV8 acupoint and non-acupoint somatic stem cells into other cell types, such as osteogenic, adipogenic, and neural stem cell-like cells.@*RESULTS@#Morphological observations showed that adipose tissues at the linea alba of the CV8 acupoint in mice had a mass-like distribution. Immunohistochemical staining confirmed the distribution of stem cell antigen-1 (Sca-1) positive cells in the multi-layered slices of CV8 acupoint tissues. Cells isolated from adipose tissues at the CV8 acupoint exhibited high expression of Sca-1 and CD44 and low expression of CD31 and CD34, and these cells possessed osteogenic, adipogenic, and neurogenic stem cell-like cell differentiation ability. The cell proliferation (day 4: 0.5138 ± 0.0111 vs. 0.4107 ± 0.0180, t = 8.447, P = 0.0011; day 5: 0.6890 ± 0.0070 vs. 0.5520 ± 0.0118, t = 17.310, P 100 μm: 2.6000 ± 0.5477 vs. 0.8000 ± 0.8367, t = 4.025, P = 0.0038) were significantly enhanced in somatic stem cells derived from the CV8 acupoint compared to somatic stem cells from the groin non-acupoint. However, cells possessed significantly weaker osteogenicity ([2.697 ± 0.627]% vs. [7.254 ± 0.958]%, t = 6.893, P = 0.0023) in the CV8 acupoint group.@*CONCLUSIONS@#Our study showed that CV8 acupoint was rich with adipose tissues that contained abundant somatic stem cells. The biological examination of somatic stem cells derived from the CV8 acupoint provided novel insights for future research on the mechanisms of umbilical therapy.
Subject(s)
Animals , Mice , Acupuncture Points , Adipose Tissue , Adult Stem Cells , Cell Differentiation , Cells, Cultured , OsteogenesisABSTRACT
PURPOSE: To present a relatively uncommon case with a secondary iris cyst in the anterior chamber and its successful management with an anterior chamber mass excision surgery. CASE REPORT: A 46-year-old Chinese woman presented with a dark shadow in her left eye for 6 months without any other discomfort. She had a history of blunt ocular trauma by a badminton strike 3 years ago. Slit-lamp examination showed a small, nearly circular, sharply demarcated, and movable mass in the anterior chamber OS, which could change its position with head tilt. The anterior segment optical coherence tomography revealed a well-circumscribed cystic lesion in the anterior chamber with higher reflective outer layer and lower internal reflectivity. An anterior chamber mass removal surgery was performed without recurrence up to 1 year. CONCLUSION: Secondary free-floating iris cyst following a blunt trauma is rarely reported. It is relatively stable and nonprogressive so it may remain asymptomatic for a long time. Appropriate imaging techniques are necessary for facilitating diagnosis and therapy. Therapeutic management should be considered if visual symptoms arise, especially when complications occur.
Subject(s)
Cysts , Iris Diseases , Wounds, Nonpenetrating , Cysts/diagnostic imaging , Cysts/etiology , Female , Humans , Iris/diagnostic imaging , Iris/surgery , Iris Diseases/diagnosis , Iris Diseases/etiology , Iris Diseases/surgery , Middle Aged , Neoplasm Recurrence, Local , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/surgeryABSTRACT
The present study aimed to compare the imaging performance of two ultra-wide-field ï¬uorescein angiography imaging systems, namely the OptosOptomap 200Tx (Optos 200Tx) and the Heidelberg Spectralis (Spectralis). A total of 18 patients (36 eyes) underwent angiography using the two systems at the Department of Ophthalmology, Beijing Friendship Hospital (Beijing, China) between January and June 2017. The images were obtained as a single shot centered on the macula. The total area and area within each of four visualized quadrants were calculated and compared. The averages of the total and individual quadrant area captured by the Optos 200Tx were all larger than those obtained with the Spectralis (P<0.05). For pair-wise comparison, the circular area centered on the macula (radius of 10 and 15 mm) was displayed: Optos 200Tx 10 mm (295.57 mm2) < Spectralis (520.11 mm2) < Optos 200Tx 15 mm (596.45 mm2) < Optos 200Tx (804.36 mm2) (P<0.01). The differences of each of the four quadrant areas were statistically significant between the two systems (P<0.05). The mean size of the areas was in the following order: Inferior < temporal < superior < nasal for the Optos 200Tx, and inferior < temporal < nasal < superior for the Spectralis. Further comparison of the four-quadrant area indicated that the inferior quadrant of the Optos 200Tx was smaller than the other three quadrants (P<0.01) and the inferior quadrant of the Spectralis was smaller than the superior quadrant (P<0.01). The total retinal area and the retinal area of each quadrant captured by the Optos 200Tx were larger than those captured with the Spectralis. The total retinal area captured with the Optos 200Tx was able to cover the mid-peripheral area and part of the far-peripheral area of the retina, whereas the Spectralis only covered the mid-peripheral area.
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AIM: To evaluate whether narrowing of internal carotid artery siphon (ICAS) may increase the risk of developing non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: Totally 30 consecutive patients who had unilateral NAION and 30 gender-matched control subjects were recruited in the present study. The diameter of ICAS of all the participants were measured using head-and-neck computed tomographic angiography (CTA). Color doppler flow imaging (CDI) was used to measure the haemodynamics parameters of ICAS and short posterior ciliary arteries (SPCAs) in all subjects. Comparison of parameters between the NAION patients and controls as well as between the two sides within the patients were performed. The correlation between the diameter of ICAS and NAION was analyzed. RESULTS: A comparison of parameters between the affected side of the NAION patients and the controls, including the diameter of ICAS, the resistance index (RI) of ICAS, the blood flow velocities of SPCAs and RI of SPCAs, showed significantly difference (P<0.01), while there was no significant difference in terms of the mean blood flow velocity (Vm) of ICAS; Similar results were found while comparing all the measurements of the affected and unaffected side of patients (P for RI of SPCAs <0.05). No marked difference was detected in nearly all parameters except for RI of ICAS and SPCAs between the unaffected side of the NAION patients and the controls (P<0.05). The diameter of ICAS were significantly positive correlated with both peak systolic velocity (PSV) of SPCAs and end diastolic velocity (EDV) of SPCAs in patients with NAION (r=0.514, P<0.01 and r=0.418, P<0.05, respectively). CONCLUSION: Narrowing of ICAS may increase the risk of developing NAION.
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This work is to establish the fingerprint of Astragalus membranaceus var. mongholicus by HPLC-ELSD method, and to analyze the simulated wildness degree of A. membranaceus var. mongholicus in the genuine region of Inner Mongolia, Ningxia and Gansu. Compared with wild A. membranaceus var. mongholicus, the quality differences of A. membranaceus var. mongholicus in the genuine region were analyzed by identification of chromatographic peaks and similarity evaluation, cluster analysis(CA), principal components analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). HPLC fingerprints of A. membranaceus var. mongholicus in different genuine regions are established. The qualitative analysis of mass spectrometry identified 18 components. The similarity evaluation shows that the similarity of 32 batches of A. membranaceus var. mongholicus samples was 0.688-0.993. Among them, the similarity of samples in Shanxi, Inner Mongolia, Ningxia is 0.688-0.993, 0.835-0.989, 0.934-0.988, respectively and the similarity of samples in Gansu is 0.729-0.876 except No. 25 sample. The results of CA show that the samples of A. membranaceus var. mongholicus can be grouped into four categories according to the production area except the No. 11 and No. 25 samples. The results of PCA indicate that 32 batches of A. membranaceus var. mongholicus samples can be clustered according to quality and origin, and the quality of A. membranaceus var. mongholicus in Inner Mongolia is the closest to the wild breed. The results of OPLS-DA indicate that there are six components that can distinguish the wild and domestic A. membranaceus var. mongholicus, which are malonylastragaloside â , astragaloside â , calycosin-7-O-ß-D-glycoside-6â³-O-malonate, calycosin-7-O-ß-D-glycoside, formononetin-7-O-ß-D-glycoside-6â³-O-malonate, and astrapterocarpan-3-O-ß-D-glycoside-6â³-O-malonate. The established method can be used to analyze differences between A. membranaceus var. mongholicus origin and planting environment, and can provide references for the protection and replacement of wild A. membranaceus var. mongholicus resources, and the cultivation, processing and production of A. membranaceus var. mongholicus.
Subject(s)
Astragalus propinquus , ChinaABSTRACT
Inflammation is considered to be critical in the pterygium progression and recurrence. However, the underlying molecular mechanism is not well understood. Herein, we investigated the potential role of RNA binding protein human antigen R (HuR) responsible for the impact of inflammation on pterygium development. The expression of HuR and matrix metallopeptidase-9 (MMP-9) in pterygium and normal conjunctiva was detected with immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The influence of interleukin-1ß (IL-1ß) on HuR expression and cellular distribution was determined with western blot and immunofluorescence. The pterygium fibroblast (PTF) migration was determined with scratch wound healing assay and Transwell migration assay. MMP-9 production was determined with qRT-PCR and gelatin zymography. The interaction between HuR and MMP-9 was investigated with RNP immunoprecipitation (IP) followed by RT-PCR and messenger RNA (mRNA) stability analysis. HuR and MMP-9 expression are elevated in pterygium, especially progressive pterygium compared with normal conjunctiva. IL-1ß could increase the expression and nucleus-cytoplasm shuttle of HuR in cultured PTFs. HuR mediated the stimulatory effect of IL-1ß on PTF migration and MMP-9 production. HuR bound to MMP-9 mRNA and in turn increased it stability. Our results suggest that posttranscriptional regulation of MMP-9 via stabilizing mRNA by HuR might contribute to the stimulatory effect of inflammatory factor IL-1ß on pterygium progression. These findings shed light on the pathogenesis of pterygium and provide a promising target for adjuvant treatment of pterygium.
Subject(s)
ELAV-Like Protein 1/genetics , Inflammation/genetics , Interleukin-1beta/genetics , Matrix Metalloproteinase 9/genetics , Pterygium/genetics , Aged , Cell Movement/genetics , Conjunctiva/growth & development , Conjunctiva/pathology , Disease Progression , Female , Fibroblasts/metabolism , Gene Expression Regulation/genetics , Humans , Inflammation/pathology , Male , Middle Aged , Protein Processing, Post-Translational/genetics , Pterygium/metabolism , Pterygium/pathology , RNA Stability/geneticsABSTRACT
The Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) complex comprises important pests and virus vectors in agricultural crops worldwide. In China, B. tabaci has spread to more than 20 provinces and caused severe losses of vegetables, fruits, and ornamental plants. However, B. tabaci has developed resistance to many insecticidal classes in Shandong Province, eastern China. In this study, we investigated the cryptic species, insecticide resistance and detoxifying enzymes of B. tabaci from six representative locations exhibiting severe damage in Shandong. At four of the six locations, B. tabaci Mediterranean (MED) comprised 100% of the samples collected. In a further two locations, species composition was predominantly (>94%) MED with B. tabaci Middle East-Asia Minor 1 (MEAM1), comprising a low proportion (<6%) of the samples collected. For all field populations, avermectin was the most effective insecticide against adult B. tabaci, pyriproxyfen had a significant effect on B. tabaci eggs and field populations were susceptible to pymetrozine. Six field populations of B. tabaci have developed low-to-moderate resistance to neonicotinoids. The detoxifying enzyme activity of carboxylesterase, glutathione S-transferase, and multifunctional oxidase were quantified. Multifunctional oxidase and glutathione S-transferase activity were positively correlated with insecticide resistance in several B. tabaci populations.
Subject(s)
Hemiptera/drug effects , Insecticides/pharmacology , Animals , China , Insecticide Resistance/drug effects , NeonicotinoidsABSTRACT
BACKGROUND: In our previous paper, we demonstrated that Connexin 43 (CX43) was highly expressed in bladder cancer (BC) tissues. But the molecular mechanism about microRNAs (miRNAs) regulation upstream of CX43 in BC has not been well elucidated and remains to be further studied. MicroRNA-139-5p (miR-139-5p) is a tumor suppressor in progression of multifarious cancers including BC. Nevertheless, the underlying mechanisms of CX43/miR-139-5p in tumorigenesis of BC are still not well illustrated. The specific objective of our study was to inquiry the effect of CX43/miR-139-5p on BC progression and its underlying mechanism. METHODS: The bioinformatics analysis softwares were applied to predict the miRNAs in the upstream of CX43. First, the expression levels of miR-139-5p in BC tissues (tumor) and paracancer tissues (normal) were investigated using the data from The Cancer Genome Atlas database. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of miR-139-5p in three human BC cell lines 5637, T24, ECV-304 and a human bladder epithelial immortalized cell line SV-HUC-1 (normal control). Then si-CX43, si-control, miR-139-5p mimic, and its negative control (NC) were transfected into BC cell line ECV-304. The relationship of miR-139-5p and CX43 was analyzed by dual-luciferase reporter assay. The qRT-PCR and Western blotting were used to test the mRNA and protein expression level of CX43. The proliferation of ECV-304 and T24 cells were examined by cell counting kit-8. The migration and invasion of ECV-304 cells were tested by transwell assay. To determine whether miR-139-5p would affect cell proliferation, migration and invasion by targeting CX43, we executed the rescue assay. The comparison between two groups was analyzed by Student's t test, and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test. RESULTS: The expression of miR-139-5p was remarkably down-regulated in BC tissues (tumor vs. normal, 2.286â±â0.017 vs. 3.211â±â0.034, tâ=â11.540, Pâ<â0.0001) and cell lines (Pâ<â0.01 in all BC cell lines). Besides, we also indicated that over-expression of miR-139-5p reduced the proliferation of ECV-304 (Pâ=â0.001) and T24 cells (Pâ=â0.005). Moreover, miR-139-5p over-expression weakened the invasion (Pâ=â0.001) and migration (Pâ=â0.001) of ECV-304 cells. Furthermore, the relative luciferase activity of CX43-wild type construct was distinctly lessened by up-regulation of miR-139-5p (miR-139-5p mimic NC vs. miR-139-5p mimic, 0.916â±â0.063 vs. 0.356â±â0.048, tâ=â7.085, Pâ=â0.002), nevertheless the activity of CX43-mutant type construct was untouched (miR-139-5p mimic NC vs. miR-139-5p mimic, 0.918â±â0.057 vs. 0.878â±â0.039, tâ=â0.577, Pâ=â0.595). Finally, the rescue assay revealed that CX43 deletion enhanced the depressor effect of miR-139-5p on ECV-304 cell proliferation (Pâ<â0.01), invasion (Pâ=â0.028), and migration (Pâ=â0.014). CONCLUSION: MiR-139-5p, as a tumor-suppressor, repressed cell proliferation, invasion, and migration in BC, which might be achieved by regulating CX43.
Subject(s)
Connexin 43/genetics , Genes, Tumor Suppressor/physiology , MicroRNAs/physiology , Urinary Bladder Neoplasms/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Humans , Neoplasm Invasiveness , Urinary Bladder Neoplasms/geneticsABSTRACT
Metaflumizone is a novel semicarbazone insecticide. It functions as a sodium channel blocker insecticide (SCBI) with excellent insecticidal activity on most economically important lepidopterous pests. This study assessed the resistance risk of Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae) to metaflumizone in the laboratory and the effects of metaflumizone selection on toxicities to other insecticides. Spodoptera exigua collected from a field population at Huizhou in 2012 were successively challenged by metaflumizone to evaluate the risk of resistance evolution. Twelve generations of selection increased resistance to metaflumizone by 3.4-fold and threshold trait analysis revealed that the realized heritability (h2) of this resistance was 0.086. When h2 was equal to 0.086 and 90% of individuals were killed at each generation, LC50 to metaflumizone increased by 10-fold after 15 generations. The selection by metaflumizone did not increase the resistance to indoxacarb, chlorantraniliprole, spinosad, methomyl, or endosulfan, suggesting a lack of cross-resistance. However, metaflumizone challenge upheld the recession of resistance to emamectin benzoate, chlorfluazuron, and tebufenozide. The block of resistance drops by metaflumizone exposure implied a possible cross-resistance between metaflumizone and these three insecticides. These results contribute to integrated resistance management of S. exigua.