ABSTRACT
Objective: To explore the impact of non-valvular atrial fibrillation (AF) on the global cognitive function and executive function of patients without dementia, and to observe the differences between different types of AF. Methods: This research is a prospective and cross-sectional study. Non-dementia patients admitted to the department of neurology in the third people's hospital of Chengdu from July 2018 to July 2019 were included. Patients with non-valvular AF were included in the AF group and those with sinus rhythm were included in the control group. General clinical data and compared global cognitive function (mini-mental state examination (MMSE) and montreal cognitive assessment (MOCA)) and executive function (shape trails test (STT) and stroop color and word test (SCWT)) data were obtained and compared between 2 groups, and between different AF type groups. Results: A total of 386 participants were included, including 203 in AF group (52.6%), age was 68 (63, 71) years old, 119 were male (58.6%) and 183 in control group, age was 68 (63, 71) years old, 101 were male (55.2%). MMSE(28 (27, 29)) and MOCA (25 (22, 26)) scores were lower in AF group than those in control group (P<0.05), while STT-A time (84 (64, 140) s), STT-B time (248 (184, 351) s), STT time difference((159 (106, 245) s), SCWT-A time (50 (50, 50) s), SCWT-B time (55 (46, 63) s), SCWT-C time (100 (86, 120) s) and SCWT time interference (46 (34, 65) s) were higher than those in control group (P<0.05). Moreover, there was no difference in above indexes between paroxysmal AF and non-paroxysmal AF. Conclusion: The global cognitive function and executive function of patients with non-valvular AF are both decreased, while there is no obvious difference of the global cognitive function and executive function between paroxysmal AF and non-paroxysmal AF patients.
Subject(s)
Atrial Fibrillation , Cognition Disorders , Humans , Male , Female , Atrial Fibrillation/diagnosis , Executive Function , Prospective Studies , Cross-Sectional Studies , Cognition Disorders/diagnosis , CognitionABSTRACT
Objective: To study the inhibitory effect of ezetimibe in an experimental model of human hepatoma cell line (HepaRG) infected with hepatitis B virus (HBV) positive human serum in vitro. Methods: Mature HepaRG cells were divided into a treatment group (received drugs) and a control group (did not receive drugs). In the ezetimibe prevention experiment, the cells in the treatment group was treated with drugs 2 h before infection and 24 h during infection. In the ezetimibe treatment experiment, the cells in the treatment group were treated with drugs for 6 ~ 10 days continuously after 24 hours of HBV infection. The expression of HBV DNA and intracellular cccDNA in the supernatant was detected by fluorescence quantitative PCR. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) content in the cell supernatant were detected by chemiluminescence. Analysis of variance was used to compare the differences between multiple groups. Pairwise comparisons among groups were followed by t- test with normal distribution. P < 0.05 was considered as statistically significant. Results: Ezetimibe prevention experiment showed that compared with control group, the treatment group was added with 20, 60, and 100 µmol/L ezetimibe before and during infection, and the HBV DNA content in the supernatant 2 days before was significantly reduced (P < 0.05) in the treatment group. Compared with the control group, the HBsAg expression level 2 days before was significantly reduced (P < 0.05) with the addition of 60 µmol/L ezetimibe in the treatment group. Compared with the control group, the expression level of intracellular cccDNA was significantly reduced (P < 0.05) after 10 days with the addition of 100µmol/L ezetimibe in the treatment group. Ezetimibe treatment experiment showed that cccDNA content in the cells were significantly lowered with the immediate addition of 60µmol/L ezetimibe 24 hours after infection for 10 days when compared to control group (P < 0.05). Conclusion: Ezetimibe, as a cytosolic inhibitor, has a certain inhibitory effect on hepatitis B virus infection in both prevention and treatment experiment.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , DNA, Viral , Ezetimibe , Hepatitis B/drug therapy , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus/genetics , Humans , Virus InternalizationABSTRACT
Objective: To establish and explore the inhibitory effect of cell entry inhibitor myrcludex-B on human liver cancer cell (HepaRG) infected with hepatitis B virus (HBV) positive serum in an in vitro infection model. Methods: HepaRG induced mature cells were divided into polyethylene glycol (PEG) infection group and non-PEG infection group, and then the two infection groups were divided into treatment group with myrcludex-B peptide fragment and control group without myrcludex-B peptide fragment, and the cells were infected with the serum of HBV DNA-positive patients. The expression of HBV DNA in supernatant was detected by fluorescence quantitative PCR, and the HBsAg and HBeAg content in supernatant were detected by chemical fluorescence. Measurement data of the non-normal distribution between the two groups was determined by rank-sum test, and normal distribution was determined by t-test. P < 0.05 was considered as statistically significant. Results: In the treatment and control group the virus titers of the PEG infection group and the non-PEG infection group were (103 877.00 ± 49 013.24) copies / ml and (5 050.09 ± 631.26) copies/ml, and (116 188.57 ± 50 957.19) copies/ml, (5 119.34 ± 1 102.43) copies/ml, respectively. Virus titers of both groups with PEG infection were significantly higher than non-PEG infection group, and the difference was statistically significant (P < 0.05). In the PEG infection group, the virus titers of the peptide-treated group and the non-peptide control group were (103 877.34 ± 49 013.24) copies /ml and (116 188.57 ± 50 957.19) copies/ml, respectively, and the virus titers of the peptide-treated group was decreased significantly (P < 0.05), and the difference was statistically significant. HBsAg content in the supernatant of this group was positive at 0, 1, 2 and 3 days, while the 0 day HBsAg supernatant treated with peptide fragment was significantly lower than that of the control group without peptide fragment. Conclusion: It is feasible to infect HepaRG cells with HBV positive serum supplemented with PEG in vitro, and the cell entry inhibitor myrcludex-B has a certain inhibitory effect on hepatitis B virus infection in this experimental model.
Subject(s)
Hepatitis B , DNA, Viral , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus , Humans , Lipopeptides , Virus InternalizationABSTRACT
AIM: To develop liver a computed tomography (CT) radiomics model to predict gastro-oesophageal variceal bleeding (GVB) secondary to hepatitis B-related cirrhosis. MATERIALS AND METHODS: Electronic medical records and image data of liver triple-phase contrast-enhanced CT examinations of 295 patients with hepatitis B-related cirrhosis were collected retrospectively from two hospitals. Two hundred and thirty-six and 59 patients were enrolled randomly into the training and validation cohorts, respectively; and 75 in the training cohort and 16 in the validation cohort endured GVB while the others did not during follow-up period. Radiomics features of the liver were extracted from the portal venous phase images, and clinical features came from medical records. The tree-based method and univariate feature selection were used to select useful features. The radiomics model, clinical model, and integration of radiomics and clinical models were built using the useful image features and/or clinical features. Predicting performance of three models was evaluated with the area under receiver-operating characteristic curve (AUC), accuracy, and F-1 score. RESULTS: Twenty-one useful radiomics features and/or three clinical features were selected to build prediction models that correlated with GVB. AUC of integration of radiomics and clinical models was larger than of clinical or radiomics models for the training cohort (0.83±0.09 versus 0.64±0.08 or 0.82±0.10) and the validation cohort (0.64 versus 0.61 or 0.61). Integration of radiomics and clinical models obtained good performance in predicting GVB for both the training and validation cohorts (accuracy: 0.76±0.07 and 0.73, and F-1 score: 0.77±0.09 and 0.72, respectively). CONCLUSION: Integration of the radiomics and clinical models may be a non-invasive method to predict GVB.
Subject(s)
Esophageal and Gastric Varices/etiology , Gastrointestinal Hemorrhage/etiology , Hepatitis B/complications , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Aged, 80 and over , Esophageal and Gastric Varices/diagnostic imaging , Female , Gastrointestinal Hemorrhage/diagnostic imaging , Hepatitis B/diagnostic imaging , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/etiology , Male , Middle Aged , Models, Statistical , Retrospective Studies , Tomography, X-Ray Computed/methods , Young AdultABSTRACT
Phenoloxidase (PO) plays a key role in melanin biosynthesis during insect development. Here, we isolated the 2310-bp full-length cDNA of PPO1 from Zeugodacus tau, a destructive horticultural pest. qRT-polymerase chain reaction showed that the ZtPPO1 transcripts were highly expressed during larval-prepupal transition and in the haemolymph. When the larvae were fed a 1.66% kojic acid (KA)-containing diet, the levels of the ZtPPO1 transcripts significantly increased by 2.79- and 3.39-fold in the whole larvae and cuticles, respectively, while the corresponding PO activity was significantly reduced; in addition, the larval and pupal durations were significantly prolonged; pupal weights were lowered; and abnormal phenotypes were observed. An in vitro inhibition experiment indicated that KA was an effective competitive inhibitor of PO in Z. tau. Additionally, the functional analysis showed that 20E could significantly up-regulate the expression of ZtPPO1, induce lower pupal weight, and advance pupation. Knockdown of the ZtPPO1 gene by RNAi significantly decreased mRNA levels after 24 h and led to low pupation rates and incomplete pupae with abnormal phenotypes during the larval-pupal interim period. These results proved that PO is important for the normal growth of Z. tau and that KA can disrupt the development of this pest insect.
Subject(s)
Catechol Oxidase/metabolism , Enzyme Precursors/metabolism , Pyrones/pharmacology , Tephritidae/enzymology , Animals , Catechol Oxidase/antagonists & inhibitors , Catechol Oxidase/genetics , Enzyme Precursors/antagonists & inhibitors , Enzyme Precursors/genetics , Gene Silencing , Tephritidae/drug effects , Tephritidae/genetics , Tephritidae/growth & developmentABSTRACT
Variations in ear size can be observed in livestock such as sheep; however, the genetic basis of variable ear size in sheep is still poorly understood. To investigate causative genes associated with ear size in sheep, a genome-wide association study was performed in 115 adult Duolang sheep with different-sized floppy ears using the Ovine Infinium HD BeadChip. We found 38 significant SNPs at the genome-wide or chromosome-wise 5% significance level after Bonferroni correction. The most significant association (P = 1.61 × 10-6 ) was found at SNP rs402740419, located in the DCC gene, which plays a critical role in ear development. Also, we observed two additional significant SNPs, rs407891215 in PTPRD and rs407769095 in SOX5, both of which are functionally associated with ear developmental processes. Our results are useful for future sheep breeding and provide insights into the genetic basis of ear size development in sheep and other livestock.
Subject(s)
Ear/anatomy & histology , Genes, DCC , Polymorphism, Single Nucleotide , Sheep, Domestic/genetics , Animals , Breeding , Female , Genetic Association Studies/veterinary , Genotype , MaleABSTRACT
Objective: To evaluate the safety and feasibility of treating de novo coronary lesions with paclitaxel-eluting balloon. Methods: This is a retrospective study, which enrolled 76 patients with 80 de novo coronary lesions treated with paclitaxel-eluting balloons(<30% residual stenosis and there was no blood flow limited dissection after pretreatment) from April 2015 to November 2016 in Guangdong general hospital. The data of basic characteristics,procedures,devices and follow-up information were retrieved and analyzed. The primary endpoint was the composite of cardiac death, recurrent myocardial infarction and target lesion revascularization. Results: (1)The age was (63.3±10.3) years. There were 68.4%(52/76) acute coronary syndrome patients, prevalence of type 2 diabetes was 36.8%(28/76), and 64.5%(49/76)patients with at least one high bleeding risk. (2)The lesion length was (17.4±7.6)mm, and the stenosis was (88.1±8.2)%.The reference vessel diameter≥2.75 mm accounted for 51.2% (41/80), and bifurcation stenosis accounted for 67.5%(54/80). (3)53.7%(43/80) lesions were pretreated with scoring balloon to optimize plaque modification. The paclitaxel-eluting balloon length and diameter were (22.3±5.5)mm and (2.74±0.52)mm.The residual stenosis was (12.3±10.3)%. Procedural success was 88.8%(71/80).Bail-out stenting rate was 5.0%(4/80). (4)The median follow-up duration was 12(6, 25) months. Primary endpoint occurred in 3 cases (3.9%), including 2 cardiac deaths(1 patient died of recurrent myocardial infarction, and 1 patient died of acute heart failure induced by severe mitral insufficiency), and one patient receivedtarget lesion revascularization. Conclusion: In case of no more than 30% residual stenosis and no blood flow limited dissection after lesion pretreatment,it is safe and feasible to treat de novo coronary lesionsusing paclitaxel-eluting balloon.
Subject(s)
Acute Coronary Syndrome/therapy , Angioplasty, Balloon, Coronary , Drug-Eluting Stents , Paclitaxel/administration & dosage , Tubulin Modulators/administration & dosage , Aged , Coronary Angiography , Diabetes Mellitus, Type 2 , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Stents , Time Factors , Treatment OutcomeABSTRACT
The morbidity of pancreatic ductal adenocarcinoma (PDAC) has been increasing over years, while the treatment efficacy and prognosis of PDAC remain far from satisfying. The newly-ermerged tumor immunotherapy has not only made lots of breakthroughs in various malignancies, but also brought an opportunity to the treatment of pancreatic cancer.PDAC immunotherapies, mainly including vaccine therapy, adoptive T cell thanfer therapy, checkpoint blockade therapy, have achieved a certain effect, however, the clinical outcomes have not been satisfactory. Therefore, the combination of immunotherapies based on different theoretical views is important and is likely to be the trend in the future. Carcinoma associated fibroblast (CAF) is the most common cell in pancreatic cancer stromal component. It will be helpful to develop more potential therapeutic targets by further exploring CAF and the mechanism of fibrosis mediated immunosuppression.
Subject(s)
Adenocarcinoma/therapy , Carcinoma, Pancreatic Ductal/therapy , Immunotherapy , Pancreatic Neoplasms/therapy , Humans , Pancreatic NeoplasmsABSTRACT
BACKGROUND: A growing body of evidence has shown that microRNA-29 (miR-29) plays a central role in the progression of fibrosis. However, the mechanisms underlying the role of miR-29 in keloid fibrogenesis remain unknown. AIM: To investigate the roles of miR-29 in dermal fibroblasts in the pathogenesis of keloids. METHODS: Primary fibroblasts from 9 patients with keloid and 6 healthy controls (HCs) were cultured and pretreated with transforming growth factor (TGF)-ß1. Next, fibroblasts were transfected with precursor miRNA and anti-miR-29a miRNA. TGF-ß1-associated miR-29 alterations were investigated by quantitative real-time PCR. Collagen I and collagen III protein levels were analysed by western blotting. RESULTS: miR-29a, miR-29b and miR-29c levels were significantly lower in keloid compared with healthy fibroblasts (P < 0.05), and in particular, miR-29a was especially markedly reduced (P < 0.001). Type I and type III collagen mRNA and protein levels were decreased in keloid fibroblasts transfected with pre-miR-29a (P < 0.05), whereas knockdown with anti-miR-29a increased type I and type III collagen mRNA and protein expression (P < 0.05) in the fibroblasts. Interestingly, pretreatment of fibroblasts with TGF-ß1 significantly decreased miR-29a (P < 0.05), whereas miR-29b and miR-29c were reduced to a lesser extent, which was not significant. CONCLUSIONS: These findings show that miR-29a exerts as a novel regulator in the fibrogenesis of keloid, suggesting that miR-29a might be a novel marker for keloid.
Subject(s)
Keloid/etiology , Keloid/genetics , MicroRNAs/genetics , Adolescent , Adult , Collagen Type I/metabolism , Collagen Type III/metabolism , Female , Fibroblasts/metabolism , Humans , Male , Transforming Growth Factor beta1/geneticsABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of pelvic arterial embolization (PAE) in women with intractable primary postpartum hemorrhage (PPH). METHODS: Clinical data of 36 cases were analyzed retrospectively in which women underwent PAE for intractable primary PPH in Peking Union Medical College Hospital between Jan 2006 and Jan 2015. The success rate of PAE were measured and possible predictive risk factors associated with treatment failure were analyzed. The complications secondary to PAE were also recorded. RESULTS: (1) The etiology of PPH. Among the 36 cases, 21 patients delivered viginally (Group VD) and 15 received cesarean section (Group CS). The most frequent cause of PPH was uterine atony (72%, 26/36). The less common causes were placental problems (28%, 10/36), genital tract trauma (6%, 2/36) and coagulation defects (3%, 1/36) in turn. Three patients (8%, 3/36) had combined causes. (2) Interventions before PAE. Uterotonic medications were used in all patients. 31 patients received carboprost methylate suppositorites, 27 received carbetocin and 31 received carboprost tromethamine. Besides, 20 patients received one or more surgical interventions before PAE. PAE was performed when these interventions failed. (3) Characteristics of PAE. Altogether 78 arteries were embolized in 36 cases. Embolization of bilateral uterine arteries was performed in 31 cases, right internal iliac artery and bilateral inferior epigastric arteries were embolized in one case. Right internal pudendal artery, bilateral uterine arteries and bilateral internal iliac arteries were embolized in one case. And bilateral uterine arteries, bilateral internal iliac arteries were embolized in one case. In the other 2 cases, bilateral internal iliac arteries were embolized. (4) Efficacy of PAE. The overall technical success rate of PAE was 100%(36/36), while the clinical success rate was 94%(34/36). All patients survived. (5) Complications of PAE. 15 patients were transferred to ICU after PAE for 1 to 7 days. Except self-limited fever, no puncture site hematoma, buttock necrosis or vessel rupture was observed. The effect on menstrual cycle and fertility were followed in 25 patients. 17 (68%, 17/25) reported resumption of normal menses and 8 (32%, 8/25) reported amenorrhea. Three pregnancies after PAE were observed. CONCLUSION: PAE is a safe and effective treatment for intractable primary PPH which can prevent hysterectomy and preserve fertility of patients.
Subject(s)
Embolization, Therapeutic/methods , Iliac Artery , Postpartum Hemorrhage/therapy , Female , Fertility , Humans , Hysterectomy , Menstrual Cycle , Pelvis , Pregnancy , Retrospective Studies , Risk Factors , Safety , Treatment Failure , Treatment Outcome , Uterine Artery , Uterine InertiaABSTRACT
OBJECTIVE: To assess the possible relationship between serum levels of 25[OH]D (25-hydroxyvitamin D) collected 24 hours after delivery and postpartum depression in a Chinese cohort sample. DESIGN: Cohort study. SETTING: One city hospital in Beijing, China. POPULATION: Women delivering a full-term, singleton, live-born infant at one city hospital in Beijing between August 2013 and November 2013. METHODS: Women were enrolled immediately postpartum. A blood sample was obtained 24-48 hours after childbirth to test serum levels of 25[OH]D. Participation consisted of a visit to an obstetric unit 3 months after delivery. MAIN OUTCOME MEASURE: At 3 months' postpartum, women were screened for depression using the Edinburgh Postnatal Depression Scale (EPDS). The primary outcome measure was a prespecified EPDS score of ≥12. RESULTS: During the study period, 323 women were admitted. In all, 248 agreed to enrol and 213 completed 3 months' follow-up (21 were lost to follow-up and 14 withdrew). Of the 213 women who were included, 26 (12.2%) were considered to meet criteria for postpartum depression. Serum 25[OH]D levels in women with no postpartum depression were significantly higher than those in women with postpartum depression (P < 0.0001). Based on the receiver operating characteristic curve, the optimal cutoff value for serum 25[OH]D level as an indicator for screening for postpartum depression was estimated to be 10.2 ng/ml, with an area under the curve of 0.801 (95%CI 0.704-0.896). In multivariate analysis, there was an increased risk of postpartum depression associated with 25[OH]D levels ≤10.2 ng/ml (OR 7.17, 95%CI 3.81-12.94; P < 0.0001) after adjusting for possible confounders. CONCLUSION: Our study demonstrated that lower serum 25[OH]D levels were associated with postpartum depression. This association was independent of other possible variables.
Subject(s)
Depression, Postpartum/etiology , Vitamin D Deficiency/complications , Vitamin D/analogs & derivatives , Adult , Beijing/epidemiology , China/epidemiology , Cohort Studies , Delivery, Obstetric , Depression, Postpartum/blood , Female , Follow-Up Studies , Humans , Infant, Newborn , Pregnancy , Risk Assessment , Vitamin D/blood , Vitamin D/therapeutic use , Vitamin D Deficiency/bloodABSTRACT
Hidradenitis suppurativa (HS) is a chronic disease of follicular occlusion. It involves the axilla, groin, perianal and perineal regions, and is characterized by recurrent draining sinuses, skin abscesses and disfiguring scars. Loss-of-function mutations in the genes encoding γ-secretase have been identified as a cause of HS. We collected skin samples from three patients with HS from a Chinese family carrying a NCSTN mutation (c.1258C>T (p.Q420X)) and three unrelated healthy controls (HCs). Expression level of nicastrin in skin tissue and cultured keratinocytes and fibroblasts of patients and HCs was determined by real-time quantitative PCR and western blotting. We found that the mRNA and protein levels of nicastrin were significantly reduced in the whole skin, epidermis, dermis, and cultured keratinocytes and fibroblasts compared with HCs. Therefore, we conclude that haploinsufficiency of the NCSTN gene caused by the nonsense mutation c.1258C>T (p.Q420X) contributes to the occurrence of HS in this family.
Subject(s)
Amyloid Precursor Protein Secretases/genetics , Codon, Nonsense , Haploinsufficiency/genetics , Hidradenitis Suppurativa/genetics , Membrane Glycoproteins/genetics , Asian People/genetics , Case-Control Studies , Female , Humans , Male , Middle AgedABSTRACT
The diversity of microbiota in waste waters has not been thoroughly examined, despite the potential impact of microbes on effluent quality. Wastewater microbial communities harbor pathogenic bacteria, viruses, and parasites. To study microbial communities in domestic sewage outfalls, 454 pyrosequencing technology was used to investigate the composition of microbial communities associated with municipal wastewater during different seasons sampled over the course of one year. A total of 195,103 16S rRNA gene sequences were obtained from 20 samples. The R software was used to calculate the number of indices describing the alpha diversity associated with each bacterial assemblage. In this study, the a-diversity index (H', D, J), in which higher numbers represent more diversity, was found to change with seasonal cycle. The diversity of bacterial assemblages was high in all samples, indicating that species diversity was also very high. The taxonomic composition of the assemblages varied considerably among samples, with some dominated by Proteobacteria, while others were dominated by Bacteroidetes or Firmicutes. In 2 samples, the relative prevalence of Proteobacteria exceeded 90%. α-Proteobacteria, b-proteobacteria, and g-proteobacteria represented 90% or more of all Proteobacteria. The present characterization of wastewater from five sewage outfalls indicated the presence of some pathogenic bacteria. The g-Proteobacteria in sewage wastefalls identified in this study included Enterobacteriaceae, Vibrionaceae, Pseudomonadaceae, Salmonella, Yersinia, Vibrio, and Pseudomonas aeruginosa.
Subject(s)
Environmental Microbiology , Microbiota , Sewage/microbiology , Bacteria/classification , Bacteria/genetics , Biodiversity , China , Cluster Analysis , Geography , Metagenome , Phylogeny , RNA, Ribosomal, 16SABSTRACT
Patients with systemic lupus erythematosus (SLE) display reduced numbers and functions of invariant natural killer T (iNK T) cells, which are restored upon treatment with corticosteroids and rituximab. It is unclear whether the iNK T cell insufficiency is a consequence of disease or is a primary abnormality that precedes the onset of disease. To address this, we analysed iNK T cell function at different stages of disease development using the genetically lupus-susceptible NZB × NZW F1 (BWF(1)) model. We found that iNK T cell in-vivo cytokine responses to an iNK T cell ligand α-galactosylceramide (α-GalCer) were lower in BWF(1) mice than in non-autoimmune BALB/c and major histocompatibility complex (MHC)-matched NZB × N/B10.PL F1 mice, although iNK T cell numbers in the periphery were unchanged in BWF(1) mice compared to control mice. Such iNK T cell hyporesponsiveness in BWF(1) mice was detected at a young age long before the animals exhibited any sign of autoimmunity. In-vivo activation of iNK T cells is known to transactivate other immune cells. Such transactivated T and B cell activation markers and/or cytokine responses were also lower in BWF(1) mice than in BALB/c controls. Finally, we show that iNK T cell responses were markedly deficient in the NZB parent but not in NZW parent of BWF(1) mice, suggesting that BWF(1) might inherit the iNK T cell defect from NZB mice. Thus, iNK T cells are functionally insufficient in lupus-prone BWF(1) mice. Such iNK T cell insufficiency precedes the onset of disease and may play a pathogenic role during early stages of disease development in SLE.
Subject(s)
Lupus Erythematosus, Systemic/immunology , Natural Killer T-Cells/immunology , Prodromal Symptoms , Animals , Antigens, CD1/immunology , Cells, Cultured/immunology , Cells, Cultured/metabolism , Crosses, Genetic , Disease Models, Animal , Female , Galactosylceramides/immunology , Humans , Lupus Erythematosus, Systemic/etiology , Lymphocyte Activation , Lymphocyte Cooperation , Lymphocyte Count , Lymphokines/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred NZB , Natural Killer T-Cells/metabolismABSTRACT
Objective: To explore the mechanism of early pancreatic exocrine function changes in severely scalded rats. Methods: The experimental research methods was used. Eighty male Sprague-Dawley rats aged 7-8 weeks were divided into simple sham injury group (n=8), sham injury+cholecystokinin octapeptide (CCK8) group (n=8), severe scald+CCK8 group (n=32), and extremely severe scald+CCK8 group (n=32) by the random number table, which were treated accordingly. Immediately after injury of rats in the 2 sham injury groups and 1, 2, 3, and 7 days after injury of rats in the 2 scald groups, the improved methods including pancreatic duct puncture and catheterization were used to dynamically collect the pancreatic-bile juice (PBJ) of rats. The PBJ secretory volume within 1 h was recorded, and the content of pancreatic lipase, α-amylase, and trypsin in PBJ was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 8. The femoral venous blood was collected, and the concentrations of pancreatic lipase and α-amylase in serum were detected by standard colorimetry to reflect their activity (n=8). The pancreatic tissue was extracted, and the levels of interleukin-1ß (IL-1ß) and IL-6 in pancreatic tissue were detected by ELISA (n=8), the expression of hypoxia-inducible factor 1α (HIF-1α) in pancreatic tissue was detected by immunofluorescence method, and the histopathological changes in pancreatic tissue were observed by hematoxylin-eosin staining, the severity of pancreatic tissue injury in the 2 scald groups was evaluated by modified Schmidt method (n=6), and the ultrastructure of acinar cells in pancreatic tissue was observed by transmission electron microscopy. Data were statistically analyzed with analysis of variance for factorial design, Tukey test, independent sample t test, and least significant difference test. Results: Compared with the PBJ secretory volume (0.740±0.030) mL in the pancreatic tissue of rats in simple sham injury group within 1 h immediately after injury, the (0.823±0.033) mL in sham injury+CCK8 group was significantly increased (t=4.92, P<0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the PBJ secretory volume of rats within 1 h in severe scald+CCK8 group ((0.681±0.024), (0.608±0.056), (0.525±0.025), and (0.720±0.044) mL) and extremely severe scald+CCK8 group ((0.540±0.025), (0.406±0.021), (0.475±0.036), and (0.690±0.018) mL) was significantly decreased on 1, 2, 3, and 7 days after injury (P<0.05). Compared with that in severe scald+CCK8 group, the PBJ secretory volume of rats within 1 h in extremely severe scald+CCK8 group was significantly decreased on 1 and 2 days after injury (P<0.05). Compared with that of rats in simple sham injury group immediately after injury, the content of pancreatic lipase, α-amylase, and trypsin in PBJ of rats in sham injury+CCK8 group immediately after injury was significantly increased (with t values of 4.56, 3.30, and 4.99, respectively, P<0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the content of pancreatic lipase and α-amylase in PBJ of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group was significantly decreased on 1, 2, 3, and 7 days after injury (P<0.05), the trypsin content in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 2 days after injury (P<0.05). Compared with that in severe scald+CCK8 group, the content of pancreatic lipase in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 1, 2, and 3 days after injury (P<0.05), and the content of α-amylase and trypsin in PBJ was significantly decreased on 1 and 2 days after injury (P<0.05). There were no statistically significant differences in the activities of pancreatic lipase and α-amylase in serum of rats among the 4 groups at various time points after injury (P>0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the levels of IL-1ß in pancreatic tissue of rats in severe scald+CCK8 group on 1, 2, and 3 days after injury and in extremely severe scald+CCK8 group on 1, 2, 3, and 7 days after injury were significantly increased (P<0.05), and the levels of IL-6 in pancreatic tissue of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group were significantly increased on 1, 2, 3, and 7 days after injury (P<0.05). Compared with that in severe scald+CCK8 group, the IL-1ß level in pancreatic tissue of rats in extremely severe scald+CCK8 group was significantly increased on 2 and 3 days after injury (P<0.05), and IL-6 level in pancreatic tissue was significantly increased on 2 days after injury (P<0.05). The expression levels of HIF-1α in pancreatic tissue of rats in simple sham injury group and sham injury+CCK8 group immediately after injury were lower; and compared with that in sham injury+CCK8 group immediately after injury, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups increased to a certain extent at different time points after injury, and the expression position was transited from the edge of the pancreatic tissue to the whole pancreas, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups tended to be normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the proportion of acinar cell cytoplasm in pancreatic tissue of rats in sham injury+CCK8 group was increased; and with the increase of time after injury, edema, hemorrhage, necrosis, and inflammatory infiltration appeared in pancreatic tissue of rats in the 2 scald groups. Compared with that in severe scald+CCK8 group, the scores of edema, inflammatory cell infiltration, bleeding, and necrosis in pancreatic tissue of rats in extremely severe scald+CCK8 group were increased to varying degrees at various time points after injury, and the scores of pancreatic tissue of rats in the 2 scald groups basically recovered to normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the number of enzyme granules in acinar cells of pancreatic tissue of rats in sham injury+CCK8 group was increased, and with the increase of time after injury, the enzyme granules in acinar cells of rats in the 2 scald groups were gradually reduced basically. Conclusions: The exocrine functions of pancreas, such as synthesis and secretion of pancreatic enzymes, are decreased in the early stage in severely scalded rats. And the greater the scalded area, the more significant the decline of pancreatic exocrine function. This change may be related to hypoxic injury and inflammation in pancreatic tissue after severe scald.
Subject(s)
Burns , Interleukin-6 , Rats , Male , Animals , Rats, Sprague-Dawley , Trypsin , Edema , Necrosis , Lipase , alpha-AmylasesABSTRACT
Coilia mystus is the most important harvested fish species in China; it inhabits quite different water environments during the different life history stages. Populations of C. mystus have dropped sharply due to overharvesting and water pollution. We developed eight microsatellite loci in C. mystus for conservation genetics studies. These new markers were tested in 20 individuals from the Min River in ChangLe. The number of alleles ranged from 3 to 8, the expected heterozygosity from 0.621 to 0.853 and the observed heterozygosity from 0.473-0.800. Only two loci deviated significantly from Hardy-Weinberg expectations due to heterozygote deficiency. These primers may provide a tool for understanding demography and population structure of this economically important and threatened species.
Subject(s)
Fishes/genetics , Microsatellite Repeats/genetics , Polymerase Chain Reaction/methods , Animals , Random Amplified Polymorphic DNA TechniqueABSTRACT
Recently, the incidence of infectious diseases continues to decline in many developed countries; however, the incidence of autoimmune diseases and allergic asthma appears a tendency towards a rise over years. "Hygiene hypothesis" provides new insights into the treatment of autoimmune disorders and allergic diseases based on parasitic infections. Increasing evidence shows that parasitic infections may effectively inhibit the development of diabetes, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis and allergic asthma. There are complex mechanisms underlying the relationship between parasitic infections and "hygiene hypothesis", among which regulatory T (Treg) cells and Th17 cells are becoming a hot topic of research. This paper reviews the progresses in the research on the relationship between parasitic infections and "hygiene hypothesis", and summarizes the roles of Treg cells and Th17 cells in the interplay between parasitic infections and "hygiene hypothesis".
Subject(s)
Hygiene Hypothesis , Parasitic Diseases , Autoimmune Diseases/immunology , Autoimmune Diseases/parasitology , Humans , Hygiene , Parasitic Diseases/immunology , Th17 Cells/immunologyABSTRACT
OBJECTIVE: Plenty of plant extracts have been used for treating hair loss. This study aims to investigate the effects of liposterolic extracts of Serenoa repens (LSESr) on hair cell growth and regeneration of hair, and clarify the associated mechanisms. MATERIALS AND METHODS: Human keratinocyte cells (HACAT) were cultured, incubated with dihydrotestosterone (DHT) and treated with LSESr. Cell viability was examined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H- tetrazolium bromide (MTT) assay. Hair loss C57BL/6 mouse model was established by inducing with DHT. Hair growth, density, and thickness were evaluated. Back skin samples were collected and stained with hematoxylin and eosin (HE) assay. B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein X (Bax), cleaved caspase 3 and transforming growth factor ß2 (TGF-ß2) were examined using Western blot assay. RESULTS: LSESr treatment significantly increased HACAT cell viabilities compared to DHT-only treated cells (p<0.05). LSESr treatment post injection of DHT significantly converted skin color from pink to gray and increased hair density, weight and thickness compared to DHT-only treated mice (p<0.05). LSESr treatment significantly triggered follicle growth and decreased inflammatory response. LSESr treatment significantly decreased TGF-ß2 and cleaved caspase 3 expression of hair loss mouse models compared to that of DHT treated mice (p<0.05). LSESr treatment significantly enhanced Bcl-2 expression and reduced Bax expression compared to that of DHT treated mice (p<0.05). Meanwhile, effects of LSESr were substantial even achieving to the potential of finasteride. CONCLUSIONS: LSESr promoted the hair regeneration and repair of hair loss mouse models by activating TGF-ß signaling and mitochondrial signaling pathway.
Subject(s)
Alopecia/drug therapy , Hair/drug effects , Mitochondria/drug effects , Plant Extracts/pharmacology , Regeneration/drug effects , Signal Transduction/drug effects , Transforming Growth Factor beta/physiology , Animals , Cells, Cultured , Disease Models, Animal , Hair/physiology , Humans , Keratinocytes/drug effects , Mice , Mice, Inbred C57BL , Mitochondria/physiology , Plant Extracts/therapeutic use , SerenoaABSTRACT
A high frequency (greater than or equal to 65%) of thymomas induced by mink cell focus-forming virus 69L1 in AKR/J mice contain proviral integrations which are clustered 0.7-kilobase upstream of the c-myc oncogene predominantly in the opposite transcriptional orientation. Blot hybridization experiments showed that on the average there was only a twofold elevation of steady-state c-myc RNA in the thymomas as compared with levels in normal AKR/J thymocytes. Such an increase would not appear to be sufficient as a mechanism of oncogene activation in this system. In contrast, S1 nuclease analysis of transcripts initiated from the two known c-myc promoters indicated a strong shift in promoter usage in virtually all thymomas tested. In normal thymus the ratio of transcripts initiated from the proximal promoter P1 to the distal promoter P2 was 0.2 to 0.3. In contrast, most of the thymomas tested (18 of 23) showed an average P1/P2 ratio of 1.2 regardless of whether or not proviral integrations could be detected within a 21-kilobase EcoRI fragment containing the three c-myc exons. We conclude that alterations in P1/P2 ratios are good indicators of c-myc deregulation in thymic lymphomas.
Subject(s)
Leukemia Virus, Murine/pathogenicity , Lymphoma/microbiology , Mink Cell Focus-Inducing Viruses/pathogenicity , Oncogenes , Thymoma/microbiology , Thymus Neoplasms/microbiology , Animals , Genes, Viral , Lymphoma/genetics , Mice , Mice, Inbred AKR , Nucleic Acid Hybridization , Thymoma/genetics , Thymus Neoplasms/geneticsABSTRACT
A block to elongation of transcription has been shown to occur within the first exon of the human and murine c-myc genes. The extent of this block was found to vary with the physiological state of cells, indicating that modulation of the transcriptional block can serve to control the expression of this gene. To determine which sequences are required in cis for the transcriptional block, we generated a series of constructs containing various portions of murine c-myc 5'-flanking and exon 1 sequences. We established populations of HeLa and CV-1 cells stably transfected with these constructs. The transcription start sites were determined by S1 nuclease mapping analysis, and the extent of transcriptional block was measured by nuclear run-on transcription assays. Our results demonstrate that at least two cis-acting elements are necessary for the transcriptional block. A 3' element was found to be located in the region where transcription stopped and showed features reminiscent of some termination sites found in procaryotes. A 5' element was positioned between the P1 and P2 (C. Asselin, A. Nepveu, and K. B. Marcu, Oncogene 4:549-558, 1989). Removal of the more 3' binding site abolished the transcriptional block.