Miracle-dz/UniFAR-FTUs huggingface dataset:
Synergistic induction of IL-10 by hypertonic saline solution and lipopolysaccharides in murine peritoneal macrophages.

BACKGROUND Liver injury after ischemia/reperfusion is an important cause of morbidity in surgical patients. We have shown that the preconditioning of animals that were subjected to liver ischemia/reperfusion with hypertonic saline solution (HTS) prevented injury by inhibiting Kupffer cell tumor necrosis factor (TNF) production. We postulated that the induction of anti-inflammatory interleukin-10 (IL-10) by HTS might contribute to protection. METHODS Murine thioglycolate--elicited peritoneal exudative macrophages (PEMs) were used to model the effects of HTS on IL-10 release from Kupffer cells. Cells were preconditioned with 500 mOsm HTS (or isotonic saline medium) for 2 hours and then stimulated with lipopolysaccharide (LPS; 1 microg/mL) or vehicle for 4 hours under isotonic conditions. TNF-alpha and IL-10 were measured in the culture supernatant by enzyme-linked immunosorbent assay; TNF, IL-10, and SOCS-3 messenger RNA expression were assessed by Northern blot. NF-kappa B activation was examined by electrophoretic mobility shift assay and Western blot for I kappa B degradation. RESULTS In the absence of LPS, isotonic medium--and HTS-pretreated PEMs produced little IL-10 (24.9 +/- 66.0 and 0 pg/mL, respectively); however, stimulation of PEMs with LPS increased IL-10 (134.9 +/- 72.2 pg/mL). Preconditioning with HTS significantly augmented LPS-induced IL-10 production, resulting in a 2-fold increase in IL-10 compared with the isotonic solution LPS group (270.7 +/- 106.8 pg/mL; P <.01). HTS alone increased IL-10 mRNA levels and markedly augmented levels induced by LPS alone. To determine whether IL-10 accounted for HTS-induced TNF inhibition, cells from IL-10 knockout animals were studied. A lack of IL-10 did not reverse the inhibitory effect of HTS on LPS-induced TNF. NF-kappa B activation was the same in HTS-and isotonic solution--pretreated groups after LPS. CONCLUSIONS HTS augments IL-10 induction by LPS at the gene level. Although TNF is reduced, it is not causally related to increased IL-10 or altered NF-kappa B signaling. HTS might exert its beneficial effects by independently modulating pro- and anti-inflammatory molecules, accounting for the potent immunomodulation exerted by HTS in vivo.
Combination Efficacy of Astragalus membranaceus and Curcuma wenyujin at Different Stages of Tumor Progression in an Imageable Orthotopic Nude Mouse Model of Metastatic Human Ovarian Cancer Expressing Red Fluorescent Protein.

BACKGROUND/AIM The present study determined the efficacy of extracts of Astragalus membranaceus (AM) and Curcuma wenyujin (CW), a traditional Chinese medicine herbal mixture, at different tumor stages of an orthotopic nude mouse model of human ovarian cancer expressing red fluorescent protein. MATERIALS AND METHODS The tumor-bearing mice were treated with cisplatinum (CDDP), AM, CW, or a combination of AM and CW in each of three tumor stages, using the same regimen. Group 1 received saline as negative control. Group 2 received CDDP i.p. as positive control with a dose of 2 mg/kg, every three days. Group 3 received AM daily via oral gavage, at a dose of 9120 mg/kg. Group 4 received CW daily via oral gavage, at a dose of 4560 mg/kg. Groups 5, 6 and 7 received combinations of AM and CW daily via oral gavage at low (AM, 2280 mg/kg; CW, 1140 mg/kg), medium (AM, 4560 mg/kg; CW 2280 mg/kg), and high (AM, 9120 mg/kg; CW, 4560 mg/kg) doses. The expression of angiogenesis- and apoptosis-related genes in the tumors were analyzed by immunohistochemistry for matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF) fibroblast growth factor 2 (FGF-2), B-cell lymphoma 2 (Bcl-2) and cyclooxygenase 2 (Cox-2), and by polymerase chain reaction for MMP-2, FGF-2 and Bcl-2. RESULTS CDDP, AM, and its combination with CW-induced significant growth inhibition of Stage I tumors. Strong efficacy of the combination of AM and CW at high dose was observed. Monotherapy with CDDP, AM, CW, and the combination treatments did not significantly inhibit Stage II and III tumors. The expression of MMP-2, VEGF, FGF-2, and Cox-2 was significantly reduced in Stage I tumors treated with AM, CW, and their combination, suggesting a possible role of these angiogenesis- and apoptosis-related genes in the observed efficacy of the agents tested. CONCLUSION This study is the first report on the efficacy of anticancer agents at different stages of ovarian cancer in an orthotopic mouse model. As the tumor progressed, it became treatment-resistant, similar to the clinical situation, further demonstrating the utility of the model and the need for agents acrtive in advanced-stage ovarian cancer.
Streptococcal Protein H Forms Soluble Complement-activating Complexes with IgG, but Inhibits Complement Activation by IgG-coated Targets*

Protein H, a surface protein ofStreptococcus pyogenes interacting with the constant Fc region of IgG, is known to be released from the streptococcal surface by a cysteine proteinase produced by the bacteria. Poststreptococcal glomerulonephritis and rheumatic fever are conditions in which immune complexes and autoimmune mechanisms have been suggested to play pathogenetic roles. The present study demonstrates that addition of protein H to human serum produces complement activation with dose-dependent cleavage of C3. The activation was IgG-dependent and the result of complexes formed between IgG and protein H. These complexes were size heterogeneous with molecular masses of 400 kDa to 1.4 MDa. Using complement-depleted serum reconstituted with complement proteins, the activation by protein H was found to be dependent of the classical, but independent of the alternative pathway of complement. In contrast to results of experiments based on soluble protein H·IgG complexes, complement activation was inhibited by protein H when IgG was immobilized on a surface. The interaction between C1q and immunoglobulins represents the first step in the activation of the classical pathway, and protein H efficiently inhibited the binding of C1q to IgG immobilized on polyacrylamide beads. Protein H reduced C3 deposition on the IgG-coated beads and inhibited immune hemolysis of IgG-sensitized erythrocytes. Finally, significantly less C3 was deposited on the surface of protein H-expressing wild-type streptococci than on the surface of isogenic mutant bacteria devoid of protein H. The results demonstrate that protein H·IgG complexes released from the streptococcal surface can produce complement breakdown at the sites of infection, whereas complement activation on bacterial surfaces is inhibited. This should have important implications for host-parasite relationships. In addition, soluble protein H·IgG complexes might contribute to immunological complications of streptococcal infections.
The microsatellites and minisatellites in the genome of Fenneropenaeus chinensis

Through two-time sequencing randomly in Fenneropenaeus chinensis, 2,597,000 bp cumulative length random genomic sequences about occupying 1.23‰ of the entire genome are obtained, in which the length of the first time sequencing is 8,84,000 bp, by cutting the genome DNA with Sau3AI enzyme, and the second is 1,713,000 bp by breaking the genome DNA with the physical method, ultrasonic. Using tandem repeat finder (TRF) soft to analyze the sequences, 4588 tandem repeats are found, in which the number of microsatellites (1–6 bp) is 3888, and 700 for minisatellites ( ≥ 7 bp). The cumulative length of repeats is 3,05,555 bp, accounting for 11.72% of total cumulative sequence length, in which the cumulative length of microsatellites is 2,32,979 bp, accounting for 8.97% of total sequence length, and greater than those of other organisms, such as human and mosquito, etc. The dinucleotide repeat type is dominant in which the dominant repeat class is AT. The second abundant repeat type is trinucleotide, of which the dominant repeat class is AAT. Interestingly, of all of repeat types, the repeat numbers and repeat classes of primer number repeat types, such as pentanucleotide, heptanucleotide, elevennucleotide, etc. are less than those of repeat types beside them. The phenomena may involve the genesis and the evolution of microsatellites and minisatellites.
Sulfation of the Bikunin Chondroitin Sulfate Chain Determines Heavy Chain·Hyaluronan Complex Formation*

Background: The chondroitin sulfate (CS) chain of bikunin has both sulfated and unsulfated regions. Results: Bikunin CS contains heterogeneous sulfation in the chain and linkage region with CS-D containing chains facilitating HA·HC formation. Conclusion: Sulfation of the bikunin CS chain regulates HC transfer to HA. Significance: Bikunin CS chain sulfation may modulate HA tissue stabilization in disease. Inter-α-trypsin inhibitor (IαI) is a complex comprising two heavy chains (HCs) that are covalently bound by an ester bond to chondroitin sulfate (CS), which itself is attached to Ser-10 of bikunin. IαI is essential for the trans-esterification of HCs onto hyaluronan (HA). This process is important for the stabilization of HA-rich matrices during ovulation and some inflammatory processes. Bikunin has been isolated previously by anion exchange chromatography with a salt gradient up to 0.5 m NaCl and found to contain unsulfated and 4-sulfated CS disaccharides. In this study, bikunin-containing fractions in plasma and urine were separated by anion exchange chromatography with a salt gradient of 0.1–1.0 m NaCl, and fractions were analyzed for their reactivity with the 4-sulfated CS linkage region antibody (2B6). The fractions that reacted with the 2B6 antibody (0.5–0.8 m NaCl) were found to predominantly contain sulfated CS disaccharides, including disulfated disaccharides, whereas the fractions that did not react with this antibody (0.1–0.5 m NaCl) contained unsulfated and 4-sulfated CS disaccharides. IαI in the 0.5–0.8 m NaCl plasma fraction was able to promote the trans-esterification of HCs to HA in the presence of TSG-6, whereas the 0.1–0.5 m NaCl fraction had a much reduced ability to transfer HC proteins to HA, suggesting that the CS containing 4-sulfated linkage region structures and disulfated disaccharides are involved in the HC transfer. Furthermore, these data highlight that the structure of the CS attached to bikunin is important for the transfer of HC onto HA and emphasize a specific role of CS chain sulfation.
Long-term outcome of gamma knife radiosurgery for metastatic brain tumors originating from lung cancer

Background: Gamma knife radiosurgery (GKRS) has emerged as an important treatment option for metastasis brain tumors (MBTs). However, the long-term outcome of GKRS on MBTs originating from lung carcinoma is not well understood. The treatment of MBTs derived from lung cancer with GKRS at our institution is reviewed. Methods: We performed a retrospective review (2000-2013) of 173 patients with MBTs from lung cancer who received GKRS. Out of 173 patients, 38 patients had recurrent tumors after microsurgical resection and whole brain radiotherapy (WBT). Results: GKRS in MBTs metastasized from lung carcinoma showed significant variations in tumor growth control (decreased in 79 [45.7%] patients, arrested growth in 54 [31.2%] patients, and increased tumor size in 40 [23.1%] patients). The median survival in the study population was 14 months. Overall survival after 3 years was 25%, whereas progression-free survival after 3 years was 45%. The predictive factors for improving survival in the patients with MBTs were recursive partitioning analysis (RPA) class I (P = 0.005), absence of hydrocephalus (P = 0.001), Karnofsky performance scale (KPS) >70 (P = 0.007), age ≤65 (P = 0.041), tumor size ≤3 cm (P = 0.023), controlled primary tumor (P = 0.049), and single number of MBTS (P = 0.044). Conclusion: Long-term follow-up revealed that GKRS offers a high rate of tumor control and good overall survival period in both new and recurrent patients with MBTs originating from lung carcinoma. Thus, GKRS is an effective treatment option for new patients with MBTs from lung cancer, as well as an adjuvant therapy in patients with recurrent MBTs derived from lung cancer.
Bandwidth Improvement Methods of Transmitarray Antennas

Despite several advantages of planar transmitarray antennas compared to conventional lens antennas, they have a narrow bandwidth. The goal of this paper is to improve the bandwidth of transmitarray antennas through the control of the transmission phase range and the optimization of the phase distribution on the transmitarray aperture. To validate the proposed approaches, two quad-layer transmitarrays using double square loop elements have been designed, fabricated, and tested at Ku-band. The transmission phase distribution is optimized for both antennas, while they differ only in the transmission phase ranges. It is shown that the transmitarray antennas designed using the proposed techniques achieve 1-dB gain bandwidth of 9.8% and 11.7%, respectively. The measured gains at 13.5 GHz are 30.22 and 29.95 dB, respectively, leading to aperture efficiencies of 50% and 47%, respectively.
Phosphate starvation enhances expression of the immunodominant 38-kilodalton protein antigen of Mycobacterium tuberculosis: demonstration by immunogold electron microscopy

In this work, we grew Mycobacterium tuberculosis in an enriched Proskauer-Beck-Youmans culture medium in the presence and in the absence of phosphate salts. Immunoblot analysis of sonic extracts showed overexpression of the 38-kDa protein antigen by bacilli grown in the medium without phosphate. These observations were confirmed by immunogold electron microscopy, which showed that the number of gold particles was significantly higher in bacilli grown in medium without phosphate than in bacilli grown in medium with phosphate. The 38-kDa protein was located mainly in the wall and on the cell surface.
Long-Term Azithromycin for Bronchiolitis Obliterans Syndrome After Lung Transplantation

Background. Bronchiolitis obliterans syndrome (BOS) is a major cause of morbidity and mortality after lung transplantation (LTx). Macrolides are a promising treatment option for BOS. The objective of this study was to determine long-term results of azithromycin treatment in patients with BOS. Variables to predict treatment response were evaluated. Methods. An observational study in a single center was performed. Eighty-one adult LTx-recipients (single, double, combined, and re-do) with at least BOS stage 0p (mean forced expired volume in 1 second [FEV1] 55±19%) were included. For treatment, 250 mg of oral azithromycin was administered three times per week. Results. Twenty-four of 81 (30%) patients showed improvement in FEV1 after 6 months, 22/24 already after 3 months of treatment. By univariate analysis, responders at 6 months had higher pretreatment bronchoalveolar lavage (BAL) neutrophils (51±29 vs. 21±24%). A cutoff value of <20% in pretreatment BAL had a negative predictive value of 0.91 for treatment response. Thirty-three patients (40%) showed disease progression during follow-up (491±165 days). Cox regression analysis identified a rapid pretreatment decline in FEV1 and comedication of an mammalian target of rapamycin inhibitor as positive predictors and proton pump inhibitor comedication and a treatment response at 3 months as negative predictors for disease progression (FEV1 <90% baseline). Conclusions. Azithromycin can improve airflow limitation in a significant proportion of patients with even long-standing BOS. The majority of responders were identified after 3 months of treatment. Results indicate the predictive value of BAL neutrophilia for treatment response and pretreatment course of FEV1 as a variable for disease progression. Beneficial effects on gastroesophageal reflux disease may be a mechanism of action.
Streptococcus pneumoniae Serotype 11D Has a Bispecific Glycosyltransferase and Expresses Two Different Capsular Polysaccharide Repeating Units*

Background: Streptococcus pneumoniae serotype 11D capsular polysaccharide (CPS) structure is unknown. Results: Serotype 11D PS contains two different repeating units; one has αGlcNAc, and the other contains αGlc. Conclusion: The 11D CPS is due to the bispecific glycosyltransferase WcrL. Based on codon 112, WcrL can transfer αGlc, αGlcNAc, or both. Significance: Minimal genetic changes can make bacteria produce different polysaccharides. Streptococcus pneumoniae (pneumococcus) expresses a capsular polysaccharide (CPS) that protects against host immunity and is synthesized by enzymes in the capsular polysaccharide synthesis (cps) locus. Serogroup 11 has six members (11A to -E) and the CPS structure of all members has been solved, except for serotype 11D. The cps loci of 11A and 11D differ by one codon (N112S) in wcrL, which putatively encodes a glycosyltransferase that adds the fourth sugar of the CPS repeating unit (RU). Gas chromatography and nuclear magnetic resonance analysis revealed that 11A and 11D PSs contain identical CPS RUs that contain αGlc as the fourth sugar. However, ∼25% of 11D CPS RUs contain instead αGlcNAc as the fourth sugar, suggesting that 11D wcrL encodes a bispecific glycosyltransferase. To test the hypothesis that codon 112 of WcrL determines enzyme specificity, and therefore the fourth sugar in the RU, we generated three isogenic pneumococcal strains with 11A cps loci containing wcrL encoding Ser-112 (MBO128) or Ala-112 (MBO130). MBO128 was serologically and biochemically identical to serotype 11D. MBO130 has a unique serologic profile; has as much αGlcNAc as 11F, 11B, and 11C CPS do; and may represent a new serotype. These findings demonstrate how pneumococci alter their CPS structure and their immunologic properties with a minimal genetic change.
The Impact of an Interprofessional Oral Health Curriculum on Trainees

Purpose Despite the prevalence of oral disease, the subject of oral health historically has been absent from medical education. We have developed an interprofessional curriculum in collaboration with our school of dentistry to teach oral health in the primary care setting to physician assistant (PA) students. The goal was to create and assess the impact of a curricular model that would be adaptable to various academic settings. Methods A blend of classroom, clinical skills lab, observations in the dental clinic, and observed structured clinical examinations was used to teach oral health to first-year (didactic year) PA students. The objectives were created in collaboration between the medical and dental faculties and included topics on general oral health, oral cancer, geriatrics, pediatrics, and fluoride varnish. Results A total of 12 hours of instructional time was delivered to 23 students over 3 semesters from 2014 to 2015. Pretesting and posttesting demonstrated long-term knowledge retention that was 14% better than baseline at 8 months (P < .001). Student surveys demonstrated that satisfaction levels were high and that the students felt better prepared and motivated to incorporate oral health into their practice of medicine. Analyses of students' write-ups of the history and the physical examination demonstrated that the students incorporated oral health concepts. Conclusions A significant impact on trainees can occur after a short, focused amount of instructional time in oral health. Students demonstrate enthusiasm and begin using oral health skills early on. A focused interprofessional oral health curriculum can likely be successfully integrated into various academic settings with a positive effect on learning and improved patient care.
Impact of Rapamycin on Peritoneal Fibrosis and Transport Function

Objectives: To observe the impact of rapamycin on peritoneal fibrosis and peritoneal transport function in a rat model of peritoneal fibrosis. Methods: A total of 40 male SD rats were randomly divided into five groups, with 8 rats in each group. Group N was the normal control. In group NS, the rats were injected daily with 20 ml of saline intraperitoneally. In groups GLU, L-RAPA and H-RAPA, rats were injected daily with 20 ml of 4.25% peritoneal dialysis solution intraperitoneally, together with 150 µg of lipopolysaccharide on days 1, 3, 5 and 7. Rapamycin was administered to groups L-RAPA (250 µg/day) and H-RAPA (500 µg/day) intragastrically. On days 21 and 35, 4 rats from each group were selected to evaluate their peritoneal transport function (ultrafiltration volume, D2/D₀ ratio). The parietal peritoneal membrane from the rats was used for pathological study. Light microscopy (HE staining and VG staining) was used to assess the morphological changes. The expression levels of Col I, α-SMA, TGF-β1, Reca and Ki67 in the parietal peritoneal membrane were observed by immunohistochemistry. Results: The ultrafiltration volume and D2/D₀ ratio decreased in group GLU compared with group N on day 21 (p < 0.05) and further decreased on day 35 (p < 0.01), whereas such a significant change was not observed in group L-RAPA or H-RAPA. Furthermore, severe loss of the peritoneal mesothelial cells, exposure of the collagen matrix under the mesothelial cells, and infiltration of fibroblasts and various inflammatory cells were detected in group GLU on days 21 and 35. The thickness of the submesothelial compact zone significantly increased in group GLU compared with group N (p < 0.01). However, in groups L-RAPA and H-RAPA, the morphological changes were clearly alleviated, and the submesothelial compact zone was thinner than in group GLU (p < 0.01). The expression levels of Col I, α-SMA, TGF-β1, Ki67 and Reca in the peritoneal membrane were significantly increased in group GLU compared with group N on days 21 and 35 (p < 0.01), whereas these changes were significantly attenuated in groups L-RAPA and H-RAPA compared with group GLU (p < 0.01). Conclusions: Rapamycin had an obvious effect in inhibiting peritoneal fibrosis and improving peritoneal membrane transport function.
Adipokines (adiponectin and plasminogen activator inhhibitor-1) in metabolic syndrome

Background: The clustering of cardiovascular risk factors is termed the metabolic syndrome (MS), which strongly predicts the risk of diabetes and cardiovascular disease (CVD). Adipokines may contribute to the development of obesity and insulin resistance and may be a causal link between MS, diabetes and CVD. Hence, we studied the adipokines – adiponectin and plasminogen activator inhibitor-1 (PAI-1) – in subjects with MS. Materials and Methods: We studied 50 subjects with MS diagnosed by International Diabetes Federation (IDF) criteria and 24 healthy age- and sex-matched controls. Clinical evaluation included anthropometry, body fat analysis by bioimpedance, highly sensitive C-reactive protein, insulin, adiponectin, and PAI-1 measurement. Results: Subjects with MS had lower adiponectin (4.01 ± 2.24 vs. 8.7 ± 1.77 μg/ml; P < 0.0001) and higher PAI-1 (53.85 ± 16.45 vs. 17.35 ± 4.45 ng/ml; P < 0.0001) levels than controls. Both were related with the number of metabolic abnormalities. Adiponectin was negatively and PAI-1 was positively associated with body mass index, waist hip ratio (WHR), body fat mass, percent body fat, and all the parameters of MS, except HDL where the pattern reversed. WHR and triglycerides were independent predictors of adipokines in multiple regression analysis. Receiver operating characteristic curve analysis showed that adiponectin (6.7 μg/ml) and PAI-1 (25.0 ng/ml) levels predicted the MS with high sensitivity, specificity and accuracy in Indian population. Conclusions: Subjects with MS have lower adiponectin and higher PAI-1 levels compared to healthy controls. Lifestyle measures have been shown to improve the various components of MS, and hence there is an urgent need for public health measures to prevent the ongoing epidemic of diabetes and CVD.