bluuebunny/crossref_metadata_2025 huggingface dataset:
Suboptimal Immune Reconstitution among HIV-Infected Saudi Patients following Successful Antiretroviral Treatment
Authors: Al-Majid Fahad , Shakoor Zahid , Barry Mazin
Published: January 2019

Background and Objectives. Variations in immune reconstitution following antiretroviral treatment (ART) among HIV patients have previously been observed. This study aims at assessing immune reconstitution after successful ART among HIV-infected Saudi patients.Methods. This retrospective study of 240 HIV-infected patients was performed between May 2010 and June 2015 in the HIV center at King Saud Hospital, Riyadh. Data were extracted for CD4, CD8 cell, and CD3/HLA-DR counts along with the viral load from patient records before and after four years of successful ART. The inclusion criterion was patients with CD4 reconstitution of either equal to or more than 400 cells/mm3with an undetectable HIV viral load following ART. Based on their presentation, the HIV patients were grouped into early treatment (ET) and delayed treatment (DT) groups with CD4 counts of 200–350 cells/mm3and less than 200 cells/mm3, respectively.Findings. The pretreatment CD8+ counts of median 865 cells/mm3(interquartile range (IQR) 774–1072) in the DT group declined to median 753 cells/mm3(IQR 574–987;p<0.0001). Moreover, there was a decline in CD8 counts from 703 cells/mm3(IQR 655–747) to 620 cells/mm3(IQR 563–645;p<0.04) in the ET group after four years of successful ART. Pretreatment activation marker (CD3/HLA-DR+) expression of median 29% in the DT group declined to 22% and in the ET group from a median of 23% to 19% after treatment. The CD4/CD8 ratio in the DT group increased from 0.14 (IQR 0.09–0.88) to 0.71 (IQR 0.54–0.9) and from 0.42 (IQR 0.35–0.55) to 0.87 (IQR 0.71–0.98) in the ET group.Conclusion. Immune reconstitution after successful ART among HIV-infected Saudi patients was associated with a CD8 T-cell population expansion with a suboptimal CD4/CD8 ratio and persistent immune activation. Early initiation of ART appears to favorably influence the CD4/CD8 ratio.
JinQi Jiangtang Tablet Regulates Gut Microbiota and Improve Insulin Sensitivity in Type 2 Diabetes Mice
Authors: Cao Ying , Yao Guowang , Sheng Yuanyuan , Yang Li , Wang Zixuan , Yang Zhen , Zhuang Pengwei , Zhang Yanjun
Published: January 2019

Background. Gut microbiota modulates the barrier function and host inflammatory state in metabolic disease. JinQi Jiangtang (JQJT) tablets are a traditional Chinese medicine for the treatment of diabetes. However, the low bioavailability of its chemical compositions makes it hard to explain the pharmacological mechanisms.Method. Diabetic mice were orally treated with JQJT tablets for 5 weeks. Fasting blood glucose and the level of HbA1c were measured, and ITT were conducted to determine the insulin improvement effect of JQJT tablets. The regulation effect on gut microbiota was assessed by 16S rRNA gene sequencing on an Illumina HiSeq platform. The concentration of short-chain fatty acids was measured by HS-GC/MS. D-LA leakage experiment and PAS staining were used to check the function of the gut barrier. The levels of the inflammatory cytokines were determined by using an ELISA kit.Results. This study showed that JQJT tablets downregulated fasting blood glucose and HbA1c and regulated gut microbiota. JQJT tablet-treated groups exhibited a more sensitive reaction after a small-dose injection of short-acting insulin. T2DM mice treated with JQJT tablets showed a higher abundance ofAkkermansiaspp. and lower abundance ofDesulfovibrio. JQJT tablets increased the concentration of acetic acid, propionic acid, and butyric acid; in particular, butyric acid was significantly increased with respect to the MOD group. Gut mucosal barrier function experiment showed that the level of D-LA was obviously decreased in JQJT tablet-treated groups compared with the model group and the number of goblet cells was significantly increased by JQJT tablet treatment. JQJT tablets could also reduce the levels of TNF-α, IL-6, and MCP-1, which were related to insulin resistance.Conclusion. We demonstrated that JQJT tablets could improve T2DM insulin resistance, regulating the gut microbiota and promoting the production of SCFAs. The mechanism was related to increasing the gut barrier function and reducing the host inflammatory reaction.
The Usefulness of Performing Biochemical Tests in the Saliva of Kickboxing Athletes in the Dynamic of Training
Authors: Volodchenko Oleksandr Anatolievich , Podrigalo Leonid Vladimirovich , Iermakov Sergii Sidorovich , Żychowska Małgorzata Teresa , Jagiełło Władysław
Published: January 2019

The study aimed to determine the suitability of testing the saliva of kickboxing athletes to show changes in biochemical parameters in dynamic of training. 8 elite male athletes (mean age 17.29± 0.31 years, body mass 66.82± 3.46kg, with 5.62±0.96 years of training experience) participated in the study. Indicators of lipid peroxidation and glycolysis (the concentration of lactic acid and pyruvic acid) were defined before and after a training session. Significant increases in indicators of lipid peroxidation activity indicators and the concentration of lactic acid (4-fold) were observed; analysis of correlation matrices confirms the absence of expressed changes. At the same time, significant decreases in catalase (10-fold from 3.69μkat/L to 0.39μkat/L) and pyruvic acid (from 3.92μl/l to 0.55μl/l) were observed. Our results confirm the value of using saliva to determine training load in an individual. Moreover, the study provided information on the importance of indexes reflecting a correlation of various biochemical indicators to estimate the sufficiency of training loads. The ease of sampling and informational content of saliva are reasons to use such tests in monitoring athletes’ functional state to prevent fatigue.
A Visible Colorimetric Fluorescent Probe for Hydrogen Sulfide Detection in Wine
Authors: Chen Haitao , Wu Xiaoming , Yang Shaoxiang , Tian Hongyu , Liu Yongguo , Sun Baoguo
Published: January 2019

A new efficient and practical fluorescent probe 6-(benzo[d]thiazol-2-yl)naphthalen-2-yl-thiophene-2-carboxylate (probe 1) was synthesized to detect hydrogen sulfide (H2S). The addition of H2S caused the solution of probe 1 to change from colorless to yellow, and the solution of probe 1 changes to different colors with respect to different concentrations of H2S. Importantly, probe 1 could help detect H2S efficiently by a distinct color response as a visible detection agent. Probe 1 reacted with various concentrations of H2S (0–200 μM), and the detection limit for H2S was 0.10 μM. Particularly, probe 1 can be applied as a sensor to detect H2S accurately in wine samples.
Early Effects of Hyperbaric Oxygen on Inducible Nitric Oxide Synthase Activity/Expression in Lymphocytes of Type 1 Diabetes Patients: A Prospective Pilot Study
Authors: Resanovic Ivana , Gluvic Zoran , Zaric Bozidarka , Sudar-Milovanovic Emina , Jovanovic Aleksandra , Milacic Davorka , Isakovic Radmilo , Isenovic Esma R.
Published: January 2019

This study aimed at examining the early effects of hyperbaric oxygen therapy (HBOT) on inducible nitric oxide synthase (iNOS) activity/expression in lymphocytes of type 1 diabetes mellitus (T1DM) patients. A group of 19 patients (mean age: 63 ± 2.1) with T1DM and with the peripheral arterial disease were included in this study. Patients were exposed to 10 sessions of HBOT in the duration of 1 h to 100% oxygen inhalation at 2.4 ATA. Blood samples were collected for the plasma C-reactive protein (CRP), plasma free fatty acid (FFA), serum nitrite/nitrate, and serum arginase activity measurements. Expression of iNOS and phosphorylation of p65 subunit of nuclear factor-κB (NFκB-p65), extracellular-regulated kinases 1/2 (ERK1/2), and protein kinase B (Akt) were examined in lymphocyte lysates by Western blot. After exposure to HBOT, plasma CRP and FFA were significantly decreased (p<0.001). Protein expression of iNOS and serum nitrite/nitrate levels were decreased (p<0.01), while serum arginase activity was increased (p<0.05) versus before exposure to HBOT. Increased phosphorylation of NFκB-p65 at Ser536 (p<0.05) and decreased level of NFκB-p65 protein (p<0.001) in lymphocytes of T1DM patients were observed after HBOT. Decreased phosphorylation of ERK1/2 (p<0.05) and Akt (p<0.05) was detected after HBOT. Our results indicate that exposure to HBO decreased iNOS activity/expression via decreasing phosphorylation of ERK1/2 and Akt followed by decreased activity of NFκB.
A Novel Mutation in the Adult-Onset Alexander’s Disease GFAP Gene
Authors: Zaver Dhillon B. , Douthit Nathan T.
Published: January 2019

The case describes a 25-year-old Caucasian female diagnosed with Alexander’s disease (AxD) as an outpatient after extensive inpatient workup. Her presenting complaints included incontinence, clumsiness, seizures, dysphagia, and dysarthria. She was also found to have pancytopenia and dysautonomia. A full neurologic and hematologic workup yielded very little results, until a thorough literature search of her presenting complaints and radiologic findings pointed to adult-onset Alexander’s Disease. Alexander’s disease is a rare genetic leukodystrophy with a broad variety of presentations. Despite its infrequency in adults and the difficulty in diagnosis, the prevalence of AxD has been increasing due to ease of genetic analysis and identification of key clinical and radiological findings. This case illustrates the necessity of vigilance and persistence in the face of unusual patient presentations; occasionally, the sound of hoofbeats is zebras.
Prophylactic Therapy of Silymarin (Milk Thistle) on Antituberculosis Drug-Induced Liver Injury: A Meta-Analysis of Randomized Controlled Trials
Authors: Tao Lina , Qu Xiaoyu , Zhang Yue , Song Yanqing , Zhang Si-xi
Published: January 2019

Background. Prophylactic therapy with silymarin to prevent the development of antituberculosis drug-induced liver injury (anti-TB DILI) has been under debate. We aimed to evaluate the effect of silymarin in the prevention of anti-TB DILI. Methods. We searched MEDLINE, PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to 30th November 2018. Randomized controlled trials (RCTs) that compared silymarin and placebo to prevent anti-TB DILI were included. All statistical analyses were conducted using STATA 12.0 software. Standardized mean difference (SMD) and risk ratio (RR) with 95% confidence intervals (CIs) were used to evaluate the effect of silymarin. The quality of included studies was assessed according to Cochrane handbook. Funnel plots and Egger’s tests were carried out to evaluate publication bias. Sensitivity analysis was conducted to assess the influence of each study. Results. A total of 1198 patients from five RCTs (585 with silymarin and 613 with placebo groups) were included. Overall, silymarin significantly reduced the occurrence of anti-TB DILI at week 4 [RR: 0.33, 95% CI (0.15, 0.75)]. In addition, silymarin exerted protective effect on liver function in patients undergoing anti-TB drugs [SMD = − 0.15, 95% CI (−0.24, −0.07), P < 0.001 (ALT); SMD =−0.14, 95% CI (−0.23, −0.06), P = 0.001(AST); SMD =−0.12, 95% CI (−0.20, −0.03), P = 0.008 (ALP)]. Silymarin led to similar AEs in placebo groups [OR: 1.09, 95% CI (0.86, 1.39), P = 0.47]. Conclusion. Prophylactic therapy of silymarin is contributed to a noticeably reduced risk of development of anti-TB DILI four weeks after the initiation. In addition, silymarin significantly improved the liver function in patients who are receiving anti-TB drugs.
Fast Simultaneous Determination of Eight Sudan Dyes in Chili Oil by Ultra-High-Performance Supercritical Fluid Chromatography
Authors: Yang Yunjia , Zhang Jing , Yin Jie , Yang Yi
Published: January 2019

A rapid and simple ultra-high-performance supercritical fluid chromatography (UHPSFC) with photodiode array (PDA) method was developed and validated for simultaneous determination of eight Sudan dyes in chili oil. In particular, a pair of isomer, Sudan red B and Sudan IV, was included in the analysis. After being diluted with dichloromethane, the analytes were separated on an Acquity UPC2 HSS C18 SB column with gradient elution using CO2 as the mobile phase and acetonitrile/methanol (v/v, 45/55, containing 0.1% formic acid) as the organic modifier. Analytes were quantified by external calibration curves over ranges of 0.5–50 mg/L, with correlation coefficients above 0.999. The method gave recoveries of the target compounds (spiked at levels of 1, 5, and 25 mg/kg) ranging from 82.6 to 108.3%, with intraday and interday relative standard deviations of less than 8.0% and 8.6%, respectively. The limits of detection (LODs) and the limits of quantification (LOQs) for eight dyes were from 0.10 to 0.30 mg/kg and 0.30–1.00 mg/kg, respectively. This method was applied for the analysis of chili oil samples collected from the supermarket in Beijing. This validated that the UHPSFC-PDA method provides a useful strategy for the simultaneous determination of Sudan dyes in chili oil for routine analysis.
Quantitative Analysis of the Corneal Collagen Distribution after In Vivo Cross-Linking with Second Harmonic Microscopy
Authors: Bueno Juan M. , Ávila Francisco J. , Martínez-García M. Carmen
Published: January 2019

Corneal cross-linking (CXL) is a surgical procedure able to modify corneal biomechanics and stabilize keratoconus progression. Although it is known that CXL produces changes in corneal collagen distribution, these are still a topic of discussion. Here we quantitatively compare the corneal stroma architecture between two animal models four weeks after in vivo conventional CXL treatment, with second harmonic generation (SHG) imaging microscopy and the structure tensor (ST). The healing stage and the stroma recovery were also analyzed by means of histological sections. Results show that the CXL effects depend on the initial arrangement of the corneal collagen. While the treatment increases the order in corneas with a low level of initial organization, corneas presenting a fairly regular pattern are hardly affected. Histological samples showed active keratocytes in anterior and middle stroma, what means that the recovery is still in progress. The combination of SHG imaging and the ST is able to objectively discriminate the changes suffered by the collagen arrangement after the CXL treatment, whose effectiveness depends on the initial organization of the collagen fibers within the corneal stroma.
Melatonin Alleviates Radiation-Induced Lung Injury via Regulation of miR-30e/NLRP3 Axis
Authors: Wu Xu , Ji Haiying , Wang Yuli , Gu Chenlin , Gu Wenyu , Hu Lijuan , Zhu Lei
Published: January 2019

Melatonin is a well-known anti-inflammatory and antioxidant molecule, which plays a crucial role in various physiological functions. In this study, mice received a single dose of 15 Gy radiation delivered to the lungs and daily intraperitoneal administration of melatonin. After 7 days, mice were processed to harvest either bronchoalveolar lavage fluid for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that melatonin markedly alleviated the oxidative stress and injury, especially suppressing the infiltration of macrophages (CD11b+CD11c−) and neutrophils (CD11b+Ly6G+) to the irradiated lungs. Moreover, in the irradiated RAW 264.7 cells, melatonin blocked the NLRP3 inflammasome activation accompanied with the inhibition of the IL-1β release and caspase-1 activity. However, melatonin restored the downregulated miR-30e levels. Quantitative PCR analysis of miR-30e and NLRP3 indicated the negative correlation between them. Notably, immunofluorescence staining showed that overexpression of miR-30e dramatically diminished the increased NLRP3 expression. Luciferase reporter assay confirmed that NLRP3 was a target gene of miR-30e. Western blotting revealed that transfection with miR-30e mimics markedly reduced the expressions of NLRP3 and cleaved caspase-1, whereas this phenomenon was reversed by the miR-30e inhibitor. Consistent with this, the beneficial effect of melatonin under irradiated exposure was blunted in cells transfected with anti-miR-30e. Collectively, our results demonstrate that the NLRP3 inflammasome contributed to the pathogenesis of radiation-induced lung injury. Meanwhile, melatonin exerted its protective effect through negatively regulating the NLRP3 inflammasome in macrophages. The melatonin-mediated miR-30e/NLRP3 signaling may provide novel therapeutic targets for radiation-induced injury.
Overlap of Characteristic Serological Antibodies in Rheumatoid Arthritis and Wheat-Related Disorders
Authors: Yang Yuanyuan , Deshpande Payal , Krishna Karthik , Ranganathan Vinodh , Jayaraman Vasanth , Wang Tianhao , Bei Kang , Rajasekaran John J. , Krishnamurthy Hari
Published: January 2019

Background and Aims. Rheumatoid arthritis (RA) and celiac disease (CD) are members of the autoimmune disease family while they have been shown to share multiple aspects in epidemiology and clinical manifestations. The aim of this study was to assess the presence of wheat protein antibodies in RA seropositive subjects and the presence of RA diagnostic markers in subjects with seropositive wheat-related disorders including CD. Methods. Serum samples were collected from 844 subjects with joint pain and/or gastrointestinal symptoms and tested by a CD panel (anti-tTG and anti-DGP), a Wheat Zoomer (WZ) antibody panel (IgG/IgA to 14 wheat proteins), and a RA panel (anti-CCP and anti-RF). Retrospective analysis was completed using de-identified clinical data and test results. Results. The prevalence of RA markers was first investigated in CD- or WZ-positive subjects and negative controls. 49 subjects were seropositive in the CD panel with 10 (20%) RA positivity. 605 subjects were seropositive in the WZ panel with 106 (18%) RA positivity. 222 subjects were seronegative in either panels with 12 (6%) RA positivity. Next, the frequency of the CD markers and the clinically relevant wheat protein antibodies were investigated in the RA-positive subjects and negative controls. 128 subjects in this cohort were seropositive in the RA panel with 10 (8%) CD positivity and 106 (83%) WZ positivity, compared to 716 RA seronegative controls with 39 (5%) CD positivity and 499 (70%) WZ positivity. Conclusions. Our data presents an apparent trend of overlapped serological antibody biomarker positivity in RA and wheat-related disorders.
Sex-Related Differences in Immune Response and Symptomatic Manifestations to Infection with Leishmania Species
Authors: Lockard Ryan D. , Wilson Mary E. , Rodríguez Nilda E.
Published: January 2019

Worldwide, an estimated 12 million people are infected with Leishmania spp. and an additional 350 million are at risk of infection. Leishmania are intracellular parasites that cause disease by suppressing macrophage microbicidal responses. Infection can remain asymptomatic or lead to a spectrum of diseases including cutaneous, mucocutaneous, and visceral leishmaniasis. Ultimately, the combination of both pathogen and host factors determines the outcome of infection. Leishmaniasis, as well as numerous other infectious diseases, exhibits sex-related differences that cannot be explained solely in terms of environmental exposure or healthcare access. Furthermore, transcriptomic evidence is revealing that biological sex is a variable impacting physiology, immune response, drug metabolism, and consequently, the progression of disease. Herein, we review the distribution, morbidity, and mortality among male and female leishmaniasis patients. Additionally, we discuss experimental findings and new avenues of research concerning sex-specific responses in cutaneous and visceral leishmaniasis. The limitations of current therapies and the emergence of drug-resistant parasites underscore the need for new treatments that could harness the host immune response. As such, understanding the mechanisms driving the differential immune response and disease outcome of males versus females is a necessary step in the development of safer and more effective treatments against leishmaniasis.
Indirect Restorations and Fixed Prosthodontics: Materials and Techniques Used by General Dentists of New Zealand
Authors: Brunton Paul A. , Ratnayake Jithendra , Loch Carolina , Veerasamy Arthi , Cathro Peter , Lee Robert
Published: January 2019

Background. To investigate the selection and use of materials and techniques for core buildup, indirect restorations, and fixed prosthodontics by general dentists in New Zealand. Methods. A questionnaire comprising 19 sections and 125 questions was distributed via mail to 351 general dentists in New Zealand who were selected from the Dental Council of New Zealand’s 2016 register. Results. The majority of the respondents (68.8%) reported using resin composite light-cured materials for the core buildup of vital posterior teeth. A large number of respondents (52%) did not use dentine pins, with the majority of them (25%) being recent graduates (<10 years). Fibre posts were used by 61.6% of the dentists surveyed. The majority of dentists (54.6%) reported using addition-cured silicone impression material for crown and bridge impressions. Glass-ionomer cements (37.5% of participants) and resin-modified glass-ionomer cements (35.8%) were the most common luting cements used. Direct resin composite veneers were the preferred material of choice rather than indirect restoration of anterior teeth (40.4%). Conclusions. The study showed that New Zealand dentists surveyed are using current state-of-the-art materials and techniques, with their choice of material being greatly influenced by clinical indications and patients aesthetic demands.
Soy Isoflavones Ameliorate Metabolic and Immunological Alterations of Ovariectomy in Female Wistar Rats: Antioxidant and Estrogen Sparing Potential
Authors: Abdelrazek Heba M. A. , Mahmoud Manal M. A. , Tag Hend M. , Greish Sahar M. , Eltamany Dalia A. , Soliman Mohammed T. A.
Published: January 2019

Hormone replacement therapy (HRT) can alleviate estrogen deficiency symptoms especially during menopause. The present study aimed at investigating the effect of soy isoflavones as HRT on immunological and bone health-related parameters with a special focus on the interactions between immunological status and metabolism. Thirty healthy cyclic female Wistar rats were used in this experiment. Ten females were sham-operated, and 20 females were subjected to ovariectomy. Overiectomized (OVX) female rats were randomly divided into 2 groups: the control group (G1, OVX/casein) was fed a casein-based diet, and the second group (G2, OVX/soy) was fed a high soy isoflavone diet. Both groups were compared to a sham-operated group (G3, sham/casein). Treatments continued for 7 weeks. Feed intake, weight gain, and lymphoid organ relative weights were recorded. Some metabolic, immunological, and bone health-related parameters were measured. Moreover, nitric oxide (NO), malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined. Bone histopathology and immunohistochemistry to estrogen receptor alpha (ERα) were done. Feeding soy to OVX females reduced feed intake, weight gain, relative lymphoid organ weight, and T-lymphocytes transformation. Soy isoflavone administration normalized nearly all metabolic and immunological parameters to a level comparable to the sham group via oxidative stress amelioration and bone ERα promotion. Soy isoflavones seemed to be good HRT in estrogen deprivation which modulated the appetite, weight gain, lipid profile, proinflammation, and bone turnover.
The Use of Rheumatic Disease Comorbidity Index for Predicting Clinical Response and Retention Rate in a Cohort of Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Alpha Inhibitors
Authors: Biggioggero Martina , Mesina Federica , Favalli Ennio Giulio
Published: January 2019

Introduction. To retrospectively evaluate the impact of comorbidities on treatment choice, 12-month clinical response, and 24-month retention rate in a cohort of patients with rheumatoid arthritis (RA) treated with a first-line tumor necrosis factor alpha inhibitor (TNFi), by using for the first time the Rheumatic Disease Comorbidity Index (RDCI). Methods. The study population was extracted from a local registry of RA patients receiving adalimumab or etanercept as first-line biologics between January 2001 and December 2013. The prevalence of comorbidities was computed, and patients were stratified according to RDCI for evaluating the role of comorbidities on TNFi choice, concomitant methotrexate, clinical response (1-year DAS28-ESR remission and low disease activity [LDA] and EULAR good-moderate response), and the 24-month retention rate. Results. 346 patients (172 adalimumab and 174 etanercept) were included. A significantly higher EULAR good/moderate response (P = 0.020) and DAS28-ESR remission (P = 0.003) were obtained according to RDCI (0, 1, 2, or ≥3). Lower RDCI (P = 0.022), male sex (P = 0.006), higher baseline DAS28-ESR (P = 0.001), ETN (P < 0.001), and concomitant methotrexate (P = 0.016) were predictors of EULAR good/moderate response. Elevated RDCI was a predictor of discontinuation of biologics (P = 0.036), whereas treatment with etanercept (P < 0.001) and methotrexate (P = 0.007) was associated with a lower risk of TNFi withdrawal. Conclusions. Multimorbidity, measured by RDCI, is a negative predictor of TNFi persistence on treatment and of achieving a good clinical response. The use of RDCI may be very useful for identifying patients with RA carrying those comorbid conditions associated with poor prognostic outcomes and for defining new treatment targets in multimorbid RA patients.
Increased HIF-1α in Knee Osteoarthritis Aggravate Synovial Fibrosis via Fibroblast-Like Synoviocyte Pyroptosis
Authors: Zhang Li , Zhang Li , Huang Zhengquan , Xing Runlin , Li Xiaochen , Yin Songjiang , Mao Jun , Zhang Nongshan , Mei Wei , Ding Liang , Wang Peimin
Published: January 2019

Fibroblast-like synoviocytes (FLSs) are the main effector cells of knee osteoarthritis (KOA) synovial fibrosis. Our last report showed that NLRP1 and NLRP3 inflammasomes may mediate LPS/ATP-induced FLSs pyroptosis in KOA. In the present study, we found an elevated hypoxia-inducible factor-1α (HIF-1α) level in the synovial tissue of KOA model rats, and inhibiting the increase of HIF-1α could improve synovial fibrosis in rats. Subsequently, we established LPS/ATP-induced model in FLSs mimicking the inflammatory environment of KOA. FLSs transfected with siRNA HIF-1α showed a reduced cell death; meanwhile, the relative expression of pyroptosis-related proteins was also downregulated. Additionally, FLSs transfected with or without siRNA GSDMD were exposed to hypoxia. GSDMD silencing can significantly reduce both gene and protein levels of fibrogenic markers transforming growth factor-β (TGF-β), procollagen-lysine, 2-oxoglutarate 5-dioxygenase2 (PLOD2), collagen type I α1 chain (COL1A1), and tissue inhibitor of metalloproteinases 1 (TIMP1). Taken together, our findings indicate that increased HIF-1α is highly involved in the KOA synovial fibrosis. Moreover, elevated HIF-1α may aggravate synovial fibrosis via FLS pyroptosis.
Percutaneous Endoscopic Lumbar Discectomy Assisted by O-Arm-Based Navigation Improves the Learning Curve
Authors: Ao Shengxiang , Wu Junlong , Tang Yu , Zhang Chao , Li Jie , Zheng Wenjie , Zhou Yue
Published: January 2019

Objective. There is a steep learning curve with traditional percutaneous endoscopic lumbar discectomy (PELD). The aim of this study is to assess the safety and efficacy of PELD assisted by O-arm-based navigation for treating lumbar disc herniation (LDH).Methods. From September of 2017 to January of 2018, 118 patients with symptomatic LDH were enrolled in the prospective cohort study. The patients undergoing PELD with O-arm-based navigation technique were defined as group A (58 cases), and those undergoing traditional X-ray fluoroscopy method were defined as group B (60 cases). We recorded the operation time, cannula placement time, radiation exposure time, visual analog scale (VAS), Oswestry Disability Index (ODI), and Macnab criteria score of the 2 groups.Results. The average operation time (95.21 ± 19.05 mins) and the cannula placement time (36.38 ± 14.67 mins) in group A were significantly reduced compared with group B (operation time, 113.83 ± 22.01 mins, P<0.001; cannula placement time, 52.63 ± 17.94 mins, P<0.001). The learning curve of PELD in group A was steeper than that in group B and was lower in the relatively flat region of the end. There were significant differences of the clinical parameters at different time points (VAS of low back, P < 0.001; VAS of leg, P < 0.001; and ODI, P < 0.001). The VAS scores for low back pain and leg pain improved significantly in both groups after surgery and gradually improved as time went by. No serious complication was observed in any patients in either group.Conclusion. The study indicated that PELD assisted by O-arm navigation is safe, accurate, and efficient for the treatment of lumbar intervertebral disc herniation. It reshaped the learning curve of PELD, reduced the difficulty of surgery, and minimized radiation exposure to surgeons. This study was registered at Chinese Clinical Trail Registry (Registration Number:ChiCTR1800019586).
Comparison of Phenolic Compound Separations by HPTLC and PPEC with SDS as the Mobile Phase Component
Authors: Polak Beata , Traczuk Adam , Kamińska Marta , Kozyra Małgorzata
Published: January 2019

The application of the surfactant (sodium dodecyl sulphate, SDS) as the component of the water-organic mobile phase in thin-layer chromatography and pressurized planar electrochromatography is presented. The influence of various variables on the separation of various phenolic compounds (flavonoids and phenolic acids) as model compounds with systems containing surfactant is discussed. The effect of concentration of butanol and SDS as well as pH of the mobile phase buffer on migration distance of the solute zones is investigated. The presence of SDS in the eluent affects the butanol solubility in the mobile phase. It allows using higher organic solvent concentration systems compared with the mode without surfactant. The amount of SDS in the eluent has the effect on the solute retention, whereas the eluent buffer pH affects the migration distances of ionisable phenolic acids both in HPTLC and PPEC. The migration distances of flavonoid glycosides are considerably longer than those of pure flavonoids. Considering second group of investigated solutes, derivatives of the benzoic acid migrate longer distances in comparison with the cinnamic acid ones. In addition, in the majority of experiments, ionisable compounds (phenolic acids) migrate longer distances in PPEC than nonionisable compounds (flavonoids). Additionally, the order of solutes differs in the PPEC and HPTLC system.
A Liquid Chromatography with Tandem Mass Spectrometry-Based Proteomic Analysis of Primary Cultured Cells and Subcultured Cells Using Mouse Adipose-Derived Mesenchymal Stem Cells
Authors: Nakashima Yoshiki , Nahar Saifun , Miyagi-Shiohira Chika , Kinjo Takao , Kobayashi Naoya , Saitoh Issei , Watanabe Masami , Fujita Jiro , Noguchi Hirofumi
Published: January 2019

Adipose-derived mesenchymal stem cells (MSC-ATs) are representative cell sources for cell therapy. However, how cell stress resulting from passage influences the MSC-AT protein expression has been unclear. In this study, a protein expression analysis was performed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) using mouse primary cultured cells (P0) and cells passaged three times (P3) as samples. A total of 256 proteins were classified as cellular process-related proteins, while 179 were classified as metabolic process-related proteins in P0. These were considered to be adaptive responses of the cells to an in vitro environment. However, seven proteins of growth were identified (Csf1, App, Adam15, Alcam, Tbl1xr1, Ninj1, and Sbds) in P0. In addition, four proteins of antioxidant activity were also identified (Srxn1, Txndc17, Fam213b, and Apoe) in P0. We identified 1139 proteins expressed in both P0 and P3 cells that had their expression decreased to 69.4% in P3 cells compared with P0 cells, but 1139 proteins are very likely proteins that are derived from MSC-AT. The function of MSC-ATs was maintained after three passages. However, the LC-MS/MS analysis data showed that the protein expression was degraded after three passages. MSC-ATs retained about 70% of their protein expression ability in P3 cells.
Start‐Up Process Modelling of Sediment Microbial Fuel Cells Based on Data Driven
Authors: Ma Fengying , Yin Yankai , Li Min
Published: January 2019

Sediment microbial fuel cells (SMFCs) are a typical microbial fuel cell without membranes. They are a device developed on the basis of electrochemistry and use microbes as catalysts to convert chemical energy stored in organic matter into electrical energy. This study selected a single‐chamber SMFC as a research object, using online monitoring technology to accurately measure the temperature, pH, and voltage of the microbial fuel cell during the start‐up process. In the process of microbial fuel cell start‐up, the relationship between temperature, pH, and voltage was analysed in detail, and the correlation between them was calculated using SPSS software. The experimental results show that, at the initial stage of SMFC, the purpose of rapid growth of power production can be achieved by a large increase in temperature, but once the temperature is reduced, the power production of SMFC will soon recover to the state before the temperature change. At the beginning of SMFC, when the temperature changes drastically, pH will change the same first, and then there will be a certain degree of rebound. In the middle stage of SMFC start‐up, even if the temperature will return to normal after the change, a continuous temperature drop in a short time will lead to a continuous decrease in pH value. The RBF neural network and ELM neural network were used to perform nonlinear system regression in the later stage of SMFC start‐up and using the regression network to forecast part of the data. The experimental results show that the ELM neural network is more excellent in forecasting SMFC system. This article will provide important guidance for shortening start‐up time and increasing power output.
Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis
Authors: Vacante Fernanda , Senesi Pamela , Montesano Anna , Paini Stefano , Luzi Livio , Terruzzi Ileana
Published: January 2019

Background and Aims. Hepatocellular carcinoma (HCC) is the common tumor of the liver. Unfortunately, most HCC seem to be resistant to conventional chemotherapy and radiotherapy. The poor efficacy of antitumor agents is also due, at least in part, to the inefficient drug delivery and metabolism exerted by the steatotic/cirrhotic liver that hosts the tumor. Thus, novel approaches in chemotherapy may be needed to improve the survival rate in patients with HCC. Metformin (METF) has been found to lower HCC risk; however, the mechanisms by which METF performs its anticancer activity are not completely elucidated. Previous studies have showed METF action on growth inhibition in the liver in a dose/time-dependent manner and its antitumor role by targeting multiple pathways. We investigated molecular effects of METF in an in vitro human hepatoma model (HepG2), studying cell cycle regulators, tumorigenesis markers, and insulin-like growth factor (IGF) axis regulation. Materials and Methods. HepG2 cells were treated with METF (400 μM) for 24, 48, and 72 hours. METF action on cell cycle progression and cellular pathways involved in metabolism regulation was evaluated by gene expression analysis, immunofluorescence, and Western blot assay. Results. By assessing HepG2 cell viability, METF significantly decreased growth cell capacity raising KLF6/p21 protein content. Moreover, METF ameliorated the cancer microenvironment reducing cellular lipid drop accumulation and promoting AMPK activity. The overexpression of IGF-II molecule and the IGF-I receptor that plays a main role in HCC progression was counteracted by METF. Furthermore, the protein content of HCC principal tumor markers, CK19 and OPN, linked to the metastasis process was significantly reduced by METF stimulus. Conclusion. Our data show that METF could suppress HepG2 proliferation, through induction of cell cycle arrest at the G0/G1 phase. In addition, METF effect on the cancer microenvironment and on the IGF axis leads to the development of new METF therapeutic use in HCC treatment.
8q22.2q22.3 Microdeletion Syndrome Associated with Hearing Loss and Intractable Epilepsy
Authors: Rincon Alejandra , Paez-Rojas Paola , Suárez-Obando Fernando
Published: January 2019

8q22.2q22.3 microdeletion syndrome has been described in only seven patients. We present a new case from Colombia. The characteristics of this condition are developmental delay, microcephaly, seizures, and typical facial dysmorphism. We discuss the clinical phenotype of the patient presenting relevant findings like hearing loss and severe epilepsy and the possible relations between the phenotype and the genes involved in the microdeletion. We describe a female with developmental delay, microcephaly, epilepsy, severe short stature, impaired speech, facial dysmorphism, and congenital deafness. A minimal/maximal deletion of 5.238 Mb and 5.374Mb, respectively, at 8q22.2q22.3 was diagnosed using a genome-wide array. The clinical phenotype is similar to the others seven patients previously reported; however, the severity of epilepsy and the concomitant hearing loss is remarkable, characteristics previously observed independently in only two patients. The KCNS2 gene is located in the deleted regions (8q22.2). Therefore it is a possible candidate for explaining the complex neurologic phenotype.
Extended Minimal Atomicity through Nondifferentiability: A Mathematical-Physical Approach
Authors: Gavriluţ Gabriel , Gavriluţ Alina , Agop Maricel
Published: January 2019

The mathematical concept of minimal atomicity is extended to fractal minimal atomicity, based on the nondifferentiability of the motion curves of physical system entities on a fractal manifold. For this purpose, firstly, different results concerning minimal atomicity from the mathematical procedure of the Quantum Measure Theory and also several physical implications are obtained. Further, an inverse method with respect to the common developments concerning the minimal atomicity concept has been used, showing that Quantum Mechanics is identified as a particular case of Fractal Mechanics at a given scale resolution. More precisely, for fractality through Markov type stochastic processes, i.e., fractalization through stochasticization, the standard Schrödinger equation is identified with the geodesics of a fractal space for motions of the physical system entities on nondifferentiable curves on fractal dimension two at Compton scale resolution. In the one-dimensional stationary case of the fractal Schrödinger type geodesics, a special symmetry induced by the homographic group in Barbilian’s form “makes possible the synchronicity” of all entities of a given physical system. The integral and differential properties of this group under the restriction of defining a parallelism of directions in Levi-Civita’s sense impose correspondences with the “dynamics” of the hyperbolic plane so that harmonic mappings between the ordinary flat space and the hyperbolic one generate (by means of a variational principle) a priori probabilities in Jaynes’ sense. The explicitation of such situation specifies the fact that the hydrodynamical variant of a Fractal Mechanics is more easily approached and, from this, the fact that Quantum Measure Theory can be a particular case of a possible Fractal Measure Theory.
A Hybrid Time-Frequency Analysis Method for Railway Rolling-Element Bearing Fault Diagnosis
Authors: Cheng Yao , Zou Dong , Zhang Weihua , Wang Zhiwei
Published: January 2019

The health condition of rolling-element bearings is important for machine performance and operating safety. Due to external interferences, the impulse-related fault information is always buried in the raw vibration signal. To solve this problem, a hybrid time-frequency analysis method combining ensemble local mean decomposition (ELMD) and the Teager-Kaiser energy operator (TKEO) is proposed for the fault diagnosis of high-speed train bearings. The ELMD method is a significant improvement over local mean decomposition (LMD) for addressing the mode-mixing problem. The TKEO method is effective for separating amplitude-modulated (AM) and frequency-modulated (FM) signals from a raw signal. But it is only valid for monocomponent AM-FM signals. The proposed time-frequency method integrates the advantages of ELMD and TKEO to detect localized defects in rolling-element bearings. First, a raw signal is decomposed into an ensemble of PFs and a residual component using ELMD. A novel sensitive parameter (SP) is introduced to select the sensitive PF that contains the most fault-related information. Subsequently, the TKEO is applied to extract both the amplitude and frequency modulations from the selected PF. The experimental results of rolling element and outer race fault signals confirmed that the proposed method could effectively recover fault information from raw signals contaminated by strong noise and other interferences.
Diagnostic and Predictive Value of Using RGD PET/CT in Patients with Cancer: A Systematic Review and Meta-Analysis
Authors: Liu Jie , Yuan Shuanghu , Wang Linlin , Sun Xindong , Hu Xudong , Meng Xue , Yu Jinming
Published: January 2019

The purpose of this study was to assess the diagnostic value of arginine-glycine-aspartic acid (RGD) PET/CT for tumor detection in patients with suspected malignant lesions and to determine the predictive performance of RGD PET/CT in identifying responders.Methods. The PubMed (Medline), EMBASE, Cochrane Library, and Web of Science databases were systematically searched for potentially relevant publications (last updated on July 28th, 2018) reporting the performance of RGD PET in the field of oncology. Pooled sensitivities, specificities, and diagnostic odds ratios (DORs) were calculated for parameters. The areas under the curve (AUCs) andQ⁎index scores were determined from the constructed summary receiver operating characteristic (SROC) curve. We explored heterogeneity by metaregression.Results. Nine studies, five including 216 patients that determined diagnostic performance and three including 75 patients that determined the predictive value of parameters, met our inclusion criteria. The pooled sensitivity, pooled specificity, DOR, AUC, andQ⁎index score of RGD PET/CT for the detection of underlying malignancy were 0.85 (0.79-0.89), 0.93 (0.90-0.96), 48.35 (18.95-123.33), 0.9262 (standard error=0.0216), and 0.8606 for SUVmax and 0.86 (0.80-0.91), 0.92 (0.88-0.94), 40.49 (14.16-115.77), 0.9312 (SE=0.0177), and 0.8665 for SUVmean, respectively. The pooled sensitivity, pooled specificity, DOR, AUC, andQ⁎index score of RGD PET/CT for identifying responders were 0.80 (0.59-0.93), 0.74 (0.60-0.85), 15.76 (4.33-57.32), 0.8682 (0.0539), and 0.7988, respectively, for SUVmax at baseline.Conclusion. The interesting but preliminary data in this meta-analysis demonstrate that RGD PET/CT may be an ideal diagnostic tool for detecting underlying malignancies in patients suspected of having tumors and may be able to efficiently predict short-term outcomes.
Blood Glucose Level Prediction for Diabetics Based on Nutrition and Insulin Administration Logs Using Personalized Mathematical Models
Authors: Gyuk Péter , Vassányi István , Kósa István
Published: January 2019

According to recent surveys, the current ways of diabetics trying to estimate their insulin need based on experience and conjecture are sometimes inefficient in practice. This paper proposes a prediction algorithm and presents the validation of the model in outpatient care. The algorithm consists of two state-of-the-art models that calculate nutrition absorption and glycaemia including insulin evolution. The combined model is extended with personalized parameter training including genetic algorithm and Nelder–Mead method, and a more realistic, diurnal parameter profile as a representation of the natural biorhythm. This method implemented in a user-friendly application can help diabetics calculate their insulin need. The tests were performed on a data set including a clinical trial involving more than 20 diabetic patients. We experienced 55% improvement in the results due to model training compared to the tests based on literature parameters. In the best case, 92.5% of the predicted blood glucose level values were in the range of clinically acceptable errors, which means around 2.8 mmol/l root mean square error. The results of the validation based on outpatient data are promising compared to others found in the literature. Handling other important factors such as physical activity and stress remains a challenge for future research.
Dipeptidyl Peptidase 4 Inhibition Ameliorates Chronic Kidney Disease in a Model of Salt-Dependent Hypertension
Authors: Cappetta Donato , Ciuffreda Loreta Pia , Cozzolino Anna , Esposito Grazia , Scavone Cristina , Sapio Luigi , Naviglio Silvio , D’Amario Domenico , Crea Filippo , Rossi Francesco , Berrino Liberato , De Angelis Antonella , Urbanek Konrad
Published: January 2019

Cardiovascular diseases frequently coexist with chronic kidney disease that constitutes a major determinant of outcome in patients with heart failure. Dysfunction of both organs is related to chronic inflammation, endothelial dysfunction, oxidative stress, and fibrosis. Widespread expression of serine protease DPP4 that degrades varieties of substrates suggests its involvement in numerous physiological processes. In this study, we tested the effects of selective DPP4 inhibition on the progression of renal disease in a nondiabetic model of hypertensive heart disease using Dahl salt-sensitive rats. Chronic DPP4 inhibition positively affected renal function with a significant reduction in albuminuria and serum creatinine. DPP4 inhibition attenuated the inflammatory component by reducing the expression of NF-κB, TNFα, IL-1β, IL-6, and MCP-1. Kidney macrophages expressed GLP-1R, and DPP4 inhibition promoted macrophage polarization toward the anti-inflammatory M2 phenotype. Finally, high degrees of NADPH oxidase 4 expression and oxidation of nucleic acids, lipids, and proteins were reduced upon DPP4 inhibition. Our study provides evidence of renoprotection by DPP4 inhibition in a nondiabetic hypertension-induced model of chronic cardiorenal syndrome, indicating that DPP4 pathway remains a valid object to study in the context of chronic multiorgan diseases.