Evaluation of regulatory T cells in obese asthmatic children

Background: Asthma is an airway inflammatory disorder with functional and structural changes. Regulatory T (T reg) cells are important in controlling immune responses. The study was aimed to investigate the frequency of Treg cells in obese asthmatic children, in comparison to non-obese asthmatics and healthy matched controls .Methods: In addition to anthropometric and body mass index (BMI) assessment, peripheral blood samples from healthy control subjects (n = 30) and asthmatic obese (n=30) and asthmatic non-obese children (n=30) were examined for serum IgE, eosinophils counts, and flowcytometric measurement of CD4+CD25+CD127 low/neg- T cells. Pulmonary function testing was performed for asthmatic children . Results: Obese asthmatics showed significantly higher levels of serum IgE and CD4+CD25+CD127 low/neg- T cells as compared to healthy controls (p<0.001, 0.001, respectively) while comparable numbers of T reg cells were found among obese and non-obese asthmatic children. Asthmatics receiving inhaled corticosteroids (ICS) showed higher percentages of CD4+CD25+CD127 low/neg- T cells than the non-receivers (median 11.8% vs 8.8%, p <0.001). No significant correlations were found between Treg and age, eosinophil percentage, total serum IgE, pulmonary functions, or BMI and its Z score . Conclusion: Our study demonstrates an increased frequency of Treg cells in asthmatic children compared to controls with possible association with the use of ICS but not with obesity. Small sample size and lack of obese non-asthmatic group are the main points of limitation in our study

New Solutions for System of Fractional Integro-Differential Equations and Abel’s Integral Equations by Chebyshev Spectral Method

Chebyshev spectral method based on operational matrix is applied to both systems of fractional integro-differential equations and Abel’s integral equations. Some test problems, for which the exact solution is known, are considered. Numerical results with comparisons are made to confirm the reliability of the method. Chebyshev spectral method may be considered as alternative and efficient technique for finding the approximation of system of fractional integro-differential equations and Abel’s integral equations

Comparing effects of L-carnitine and sildenafil citrate on histopathologic recovery from sciatic nerve crush injury in female albino rats

Background: The sciatic nerve is a peripheral nerve and is more vulnerable to compression with subsequent short- or long-term neuronal dysfunction. The current study was designed to elucidate the possible ameliorative effect of L-carnitine and sildenafil (SIL) on sciatic nerve crush injury. We sought to determine the effects of L-carnitine, a neuroprotective and a neuro-modulatory agent, and sildenafil citrate, a selective peripheral phosphodiesterases inhibitor on modulating neuro-degenerative changes due to sciatic nerve compression. Materials and methods: The comparative effect of L-carnitine (at an oral dose of 20 mg/kg/day) or SIL citrate (20 mg/kg/day orally) administration for 21 days was studied in a rat model of sciatic nerve compression. Sciatic nerve sections were subjected to biochemical, histological, ultrastructure, and immunohistochemical studies to observe the effects of these treatments on neurofilament protein. Results: The sciatic nerve crush injury group (group II) showed a significant decrease in tissue catalase (CAT), superoxide dismutase (SOD) and increase in malondhyde (MDA) as compared to control group (P < 0.01). Histological changes in the form of degenerated and vacuolated axoplasm with areas of nerve fiber loss and pyknotic nuclei were reported. The blood vessels were dilated, congested with areas of hemorrhage and mononuclear cell infiltration. Histo-morphometrically, a statistically significant reduction in the nerve fibers number, mean axon cross-sectional area, myelin sheath thickness and a significant increase in collagen fibers percentage (P < 0.05) as compared to control group. Immunohistochemically, neurofilament protein was significantly downregulated as proved by a significant reduction in mean area % of neurofilament expression. L-carnitine ameliorated the studied parameters through it`s neuroprotective effect while Sildenafil (SIL) is a selective peripheral phosphodiesterases (PDE-5) inhibitor had improved crush injury parameters but with less extent than L-carnitine. Conclusions: These findings indicate the valuable effects of L-carnitine administration compared to that of SIL citrate in alleviating the serious debilitating effects of sciatic nerve crush injury. Our results provide a new insight into the scope of neuroprotective and, neuro-regenerative effects of L-carnitine in a sciatic nerve compression model

Синтез та дослідження фізико-хімічних властивостей 2-((5-(феноксиметил)-4-R-1,2,4-триазол-3-іл)тіо)етан-1-олів і їх похідних

The number of new various diseases increases with the development of science and technology. But currently medicine does not have effective ways to overcome this problem. There is a large number of different pharmacological groups of drugs at the pharmaceutical market, but some of them are not available for the Ukrainian consumers. Therefore, the main task of national scientists in the field of pharmaceutical synthesis is the search for new biologically active substances and their further introduction into medical practice as new, low-toxic, original medicines of the Ukrainian production at an affordable price. The aim of our research is the synthesis of a new class of biologically active substances, namely 2-((5-(phenoxymethyl)-4-R-1,2,4-triazol-3-yl)thio)ethan-1- ols and their derivatives. All compounds obtained have been synthesized from 5-(phen-oxymethyl)-4-R-1,2,4- triazol-3-thiones (R = H, C2H5, C6H5) using electrophilic and nucleophilic substitution reactions when heating. The structure of the compounds synthesized has been confirmed by using a modern set of physical and chemical methods such as IR-spectrometry, 1H NMR spectrometry and elemental analysis, and their individuality by high performance liquid chromatography-mass spectrometry. The work in determining the parameters of acute toxicity and biological activity is continued.С развитием научно-технического прогресса увеличивается количество новых разнообразных заболеваний, на преодоление которых медицина сегодня не имеет эффективных методов лечения. На мировом фармацевтическом рынке существует многочисленное количество различных фармакотерапевтических групп лекарственных средств, но не все они доступны украинскому потребителю. Поэтому основной задачей отечественных ученых в области фармацевтического синтеза является поиск новых биологически активных веществ и дальнейшее их внедрение во врачебную практику в качестве новых, малотоксичных, оригинальных лекарственных препаратов украинского производства по доступной цене. Целью нашего исследования является синтез нового класса биологически активных веществ – 2-((5-(феноксиметил)-4-R-1,2,4-триазол-3-ил)тио)этан-1-олов и их производных. Все полученные соединения были синтезированы на основе 5-(феноксиметил)-4-R-1,2,4-триазол-3-тионов (R=H, C2H5, C6H5) с использованием реакций электрофильного и нуклеофильного замещения при нагревании. Строение синтезированных соединений подтверждено комплексным использованием современных фи- зико-химических методов: ИК-спектрофотометрии, 1Н ЯМР-спектрометрии, элементного анализа, а их индивидуальность – ультравысокоэффективной жидкостной хромато-масс-спектрометрии. Про- должается работа по установлению показателей острой токсичности и биологической активности.З розвитком науково-технічного прогресу зростає кількість нових різноманітних захворювань, на подолання яких у медицині не існує на сьогодні ефективних методів лікування. На світовому фармацевтичному ринку існує численна кількість різних фармакотерапевтичних груп лікарських засобів, але не всі вони доступні українському споживачу. Тому основним завданням вітчизняних науковців у галузі фармацевтичного синтезу є пошук нових біологічно активних речовин та подальше їх впровадження у лікарську практику в якості нових, малотоксичних, оригінальних лікарських препаратів українського виробництва за доступною ціною. Метою нашого дослідження є синтез нового класу біологічно активних речовин – 2-((5-(феноксиметил)-4-R-1,2,4-триазол-3-іл)тіо)етан-1-олів та їх похідних. Всі отримані сполуки були синтезовані на основі 5-(феноксиметил)-4-R-1,2,4-триазол-3-тіонів (R = H, C2H5, C6H5) з використанням реакцій електрофільного та нуклеофільного заміщення при нагріванні. Будова синтезованих сполук підтверджена комплексним використанням сучасних фізико-хімічних методів: ІЧ-спектрофотометрії, 1Н ЯМР-спектрометрії та елементного аналізу, а їх індивідуальність – ультрависокоефективною рідинною хромато-мас-спектрометрією. Продовжується робота зі встановлення показників гострої токсичності та біологічної активності

Protective effects of some fruit juices with low-fat diet on rat testis damaged by carbon tetrachloride: A genetic and histological study

Oxidative stress, free radical, lipid peroxidation and antioxidant have become a common expression with most disease and methods for protection. Carbon tetrachloride (CCl4) is an industrial solvent which has destructive effects on a cell while most fruit juices have antioxidant effects. The aim of this study was to investigate the protective role of fruit juice on testis after toxic effect with CCl4 through oxidative stress with basal diet and low-fat diet. Seventy-five male albino rats were used for this study in which the juices of three fresh fruit, yellow apples (Malus domestica, L.), red grapes containing seeds (Vitis vinifera, L.) and pomegranates (Punica granatum, L.) were used as therapeutic agents. Histological sections of testis indicated that low-fat diet has obvious effects than basal diet in both the low-fat diet with CCl4 "LdC""con++", LdC with grape juice 2 ml "grpL2", LdC with pomegranate juice 2 ml "pomL2" and hyper effect in LdC with pomegranate juice 4 ml "pomL4" while it was equal in effect with basal diet in the other treatments. Low-fat diet gave significant effects (about 75% recovery in con++, LdC with Apple juice 2 ml and 4 ml "appL2, appL4" , LdC with grape juice 4 ml "grpL4" and pomL2) while 25% began to recover as shown in basal diet with pomegranate juice 4 ml "pomB4" and grpL2. Treatment of rats with pomegranate juice ameliorated the toxic effects of CCl4 with low-fat diet on Semi-random RAPD-DNA profile. Low-fat diet with fruit juice had positive effect against toxicity induced by CCl4 in testes of rats on the level of histological and DNA-RAPD studies.Key words: CCl4, rat testis, yellow apples, red grapes, pomegranates, low-fat diet, oxidative stress

Description of the Magnetic Field and Divergence of Multisolenoid Aharonov-Bohm Potential

Explicit formulas for the magnetic field and divergence of multisolenoid Aharonov-Bohm potential are obtained; the mathematical essence of this potential is explained. It is shown that the magnetic field and divergence of this potential are very singular generalized functions concentrated at a finite number of thin solenoids. Deficiency index is found for the minimal operator generated by the Aharonov-Bohm differential expression

Cilia Proteins are Biomarkers of Altered Flow in the Vasculature

Cilia, microtubule-based organelles that project from the apical luminal surface of endothelial cells (ECs), are widely regarded as low-flow sensors. Previous reports suggest that upon high shear stress, cilia on the EC surface are lost, and more recent evidence suggests that deciliation—the physical removal of cilia from the cell surface—is a predominant mechanism for cilia loss in mammalian cells. Thus, we hypothesized that EC deciliation facilitated by changes in shear stress would manifest in increased abundance of cilia-related proteins in circulation. To test this hypothesis, we performed shear stress experiments that mimicked flow conditions from low to high shear stress in human primary cells and a zebrafish model system. In the primary cells, we showed that upon shear stress induction, indeed, ciliary fragments were observed in the effluent in vitro, and effluents contained ciliary proteins normally expressed in both endothelial and epithelial cells. In zebrafish, upon shear stress induction, fewer cilia-expressing ECs were observed. To test the translational relevance of these findings, we investigated our hypothesis using patient blood samples from sickle cell disease and found that plasma levels of ciliary proteins were elevated compared with healthy controls. Further, sickled red blood cells demonstrated high levels of ciliary protein (ARL13b) on their surface after adhesion to brain ECs. Brain ECs postinteraction with sickle RBCs showed high reactive oxygen species (ROS) levels. Attenuating ROS levels in brain ECs decreased cilia protein levels on RBCs and rescued ciliary protein levels in brain ECs. Collectively, these data suggest that cilia and ciliary proteins in circulation are detectable under various altered-flow conditions, which could serve as a surrogate biomarker of the damaged endothelium

Evaluation of commercially available fully automated and ELISA-based assays for detecting anti-SARS-CoV-2 neutralizing antibodies

Rapid and accurate measurement of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-specific neutralizing antibodies (nAbs) is paramount for monitoring immunity in infected and vaccinated subjects. The current gold standard relies on pseudovirus neutralization tests which require sophisticated skills and facilities. Alternatively, recent competitive immunoassays measuring anti-SARS-CoV-2 nAbs are proposed as a quick and commercially available surrogate virus neutralization test (sVNT). Here, we report the performance evaluation of three sVNTs, including two ELISA-based assays and an automated bead-based immunoassay for detecting nAbs against SARS-CoV-2. The performance of three sVNTs, including GenScript cPass, Dynamiker, and Mindray NTAb was assessed in samples collected from SARS-CoV-2 infected patients (n = 160), COVID-19 vaccinated individuals (n = 163), and pre-pandemic controls (n = 70). Samples were collected from infected patients and vaccinated individuals 2–24 weeks after symptoms onset or second dose administration. Correlation analysis with pseudovirus neutralization test (pVNT) and immunoassays detecting anti-SARS-CoV-2 binding antibodies was performed. Receiver operating characteristic (ROC) curve analysis was generated to assess the optimal threshold for detecting nAbs by each assay. All three sVNTs showed an excellent performance in terms of specificity (100%) and sensitivity (100%, 97.0%, and 97.1% for GenScript, Dynamiker, and Mindray, respectively) in samples collected from vaccinated subjects. GenScript demonstrated the strongest correlation with pVNT (r = 0.743, R2 = 0.552), followed by Mindray (r = 0.718, R2 = 0.515) and Dynamiker (r = 0.608, R2 = 0.369). Correlation with anti-SARS-CoV-2 binding antibodies was variable, but the strongest correlations were observed between anti-RBD IgG antibodies and Mindray (r = 0.952, R2 = 0.907). ROC curve analyses demonstrated excellent performance for all three sVNT assays in both groups, with an AUC ranging between 0.99 and 1.0 (p < 0.0001). Also, it was shown that the manufacturer's recommended cutoff values could be modified based on the tested cohort without significantly affecting the sVNT performance. The sVNT provides a rapid, low-cost, and scalable alternative to conventional neutralization assays for measuring and expanding nAbs testing across various research and clinical settings. Also, it could aid in evaluating actual protective immunity at the population level and assessing vaccine effectiveness to lay a foundation for boosters' requirements.Funding was provided by Qatar Foundation (Grant number: UREP28-173-3-057), Shenzhen Mindray Bio-Medical Electronics Co., Ltd., Shenzhen, China, Qatar University (Grant number: RRC-2-032)

Assessment of Broadly Reactive Responses in Patients With MERS-CoV Infection and SARS-CoV-2 Vaccination

Importance: In the ongoing COVID-19 pandemic, there remain unanswered questions regarding the nature and importance of the humoral immune response against other coronaviruses. Although coinfection of the Middle East respiratory syndrome coronavirus (MERS-CoV) with the SARS-CoV-2 has not been documented yet, several patients previously infected with MERS-CoV received the COVID-19 vaccine; data describing how preexisting MERS-CoV immunity may shape the response to SARS-CoV-2 following infection or vaccination are lacking. Objective: To characterize the cross-reactive and protective humoral responses in patients exposed to both MERS-CoV infection and SARS-CoV-2 vaccination. Design, Setting, and Participants: This cohort study involved a total of 18 sera samples collected from 14 patients with MERS-CoV infection before (n = 12) and after (n = 6) vaccination with 2 doses of COVID-19 mRNA vaccine (BNT162b2 or mRNA-1273). Of those patients, 4 had prevaccination and postvaccination samples. Antibody responses to SARS-CoV-2 and MERS-CoV were assessed as well as cross-reactive responses to other human coronaviruses. Main Outcomes and Measures: The main outcomes measured were binding antibody responses, neutralizing antibodies, and antibody-dependent cellular cytotoxicity (ADCC) activity. Binding antibodies targeting SARS-CoV-2 main antigens (spike [S], nucleocapsid, and receptor-binding domain) were detected using automated immunoassays. Cross-reactive antibodies with the S1 protein of SARS-CoV, MERS-CoV, and common human coronaviruses were analyzed using a bead-based assay. Neutralizing antibodies (NAbs) against MERS-CoV and SARS-CoV-2 as well as ADCC activity against SARS-CoV-2 were assessed. Results: A total of 18 samples were collected from 14 male patients with MERS-CoV infection (mean [SD] age, 43.8 [14.6] years). Median (IQR) duration between primary COVID-19 vaccination and sample collection was 146 (47-189) days. Prevaccination samples had high levels of anti-MERS S1 immunoglobin M (IgM) and IgG (reactivity index ranging from 0.80 to 54.7 for IgM and from 0.85 to 176.3 for IgG). Cross-reactive antibodies with SARS-CoV and SARS-CoV-2 were also detected in these samples. However, cross-reactivity against other coronaviruses was not detected by the microarray assay. Postvaccination samples showed significantly higher levels of total antibodies, IgG, and IgA targeting SARS-CoV-2 S protein compared with prevaccination samples (eg, mean total antibodies: 8955.0 AU/mL; 95% CI, -5025.0 to 22936.0 arbitrary units/mL; P =.002). In addition, significantly higher anti-SARS S1 IgG levels were detected following vaccination (mean reactivity index, 55.4; 95% CI, -9.1 to 120.0; P =.001), suggesting potential cross-reactivity with these coronaviruses. Also, anti-S NAbs were significantly boosted against SARS-CoV-2 (50.5% neutralization; 95% CI, 17.6% to 83.2% neutralization; P <.001) after vaccination. Furthermore, there was no significant increase in antibody-dependent cellular cytotoxicity against SARS-CoV-2 S protein postvaccination. Conclusions and Relevance: This cohort study found a significant boost in cross-reactive NAbs in some patients exposed to MERS-CoV and SARS-CoV-2 antigens. These findings suggest that isolation of broadly reactive antibodies from these patients may help guide the development of a pancoronavirus vaccine by targeting cross-reactive epitopes between distinct strains of human coronaviruses..This work was supported by internal funds from the Biomedical Research Center of Qatar University. Dr Nasrallah received funding from The WHO Eastern Mediterranean Regional Office (WHO-EMRO) Special Grant for COVID-19 Research