Sustained linagliptin administration: superior glycemic control and less pancreatic injury in diabetic rats.

While linagliptin is the most potent dipeptidyl peptidase 4 inhibitor, its use is limited due to poor bioavailability and the potential risk of pancreatic injury. Here, we investigated whether the sustained weekly administration of linagliptin could provide better effect compared to frequent daily oral administration. Type 2 diabetes was induced by feeding rats a high fructose/fat/salt diet followed by STZ injection.

Assessment of the potential occurrence of species in various water sources in Sharqia Governorate, Egypt.

Unlabelled: species are enteric apicomplexan parasites associated with diarrhoeal disease in humans and animals globally. Waterborne outbreaks resulting from contamination with the infective oocysts are common worldwide. Updated reports on waterborne protozoal infections are needed to identify emerging pathogens and susceptible populations.

Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in Rats.

Background: The harmful consequences of non-alcoholic fatty liver disease (NAFLD) are posing an increasing threat to public health as the incidence of diabetes and obesity increases globally. A non-invasive treatment with a range of autonomic and metabolic benefits is transcutaneous vagus nerve stimulation (tVNS).

Aim Of The Study: To investigate the possible preventive impacts of VNS against adult rats' NAFLD caused by a high-fat diet (HFD) and to clarify the underlying mechanisms.

Tenascin-C Activation of Lung Fibroblasts in a 3D Synthetic Lung Extracellular Matrix Mimic.

The lung extracellular matrix (ECM) maintains the structural integrity of the tissue and regulates the phenotype and functions of resident fibroblasts. Lung-metastatic breast cancer alters these cell-ECM interactions, promoting fibroblast activation. There is a need for bio-instructive ECM models that match the ECM composition and biomechanics of the lung to study these cell-matrix interactions in vitro.

Tenascin-C activation of lung fibroblasts in a 3D synthetic lung extracellular matrix mimic.

The lung extracellular matrix (ECM) maintains the structural integrity of the tissue and regulates the phenotype and functions of resident fibroblasts. Lung-metastatic breast cancer alters these cell-ECM interactions, promoting fibroblast activation. There is a need for bio-instructive ECM models that contain the ECM composition and biomechanics of the lung to study these cell-matrix interactions .

Anticancer evaluation and molecular docking of new pyridopyrazolo-triazine and pyridopyrazolo-triazole derivatives.

3-Amino-4,6-dimethylpyrazolopyridine was applied as a precursor for the synthesis of some new pyridopyrazolo-triazine and pyridopyrazolo-triazole derivatives through diazotization, followed by coupling with many 2-cyanoacetamide compounds, ethyl 3-(phenylamino)-3-thioxopropanoate, 3-oxo-N-phenylbutanethioamide, and α-bromo-ketone reagents [namely; 2-bromo-1-(4-fluorophenyl)ethan-1-one, 5-bromo-2-(bromoacetyl)thiophene, 3-(2-bromoacetyl)-2H-chromen-2-one and/or 3-chloroacetylacetone]. The prepared compounds were identified by spectroscopic analyses as IR, H NMR, and mass data. The anticancer activity of these pyrazolopyridine analogues was investigated in colon, hepatocellular, breast, and cervix carcinoma cell lines.

Synthesis, biological evaluation and molecular docking of new triphenylamine-linked pyridine, thiazole and pyrazole analogues as anticancer agents.

A new series of pyridine, thiazole, and pyrazole analogues were synthesized. The pyridone analogues 4a-e were synthesized by treating N-aryl-2-cyano-3-(4-(diphenylamino)phenyl)acrylamides 3a-e with malononitrile. Many 4-arylidene-thiazolidin-5-one analogues 6a-d were obtained by Knoevenagel reactions of 4-(diphenylamino)benzaldehyde (1) with their corresponding thiazolidin-5-one derivatives 5a-d.

Cardiac autonomic neuropathy linked to left ventricular dysfunction in type 1 diabetic patients.

Unlabelled: Type 1 diabetes is a major cause of cardiovascular death; diabetic cardiomyopathy (DCM) is the most important cause of mortality among diabetic patients. There is an increasing body of evidence that the most important inducer of DCM is microvascular injury. The aim of this study is to establish a potential relationship between low frequency/high frequency (LF/HF) ratio and DCM and to set a possible predictive cutoff of LF:HF ratio for early detection of DCM.

ATP hydrolysis tunes specificity of a AAA+ protease.

In bacteria, AAA+ proteases such as Lon and ClpXP degrade substrates with exquisite specificity. These machines capture the energy of ATP hydrolysis to power unfolding and degradation of target substrates. Here, we show that a mutation in the ATP binding site of ClpX shifts protease specificity to promote degradation of normally Lon-restricted substrates.

Bioprospecting endophytic fungi for antifeedants and larvicides and their enhancement by gamma irradiation.

The search and discovery of new natural products with antifeedant and larvicidal potentials to mitigate harmful insects are scientific pressing issues in the modern agriculture. In this paper, the antifeedant and larvicidal potentials of 69 fungal isolates were screened against the Egyptian cotton leafworm Spodoptera littoralis. A total of 17 isolates showed the insecticidal potentials with three promising isolates.

Synthesis of Novel Triphenylamine-Based Organic Dyes with Dual Anchors for Efficient Dye-Sensitized Solar Cells.

A new series of metal-free organic dyes (SM1-5) with dual anchors are synthesized for application in dye-sensitized solar cells (DSSC). Here, a simple triphenylamine (TPA) moiety serves as the electron donor, while di-cyanoacrylamide and di-thiazolidine-5-one units serve as the electron acceptors and anchoring groups. To understand the effect of dye structure on the photovoltaic characteristics of DSSCs, the photophysical and electrochemical properties, as well as molecular geometries calculated from density functional theory (DFT), are used for dyes SM1-5.

Bioprospecting endophytic fungi for bioactive metabolites and use of irradiation to improve their bioactivities.

The search for new bioactive compounds with innovative modes of action and chemistry are desperately needed to tackle the increased emergence of drug-resistant microbes. With this view, this paper was conducted for the isolation, identification, and biological evaluation of fungal endophytes of eleven different plant species. A total of 69 endophytic strains were isolated and tested for the presence of bioactive metabolites with antifungal, antibacterial, anticancer, and antioxidant properties in their extracts.

Prediction of In Vivo Pharmacokinetic Parameters and Time-Exposure Curves in Rats Using Machine Learning from the Chemical Structure.

Animal pharmacokinetic (PK) data as well as human and animal in vitro systems are utilized in drug discovery to define the rate and route of drug elimination. Accurate prediction and mechanistic understanding of drug clearance and disposition in animals provide a degree of confidence for extrapolation to humans. In addition, prediction of in vivo properties can be used to improve design during drug discovery, help select compounds with better properties, and reduce the number of in vivo experiments.

Repurposing Lovastatin Cytotoxicity against the Tongue Carcinoma HSC3 Cell Line Using a Eucalyptus Oil-Based Nanoemulgel Carrier.

Tongue cancer is one of the most common carcinomas of the head and neck region. The antitumor activities of statins, including lovastatin (LV), and the essential oil of eucalyptus (Eu oil), have been adequately reported. The aim of this study was to develop a nanoemulgel containing LV combined with Eu oil that could then be made into a nanoemulsion and assessed to determine its cytotoxicity against the cell line human chondrosarcoma-3 (HSC3) of carcinoma of the tongue.

Imputation of sensory properties using deep learning.

Predicting the sensory properties of compounds is challenging due to the subjective nature of the experimental measurements. This testing relies on a panel of human participants and is therefore also expensive and time-consuming. We describe the application of a state-of-the-art deep learning method, Alchemite™, to the imputation of sparse physicochemical and sensory data and compare the results with conventional quantitative structure-activity relationship methods and a multi-target graph convolutional neural network.

Impact of cisplatin administration on cerebellar cortical structure and locomotor activity of infantile and juvenile albino rats: the role of oxidative stress.

The central neurotoxicity of cisplatin (CisPt) has always raised questions especially during development, but few studies are available. Hence, this work was designed to assess the CisPt's impacts on the postnatal rat cerebellum via evaluation of locomotor activity, histological and immunohistochemical studies, and to focus on cerebellar oxidative stress-related alterations. Eighty newborn pups were divided into 2 equal experimental groups: the control group was kept without any treatment and CisPt-treated group received a single subcutaneous injection of CisPt (5 μg /g b.

Molecular detection of brucellosis in dromedary camels of Qatar by real-time PCR technique.

Background And Methodology: Brucellosis in livestock causes huge economic loses of developing countries and demonstrates a serious health risks to the patrons of infected dairy goods and meat. Prevention of brucellosis in cattle relies on the trustworthiness of the techniques utilized to detect the causative pathogen. In the current investigation, we described the exploration of the well-known real-time PCR technique based on the Brucella-specific IS711 with different tissue samples of dromedary camels in Qatar.

Degradation of Lon in Caulobacter crescentus.

Protein degradation is an essential process in all organisms. This process is irreversible and energetically costly; therefore, protein destruction must be tightly controlled. While environmental stresses often lead to upregulation of proteases at the transcriptional level, little is known about posttranslational control of these critical machines.

c-di-GMP inhibits LonA-dependent proteolysis of TfoY in Vibrio cholerae.

The LonA (or Lon) protease is a central post-translational regulator in diverse bacterial species. In Vibrio cholerae, LonA regulates a broad range of behaviors including cell division, biofilm formation, flagellar motility, c-di-GMP levels, the type VI secretion system (T6SS), virulence gene expression, and host colonization. Despite LonA's role in cellular processes critical for V.

Understanding Conditional Associations between ToxCast Readouts and the Hepatotoxicity of Compounds Using Rule-Based Methods.

Current models for hepatotoxicity commonly suffer from low detection rates due to incomplete coverage of bioactivity space. Additionally, exposure measures such as are used for hepatotoxicity screening and are unavailable early on. Here we propose a novel rule-based framework to extract interpretable and biologically meaningful multiconditional associations to prioritize end points for hepatotoxicity and understand the associated physicochemical conditions.

Leveraging heterogeneous data from GHS toxicity annotations, molecular and protein target descriptors and Tox21 assay readouts to predict and rationalise acute toxicity.

Despite the increasing knowledge in both the chemical and biological domains the assimilation and exploration of heterogeneous datasets, encoding information about the chemical, bioactivity and phenotypic properties of compounds, remains a challenge due to requirement for overlap between chemicals assayed across the spaces. Here, we have constructed a novel dataset, larger than we have used in prior work, comprising 579 acute oral toxic compounds and 1427 non-toxic compounds derived from regulatory GHS information, along with their corresponding molecular and protein target descriptors and qHTS in vitro assay readouts from the Tox21 project. We found no clear association between the results of a FAFDrugs4 toxicophore screen and the acute oral toxicity classifications for our compound set; and a screen using a subset of the ToxAlerts toxicophores was also of limited utility, with only slight enrichment toward the toxic set (odds ratio of 1.

Epidemiological and Clinical Features of Typhi Infection Among Adult Patients in Qatar: A Hospital-based Study.

Objectives: We sought to describe the epidemiological and clinical features of typhoid fever in Qatar.

Methods: We conducted a retrospective study of adult patients treated for typhoid fever at Hamad General Hospital and Alkhor Hospital between 2005 and 2012.

Results: The mean age of the 354 patients enrolled in the study was 28.

Information-Derived Mechanistic Hypotheses for Structural Cardiotoxicity.

Adverse events resulting from drug therapy can be a cause of drug withdrawal, reduced and or restricted clinical use, as well as a major economic burden for society. To increase the safety of new drugs, there is a need to better understand the mechanisms causing the adverse events. One way to derive new mechanistic hypotheses is by linking data on drug adverse events with the drugs' biological targets.

Regulated Proteolysis in Bacteria.

Regulated proteolysis is a vital process that affects all living things. Bacteria use energy-dependent AAA+ proteases to power degradation of misfolded and native regulatory proteins. Given that proteolysis is an irreversible event, specificity and selectivity in degrading substrates are key.