Glucose metabolism abnormalities among pediatric acute lymphoblastic leukemia survivors: Assessment and relation to body mass index and waist to hip ratio

AbstractBackgroundAs survival rates of pediatric acute lymphoblastic leukemia (ALL) improve, attention is turning to side and late effects of therapy including glucose metabolism abnormalities.ObjectiveTo asses the presence of abnormal glucose metabolism in pediatric ALL survivors and its possible relation to body mass index (BMI), waist to hip ratio and treatment related factors.Subjects and methodsRetrospective study with a prospective follow-up of 12 ALL survivors who had been off chemotherapy for >9months was done. Fifteen healthy sex and age matched children were involved as controls. Body mass index (BMI) waist to hip ratio (WHR), and Oral glucose tolerance test (OGTT) were performed with assessment of glycated hemoglobin (Hb A1C) and insulin sensitivity indices.ResultsAt study time the mean BMI, WHR, all components of the OGTT (except the 2h post load glucose), all indices of insulin sensitivity and the mean Hb A1C% were significantly higher compared to those of the controls. Two survivors (16.6%) developed transient hyperglycemia during therapy, one (8.3%) had pre-diabetes, seven (58.3%) had a risk level of Hb A1C but no one had diabetes mellitus (DM) or insulin resistance (IR). At study time the two survivors with transient hyperglycemia during therapy had a significantly high WHR compared to the remainders. WHR of the survivors at study time correlated significantly with fasting plasma glucose and area of insulin under the curve (AUC). The 2h post-prandial plasma glucose correlated with the duration after therapy completion.ConclusionsWHR may play a better role than BMI in the prediction of insulin resistance in those patients. Hb A1C may increase earlier than other indices of glucose tolerance

Quinazolinone-based rhodanine-3-acetic acids as potent aldose reductase inhibitors: Synthesis, functional evaluation and molecular modeling study

A series of quinazolinone-based rhodanine-3-acetic acids was synthesized and tested for in vitro aldose reductase inhibitory activity. All the target compounds displayed nanomolar activity against the target enzyme. Compounds 3a, 3b, and 3e exhibited almost 3-fold higher activity as compared to the only marketed reference drug epalrestat. Structure-activity relationship studies indicated that bulky substituents at the 3-phenyl ring of the quinazolinone moiety are generally not tolerated in the active site of the enzyme. Insertion of a methoxy group on the central benzylidene ring was found to have a variable effect on ALR-2 activity depending on the nature of peripheral quinazolinone ring substituents. Removal of the acetic acid moiety led to inactive or weakly active target compounds. Docking and molecular dynamic simulations of the most active rhodanine-3-acetic acid derivatives were also carried out, to provide the basis for further structure-guided design of novel inhibitors

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Phytochemical Investigation of <i>Cordia africana</i> Lam. Stem Bark: Molecular Simulation Approach

Background: The current work planned to evaluate Cordia africana Lam. stem bark, a traditionally used herb in curing of different ailments in Africa such as gastritis and wound infections, based on phytochemical and antibacterial studies of two pathogenic microorganisms: methicillin-resistant Staphylococcus aureus (MRSA) and Helicobacter pylori. Methods: High performance liquid chromatography (HPLC) profiling was used for qualitative and quantitative investigation of the ethanol extract. The minimum inhibitory concentration (MIC) of the ethanolic extract and isolated compounds was estimated using the broth microdilution method and evidenced by molecular dynamics simulations. Results: Four compounds were isolated and identified for the first time: α-amyrin, β-sitosterol, rosmarinic acid (RA) and methyl rosmarinate (MR). HPLC analysis illustrated that MR was the dominant phenolic acid. MR showed the best bacterial inhibitory activity against MRSA and H. pylori with MIC 7.81 ± 1.7 μg/mL and 31.25 ± 0.6, respectively, when compared to clarithromycin and vancomycin, respectively. Conclusion: The antibacterial activity of the stem bark of Cordia africana Lam. was evidenced against MRSA and H. pylori. Computational modeling of the studied enzyme-ligands systems reveals that RA and MR can potentially inhibit both MRSA peptidoglycan transpeptidases and H. pylori urease, thereby creating a pathway via the use of a double target approach in antibacterial treatment

LC-MS/MS profiling of Tipuana tipu flower, HPLC-DAD quantification of its bioactive components, and interrelationships with antioxidant, and anti-inflammatory activity: in vitro and in silico approaches

Abstract Background Fabaceae plays a crucial role in African traditional medicine as a source of large number of important folk medication, agriculture and food plants. In a search of potential antioxidant and anti-inflammatory candidates derived from locally cultivated plants, the flowers of Tipuana tipu (Benth.) Lillo growing in Egypt were subjected to extensive biological and phytochemical studies. The impact of the extraction technique on the estimated biological activities was investigated. Methods The flowers were extracted using different solvents (aqueous, methanol, water/methanol (1:1), methanol/methylene chloride (1:1), and methylene chloride). The different extracts were subjected to antioxidant (DPPH, ABTS, and FRAP) and anti-inflammatory (COX-2 and 5-LOX) assays. The methanol extract was assessed for its inhibitory activity against iNOS, NO production, and pro-inflammatory cytokines (NF-KB, TNF-R2, TNF-α, IL-1β, and IL-6) in LPS-activated RAW 264.7 macrophages. The composition-activity relationship of the active methanol extract was further investigated using a comprehensive LC–QTOF-MS/MS analysis. The major identified phenolic compounds were further quantified using HPLC-DAD technique. The affinity of representative compounds to iNOS, COX-2, and 5-LOX target active sites was investigated using molecular docking and molecular dynamics simulations. Results The methanol extract exhibited the highest radical scavenging capacity and enzyme inhibitory activities against COX-2 and 5-LOX enzymes with IC50 values of 10.6 ± 0.4 and 14.4 ± 1.0 µg/mL, respectively. It also inhibited iNOS enzyme activity, suppressed NO production, and decreased the secretion of pro-inflammatory cytokines. In total, 62 compounds were identified in the extract including flavonoids, coumarins, organic, phenolic, and fatty acids. Among them 18 phenolic compounds were quantified by HPLC-DAD. The highest docking scores were achieved by kaempferol-3-glucoside and orientin. Additionally, molecular dynamics simulations supported the docking findings. Conclusion The flower could be considered a potentially valuable component in herbal medicines owing to its unique composition and promising bioactivities. These findings encourage increased propagation of T. tipu or even tissue culturing of its flowers for bioprospecting of novel anti-inflammatory drugs. Such applications could be adopted as future approaches that benefit the biomedical field

Design, Synthesis, Docking Studies and Biological Evaluation of Novel Benzochromenopyrimidines via Silica Sulfuric Acid Catalyzed Reaction on Apoptosis in Human Cancer Cells

Via one-pot reaction of 2-naphthol, thiobarbituric acid and aldehyde in the presence of silica sulfuric acid (SSA) as a catalyst to synthesis benzochromenopyrimidines derivatives. Then we studied the reaction of benzochromenopyrimidines derivatives with bromoacetic acid to obtain benzo[5,6]chromeno[2,3-d]thiazolo[3,2-a]pyrimidine-11,13(10H,14H)-dione derivatives. Meanwhile, dichloroethane was reacted with 12-(4-fluorophenyl)-9-thioxo-9,10-dihydro-8H-benzo[5,6]chromeno[2,3-d]pyrimidin-11(12H)-one to form 14-(4-fluorophenyl)-10,11-dihydrobenzo[5,6]chromeno[2,3-d]thiazolo[3,2-a]pyrimidin-13(14H)-one. All new products structure was elucidated based on analytical and spectroscopic analyses. Anti-cancer activity of newly synthesized structures was investigated. Cancer cells (MDA-MB-231 and HepG2) were used to evaluate the anti-cancer activity of tested compounds using neutral red uptake assay. Treatment of MDA-MB-231 and HepG2 cells with tested compound 6h revealed more inhibitory influence after 48 h. The expression levels of BCL2, BAX, Caspase3, Survivin and P53 genes were investigated using QRT-PCR. This study exhibited that compound 6h revealed significant pro-apoptotic effect via down regulation of BCL2 and Survivin genes and up-regulation of BAX, Caspase3 and P53 genes when treated with MDA-MB-231 and HepG2 cells as compared to control values. The biological studies of these compounds were proved through molecular docking studies with human cyclin-dependent kinase 2 (PDB code: 2A4L) and compound 6h showed low binding energy and shortage bond length with different amino acids. Noteworthy, the tested compound 6h exhibited the most pronounced effect in this respect.</p

Evaluation and Characterization of Alginate Extracted from Brown Seaweed Collected in the Red Sea

Alginates are one of the most important compounds of brown seaweeds. These compounds are employed in the food area, because of their important rheological properties, such as viscosity, gelling, and stabilizing features and as dietary fiber source. In this study, five species of dominant brown seaweeds were collected in the Red Sea (Padina boergesenii, Turbinaria triquetra, Hormophysa cuneiformis, Dictyota ciliolata, and Sargassum aquifolium) so as to characterize the alginate yield and its properties. The analysis demonstrated differences in the alginate yield among the seaweeds. The highest yield of alginate was recorded in the species T. triquetra (22.2 0.56% DW), while the lowest content was observed in H. cuneiformis (13.3 0.52% DW). The viscosity from the alginates varied greatly between the species, whereas the pH varied slightly. The alginate exhibited a moisture content between 6.4 and 13.1%, the ash content ranged between 12.3 and 20%DW, the protein reached values from 0.57 to 1.47% DW, and the lipid concentration varied from 0.3 to 3.5% DW. Thus, the phytochemical analysis demonstrated that the extracted alginates can be safely applied in the food industry. Furthermore, the alginate yield reveals the potential application of these seaweeds as a nutraceutical raw source, which can be exploited by the food industry

Fillet Fish Fortified with Algal Extracts of <i>Codium tomentosum</i> and <i>Actinotrichia fragilis</i>, as a Potential Antibacterial and Antioxidant Food Supplement

With respect to the potential natural resources in the marine environment, marine macroalgae or seaweeds are recognized to have health impacts. Two marine algae that are found in the Red Sea, Codium tomentosum (Green algae) and Actinotrichia fragilis (Red algae), were collected. Antibacterial and antioxidant activities of aqueous extracts of these algae were evaluated in vitro. Polyphenols from the extracts were determined using HPLC. Fillet fish was fortified with these algal extracts in an attempt to improve its nutritional value, and sensory evaluation was performed. The antibacterial effect of C. tomentosum extract was found to be superior to that of A. fragilis extract. Total phenolic contents of C. tomentosum and A. fragilis aqueous extract were 32.28 ± 1.63 mg/g and 19.96 ± 1.28 mg/g, respectively, while total flavonoid contents were 4.54 ± 1.48 mg/g and 3.86 ± 1.02 mg/g, respectively. Extract of C. tomentosum demonstrates the highest antioxidant activity, with an IC50 value of 75.32 ± 0.07 μg/mL. The IC50 of L-ascorbic acid as a positive control was 22.71 ± 0.03 μg/mL. The IC50 values for inhibiting proliferation on normal PBMC cells were 33.7 ± 1.02 µg/mL and 51.0 ± 1.14 µg/mL for C. tomentosum and A. fragilis, respectively. The results indicated that both algal aqueous extracts were safe, with low toxicity to normal cells. Interestingly, fillet fish fortified with C. tomentosum extract demonstrated the greatest overall acceptance score. These findings highlight the potential of these seaweed species for cultivation as a sustainable and safe source of therapeutic compounds for treating human and fish diseases, as well as effective food supplements and preservatives instead of chemical ones after performing in vivo assays