Metformin: A Small Molecule with Multi-Targets and Diverse Therapeutic Applications

Metformin is one of the most prescribed agents in the treatment of type 2 diabetes. Its history goes back to the use of goat’s rue (Galega officinalis Linn., Fabaceae). G. officinalis is rich in galegine, a guanidine derivative with a blood glucose-lowering effect. Research based on the effects of guanidine rich on this traditional herbal medicine led to the development of metformin. Metformin continues to serve as a multi-target drug. Its benefits for treating/controlling several diseases were thoroughly discovered over time. These include health disorders such as cancers, obesity, periodontitis, cardiovascular, liver, skin, and renal disorders. Moreover, there is evidence to propose that metformin postpones the aging processes as well as modulates the microbiota to promote better health. So far, it is not fully understood, how metformin can accomplish such pleiotropic pharmacological and therapeutic effects. Metformin may decrease malignancy via suppressing the signal of insulin/IGF-1, avoiding the release of cytokines via NF-κB, and increasing the immune reaction to cancer cells. This chapter discusses the history of metformin discovery, chemistry, its role in diabetic patients, and proposed molecular mechanisms to shed more light on the diverse effects and its ability to target multiple signaling pathways

Cytotoxic activity of silver nanoparticles prepared from Psidium guajava L. (Myrtaceae) and Lawsonia inermis L. (Lythraceae) extracts

Purpose: To biosynthesize silver nanoparticles (AgNPs) using Psidium guajava L. and Lawsonia inermis L. leaf extracts, and investigate their antioxidant and cytotoxic activities.Methods: The aqueous extracts were prepared by maceration in distilled H2O followed by partitioning with EtOAc. AgNPs were prepared by treating the extracts with 1 mM AgNO3 and then were characterized by UV-vis and FTIR analyses, and transmission electron microscopy (TEM). MTT cytotoxicity and 2,2`-azinobis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) antioxidant assays were used to assess their cytotoxic and antioxidant properties, respectively.Results: AgNPs from P. guajava and L. inermis extracts exhibited good morphological stability and showed moderate antioxidant activity (68.1 and 71.9%, respectively) compared to their extracts. Equipotent cytotoxicity against HCT-116 and MCF-7 cells was observed for AgNPs derived from P.guajava, while AgNPs derived from L. inermis possessed two-fold cytotoxicity compared to their corresponding extracts. Phytochemical analysis of P. guajava afforded pyrogallol, quercetin, quercetin-3-O-β-xylopyranoside, quercetin-3-O-β-arabinopyranoside, and quercetin-3-O-α-rabinofuranoside, while L. inermis afforded lawsone and luteolin.Conclusion: Flavonoids and phenolics play a major role in reducing Ag+ ions, surface coating, antioxidant, and cytotoxic activities of AgNPs. The biocompatible AgNPs produced by L. inermis demonstrate promising cytotoxic activity that could contribute to new cancer treatments

Corrigendum to “Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma”

This is a critical needed correction. In Fig. 15, the image corresponding to the lung from mouse treated with 25 mg/kg was taken from the same section of the mouse that was treated with 10 mg/kg. The corrected Fig. 15 [Formula presented] Fig. 15. Microscopic pictures of H&amp;E stained lung sections from groups received (A) 4*106 cells/200 μL showing congested blood vessels (red arrows), peribronchial and interstitial aggregation (black arrows) of tumour cells admixed with MNCs. Microscopic pictures of H&amp;E stained lungs sections from treated groups (B) 10 or (c) 25 mg/kg) showing disappeared congestion with decreased numbers of perivascular and interstitial infiltration of tumour cells. Increasing dose of treatment 25 mg/kg was more efficient than 10 mg/kg. Low magnification X: 100 with 100 μm scale bar.</p

Corrigendum to “Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma”

This is a critical needed correction. In Fig. 15, the image corresponding to the lung from mouse treated with 25 mg/kg was taken from the same section of the mouse that was treated with 10 mg/kg. The corrected Fig. 15 [Formula presented] Fig. 15. Microscopic pictures of H&amp;E stained lung sections from groups received (A) 4*106 cells/200 μL showing congested blood vessels (red arrows), peribronchial and interstitial aggregation (black arrows) of tumour cells admixed with MNCs. Microscopic pictures of H&amp;E stained lungs sections from treated groups (B) 10 or (c) 25 mg/kg) showing disappeared congestion with decreased numbers of perivascular and interstitial infiltration of tumour cells. Increasing dose of treatment 25 mg/kg was more efficient than 10 mg/kg. Low magnification X: 100 with 100 μm scale bar.</p

Corrigendum to “Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma”

This is a critical needed correction. In Fig. 15, the image corresponding to the lung from mouse treated with 25 mg/kg was taken from the same section of the mouse that was treated with 10 mg/kg. The corrected Fig. 15 [Formula presented] Fig. 15. Microscopic pictures of H&amp;E stained lung sections from groups received (A) 4*106 cells/200 μL showing congested blood vessels (red arrows), peribronchial and interstitial aggregation (black arrows) of tumour cells admixed with MNCs. Microscopic pictures of H&amp;E stained lungs sections from treated groups (B) 10 or (c) 25 mg/kg) showing disappeared congestion with decreased numbers of perivascular and interstitial infiltration of tumour cells. Increasing dose of treatment 25 mg/kg was more efficient than 10 mg/kg. Low magnification X: 100 with 100 μm scale bar.</p

Corrigendum to “Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma”

This is a critical needed correction. In Fig. 15, the image corresponding to the lung from mouse treated with 25 mg/kg was taken from the same section of the mouse that was treated with 10 mg/kg. The corrected Fig. 15 [Formula presented] Fig. 15. Microscopic pictures of H&amp;E stained lung sections from groups received (A) 4*106 cells/200 μL showing congested blood vessels (red arrows), peribronchial and interstitial aggregation (black arrows) of tumour cells admixed with MNCs. Microscopic pictures of H&amp;E stained lungs sections from treated groups (B) 10 or (c) 25 mg/kg) showing disappeared congestion with decreased numbers of perivascular and interstitial infiltration of tumour cells. Increasing dose of treatment 25 mg/kg was more efficient than 10 mg/kg. Low magnification X: 100 with 100 μm scale bar.</p

Corrigendum to “Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma”

This is a critical needed correction. In Fig. 15, the image corresponding to the lung from mouse treated with 25 mg/kg was taken from the same section of the mouse that was treated with 10 mg/kg. The corrected Fig. 15 [Formula presented] Fig. 15. Microscopic pictures of H&amp;E stained lung sections from groups received (A) 4*106 cells/200 μL showing congested blood vessels (red arrows), peribronchial and interstitial aggregation (black arrows) of tumour cells admixed with MNCs. Microscopic pictures of H&amp;E stained lungs sections from treated groups (B) 10 or (c) 25 mg/kg) showing disappeared congestion with decreased numbers of perivascular and interstitial infiltration of tumour cells. Increasing dose of treatment 25 mg/kg was more efficient than 10 mg/kg. Low magnification X: 100 with 100 μm scale bar.</p

Prevalence and Determinants of Metabolic Syndrome in Qatar: Results from a National Health Survey

OBJECTIVES: To determine optimum measurements for abdominal obesity and to assess the prevalence and determinants of metabolic syndrome in Qatar. DESIGN: National health survey. SETTING: Qatar National STEPwise Survey conducted by the Supreme Council of Health during 2012. PARTICIPANTS: 2496 Qatari citizens aged 18-64 representative of the general population. PRIMARY AND SECONDARY OUTCOME MEASURES: Measure of obesity (body mass index, waist circumference or waist-to-height ratio) that best identified the presence of at least 2 other factors of metabolic syndrome; cut-off values of waist circumference; frequency of metabolic syndrome. RESULTS: Waist circumference ≥102 for men and ≥94 cm for women was the best predictor of the presence of other determinants of metabolic syndrome (raised blood pressure, fasting blood glucose, triglycerides and reduced high-density lipoprotein cholesterol). Using these values, we identified 28% of Qataris with metabolic syndrome, which is considerably lower than the estimate of 37% calculated using the International Diabetes Federation (IDF) criteria. Restricting the analysis to participants without known elevated blood pressure, elevated blood sugar or diabetes 16.5% would be classified as having metabolic syndrome. In a multivariable logistic regression analysis, the prevalence of metabolic syndrome increased steadily with age (OR=3.40 (95% CI 2.02 to 5.74), OR=5.66 (3.65 to 8.78), OR=10.2 (5.98 to 17.6) and OR=18.2 (7.01 to 47.5) for those in the age group \u2730-39\u27, \u2740-49\u27, \u2750-59\u27, \u2760-64\u27 vs \u2718-29\u27; p CONCLUSIONS: Waist circumference was the best measure of obesity to combine with other variables to construct a country-specific definition of metabolic syndrome in Qatar. Approximately 28% of adult Qatari citizens satisfy the criteria for metabolic syndrome, which increased significantly with age. Education and physical activity were inversely associated with this syndrome

Towards a sterile insect technique field release of Anopheles arabiensis mosquitoes in Sudan: Irradiation, transportation, and field cage experimentation

<p>Abstract</p> <p>Background</p> <p>The work described in this article forms part of a study to suppress a population of the malaria vector <it>Anopheles arabiensis </it>in Northern State, Sudan, with the Sterile Insect Technique. No data have previously been collected on the irradiation and transportation of anopheline mosquitoes in Africa, and the first series of attempts to do this in Sudan are reported here. In addition, experiments in a large field cage under near-natural conditions are described.</p> <p>Methods</p> <p>Mosquitoes were irradiated in Khartoum and transported as adults by air to the field site earmarked for future releases (400 km from the laboratory). The field cage was prepared for experiments by creating resting sites with favourable conditions. The mating and survival of (irradiated) laboratory males and field-collected males was studied in the field cage, and two small-scale competition experiments were performed.</p> <p>Results</p> <p>Minor problems were experienced with the irradiation of insects, mostly associated with the absence of a rearing facility in close proximity to the irradiation source. The small-scale transportation of adult mosquitoes to the release site resulted in minimal mortality (< 6%). Experiments in the field cage showed that mating occurred in high frequencies (i.e. an average of 60% insemination of females after one or two nights of mating), and laboratory reared males (i.e. sixty generations) were able to inseminate wild females at rates comparable to wild males. Based on wing length data, there was no size preference of males for mates. Survival of mosquitoes from the cage, based on recapture after mating, was satisfactory and approximately 60% of the insects were recaptured after one night. Only limited information on male competitiveness was obtained due to problems associated with individual egg laying of small numbers of wild females.</p> <p>Conclusion</p> <p>It is concluded that although conditions are challenging, there are no major obstacles associated with the small-scale irradiation and transportation of insects in the current setting. The field cage is suitable for experiments and studies to test the competitiveness of irradiated males can be pursued. The scaling up of procedures to accommodate much larger numbers of insects needed for a release is the next challenge and recommendations to further implementation of this genetic control strategy are presented.</p