Bioactive Phytochemicals: Efficient Synthesis of Optically Active Substituted Flav-3-enes and Flav-3-en-3-o-R Derivatives

Published ArticleThe structural core of flavene (2-phenyl-2H-chromene) is commonly found in plant flavonoids, which exhibit a wide range of biological activities and diverse pharmacological profiles (e.g., antioxidant and anticancer activities). Flavonoids have attracted significant interest inmedicinal and synthetic chemistry. Substituted flav-3-ene 13 was exclusively synthesized by the stereoselective elimination of the O-mesyl moiety on C-3 of 5,7,3,4-tetramethoxyflavan-3-mesylate 12 with 1,8-diazabicyclo[5.4.0]undec-7-ene. The reaction of 5,7,3,4-tetramethoxyflavan-3-one 15 with ytterbium trifluoromethanesulfonate in methanol afforded a novel 3-Osubstituted flav-3-ene derivative (3,5,7,3,4-pentamethoxyflav-3-ene) 17. The reduction of 4-(1,3,5-trihydroxybenzene)-5,7,3,4- tetra-O-benzylflavan-3-one 19b with hydrogen afforded a new compound: 3-hydroxy-4-(1,3,5-trihydroxybenzene)-5,7,3,4- tetrahydroxyflavan-3-en-3-ol 21 in good yield (95%), while the acetylation of 19a and 21 afforded the expected novel flav-3-en- 3-acetoxy derivatives 20 (92%) and 22 (90%), respectively

Bioactive Phytochemicals: Efficient Synthesis of Optically Active Substituted Flav-3-enes and Flav-3-en-3-o-R Derivatives

The structural core of flavene (2-phenyl-2H-chromene) is commonly found in plant flavonoids, which exhibit a wide range of biological activities and diverse pharmacological profiles (e.g., antioxidant and anticancer activities). Flavonoids have attracted significant interest in medicinal and synthetic chemistry. Substituted flav-3-ene 13 was exclusively synthesized by the stereoselective elimination of the O-mesyl moiety on C-3 of 5,7,3′,4′-tetramethoxyflavan-3-mesylate 12 with 1,8-diazabicyclo[5.4.0]undec-7-ene. The reaction of 5,7,3′,4′-tetramethoxyflavan-3-one 15 with ytterbium trifluoromethanesulfonate in methanol afforded a novel 3-O-substituted flav-3-ene derivative (3,5,7,3′,4′-pentamethoxyflav-3-ene) 17. The reduction of 4-(1,3,5-trihydroxybenzene)-5,7,3′,4′-tetra-O-benzylflavan-3-one 19b with hydrogen afforded a new compound: 3-hydroxy-4-(1,3,5-trihydroxybenzene)-5,7,3′,4′-tetrahydroxyflavan-3-en-3-ol 21 in good yield (95%), while the acetylation of 19a and 21 afforded the expected novel flav-3-en-3-acetoxy derivatives 20 (92%) and 22 (90%), respectively

Chemical Composition and Nutritive Benefits of Chicory (Cichorium intybus)

Chicory is a perennial plant grown in different parts of the world, used as forage for livestock, as folklore remedies, or as a vegetable addition in human diets. There are several varieties of the chicory plant, known differently globally due to its numerous medicinal, culinary, and nutritional qualities. Most parts of the plant contain a potpourri of nutrients ranging within carbohydrates, proteins, vitamins, minerals, soluble fiber, trace elements, and bioactive phenolic compounds, which are responsible for the various nutritive, prophylactic, and therapeutic qualities of chicory. Inulin, coumarins, tannins, monomeric flavonoids, and sesquiterpene lactones are some of the major phytocompounds mostly found in chicory plants. The health-promoting activities attributed to chicory comprise, among others, anti-inflammatory, anticarcinogenic, antiviral, antibacterial, antimutagenic, antifungal, anthelmintic, immune-stimulating, and antihepatotoxic and its antioxidative qualities. As a versatile plant, chicory’s chemical composition and use as a suitable livestock feed supplement or as an alternative feed ingredient (AFI) are thus reviewed

Association of operative approach with postoperative outcomes in neonates undergoing surgical repair of esophageal atresia and tracheoesophageal fistula

Introduction: Minimally invasive surgery (MIS) is gaining traction as a first-line approach to repair congenital anomalies. This study aims to evaluate outcomes for neonates undergoing open versus MIS repairs for esophageal atresia/tracheoesophageal fistula (EA/TEF). Methods: Neonates undergoing EA/TEF repair from 2013-2020 were identified using the National Surgical Quality Improvement Program-Pediatric database. Proportions of operative approach (open vs. MIS) over time were analyzed. A propensity score-matched analysis using preoperative characteristics was performed and outcomes were compared including composite morbidity and reintervention rates (overall, major [thoracoscopy, thoracotomy], and minor [chest/feeding tube placement, endoscopy]) between operative approaches. Pearson’s chi-square or Fisher’s exact test were used as appropriate. Results: We identified 1738 neonates who underwent EA/TEF repair. MIS utilization increased over time (p=0.019). Pre-match, neonates undergoing open repair were more likely premature, lower weight, and higher ASA class. Post-match, the groups were similar and included 183 neonates per group. MIS repair was associated with longer median operative time (206 vs. 180 minutes, p\u3c0.001), increased overall reintervention rates (MIS 9.8% vs. open 3.3%, p=0.011), and increased minor reintervention rates (MIS 7.7% vs. open 2.2%, p=0.016). There were no differences in composite morbidity (MIS 20.2% vs. open 26.8%, p=0.14) or major reinterventions (MIS 2.2% vs. open 1.1%, p=0.41). Discussion: MIS is gaining traction as a first-line approach for neonates with EA/TEF but appears to be associated with a higher rate of reinterventions. Further studies evaluating MIS approaches for the repair of EA/TEF are needed to better define short and long-term outcomes to optimize patient selection

Traumatic injury in the United States: In-patient epidemiology 2000–2011

Background Trauma is a leading cause of death and disability in the United States (US). This analysis describes trends and annual changes in in-hospital trauma morbidity and mortality; evaluates changes in age and gender specific outcomes, diagnoses, causes of injury, injury severity and surgical procedures performed; and examines the role of teaching hospitals and Level 1 trauma centres in the care of severely injured patients. Methods We conducted a retrospective descriptive and analytic epidemiologic study of an inpatient database representing 20,659,684 traumatic injury discharges from US hospitals between 2000 and 2011. The main outcomes and measures were survey-adjusted counts, proportions, means, standard errors, and 95% confidence intervals. We plotted time series of yearly data with overlying loess smoothing, created tables of proportions of common injuries and surgical procedures, and conducted survey-adjusted logistic regression analysis for the effect of year on the odds of in-hospital death with control variables for age, gender, weekday vs. weekend admission, trauma-centre status, teaching-hospital status, injury severity and Charlson index score. Results The mean age of a person discharged from a US hospital with a trauma diagnosis increased from 54.08 (s.e. = 0.71) in 2000 to 59.58 (s.e. = 0.79) in 2011. Persons age 45–64 were the only age group to experience increasing rates of hospital discharges for trauma. The proportion of trauma discharges with a Charlson Comorbidity Index score greater than or equal to 3 nearly tripled from 0.048 (s.e. = 0.0015) of all traumatic injury discharges in 2000 to 0.139 (s.e. = 0.005) in 2011. The proportion of patients with traumatic injury classified as severe increased from 22% of all trauma discharges in 2000 (95% CI 21, 24) to 28% in 2011 (95% CI 26, 30). Level 1 trauma centres accounted for approximately 3.3% of hospitals. The proportion of severely injured trauma discharges from Level 1 trauma centres was 39.4% (95% CI 36.8, 42.1). Falls, followed by motor-vehicle crashes, were the most common causes of all injuries. The total cost of trauma-related inpatient care between 2001 and 2011 in the US was $240.7 billion (95$12.0 billion (95% CI 10.5, 13.4) in 2001 to 29.1 billion (95% CI 25.2, 32.9) in 2011. Conclusions Trauma, which has traditionally been viewed as a predicament of the young, is increasingly a disease of the old. The strain of managing the progressively complex and costly care associated with this shift rests with a small number of trauma centres. Optimal care of injured patients requires a reappraisal of the resources required to effectively provide it given a mounting burden

Studies of intestinal inflammation: the roles of IL-23R, gamma-delta T-cells and IL-21i

The aetiology of the inflammatory bowel diseases ulcerative colitis and Crohn’s disease remains uncertain. Genetic studies and model systems strongly implicate components of the IL-23/type-17 axis in the pathogenesis of disease, but the cellular and molecular mediators are uncertain. Using an IL-23Rgfp reporter mouse we analysed the cellular expression of IL-23R in homeostasis and disease. Whereas steady state expression in the intestine was dominated by a collection of unconventional lymphoid cells including gamma delta T-cells, we found rapid accumulation of IL-23R+CD4+-/- mice developing increased bacterial colonisation and severe colitis, shown to be driven by increased Th1/IFN-;gamma& responses. These studies provide novel insights into aspects of IL-23 driven cellular and molecular pathways in homeostasis and inflammation in the intestine, with implications for future therapeutic approaches to IBD

Studies of intestinal Inflammation: The Roles of IL-23R, gamma-delta T-cells and IL-21i

The aetiology of the inflammatory bowel diseases ulcerative colitis and Crohn’s disease remains uncertain. Genetic studies and model systems strongly implicate components of the IL-23/type-17 axis in the pathogenesis of disease, but the cellular and molecular mediators are uncertain. Using an IL-23Rgfp reporter mouse we analysed the cellular expression of IL-23R in homeostasis and disease. Whereas steady state expression in the intestine was dominated by a collection of unconventional lymphoid cells including ;gamma& ;delta& T-cells, we found rapid accumulation of IL-23R+CD4+-/- mice developing increased bacterial colonisation and severe colitis, shown to be driven by increased Th1/IFN-;gamma& responses. These studies provide novel insights into aspects of IL-23 driven cellular and molecular pathways in homeostasis and inflammation in the intestine, with implications for future therapeutic approaches to IBD.This thesis is not currently available in ORA

Phytochemical Benefits of Agroresidues as Alternative Nutritive Dietary Resource for Pig and Poultry Farming

The growing world population is challenging the animal products supply system, particularly in developing countries, where demand for meat and milk in 2050 is estimated to increase to 109% and 116%, respectively, amidst deteriorating livestock feed sources. Globally, adequate production and availability of animal feed products to subsistence farmers has been declining due to factors such as global warming, growth in population, and low economic growth. This paper seeks to examine the existing scientific literature on the utilization of some unconventional feed resources, to abate the challenge of feed deficit and thus improve animal nutrition. The use of fruit waste and agricultural farm residues affords alternative, nutritive livestock dietary supplements; it has been proven they contain a spectrum of vital bioactive phytochemicals essential for sustainable growth and development of animals. The biochemical composition of the plant wastes and residues include carbohydrates, proteins, nucleic acids, and fatty acids, while the common bioactive phytochemicals are polyphenols, alkaloids, carotenoids, and flavonoids, along with tannins, terpenes, and saponins, which play vital roles in reducing disease-causing agents, such as bacteria, viruses, and free radical-associated diseases. The phytochemicals exhibit antioxidant, antimicrobial, antifungal, and anti-inflammatory, as well as anti-parasitic and antiprotozoal properties. However, it is important to guard against antinutritive and toxicity levels in animal feed products. The paper concludes that agroresidues’/wastes’ nutritive and therapeutic potential could serve as alternative livestock feed resource, while also acting as additional job and income generator for communities

Gene silencing in Caenorhabditis elegans by transitive RNA interference

When a cell is exposed to double-stranded RNA (dsRNA), mRNA from the homologous gene is selectively degraded by a process called RNA interference (RNAi). Here, we provide evidence that dsRNA is amplified in Caenorhabditis elegans to ensure a robust RNAi response. Our data suggest a model in which mRNA targeted by RNAi functions as a template for 5' to 3' synthesis of new dsRNA (termed transitive RNAi). Strikingly, the effect is nonautonomous: dsRNA targeted to a gene expressed in one cell type can lead to transitive RNAi-mediated silencing of a second gene expressed in a distinct cell type. These data suggest dsRNA synthesized in vivo can mediate systemic RNAi