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Carbohydrate-based low molecular weight gelators (LMWGs) are compounds with the capability to self-assemble into complex molecular networks within a solvent, leading to solvent immobilization. This process of gel formation depends on noncovalent interactions, including Van der Waals, hydrogen bonding, and π–π stacking. Due to their potential applications in environmental remediation, drug delivery, and tissue engineering, these molecules have emerged as an important area of research. In particular, various 4,6-O-benzylidene acetal-protected D-glucosamine derivatives have shown promising gelation abilities. In this study, a series of C-2-carbamate derivatives containing a para-methoxy benzylidene acetal functional group were synthesized and characterized. These compounds exhibited good gelation properties in several organic solvents and aqueous mixtures. Upon removal of the acetal functional group under acidic conditions, a number of deprotected free sugar derivatives were also synthesized. Analysis of these free sugar derivatives revealed two compounds were hydrogelators while their precursors did not form hydrogels. For those protected carbamates that are hydrogelators, removal of the 4,6-protection will result in a more water-soluble compound that produces a transition from gel to solution. Given the ability of these compounds to form gels from solution or solution from gels in situ in response to acidic environments, these compounds may have practical applications as stimuli-responsive gelators in an aqueous medium. In turn, one hydrogelator was studied for the encapsulation and release of naproxen and chloroquine. The hydrogel exhibited sustained drug release over a period of several days, with the release of chloroquine being faster at lower pH due to the acid lability of the gelator molecule. The synthesis, characterization, gelation properties, and studies on drug diffusion are discussed. [ABSTRACT FROM AUTHOR]

Purpose To examine potential detrimental long-term effects of acute diet-induced weight loss on visceral adiposity, insulin resistance, cortisol, and adipokines in obese individuals at risk for type-2 diabetes. Data sources Anthropometric measures (height, weight, waist circumference), self-report instruments, abdominal computed tomography (CT) scan, and blood samples (glucose, insulin, interleukin-6, leptin, adiponectin) were obtained from a convenience sample of 20 participants at baseline, after a 28-day low-calorie diet (800 kcal/day) intervention, and again 6 months later. Conclusions Fifteen of 20 participants completed the 28-day diet intervention and had a mean weight loss of 15 pounds. Comparison between baseline, postdiet, and 6-month data, demonstrated that although participants had significant improvements after the diet, they regained fat mass, particularly in the visceral area. Implications for practice Clinicians may need to revise recommendations for using low-calorie diets to achieve weight loss. Diet-induced weight cycling may contribute to dysregulation of metabolism and have long-term detrimental consequences for accumulation of visceral adipose tissue. The likelihood of success is low, with high dropout rates, and those patients who achieve weight loss are very likely to regain it. Thus, the perceived short-term benefits of calorie-restricted diets in this population likely do not outweigh the potential long-term detrimental effects. [ABSTRACT FROM AUTHOR]

EGFR-targeted therapies are efficacious, but toxicity is common and can be severe. Urokinase type plasminogen activator receptor (uPAR)-targeted drugs are only emerging, so neither their efficacy nor toxicity is fully established. Recombinant eBAT was created by combining cytokines EGF and uPA on the same single-chain molecule with truncated Pseudomonas toxin. Its purpose was to simultaneously target tumors and their vasculature in the tumor microenvironment. In prior studies on mice and dogs, the drug proved efficacious. Here, we report the safety of eBAT in normal wildtype, uPAR knockout, and immunoreplete and immunodeficient tumor-bearing mice, as well as in dogs with spontaneous sarcoma that more closely mirror human cancer onset. In immunocompetent mice, tumor-bearing mice, uPAR knockout mice, and mice receiving species-optimized eBAT, toxicities were mild and self-limiting. Likewise, in dogs with life-threatening sarcoma given dosages found to be biologically active, eBAT was well tolerated. In mice receiving higher doses, eBAT was associated with dose-dependent evidence of liver injury, including portal biliary hyperplasia, oval cell proliferation, lymphoplasmacytic inflammation, periportal hepatocellular microvesicular change, hemorrhage, necrosis, and apoptosis. The results support continuing the clinical development of eBAT as a therapeutic agent for individuals with sarcoma and other cancers. [ABSTRACT FROM AUTHOR]