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Enhanced safety and efficacy profile of CD40 antibody upon encapsulation in pHe-triggered membrane-adhesive nanoliposomes.

Nanomedicine (Lond)

January 2025

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.

Aim: To develop pH (pHe)-triggered membrane adhesive nanoliposome (pHTANL) of CD40a to enhance anti-tumor activity in pancreatic cancer while reducing systemic toxicity.

Materials And Methods: A small library of nanoliposomes (NL) with various lipid compositions were synthesized to prepare pH (pHe)-triggered membrane adhesive nanoliposome (pHTANL). Physical and functional characterization of pHTANL-CD40a was performed via dynamic light scattering (DLS), Transmission Electron Microscopy (TEM), confocal microscopy, and flow cytometry.

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The prevalence of childhood obesity is rising globally, with some obese children progressing to develop metabolic syndrome (MS). However, the specific differences between these groups remain unclear. To investigate the differences in gut microbiota, we conducted physiological and biochemical assessments, alongside 16S rRNA sequencing, in a cohort of 32 children from Southeastern China, which included 4 normal-weight children, 5 with mild obesity, 9 with moderate obesity, 9 with severe obesity, and 5 with metabolic syndrome.

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Unlabelled: Although tryptophan (Trp) is the largest and most structurally complex amino acid, it is the least abundant in the proteome. Its distinct indole ring and high carbon content enable it to generate various biologically active metabolites such as serotonin, kynurenine (Kyn), and indole-3-pyruvate (I3P). Dysregulation of Trp metabolism has been implicated in diseases ranging from depression to cancer.

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Citrin Deficiency (CD) is caused by inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. We discovered that SLC25A13 loss causes accumulation of glycerol-3-phosphate (G3P), which activates carbohydrate response element binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol, and to transcribe key genes of lipogenesis.

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Background: Type 2 Diabetes Mellitus (T2DM) is a significant public health burden. Emerging evidence links volatile organic compounds (VOCs), such as benzene to endocrine disruption and metabolic dysfunction. However, the effects of chronic environmentally relevant VOC exposures on metabolic health are still emerging.

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