Nanomedicine-Driven Modulation of Reductive Stress for Cancer Therapy.

Redox balance is crucial for cellular function and adaptation to environmental changes, with its disruption playing a key role in the progression of various diseases, including cancer. While oxidative stress caused by excessive reactive oxygen species (ROS) has been widely studied and targeted in cancer therapies, such approaches face significant challenges within the tumor microenvironment. On the opposite end, reductive stress results from an overabundance of reducing equivalents, disrupting normal ROS-dependent signaling pathways and leading to cellular dysfunction.

LDL regulates intestinal stem cell homeostasis via PPAR pathway.

Epidemiological studies have highlighted a strong association between hyperlipidemia and an increased risk of cancer in the gut. Intestinal stem cells (ISCs) have been demonstrated as the cells of origin for tumorigenesis in the gut. However, the impact of hyperlipidemia on ISC homeostasis remains unclear.

Cholesterol-targeting Wnt-β-catenin signaling inhibitors for colorectal cancer.

Most persons with colorectal cancer (CRC) carry adenomatous polyposis coli (APC) truncation leading to aberrant Wnt-β-catenin signaling; however, effective targeted therapy for them is lacking as the mechanism by which APC truncation drives CRC remains elusive. Here, we report that the cholesterol level in the inner leaflet of the plasma membrane (IPM) is elevated in all tested APC-truncated CRC cells, driving Wnt-independent formation of Wnt signalosomes through Dishevelled (Dvl)-cholesterol interaction. Cholesterol-Dvl interaction inhibitors potently blocked β-catenin signaling in APC-truncated CRC cells and suppressed their viability.

Nutrient metabolism in regulating intestinal stem cell homeostasis.

Intestinal stem cells (ISCs) are known for their remarkable proliferative capacity, making them one of the most active cell populations in the body. However, a high turnover rate of intestinal epithelium raises the likelihood of dysregulated homeostasis, which is known to cause various diseases, including cancer. Maintaining precise control over the homeostasis of ISCs is crucial to preserve the intestinal epithelium's integrity during homeostasis or stressed conditions.

Targeting phospholipid remodeling pathway improves insulin resistance in diabetic mouse models.

Previous studies have revealed that membrane phospholipid composition controlled by lysophosphatidylcholine acyltransferase 3 (LPCAT3) is involved in the development of insulin resistance in type 2 diabetes. In this study, we aimed to investigate the therapeutic potential of targeting Lpcat3 in the treatment of insulin resistance in diabetic mouse models. Lpcat3 expression was suppressed in the whole body by antisense oligonucleotides (ASO) injection or in the liver by adeno-associated virus (AAV)-encoded Cre in high-fat diet (HFD)-induced and genetic ob/ob type 2 diabetic mouse models.

Hepatic Phospholipid Remodeling Modulates Insulin Sensitivity and Systemic Metabolism.

The liver plays a central role in regulating glucose and lipid metabolism. Aberrant insulin action in the liver is a major driver of selective insulin resistance, in which insulin fails to suppress glucose production but continues to activate lipogenesis in the liver, resulting in hyperglycemia and hypertriglyceridemia. The underlying mechanisms of selective insulin resistance are not fully understood.

Membrane phospholipid remodeling modulates nonalcoholic steatohepatitis progression by regulating mitochondrial homeostasis.

Background And Aims: NASH, characterized by inflammation and fibrosis, is emerging as a leading etiology of HCC. Lipidomics analyses in the liver have shown that the levels of polyunsaturated phosphatidylcholine (PC) are decreased in patients with NASH, but the roles of membrane PC composition in the pathogenesis of NASH have not been investigated. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), a phospholipid (PL) remodeling enzyme that produces polyunsaturated PLs, is a major determinant of membrane PC content in the liver.

Intestinal SEC16B modulates obesity by regulating chylomicron metabolism.

Objective: Genome-wide association studies (GWAS) have identified genetic variants in SEC16 homolog B (SEC16B) locus to be associated with obesity and body mass index (BMI) in various populations. SEC16B encodes a scaffold protein located at endoplasmic reticulum (ER) exit sites that is implicated to participate in the trafficking of COPII vesicles in mammalian cells. However, the function of SEC16B in vivo, especially in lipid metabolism, has not been investigated.

Ultrasonic microwave-assisted extraction coupled with macroporous resin chromatography for the purification of antioxidant phenolics from waste jackfruit ( Lam.) peels.

An efficient ultrasonic microwave-assisted extraction (UMAE) coupled with macroporous resin chromatography technique was successfully used for the extraction and purification of antioxidant phenolics from jackfruit by-products (peels). After optimization by single factor experiments and response surface methodology, the optimum extraction conditions for UMAE were: ethanol concentration 63%, solvent-to-solid ratio 34 mL/g, microwave power 160 W and irradiation time 20 min. Under the optimal condition, the phenolics extraction yield was 8.

AAV9 Edits Muscle Stem Cells in Normal and Dystrophic Adult Mice.

CRISPR editing of muscle stem cells (MuSCs) with adeno-associated virus serotype-9 (AAV9) holds promise for sustained gene repair therapy for muscular dystrophies. However, conflicting evidence exists on whether AAV9 transduces MuSCs. To rigorously address this question, we used a muscle graft model.

Eco-friendly extraction and physicochemical properties of pectin from jackfruit peel waste with subcritical water.

Background: Water is generally considered to be a safe and green solvent suitable for use in natural product extraction. In this study, an eco-friendly subcritical water method was used to extract pectin from waste jackfruit peel (JFP-S), which was compared with pectin obtained by the traditional citric acid method (JFP-C).

Results: The extraction process was optimized using response surface methodology (RSM), and the optimum process parameters were as follows: extraction temperature 138 °C, extraction time 9.

Generation and Single-Molecule Characterization of a Sequence-Selective Covalent Cross-Link Mediated by Mechlorethamine at a C-C Mismatch in Duplex DNA for Discrimination of a Disease-Relevant Single Nucleotide Polymorphism.

Many strategies for the detection of nucleic acid sequence rely upon Watson-Crick hybridization of a probe strand to the target strand, but the reversible nature of nucleic acid hybridization presents an inherent challenge: short probes that provide high target specificity have relatively low target affinity resulting in signal losses. Sequence-specific covalent cross-linking reactions have the potential to provide both selective target capture and durable signal. We explore a novel approach involving sequence-specific covalent cross-linking of a probe to target DNA combined with single-molecule nanopore detection of the cross-linked DNA.

Remote Activation of a Nanopore for High-Performance Genetic Detection Using a pH Taxis-Mimicking Mechanism.

Aerolysin protein pore has been widely used for sensing peptides and proteins. However, only a few groups explored this nanopore for nucleic acids detection. The challenge is the extremely low capture efficiency for nucleic acids (>10 bases), which severely lowers the sensitivity of an aerolysin-based genetic biosensor.

Nanopore electric snapshots of an RNA tertiary folding pathway.

The chemical properties and biological mechanisms of RNAs are determined by their tertiary structures. Exploring the tertiary structure folding processes of RNA enables us to understand and control its biological functions. Here, we report a nanopore snapshot approach combined with coarse-grained molecular dynamics simulation and master equation analysis to elucidate the folding of an RNA pseudoknot structure.

Nanolock-Nanopore Facilitated Digital Diagnostics of Cancer Driver Mutation in Tumor Tissue.

Cancer driver mutations are clinically significant biomarkers. In precision medicine, accurate detection of these oncogenic changes in patients would enable early diagnostics of cancer, individually tailored targeted therapy, and precise monitoring of treatment response. Here we investigated a novel nanolock-nanopore method for single-molecule detection of a serine/threonine protein kinase gene BRAF V600E mutation in tumor tissues of thyroid cancer patients.

Polycationic Probe-Guided Nanopore Single-Molecule Counter for Selective miRNA Detection.

MicroRNAs (miRNAs) are a class of noncoding RNAs that are being explored as a new type of disease biomarkers. The nanopore single-molecule sensor offers a potential noninvasive tool to detect miRNAs for diagnostics and prognosis applications. However, one of the challenges that limits its clinical applications is the presence of a large variety of nontarget nucleic acids in the biofluid extracts.

Sequence-Specific Covalent Capture Coupled with High-Contrast Nanopore Detection of a Disease-Derived Nucleic Acid Sequence.

Hybridization-based methods for the detection of nucleic acid sequences are important in research and medicine. Short probes provide sequence specificity, but do not always provide a durable signal. Sequence-specific covalent crosslink formation can anchor probes to target DNA and might also provide an additional layer of target selectivity.

Feasibility study on repair for cranial defect of immaturity.

Aim: To evaluate use of a titanium mesh to fill cranial defects in growing animals, as a model for juvenile humans.

Material And Methods: Thirty two-month-old Seghers pigs were evenly assigned to one of three groups: controls, a defect group (unrepaired 5 x 5 cm lesion), and a repair group (repaired 5 x 5 cm lesions). Histological evaluations and morphological measurements were conducted to compare the groups.