Zein-PEG nanoparticles modified with hyaluronic acid for paclitaxel delivery in SKOV3 ovarian cancer cells.

Ovarian cancer is a leading gynecological cancer globally. This study aimed to develop hyaluronic acid-modified polyethylene glycol conjugated zein nanoparticles (zein-PEG/HA NPs) to enhance paclitaxel (PTX) cytotoxicity in SKOV3 ovarian cancer cells. Zein-PEG, with its amphiphilic nature, self-assembled into micelles to encapsulate the hydrophobic PTX, while the PEG shell retained micelle stability and hemolytic resistance.

iLipidome: enhancing statistical power and interpretability using hidden biosynthetic interdependencies in the lipidome.

Numerous biological processes and diseases are influenced by lipid composition. Advances in lipidomics are elucidating their roles, but analyzing and interpreting lipidomics data at the systems level remain challenging. To address this, we present iLipidome, a method for analyzing lipidomics data in the context of the lipid biosynthetic network, thus accounting for the interdependence of measured lipids.

LipidSig 2.0: integrating lipid characteristic insights into advanced lipidomics data analysis.

In the field of lipidomics, where the complexity of lipid structures and functions presents significant analytical challenges, LipidSig stands out as the first web-based platform providing integrated, comprehensive analysis for efficient data mining of lipidomic datasets. The upgraded LipidSig 2.0 (https://lipidsig.

LipidSIM: Inferring mechanistic lipid biosynthesis perturbations from lipidomics with a flexible, low-parameter, Markov modeling framework.

Lipid metabolism is a complex and dynamic system involving numerous enzymes at the junction of multiple metabolic pathways. Disruption of these pathways leads to systematic dyslipidemia, a hallmark of many pathological developments, such as nonalcoholic steatohepatitis and diabetes. Recent advances in computational tools can provide insights into the dysregulation of lipid biosynthesis, but limitations remain due to the complexity of lipidomic data, limited knowledge of interactions among involved enzymes, and technical challenges in standardizing across different lipid types.

Phenotypic and metabolomic characteristics of mouse models of metabolic associated steatohepatitis.

Background: Metabolic associated steatohepatitis (MASH) is metabolic disease that may progress to cirrhosis and hepatocellular carcinoma. Mouse models of diet-induced MASH, which is characterized by the high levels of fats, sugars, and cholesterol in diets, are commonly used in research. However, mouse models accurately reflecting the progression of MASH in humans remain to be established.

DriverDBv4: a multi-omics integration database for cancer driver gene research.

Advancements in high-throughput technology offer researchers an extensive range of multi-omics data that provide deep insights into the complex landscape of cancer biology. However, traditional statistical models and databases are inadequate to interpret these high-dimensional data within a multi-omics framework. To address this limitation, we introduce DriverDBv4, an updated iteration of the DriverDB cancer driver gene database (http://driverdb.

Improve BBB Penetration and Cytotoxicity of Palbociclib in U87-MG Glioblastoma Cells Delivered by Dual Peptide Functionalized Nanoparticles.

Palbociclib (PBC) is an FDA-approved CDK4/6 inhibitor used for breast cancer treatment. PBC has been demonstrated its ability to suppress the proliferation of glioma cells by inducing cell cycle arrest. However, the efflux transporters on the blood-brain barrier (BBB) restricts the delivery of PBC to the brain.

Synergistic cytotoxicity of irinotecan combined with polysaccharide-based nanoparticles for colorectal carcinoma.

Functional polymeric nanoparticles (NPs) with antitumor potential were combined with the topoisomerase I inhibitor, irinotecan (IRT), to enhance cytotoxicity against colorectal cancers. The negatively charged γ-polyglutamic acid (γ-PGA) or fucoidan (FCD) was complexed with the positively charged chitosan (CS) to encapsulate IRT. The size of the γ-PGA/CS/IRT NPs and FCD/CS/IRT NPs were 146.

Structural snapshots of base excision by the cancer-associated variant MutY N146S reveal a retaining mechanism.

DNA glycosylase MutY plays a critical role in suppression of mutations resulted from oxidative damage, as highlighted by cancer-association of the human enzyme. MutY requires a highly conserved catalytic Asp residue for excision of adenines misinserted opposite 8-oxo-7,8-dihydroguanine (OG). A nearby Asn residue hydrogen bonds to the catalytic Asp in structures of MutY and its mutation to Ser is an inherited variant in human MUTYH associated with colorectal cancer.

The Dawn of a New Era in Drug Discovery? Drug Screening and the Increasing Biological Complexity of Testing Models.

Whole-organism phenotype screening and complex model technology increase the likelihood in identifying successful lead compounds and lower drug attrition rates at later and more expensive stages of the drug discovery process.

Structure, function and evolution of the Helix-hairpin-Helix DNA glycosylase superfamily: Piecing together the evolutionary puzzle of DNA base damage repair mechanisms.

The Base Excision Repair (BER) pathway is a highly conserved DNA repair system targeting chemical base modifications that arise from oxidation, deamination and alkylation reactions. BER features lesion-specific DNA glycosylases (DGs) which recognize and excise modified or inappropriate DNA bases to produce apurinic/apyrimidinic (AP) sites and coordinate AP-site hand-off to subsequent BER pathway enzymes. The DG superfamilies identified have evolved independently to cope with a wide variety of nucleobase chemical modifications.

Ergosta-7,9(11),22-trien-3β-ol Attenuates Inflammatory Responses via Inhibiting MAPK/AP-1 Induced IL-6/JAK/STAT Pathways and Activating Nrf2/HO-1 Signaling in LPS-Stimulated Macrophage-like Cells.

Chronic inflammation induces autoimmune disorders and chronic diseases. Several natural products activate nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, attenuating inflammatory responses. Ergosta-7,9(11),22-trien-3β-ol (EK100) isolated from showed anti-inflammatory and antioxidative activity, but those mechanisms are still unclear.

Benefit of a Short Chain Peptide as a Targeting Ligand of Nanocarriers for a Brain-Driven Purpose.

Treatment of glioma remains a critical challenge worldwide, since the therapeutic effect is greatly hindered by poor transportation across the blood brain barrier (BBB) and low penetration into tumor cells. In this study, a peptide-conjugated nano-delivery system was explored for the purpose of glioma therapy. A peptide-decorated copolymer was used to prepare nanoparticles (NPs) by a solvent evaporation method.

Using bioinformatics approaches to investigate driver genes and identify BCL7A as a prognostic gene in colorectal cancer.

Colorectal cancer (CRC) results from the uncontrolled growth of cells in the colon, rectum, or appendix. The 5-year relative survival rate for patients with CRC is 65% and is correlated with the stage at diagnosis (being 91% for stage I at diagnosis versus 12% for stage IV). This study aimed to identify CRC driver genes to assist in the design of a cancer panel to detect gene mutations during clinical early-stage screening and identify genes for use in prognostic assessments and the evaluation of appropriate treatment options.

Ergosta-7, 9 (11), 22-trien-3β-ol Interferes with LPS Docking to LBP, CD14, and TLR4/MD-2 Co-Receptors to Attenuate the NF-κB Inflammatory Pathway and .

Ergosta-7, 9 (11), 22-trien-3β-ol (EK100) was isolated from , which has been used as a traditional anti-inflammatory medicine. EK100 has been reported to attenuate inflammatory diseases, but its anti-inflammatory mechanism is still unclear. We were the first to investigate the effect of EK100 on the Toll-like receptor 4 (TLR4)/nuclear factor of the κ light chain enhancer of B cells (NF-κB) signaling in the lipopolysaccharide (LPS)-stimulated RAW264.

Structural Insights into the Mechanism of Base Excision by MBD4.

DNA glycosylases remove damaged or modified nucleobases by cleaving the N-glycosyl bond and the correct nucleotide is restored through subsequent base excision repair. In addition to excising threatening lesions, DNA glycosylases contribute to epigenetic regulation by mediating DNA demethylation and perform other important functions. However, the catalytic mechanism remains poorly defined for many glycosylases, including MBD4 (methyl-CpG binding domain IV), a member of the helix-hairpin-helix (HhH) superfamily.

LipidSig: a web-based tool for lipidomic data analysis.

With the continuing rise of lipidomic studies, there is an urgent need for a useful and comprehensive tool to facilitate lipidomic data analysis. The most important features making lipids different from general metabolites are their various characteristics, including their lipid classes, double bonds, chain lengths, etc. Based on these characteristics, lipid species can be classified into different categories and, more interestingly, exert specific biological functions in a group.

Peptide-Functionalized Nanoparticles-Encapsulated Cyclin-Dependent Kinases Inhibitor Seliciclib in Transferrin Receptor Overexpressed Cancer Cells.

Seliciclib, a broad cyclin-dependent kinases (CDKs) inhibitor, exerts its potential role in cancer therapy. For taking advantage of overexpressive transferrin receptor (TfR) on most cancer cells, T7 peptide, a TfR targeting ligand, was selected as a targeting ligand to facilitate nanoparticles (NPs) internalization in cancer cells. In this study, poly(d,l-lactide-co-glycolide) (PLGA) was conjugated with maleimide poly(ethylene glycol) amine (Mal-PEG-NH) to form PLGA-PEG-maleimide copolymer.

Dual Peptide-Modified Nanoparticles Improve Combination Chemotherapy of Etoposide and siPIK3CA Against Drug-Resistant Small Cell Lung Carcinoma.

Small cell lung carcinoma (SCLC) is a highly aggressive form of malignancy with rapid recurrence and poor prognosis. The dual peptide-modified nanoparticles (NPs) for improving chemotherapy against drug-resistant small cell lung carcinoma cells has been developed. In this study, the SCLC targeting ligand, antagonist G peptide (AG), and cell-penetrating peptide, TAT, modified NPs were used to encapsulate both anticancer drugs etoposide (ETP) and PIK3CA small-interfering RNA (siPIK3CA).

A novel iron-conjugated acid-modified chitosan derivatives as an oral phosphate binding agent to improve phosphorus adsorption efficacy in vitro and in vivo, synthesis and their characterization.

Current phosphate binders used for hyperphosphatemia treatment need large daily dose which make patients' compliance worse and the therapeutic efficacy may not conform the expectation. In this study, three polyacid modified iron-based chitosan derivatives were developed as an oral phosphate binding agent to improve phosphorus adsorption efficacy. The result showed that modification of chitosan by citric acid (CA) could facilitate the conjugation of iron by two folds (272.

Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery.

Background: Hyaluronic acid (HA) and chondroitin sulfate (CD) are endogenous polysaccharides. In recent years, they have aroused the interest of scientists because of specific binding to CD44 receptors, which are overexpressed in several types of tumors.

Methods: In this study, HA- and CD-modified poly(D,L-lactide--glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymers were synthesized and applied to encapsulate 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP)/DNA (D/P) lipoplex as CD44 receptor targeting gene delivery nanoparticles (NPs).

Hyaluronic acid conjugated micelles possessing CD44 targeting potential for gene delivery.

The high- and low-molecular weight hyaluronic acid (HHA and LHA) were used to conjugate with PLGA-PEG copolymers which were applied to encapsulate DOTAP/pDNA (D/P) lipoplex as a CD44-targeted micelle delivery system. The size and zeta potential of DNA loaded micelles were measured. The cytotoxicity and cellular transfection of DNA loaded micelles were performed in CD44-positive MDA-MB-231 and MCF-7 cancer cells and CD44-negative HepG2 cells.

Nanostructured lipid carriers for transdermal delivery of acid labile lansoprazole.

The aim of this study was to develop nanostructured lipid carriers (NLCs) for transdermal delivery of acid-labile lansoprazole (LPZ). The drug loading, particle size, zeta potential, thermal behavior and stability of NLCs were evaluated. The particle size of NLCs was in the range of 90-210nm and the zeta potential was -61.

Application of polymeric nanoparticles and micelles in insulin oral delivery.

Diabetes mellitus is an endocrine disease in which the pancreas does not produce sufficient insulin or the body cannot effectively use the insulin it produces. Insulin therapy has been the best choice for the clinical management of diabetes mellitus. The current insulin therapy is via subcutaneous injection, which often fails to mimic the glucose homeostasis that occurs in normal individuals.