Publications by authors named "Wen-Jen Lin"

A niosome-based delivery system incorporating hyaluronic acid-modified Poloxamer 407 (P407-LHA) was developed to enhance the topical delivery of resveratrol (RSV). It was proposed that the system targets CD44 receptors on human fibroblast cells to improve skin penetration, drug accumulation, and anti-aging efficacy. In this study, the niosome formulations composed of non-ionic P407, P407-LHA, and their blends (P407/P407-LHA(2/1) and P407/P407-LHA(1/2)) were investigated.

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Seliciclib, a cyclin-dependent kinase 5 (CDK5) inhibitor, has demonstrated neuroprotective potential. However, its therapeutic application is limited by poor permeability across the blood-brain barrier (BBB). In this study, polymeric nanoparticles (NPs) modified with a BBB-targeting peptide ligand (His-Ala-Ile-Tyr-Pro-Arg-His) were employed to encapsulate seliciclib.

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MUTYH is a clinically important DNA glycosylase that thwarts mutations by initiating base-excision repair at 8-oxoguanine (OG):A lesions. The roles for its [4Fe-4S] cofactor in DNA repair remain enigmatic. Functional profiling of cancer-associated variants near the [4Fe-4S] cofactor reveals that most variations abrogate both retention of the cofactor and enzyme activity.

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Motivation: Lipidomics is a rapidly expanding field focused on studying lipid species and classes within biological systems. As the field evolves, there is an increasing demand for user-friendly, open-source software tools capable of handling large and complex datasets while keeping pace with technological advancements. LipidSig, a widely used web-based platform, has been instrumental in data analysis and visualization of lipidomics.

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Motivation: Lipids play crucial roles in various biological functions and diseases. However, a gap exists in databases providing information of lipids functions based on curated information. Consequently, LipidFun is purposed as the first lipid function database with sentence-level evidence detailing lipid-related phenotypes and biological functions.

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Article Synopsis
  • Lipid reprogramming plays a significant role in cancer development, prognosis, and response to treatment, with both autonomous and nonautonomous sources contributing to this process.
  • Research has identified ether-linked phosphatidyl-ethanolamine (PE O-) as a key lipid that enhances resistance to chemotherapy and promotes tumor progression in epithelial ovarian cancer (EOC).
  • Analysis revealed that PE O- is associated with reduced sensitivity to common chemotherapy drugs (cisplatin/paclitaxel) and its gene expression correlates positively with patient outcomes, suggesting that targeting PE O- could improve treatment effectiveness in EOC.
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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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Article Synopsis
  • MutY, a DNA glycosylase, is crucial for preventing mutations caused by oxidative damage, with its human variant linked to colorectal cancer.
  • The enzyme relies on a conserved Asp residue to remove misinserted adenines opposite oxidative damage and a nearby Asn that stabilizes its catalytic function.
  • Research with a specific N146S mutant of MutY revealed structural insights into its catalytic mechanism, showing how calcium affects substrate conformation and supporting a retaining mechanism during base excision.
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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.

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Article Synopsis
  • The Base Excision Repair (BER) pathway is an essential DNA repair mechanism that addresses damage from various chemical modifications like oxidation and alkylation.
  • DNA glycosylases (DGs) play a key role in BER by identifying and removing damaged bases, creating apurinic/apyrimidinic (AP) sites, and facilitating the repair process.
  • The Helix-hairpin-Helix (HhH) DG superfamily stands out due to its ability to recognize a wide range of base modifications, and this paper explores their unique structural properties and evolutionary development.
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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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).

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