An oral liraglutide nanomicelle formulation conferring reduced insulin-resistance and long-term hypoglycemic and lipid metabolic benefits.

Type 2 diabetes is a chronic disease characterized by insulin resistance and often worsened by obesity. Effective management involves the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to assist with glycemic control and weight management. However, these drugs must be administered subcutaneously due to their low oral bioavailability.

Activation of p38 and JNK by ROS Contributes to Deoxybouvardin-Mediated Intrinsic Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells.

Colorectal cancer (CRC) remains a global health burden, accounting for almost a million deaths annually. Deoxybouvardin (DB), a non-ribosomal peptide originally isolated from , has been reported to possess antitumor activity; however, the detailed mechanisms underlying this anticancer activity have not been elucidated. We investigated the anticancer activity of the cyclic hexapeptide, DB, in human CRC HCT116 cells.

Ameliorative effects of Linn. flower against desiccation stress-induced dry eye symptoms in the mice model.

Background: Tagetes erecta Linn, popularly known as Marigold, has various pharmacological effects. It is used as a dietary supplement, especially for the posterior segment of the eye. However, the effect of T.

Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage.

Mangiferin is a kind of natural xanthone glycosides and is known to have various pharmacological activities. However, since the beneficial efficacy of this compound has not been reported in retinal pigment epithelial (RPE) cells, this study aimed to evaluate whether mangiferin could protect human RPE ARPE-19 cells from oxidative injury mimicked by hydrogen peroxide (HO). The results showed that mangiferin attenuated HO-induced cell viability reduction and DNA damage, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione (GSH).

Coordinated ASBT and EGFR Mechanisms for Optimized Liraglutide Nanoformulation Absorption in the GI Tract.

Background: For maintenance therapy in type 2 diabetes, glucagon-like peptide-1 agonist (GLP-1A), which exhibits low cardiovascular risk and high efficacy, is a promising peptide therapeutic. However, developing an oral GLP-1A presents challenges due to the analog's poor cellular permeability and gastrointestinal (GI) stability.

Methods: To mitigate such limitations, an oral nanoformulation of liraglutide (LG) was designed and achieved by combining LG with bile acid derivatives using the nanoprecipitation method.

Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin.

Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of , has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance.

Licochalcone D Inhibits Skin Epidermal Cells Transformation through the Regulation of AKT Signaling Pathways.

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells.

Licochalcone H Targets EGFR and AKT to Suppress the Growth of Oxaliplatin -Sensitive and -Resistant Colorectal Cancer Cells.

Treatment of colorectal cancer (CRC) has always been challenged by the development of resistance. We investigated the antiproliferative activity of licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata, in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells.

Design of chimeric GLP-1A using oligomeric bile acids to utilize transporter-mediated endocytosis for oral delivery.

Background: Despite the effectiveness of glucagon-like peptide-1 agonist (GLP-1A) in the treatment of diabetes, its large molecular weight and high hydrophilicity result in poor cellular permeability, thus limiting its oral bioavailability. To address this, we developed a chimeric GLP-1A that targets transporter-mediated endocytosis to enhance cellular permeability to GLP-1A by utilizing the transporters available in the intestine, particularly the apical sodium-dependent bile acid transporter (ASBT).

Methods: In silico molecular docking and molecular dynamics simulations were used to investigate the binding interactions of mono-, bis-, and tetra-deoxycholic acid (DOCA) (monoDOCA, bisDOCA, and tetraDOCA) with ASBT.

Spermidine Attenuates High Glucose-Induced Oxidative Damage in Retinal Pigment Epithelial Cells by Inhibiting Production of ROS and NF-κB/NLRP3 Inflammasome Pathway.

Diabetic retinopathy (DR) is the leading cause of vision loss and a critical complication of diabetes with a very complex etiology. The build-up of reactive oxygen species (ROS) due to hyperglycemia is recognized as a primary risk factor for DR. Although spermidine, a naturally occurring polyamine, has been reported to have antioxidant effects, its effectiveness in DR has not yet been examined.

Urban aerosol particulate matter promotes mitochondrial oxidative stress-induced cellular senescence in human retinal pigment epithelial ARPE-19 cells.

Environmental exposure to urban particulate matter (UPM) is a serious health concern worldwide. Although several studies have linked UPM to ocular diseases, no study has reported effects of UPM exposure on senescence in retinal cells. Therefore, this study aimed to investigate the effects of UPM on senescence and regulatory signaling in human retinal pigment epithelial ARPE-19 cells.

3-Deoxysappanchalcone Inhibits Cell Growth of Gefitinib-Resistant Lung Cancer Cells by Simultaneous Targeting of EGFR and MET Kinases.

The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells.

Licochalcone B Induces ROS-Dependent Apoptosis in Oxaliplatin-Resistant Colorectal Cancer Cells via p38/JNK MAPK Signaling.

Licochalcone B (LCB) exhibits anticancer activity in oral cancer, lung cancer, and hepatocellular carcinoma cells. However, little is known about its antitumor mechanisms in human oxaliplatin-sensitive and -resistant colorectal cancer (CRC) cells. The purpose of the present study was to investigate the antitumor potential of LCB against human colorectal cancer in vitro and analyze its molecular mechanism of action.

Phloroglucinol Inhibits Oxidative-Stress-Induced Cytotoxicity in C2C12 Murine Myoblasts through Nrf-2-Mediated Activation of HO-1.

Phloroglucinol is a class of polyphenolic compounds containing aromatic phenyl rings and is known to have various pharmacological activities. Recently, we reported that this compound isolated from , a brown alga belonging to the family , has potent antioxidant activity in human dermal keratinocytes. In this study, we evaluated whether phloroglucinol could protect against hydrogen peroxide (HO)-induced oxidative damage in murine-derived C2C12 myoblasts.

Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids.

Atorvastatin (ATV) has attracted considerable attention as a potential therapeutic agent for cancer because it inhibits cancer cell proliferation by suppressing the mevalonate pathway. However, because of its low oral absorption, high doses of ATV are required for chemotherapeutic applications. In this study, we constructed ATV-loaded nanoemulsions (ATV-NEs) containing multivalent intestinal transporter-targeting lipids to improve the oral bioavailability of ATV.

Novel dual inhibitor for targeting PIM1 and FGFR1 kinases inhibits colorectal cancer growth and patient-derived xenografts .

Colorectal cancer (CRC) is the second most common cause of cancer-related death in the world. The pro-viral integration site for Moloney murine leukemia virus 1 (PIM1) is a proto-oncogene and belongs to the serine/threonine kinase family, which are involved in cell proliferation, migration, and apoptosis. Fibroblast growth factor receptor 1 (FGFR1) is a tyrosine kinase that has been implicated in cell proliferation, differentiation and migration.

Hydroxyzine Induces Cell Death in Triple-Negative Breast Cancer Cells via Mitochondrial Superoxide and Modulation of Jak2/STAT3 Signaling.

Treatment of triple-negative breast cancer (TNBC) has been limited due to the lack of molecular targets. In this study, we evaluated the cytotoxicity of hydroxyzine, a histamine H1 receptor antagonist in human triple-negative breast cancer BT-20 and HCC-70 cells. Hydroxyzine inhibited the growth of cells in dose- and time-dependent manners.

Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET.

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resistance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of , inhibited both EGFR and MET in NSCLC cells.