Targeting the NRF2 pathway with linagliptin to inhibit human hepatocellular carcinoma growth.

Linagliptin, a potent dipeptidyl peptidase 4 (DPP4) inhibitor, demonstrates significant potential as a therapeutic agent for hepatocellular carcinoma (HCC). This study evaluated the effects of linagliptin on HCC cell lines, focusing on mechanisms involving reactive oxygen species (ROS) production, nuclear factor erythroid 2-related factor 2 (NRF2) pathway activation, and autophagy. Linagliptin effectively suppressed cell proliferation and induced apoptosis in HCC cell lines, particularly Hep3B cells, while sparing normal hepatic cells.

Targeting mitophagy using isoliensinine as a therapeutic strategy for renal cell carcinoma treatment.

Renal cell carcinoma (RCC) is a formidable and lethal form of kidney cancer, necessitating the exploration of novel therapeutic options. Isoliensinine, an alkaloid derived from lotus seed embryos, has shown promising anti-cancer properties. However, its mechanistic actions and impact on mitochondrial dynamics remain poorly understood.

Use of Sodium-Glucose Transport Protein 2 Inhibitors and the Incidence of Urolithiasis: A Multi-Database and Cross-Country Study in Patients With Type 2 Diabetes Mellitus.

The benefits of sodium-glucose transport protein 2 inhibitor (SGLT2i) use on severe urolithiasis requiring surgery remains unclear. All patients with incident T2D in Taiwan National Health Institution databases (2016-2021) and TriNetX datasets (2014-2023) were retrospectively analyzed. The study analyzed a propensity score-matched pairs with T2D treated with SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i).

The Protective Effects of Mcl-1 on Mitochondrial Damage and Oxidative Stress in Imiquimod-Induced Cancer Cell Death.

Mitochondria, vital organelles that generate ATP, determine cell fate. Dysfunctional and damaged mitochondria are fragmented and removed through mitophagy, a mitochondrial quality control mechanism. The FDA-approved drug IMQ, a synthetic agonist of Toll-like receptor 7, exhibits antitumor activity against various skin malignancies.

Short-chain fatty acids ameliorate imiquimod-induced skin thickening and IL-17 levels and alter gut microbiota in mice: a metagenomic association analysis.

Short-chain fatty acids (SCFAs) have been proposed to have anti-inflammatory effects and improve immune homeostasis. We aimed to examine the effects of SCFAs on skin phenotype, systemic inflammation, and gut microbiota in mice with psoriasis-like inflammation. Imiquimod (IMQ)-treated C57BL/6 mice served as the study model.

Lipopolysaccharide-Induced Lysosomal Cell Death Through Reactive Oxygen Species in Rat Liver Cell Clone 9.

In sepsis, bacterial components, particularly lipopolysaccharide (LPS), trigger organ injuries such as liver dysfunction. Although sepsis induces hepatocyte damage, the mechanisms underlying sepsis-related hepatic failure remain unclear. In this study, we demonstrated that the LPS-treated rat hepatocyte cell line Clone 9 not only induced reactive oxygen species (ROS) generation and apoptosis but also increased the expression of the autophagy marker proteins LC3-II and p62, and decreased the expression of intact Lamp2A, a lysosomal membrane protein.

Sodium-Glucose Transport Protein 2 Inhibitor Use for Type 2 Diabetes and the Incidence of Acute Kidney Injury in Taiwan.

Importance: The association between sodium-glucose transport protein 2 inhibitor (SGLT2i) use and the incidence of acute kidney injury (AKI) remains controversial. The benefits of SGLT2i use in patients to reduce AKI requiring dialysis (AKI-D) and concomitant diseases with AKI as well as improve AKI prognosis have not yet been established.

Objective: To investigate the association between SGLT2i use and AKI incidence in patients with type 2 diabetes (T2D).

Imiquimod-induced ROS production causes lysosomal membrane permeabilization and activates caspase-8-mediated apoptosis in skin cancer cells.

Background: Lysosomal cell death is induced by lysosomal membrane permeabilization (LMP) and the subsequent release of lysosomal proteolytic enzymes, including cathepsins (CTSs), which results in mitochondrial dysfunction and apoptosis. Imiquimod (IMQ), a synthetic TLR7 ligand, has both antiviral and antitumor activity against various skin malignancies in clinical treatment. Previously, we demonstrated IMQ not only caused lysosomal dysfunction but also triggered lysosome biogenesis to achieve lysosomal adaptation in cancer cells.

Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model.

Context: Protocatechuic aldehyde (PCA) is a natural product that has various benefits for fibrosis.

Objective: This study evaluated the effects of PCA on renal fibrosis.

Materials And Methods: Epithelial-mesenchymal transition (EMT) was induced by 20 ng/mL transforming growth factor-β1 (TGF-β1), followed by treatment with 1 and 5 μM PCA, in the rat renal proximal tubular cell line NRK-52E.

Association of SGLT2 inhibitors with lower incidence of death in type 2 diabetes mellitus and causes of death analysis.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) potentially decrease all-cause and cardiovascular death, however, associations with non-cardiovascular death remain unclear. Therefore, we investigated SGLT2i associations with death and the cause of death. We used the Taiwanese National Health Institutes Research database linked to the National Register of Deaths (NRD).

Association of Sodium-Glucose Transport Protein 2 Inhibitor Use for Type 2 Diabetes and Incidence of Gout in Taiwan.

Importance: The use of sodium-glucose transport protein 2 (SGLT2) inhibitors is currently a standard intervention in patients with type 2 diabetes (T2DM) and exerts favorable pleiotropic effects to consistently lower blood urate levels. However, to date, no association between SGLT2 inhibitor use and the incidence of gout have been established.

Objective: To investigate whether prescribed SGLT2 inhibitors are associated with lower gout incidence in patients with T2DM.

Evaluation of the Therapeutic Effects of Protocatechuic Aldehyde in Diabetic Nephropathy.

Diabetic nephropathy (DN) is one of the most severe chronic kidney diseases in diabetes and is the main cause of end-stage renal disease (ESRD). Protocatechuic aldehyde (PCA) is a natural product with a variety of effects on pulmonary fibrosis. In this study, we examined the effects of PCA in C57BL/KS db/db male mice.

Impact of peritoneal dialysis-related peritonitis on PD discontinuation and mortality: A population-based national cohort study.

Background: The impact of peritoneal dialysis-associated peritonitis (PD peritonitis) on long-term outcomes is uncertain. This nationwide retrospective study was conducted in Taiwan to understand the incidence, risk factors and long-term outcomes of PD peritonitis.

Methods: A total of 11,202 incident adult peritoneal dialysis (PD) patients from 2000 to 2010 were collected from a Longitudinal Health Insurance Database and followed up until the end of 2011.

Primary aldosteronism is associated with risk of urinary bladder stones in a nationwide cohort study.

We analyzed database from the Taiwan National Health Insurance to investigate whether primary aldosteronism (PA) increases the risk of bladder stones. This retrospective nationwide population-based cohort study during the period of 1998-2011 compared patients with and without PA extracted by propensity score matching. Cox proportional hazard models and competing death risk model were used to estimate the hazard ratios (HRs), sub-hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs).

Imiquimod Accelerated Antitumor Response by Targeting Lysosome Adaptation in Skin Cancer Cells.

Lysosomal adaptation is a cellular physiological process in which the number and function of lysosomes are regulated at the transcriptional and post-transcriptional levels in response to extracellular and/or intracellular cues or lysosomal damage. Imiquimod (IMQ), a synthetic toll-like receptor 7 ligand with hydrophobic and weak basic properties, exhibits both antitumor and antiviral activity against various skin malignancies as a clinical treatment. Interestingly, IMQ has been suggested to be highly concentrated in the lysosomes of plasmacytoid dendritic cells, indicating that IMQ could modulate lysosome function after sequestration in the lysosome.

EGR-1 plays a protective role in AMPK inhibitor compound C-induced apoptosis through ROS-induced ERK activation in skin cancer cells.

Skin cancer is caused by abnormal proliferation, gene regulation and mutation of epidermis cells. Compound C is commonly used as an inhibitor of AMP-activated protein kinase (AMPK), which serves as an energy sensor in cells. Recently, compound C has been reported to induce apoptotic and autophagic death in various skin cancer cell lines via an AMPK-independent pathway.

Atorvastatin-induced senescence of hepatocellular carcinoma is mediated by downregulation of hTERT through the suppression of the IL-6/STAT3 pathway.

Hepatocellular carcinoma (HCC), a hepatic malignancy, has a poor prognosis and contributes to cancer-related death worldwide. Cellular senescence is an anticancer therapeutic strategy that causes irreversible cell cycle arrest and enables immune-mediated clearance of cancer cells. Atorvastatin, an HMG-CoA reductase inhibitor, has been shown to inhibit tumor growth and induce apoptosis or autophagy in malignant tumors.

Imiquimod Exerts Antitumor Effects by Inducing Immunogenic Cell Death and Is Enhanced by the Glycolytic Inhibitor 2-Deoxyglucose.

The induction of immunogenic cell death (ICD) in cancer cells triggers specific immune responses against the same cancer cells. Imiquimod (IMQ) is a synthetic ligand of toll-like receptor 7 that exerts antitumor activity by stimulating cell-mediated immunity or by directly inducing apoptosis. Whether IMQ causes tumors to undergo ICD and elicits a specific antitumor immune response is unknown.

M2-like polarization of THP-1 monocyte-derived macrophages under chronic iron overload.

Macrophages are characterized by phenotypical and functional heterogeneity. In different microenvironments, macrophages can polarize into two types: classically activated macrophages (M1) or alternatively activated macrophages (M2). M1 macrophages are a well-known bacteriostatic macrophage, and conversely, M2 macrophages may play an important role in tumor growth and tissue remodeling.

Subcutaneous injection of recombinant heat shock protein 70 ameliorates atopic dermatitis skin lesions in a mouse model.

Atopic dermatitis (AD) is a chronic inflammatory skin disease and sometimes is a tough challenge for physicians. We previously reported that in Th2 environment, the production and secretion of thymic stromal lymphopoietin (TSLP) from human keratinocytes was inhibited by recombinant heat shock protein 70 (rHSP70). The present study assessed the therapeutic effectiveness of rHSP70 in a mouse model of AD.

Intestinal microbiota profiling and predicted metabolic dysregulation in psoriasis patients.

Objectives: The intestinal microbiota has been known to involve in obesity and host immune response. We aimed to investigate the intestinal microbiota and potential genetic function in relation to clinical presentation in psoriasis patients.

Methods: Faecal microbiota and predicted genetic function inferred from high-throughput 16S ribosomal RNA sequencing were analysed between psoriasis (n = 32) and age-, gender- and body mass index (BMI)-matched non-psoriasis subjects (n = 64), from a referral medical centre.