Lipidomics Analysis Unravels Aberrant Lipid Species and Pathways Induced by Zinc Oxide Nanoparticles in Kidney Cells.

Zinc oxide nanoparticles (ZnO NPs) are widely used in versatile applications, from high technology to household products. While numerous studies have examined the toxic gene profile of ZnO NPs across various tissues, the specific lipid species associated with adverse effects and potential biomarkers remain elusive. In this study, we conducted a liquid chromatography-mass spectrometry based lipidomics analysis to uncover potential lipid biomarkers in human kidney cells following treatment with ZnO NPs.

Metabolomic Approach to Identify Potential Biomarkers in KRAS-Mutant Pancreatic Cancer Cells.

Pancreatic cancer is characterized by its high mortality rate and limited treatment options, often driven by oncogenic RAS mutations. In this study, we investigated the metabolomic profiles of pancreatic cancer cells based on their KRAS genetic status. Utilizing both KRAS-wildtype BxPC3 and KRAS-mutant PANC1 cell lines, we identified 195 metabolites differentially altered by KRAS status through untargeted metabolomics.

The Effect of Severe Varus Deformity on Clinical and Radiographic Outcomes in Mechanical Aligned Total Knee Arthroplasty with Medial Stabilizing Technique.

The purpose was to compare the clinical and radiographic outcomes between preoperative mild and severe varus deformity after total knee arthroplasty (TKA) with medial stabilizing technique (MST). We retrospectively analyzed 158 knees of 125 female patients with a 2-year follow-up who underwent mechanically aligned TKA with MST between April 2018 and February 2021. Patients were divided into two groups; the severe varus group was defined as one with preoperative hip-knee ankle (HKA) angle ≥ 15° and the mild varus group with HKA angle < 15°.

Impact of Obesity and Lysosomal Dysfunction on Chemoresistance in Ovarian Cancer.

Obesity is recognized as a significant risk factor for ovarian cancer, with accumulating evidence highlighting its impact on disease progression and chemoresistance. This review synthesizes current research elucidating the link between obesity-induced lysosomal dysfunction and ovarian cancer chemoresistance. Epidemiological studies consistently demonstrate a positive correlation between body mass index (BMI) and ovarian cancer risk, attributed in part to the predilection of epithelial ovarian cancer cells for adipose tissue, particularly the omentum.

Modulation of Cisplatin Sensitivity through TRPML1-Mediated Lysosomal Exocytosis in Ovarian Cancer Cells: A Comprehensive Metabolomic Approach.

Background: The lysosome has emerged as a promising target for overcoming chemoresistance, owing to its role in facilitating the lysosomal sequestration of drugs. The lysosomal calcium channel TRPML1 not only influences lysosomal biogenesis but also coordinates both endocytosis and exocytosis. This study explored the modulation of cisplatin sensitivity by regulating TRPML1-mediated lysosomal exocytosis and identified the metabolomic profile altered by TRPML1 inhibition.

Yeast Hydrolysate Inhibits Lipid Accumulation via Regulation of Lipid Accumulation-Related Genes in a Model of High-Sugar Diet-Induced Obesity.

The increasing frequency of processed food consumption has led to the higher ingestion of sugar, increasing the risk of chronic diseases, such as obesity. Yeast hydrolysates (YHs) inhibit body fat accumulation. However, the action mechanism of YH in relation to high-sugar diet-induced obesity is still unclear.

Zinc oxide nanoparticles trigger autophagy-mediated cell death through activating lysosomal TRPML1 in normal kidney cells.

Zinc oxide nanoparticles (ZnO NPs) have been widely used in various materials including sunscreens, cosmetics, over-the-counter topical skin products, and pigments. As traces of the used ZnO NPs have been found in the kidney, it is crucial to uncover their potential risks. The aim of this study is to elucidate detrimental effects of ZnO NPs and the molecular mechanism behind their renal toxicity.

Effects of Collagen-Tripeptide and Galacto-oligosaccharide Mixture on Skin Photoaging Inhibition in UVB-exposed Hairless Mice.

Collagen-tripeptide (CTP) and galacto-oligosaccharide (GOS), which improve collagen homeostasis and barrier function in the skin, are widely used in the food industry to improve wrinkle-related parameters and skin health. In this study, the photoprotective effect of CTP/GOS mixtures (3:1, 1:1, and 1:3) in ultraviolet (UV) B-irradiated hairless mice was examined. Skin parameter analysis, histological approaches, molecular biology techniques and HPLC analysis were applied to investigate the photoaging protective effect, signaling pathways and changes in the microbiota.

p53 mitigates the effects of oncogenic HRAS in urothelial cells via the repression of .

Inhibition of TRPML1, which is encoded by , is known to deter cell proliferation in various malignancies. Here, we report that the tumor suppressor, p53, represses in the urothelium such that either the constitutive loss or ectopic knockdown of -in both healthy and bladder cancer cells-increased expression. Conversely, nutlin-mediated activation of p53 led to the repression of .

Regulation of longevity by depolarization-induced activation of PLC-β-IPR signaling in neurons.

Mitochondrial ATP production is a well-known regulator of neuronal excitability. The reciprocal influence of plasma-membrane potential on ATP production, however, remains poorly understood. Here, we describe a mechanism by which depolarized neurons elevate the somatic ATP/ADP ratio in glutamatergic neurons.

Author Correction: Characterization and its implication of a novel taste receptor detecting nutrients in the honey bee, Apis mellifera.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

TRPing the homeostatic alarm - Melanoma cells are selectively vulnerable to TRPML1 deletion.

To thrive in otherwise inhospitable conditions, cancer cells utilize endolysosomes to impose homeostatic control over cellular metabolism and growth. In a recent study, Kasitinon et al. demonstrate a requirement for the endolysosomal channel, TRPML1, in proliferation and survival of melanoma cells.

TRPML1 and RAS-driven cancers - exploring a link with great therapeutic potential.

Activating mutations in the family of proto-oncogenes represent some of the leading causes of cancer. Unmitigated proliferation of cells harboring oncogenic mutations is accompanied by a massive increase in cellular bioenergetic demands, which offers unique opportunities for therapeutic intervention. To withstand the steep requirements for metabolic intermediates, RAS-driven cancer cells enhance endolysosome and autophagosome biogenesis.

Characterization and its implication of a novel taste receptor detecting nutrients in the honey bee, Apis mellifera.

Umami taste perception indicates the presence of amino acids, which are essential nutrients. Although the physiology of umami perception has been described in mammals, how insects detect amino acids remains unknown except in Drosophila melanogaster. We functionally characterized a gustatory receptor responding to L-amino acids in the western honey bee, Apis mellifera.

HRAS-driven cancer cells are vulnerable to TRPML1 inhibition.

By serving as intermediaries between cellular metabolism and the bioenergetic demands of proliferation, endolysosomes allow cancer cells to thrive under normally detrimental conditions. Here, we show that an endolysosomal TRP channel, TRPML1, is necessary for the proliferation of cancer cells that bear activating mutations in Expression of , which encodes TRPML1, is significantly elevated in -positive tumors and inversely correlated with patient prognosis. Concordantly, knockdown or TRPML1 inhibition selectively reduces the proliferation of cancer cells that express oncogenic, but not wild-type, Mechanistically, TRPML1 maintains oncogenic HRAS in signaling-competent nanoclusters at the plasma membrane by mediating cholesterol de-esterification and transport.

The Effects of High Fat Diet-Induced Stress on Olfactory Sensitivity, Behaviors, and Transcriptional Profiling in .

High-fat diet (HFD) often causes obesity and it has detrimental effects on the sensory system. In particular, sensory-mediated responses are crucial for maintaining energy balance, as they are involved in a metabolic regulation; however, there is still no clear explanation about the relationship between HFD-induced stress and sensory system. To gain insight on how HFD-induced stress affects olfactory sensitivity and behavioral responses, we have used a model for olfactory and nutrient-related signaling and accessed physiological, behavioral, and transcriptional changes.

Behavioural and electroantennogram responses of the stable fly (Stomoxys calcitrans L.) to plant essential oils and their mixtures with attractants.

Background: Insect olfactory organs possess many olfactory receptor neurons, which detect many different sets of odorants in nature. In order to feed on blood meals, stable flies locate host animals and humans using chemical cues such as 1-octen-3-ol and butyric acid. In the present study, behavioural and electroantennogram (EAG) response patterns to repellent volatiles from essential oils (EOs) of Zanthoxylum piperitum and Z.