Nuclear lipid microdomains regulate daunorubicin resistance in hepatoma cells

Daunorubicin is an anticancer drug, and cholesterol is involved in cancer progression, but their relationship has not been defined. In this study, we developed a novel experimental model that utilizes daunorubicin, cholesterol, and daunorubicin plus cholesterol in the same cells (H35) to search for the role of nuclear lipid microdomains, rich in cholesterol and sphingomyelin, in drug resistance. We find that the daunorubicin induces perturbation of nuclear lipid microdomains, localized in the inner nuclear membrane, where active chromatin is anchored. As changes of sphingomyelin species in nuclear lipid microdomains depend on neutral sphingomyelinase activity, we extended our studies to investigate whether the enzyme is modulated by daunorubicin. Indeed the drug stimulated the sphingomyelinase activity that induced reduction of saturated long chain fatty acid sphingomyelin species in nuclear lipid microdomains. Incubation of untreated-drug cells with high levels of cholesterol resulted in the inhibition of sphingomyelinase activity with increased saturated fatty acid sphingomyelin species. In daunodubicin-treated cells, incubation with cholesterol reversed the action of the drug by acting via neutral sphingomyelinase. In conclusion, we suggest that cholesterol and sphingomyelin-forming nuclear lipid microdomains are involved in the drug resistance

A Chiroptical Molecular Switch with Distinct Chiral and Photochromic Entities and Its Application in Optical Switching of a Cholesteric Liquid Crystal

Two new structurally related photoswitches are described, in which azobenzene photochromism is combined with the chirality of a 2,2’-dihydroxy-1,1’-binaphthyl unit. In system 1 the chiral binaphthyl moiety is bridged by a methylene tether, locking the biaryl chirality while in system 2 the biaryl core is unbridged and has considerable conformational flexibility. Both compound are capable of inducing cholesteric liquid crystalline phases and proved to be good photoswitches both in solution and in a liquid crystalline matrix. Compound 2 is capable of completely reversing the liquid crystalline chirality which is unique for a chiroptical molecular switch where the switching unit and the chiral moiety are separate entities.

Validation rules for blood smear revision after automated hematological testing using Mindray CAL-8000

This article was aimed to test the use of validation rules for blood smear review after automated hematological testing using Mindray CAL-8000 (two hematological analyzers and one autoslider)

N-alkyl-D-glucamine based macroporous polymeric cryogel for sequestering and/or removing toxic contaminants

The present invention refers to the field of chemistry and in particular to a N-alkyl-D-glucamine based macroporous polymeric cryogel, the method for the preparation thereof and its use for sequestering and/or removing toxic contaminants such as metalloids and/or toxic heavy metals, for example from water and/or soil

Life Cycle Assessment of Polyol Production from Lignin via Organosolv and Liquefaction Treatments

This study aimed to conduct a comprehensive Life Cycle Assessment (LCA) of lignin-based polyol production through organosolv fractionation of cardoon stalks and subsequent lignin liquefaction. The LCA employed a cradle-to-gate approach, encompassing cardoon cultivation and all processing steps leading to polyol production. The research involved laboratory-scale optimization of the organosolv and liquefaction processes, followed by industrial-scale implementation. The analysis revealed that all stages of the production chain, including crop cultivation, organosolv, and liquefaction, significantly influenced overall environmental impacts. Specific materials and processes played pivotal roles, such as harvesting machinery and fertilizers in crop production, γ-Valerolactone (GVL) as the primary contributor (72–100%) to environmental impacts in the organosolv phase, and materials like polyethylene glycol 400 (PEG 400) and glycerin in the liquefaction phase, accounting for the majority (96–100%) of environmental impacts in this stage. When considering endpoint damage categories, it became evident that this production chain had a notable impact on human health, primarily due to emissions in air, water, and soil from agricultural processes. Lignin-based polyols demonstrated a moderate improvement compared to their petroleum-based counterparts, with an approximate reduction of 3–16% in environmental impact

Cell population data and reflex testing rules of cell analysis in pleural and ascitic fluids using body fluid mode on sysmex XN-9000

BACKGROUND: Although optical microscopy (OM) remains the reference technique for analysis of ascitic (AF) and pleural (PF) fluids, novel hematological analyzers are equipped with modules for body fluids (BFs) analysis. This study was aimed to analyze the performance of XN-BF module in Sysmex XN-9000, and to develop validation rules for automated cell counts in BFs.METHODS: The evaluation of XN-BF module included assessment of carryover, Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ), linearity, data comparison with OM, and development of rules for assisting the validation of automated analysis of BFs and activating reflex testing.RESULTS: The carryover was negligible. The LoB, LoD, LoQ and linearity were always excellent. The comparison with OM was characterized by Pearson's correlations ranging from r=0.50 to r=0.99 (p<0.001), modest bias and high diagnostic concordance (Area Under the Curve between 0.85-0.99). The use of instrument-specific cut-offs further increased diagnostic concordance. The implementation of reflex testing rules based on XN-BF data increased sensitivity and specificity of BFs classification to 0.98 and 0.95.CONCLUSIONS: Our results suggest that the XN-BF module on Sysmex-9000 may be a suitable alternative to OM for screening BF samples, especially when specific validation rules are used

Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor

Sphingomyelinase (SMase) is responsible for the breakdown of sphingomyelin (SM) with production of ceramide. The absence of acid sphingomyelinase (aSMase) causes abnormal synapse formation in Niemann-Pick type A (NPA) disease. Because high levels of ceramide in the NPA brain were demonstrated, the involvement of other SMases were supposed. In the present study we focused the attention on the neurogenic niches in the hippocampal gyrus dentatus (GD), a brain structure essential for forming cohesive memory. We demonstrated for the first time the increase of (Sex determining region Y)-box 2 (SOX2), and the down-regulation of glial fibrillary acidic protein (GFAP) NPA mice GD. Moreover, we found that the expression of Toll like receptors (TLRs), was increased in NPA mice, particularly TLR2, TLR7, TLR8 and TLR9 members. Although no significant change in neutral sphingomyelinase (nSMase) gene expression was detected in the NPA mice hippocampus of, protein levels were enhanced, probably because of the slower protein degradation rate in this area. Many studies demonstrated that vitamin D receptor (VDR) is expressed in the hippocampus GD. Unexpectedly, we showed that NPA mice exhibited VDR gene and protein expression up-regulation. In summary, our study suggests a relation between hippocampal cell differentiation defect, nSMase and VDR increase in NPA mice

Assessment of blood sample stability for complete blood count using the Sysmex XN-9000 and Mindray BC-6800 analyzers

Different hematological analyzers have different analytical performances that are often reflected in the criteria for sample stability of the complete blood count. This study aimed to assess the stability of several hematological parameters using the XN-9000 Sysmex and BC-6800 Mindray analyzers