CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.

BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Blockage of CacyBP inhibits macrophage recruitment and improves anti-PD-1 therapy in hepatocellular carcinoma.

BACKGROUND: Despite remarkable advancements in cancer immunotherapy, the overall response rate to anti-programmed cell death-1 (anti-PD-1) therapy in hepatocellular carcinoma (HCC) patients remains low. Our previous study has demonstrated the critical role of CacyBP/SIP (Calcyclin-Binding Protein and Siah-1 Interacting Protein) as a regulator of HCC development and progression. However, the possible impact of CacyBP on the tumor immune microenvironment has not yet been clarified. METHODS: The expressions of CacyBP and Myd88 in HCC cell lines and tissues was detected by bioinformatics analysis, real-time quantitative PCR, western blotting and immunohistochemistry. The interaction between CacyBP and Myd88 was measured using co-immunoprecipitation and immunofluorescence. In vitro and in vivo assays were used to investigate the regulation of CacyBP on tumor-associated macrophages (TAMs). RESULTS: We identified that CacyBP was positively correlated with Myd88, a master regulator of innate immunity, and Myd88 was a novel binding substrate downstream of CacyBP in HCC. Additionally, CacyBP protected Myd88 from Siah-1-mediated proteasome-dependent degradation by competitively binding to its Toll/interleukin-1 receptor (TIR) domain. Inhibition of CacyBP-Myd88 signaling subsequently diminished HDAC1-mediated H3K9ac and H3K27ac modifications on the CX3CL1 promoter and reduced its transcription and secretion in HCC cells. Moreover, by using in vitro and in vivo strategies, we demonstrated that depletion of CacyBP impaired the infiltration of TAMs and the immunosuppressive state of the tumor microenvironment, further sensitizing HCC-bearing anti-PD-1 therapy. CONCLUSIONS: Our findings suggest that targeting CacyBP may be a novel treatment strategy for improving the efficacy of anti-PD-1 immunotherapy in HCC.

Impact of ultra-low temperature storage on serum sIgE detection and allergic disease biobank feasibility.

Research has shown that the concentration and composition of biological samples may change after long-term ultra-low temperature storage. Consequently, this study examined the effect of ultra-low temperature storage on serum sIgE detection by comparing sIgE concentrations at various durations from the time of sample storage to subsequent testing. We selected 40 serum samples from the Guangzhou Medical University Affiliated First Hospital Biobank, which had been tested for house dust mites, dog hair, tobacco mold, cockroaches, and cow milk allergen sIgE. Samples were categorized by storage duration: 14 samples stored for 10 years, 12 for 5 years, and 14 for 3 years. They were also classified by sIgE positive levels: 15 samples at levels 1-2, 15 at levels 3-4, and 10 at levels 5-6. The allergen sIgE of these samples was retested using the same technology. Regardless of the type of allergen or the level of positivity, the majority of sIgE concentrations measured at the time of storage were higher than the current measurements, but the difference was not statistically significant. The correlation between the sIgE results at the time of storage and the current results was high for samples stored for 10 years (rs = 0.991, P < 0.001) and 5 years (rs = 0.964, P < 0.001). Serum allergen sIgE is stable when stored under ultra-low temperature conditions, making the construction of a biological sample bank for allergic diseases feasible. This will facilitate researchers in quickly obtaining samples, conducting technical research, and translating findings, thereby promoting the development of the field of allergy through integration of industry, academia, and research.

Allergy patient-specific IgE antibody shows significantly stability during 3 months of storage at multiple temperatures from -80 to 25°C.

The detection of allergen-specific IgE antibodies is an important biomarker for the diagnosis and treatment monitoring of allergic diseases. And the pre-analytical phase is an important part of the overall quality of the laboratory. In this study, 44 patients with allergic diseases (including 23 patients with allergic rhinitis, 12 patients with allergic rhinitis and asthma, and 9 patients with allergic dermatitis) were included in the outpatient center of the Department of Allergy, the First Affiliated Hospital of Guangzhou Medical University. We mixed the serums of the above 44 patients (approximately 0.8 ml of serum volume per patient) into a large volume of serum pool (about 35 ml in total) and divided into 26 parts. And 26 serum samples were stored at 4 different temperatures for 90 days to observe the stability of sIgE antibodies to 16 allergens in serum. The results show that serum sIgE antibody titers in patients with allergic diseases show significant stability during 90 days of storage, even at room temperature. Good stability even after up to 10 freeze-thaw cycles under low temperature storage conditions.

COLEC10 Induces Endoplasmic Reticulum Stress by Occupying GRP78 and Inhibits Hepatocellular Carcinoma.

Collectin subfamily member 10 (COLEC10), a C-type lectin mainly expressed in the liver, is involved in the development of hepatocellular carcinoma (HCC). However, its underlying molecular mechanism in HCC progression remains unknown. In this study, reduced COLEC10 expression in tumor tissues was validated using various HCC cohorts and was associated with poor patient prognosis. COLEC10 overexpression attenuated HCC cell growth and migration abilities in vitro and in vivo. We identified that COLEC10 was a novel interactor of 78-kDa glucose-regulated protein (GRP78), a master modulator of the unfolded protein response in the endoplasmic reticulum (ER). COLEC10 overexpression potentiated ER stress in HCC cells, as demonstrated by elevated expression levels of phosphorylated protein kinase RNA-like ER kinase, phosphorylated inositol-requiring protein 1α, activating transcription factor 4, DNA damage-inducible transcript 3, and X-box-binding protein 1s. The ER in COLEC10-overexpressing cells also showed a dilated and fragmented pattern. Mechanistically, COLEC10 overexpression increases GRP78 occupancy through direct binding by the C-terminal carbohydrate recognition domain in the ER, which released and activated the ER stress transducers protein kinase RNA-like ER kinase and phosphorylated inositol-requiring protein 1α, triggering the unfolded protein response activity. COLEC10-overexpressing HCC cells generated a relatively high reactive oxygen species level and switched to apoptotic cell death under sorafenib-treated conditions. Our study provides the first novel view that COLEC10 inhibits HCC progression by regulating GRP78-mediated ER stress signaling and may serve as a promising therapeutic and prognostic biomarker.

Sustainable fashion: eco-friendly dyeing of wool fiber with novel mixtures of biodegradable natural dyes.

Natural materials, especially natural colorants, have achieved global prominence and might be regarded as an environmentally beneficial alternative to hazardous synthetic dyes. The color limitation of natural dyes hinders their application in textiles. The present work aims to prepare more color shades of wool yarns via dyeing with ternary natural dye mixtures without adding mordants. In this study, a sustainable dyeing approach for wool yarn was evaluated with three natural dyes, madder red (MR), gardenia blue (GB), and gardenia yellow (GY), by following an industrial dyeing procedure in the absence of a mordant. In the beginning, a preliminary assessment of dye stabilities was carried out, and it was found that the three natural dyes were sensitive to temperature and acid (degradation tendency). Then, the dyeing behavior was systematically evaluated, including a single natural dye, a binary natural dye mixture, and a ternary natural dye mixture. The results of wool yarn dyeing with a single natural dye show that the dye exhaustion percentage (E%) of MR, GY, and GB was in the ranges of 78.7-94.1%, 13.4-44.1%, and 54.8-68.5%, respectively. The dyeing results of wool yarns dyed with binary and ternary natural dye mixtures (a color triangle framework of dyed wool yarn) were characterized by colorimetric values (L*, a*, b*, C*, h, and K/S), and are presented to enlighten various colorful shades. Finally, color uniformity and colorfastness tests confirmed the vital contribution of natural dyes toward wool yarn coloration. Particularly, colorfastness to washing confirmed the stability of natural dyes with reference to the lower amount of dyes released into the effluent, which is beneficial for the environment. Overall, this study provides a good background for enhancing the industrialization trend of natural dyes by modulating their dyeing scheme.

Sustainable and eco-friendly dyeing of traditional grass cloth with a reactive dye in palm oil medium.

Traditional grass cloth has been used in China for a long time for the manufacturing of various household furnishing textiles and ladieswear. However, traditionally the grass cloth is dyed with reactive dyes in an aqueous medium, but the dyeing process is not sustainable because of high energy and water usage and the production of coloured effluent. In this work, the possibility of palm oil/water dual-phase dyeing of traditional grass cloth with a reactive dye, C.I. Reactive Blue 194 (Reactive Blue 194), was explored. The grass cloth soaked in an alkaline solution with 80-140% pick-up was dyed in a palm oil dyebath containing dye powder dispersed in a palm oil medium. The initial study confirmed that the pre-treatment of the fabric with an alkaline solution with 140% pick-up was beneficial for the uniform distribution of the dye in the fibres. The dyeing process parameters (e.g., fixation temperature, solution pH, and fixation time) for the grass cloth dyeing with the Reactive Blue 194 were optimised by using the Taguchi method. The pH of the alkali pre-treatment solution was found to be the most influential factor, as confirmed by the analysis of variance in terms of the percentage of contribution (94.41%), which was statistically significant (P < 0.05). The confirmation tests were carried out under optimal settings, and a higher K/S (24.06) was found compared with the initial condition (21.51). X-ray diffraction analysis indicated that the dyeing process did not affect the crystallinity of the grass cloth fibres. Furthermore, the recovery of palm oil from the spent dyebath was around 99%, and up to five times recycling and reuse of palm oil were studied for the dyeing of grass cloth. The colour strength of the grass cloths dyed in the palm oil recycled up to five times was similar to the cloth dyed in fresh palm oil. The results show that palm oil can be used as a dyeing medium for the sustainable dyeing of grass cloth with effluent reduction, which can be extended to the dyeing of other textile fibres.

Adsorption Behaviour of Reactive Blue 194 on Raw Ramie Yarn in Palm Oil and Water Media.

As an edible oil, palm oil is also safe and reliable in dyeing, and the residual palm oil after dyeing can be recycled and used continuously, which is green and environmentally friendly and has great research prospects. In this research, raw ramie yarn, used for traditional grass cloth, was dyed in a palm oil medium using Reactive Blue 194. Studying the adsorption and diffusion behaviour in the dyeing process is necessary. Additionally, the kinetics and isotherm model of dyeing raw ramie yarn with Reactive Blue 194 in palm oil is studied, and the adsorption behaviour between them is discussed. For a better understanding, the raw ramie yarn dyeing adsorption behaviour was also carried out in a water medium. It was found that the dyeing rates in palm oil are distinctly faster than in water. Kinetics data suggested that the pseudo-second-order model fitted for both dyeing mediums (palm oil and water) of the adsorption of the Reactive Blue 194 dye onto raw ramie yarn. Afterward, the adsorption isotherms' results denote that the Langmuir model was suitable for palm oil dyeing medium while the Freundlich model was suited for water medium. Overall, this study has demonstrated that raw ramie yarn dyeing in a palm oil medium could be a sustainable colouration route for textile fibres with a greater dye exhaustion percentage.

Whole-exome sequencing analysis identifies distinct mutational profile and novel prognostic biomarkers in primary gastrointestinal diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, and about 10% of DLBCL cases primarily occur in the gastrointestinal tract. Previous reports have revealed that primary gastrointestinal-DLBCL (pGI-DLBCL) harbors different genetic mutations from other nodal or extranodal DLBCL. However, the exonic mutation profile of pGI-DLBCL has not been fully addressed. METHODS: We performed whole-exome sequencing of matched tumor tissues and blood samples from 53 pGI-DLBCL patients. The exonic mutation profiles were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. RESULTS: A total of 6,588 protein-altering events were found and the five most frequent mutated genes in our pGI-DLBCL cohort were IGLL5 (47%), TP53 (42%), BTG2 (28%), P2RY8 (26%) and PCLO (23%). Compared to the common DLBCL, significantly less or absence of MYD88 (0%), EZH2 (0%), BCL2 (2%) or CD79B (8%) mutations were identified in pGI-DLBCL. The recurrent potential driver genes were mainly enriched in pathways related to signal transduction, infectious disease and immune regulation. In addition, HBV infection had an impact on the mutational signature in pGI-DLBCL, as positive HBsAg was significantly associated with the TP53 and LRP1B mutations, two established tumor suppressor genes in many human cancers. Moreover, IGLL5 and LRP1B mutations were significantly correlated with patient overall survival and could serve as two novel prognostic biomarkers in pGI-DLBCL. CONCLUSIONS: Our study provides a comprehensive view of the exonic mutation profile of the largest pGI-DLBCL cohort to date. The results could facilitate the clinical development of novel therapeutic and prognostic biomarkers for pGI-DLBCL.