Breast cancer is the most common diagnosed cancer, the HER2-positive subtype account for 15% of all breast cancer. HER2-targeted therapy is the mainstay treatment for HER2-positive breast cancer. ...Cuproptosis is a novel form of programmed cell death, and is caused by mitochondrial lipoylation and destabilization of iron-sulfur proteins triggered by copper, which was considered as a key player in various biological processes. However, the roles of cuproptosis-related genes in HER2-positive breast cancer remain largely unknown. In the present study, we constructed a prognostic prediction model of HER2-positive breast cancer patients using TCGA database. Dysregulated genes for cells resistant to HER2-targeted therapy were analyzed in the GEO dataset. KEGG pathway, GO enrichment and GSEA was performed respectively. The immune landscape of DLAT was analyzed by CIBERSORT algorithm and TIDE algorithm. HER2-positive breast cancer patients with high CRGs risk score showed shorter OS. DLAT was downregulated and correlated with better survival of HER2-positive breast cancer patients (HR = 3.30, p = 0.022). High expressed DLAT was associated with resistant to HER2-targeted therapy. Knocking down DLAT with siRNA increased sensitivity of breast cancer to trastuzumab. KEGG pathway and GO enrichment of DEGs indicated that DLAT participates in various pathways correlated with organelle fission, chromosome segregation, nuclear division, hormone-mediated signaling pathway, regulation of intracellular estrogen receptor signaling pathway, condensed chromosome and PPAR signaling pathway. There was a negative correlation between TIDE and DLAT expression (r = - 0.292, p < 0.001), which means high DLAT expression is an indicator of sensitivity to immunotherapy. In conclusion, our study constructed a four CRGs signature prognostic prediction model and identified DLAT as an independent prognostic factor and associated with resistant to HER2-targeted therapy for HER2-positive breast cancer patients.
Lipid metabolism and tumor immunotherapy Wang, Yue; Guo, Zongjin; Isah, Adamu Danbala ...
Frontiers in cell and developmental biology,
05/2023, Letnik:
11
Journal Article
Recenzirano
Odprti dostop
In recent years, the relationship between lipid metabolism and tumour immunotherapy has been thoroughly investigated. An increasing number of studies have shown that abnormal gene expression and ...ectopic levels of metabolites related to fatty acid synthesis or fatty acid oxidation affect tumour metastasis, recurrence, and drug resistance. Tumour immunotherapy that aims to promote an antitumour immune response has greatly improved the outcomes for tumour patients. However, lipid metabolism reprogramming in tumour cells or tumour microenvironment-infiltrating immune cells can influence the antitumour response of immune cells and induce tumor cell immune evasion. The recent increase in the prevalence of obesity-related cancers has drawn attention to the fact that obesity increases fatty acid oxidation in cancer cells and suppresses the activation of immune cells, thereby weakening antitumour immunity. This article reviews the changes in lipid metabolism in cells in the tumour microenvironment and describes the relationship between lipid metabolism reprogramming in multiple cell types and tumour immunotherapy.
Purpose
We report a case of revascularization for an occluded renal artery using endovascular renal thrombus aspiration followed by catheter-directed thrombolysis.
Case Report
A 56-year-old man ...presented with sudden onset severe left-sided abdominal and loin pain for 6 hours. Urgent computed tomography (CT) angiogram showed occlusion of left renal artery. Emergency selective left renal angiogram and thrombus aspiration using a 5-French Cobra catheter was performed. Catheter-directed thrombolysis with urokinase was initiated after aspiration thrombectomy. Angiogram 24 hours after thrombolysis showed the left renal artery and its segmental branches were successfully revascularized. Patient was put on anticoagulation after operation and his renal function recovered well.
Conclusion
Percutaneous aspiration thrombectomy with conventional catheters combined with intra-arterial local fibrinolysis could be used to salvage the renal function in case of complete renal artery thromboembolic occlusion.
Tissue regeneration following injury from disease or medical treatment still represents a challenge in regeneration medicine. Prostaglandin E2 (PGE2), which involves diverse physiological processes ...via E-type prostanoid (EP) receptor family, favors the regeneration of various organ systems following injury for its capabilities such as activation of endogenous stem cells, immune regulation, and angiogenesis. Understanding how PGE2 modulates tissue regeneration and then exploring how to elevate the regenerative efficiency of PGE2 will provide key insights into the tissue repair and regeneration processes by PGE2. In this review, we summarized the application of PGE2 to guide the regeneration of different tissues, including skin, heart, liver, kidney, intestine, bone, skeletal muscle, and hematopoietic stem cell regeneration. Moreover, we introduced PGE2-based therapeutic strategies to accelerate the recovery of impaired tissue or organs, including 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitors boosting endogenous PGE2 levels and biomaterial scaffolds to control PGE2 release.
Stem cell therapy is widely recognized as a promising strategy for exerting therapeutic effects after injury in degenerative diseases. However, limitations such as low cell retention and survival ...rates after transplantation exist in clinical applications. In recent years, emerging biomaterials that provide a supportable cellular microenvironment for transplanted cells have optimized the therapeutic efficacy of stem cells in injured tissues or organs. Advances in the engineered microenvironment are revolutionizing our understanding of stem cell-based therapies by co-transplanting with synthetic and tissue-derived biomaterials, which offer a scaffold for stem cells and propose an unprecedented opportunity to further employ significant influences in tissue repair and regeneration.
•The PAM is formed through the in-situ free-radical polymerization during the cement hydration.•The flexural strength is increased by 100% with the addition of 3% PAM.•Interactions between hydrated ...products and PAM significantly improve the flexural strength.•ULCC incorporating PAM has higher water resistance.
This research aims at developing the ultra-lightweight cement composites (ULCC) with high flexural strength, good thermal insulation, and great water resistance by incorporating the acrylamide. Polyacrylamide (PAM) is formed by in-situ free-radical polymerization during the hydration of cement. The physico-mechanical properties, thermal performance, interactions between hydrated cement and PAM, microstructure and water absorption of the composites are characterized in detail. Fly ash cenospheres (FAC) is used to fabricate the ULCC with a density and thermal conductivity of approximately 1250 kg/m3 and 0.3 W/m K, respectively. The flexural strength is impressively improved by adding PAM, where the composites with 3% PAM have the highest flexural strength while still maintain sufficient compressive strength. The physical and chemical interactions between PAM and hydrated products are found to dominate the flexural strength and toughness of the composites. PAM-modified ULCC displays much higher resistance against water in comparison to the neat mixture as well.
Flexible electronics greatly facilitate human life due to their convenience and comfortable utilization. Liquid metals are an ideal candidate for flexible devices; however, the high surface tension ...and poor surface wettability restrict their application on diverse substrates. Herein, a printable and recyclable ink composed of poly(vinyl alcohol) and a liquid metal (PVA-LM) was developed to resolve these problems. The materials were designed considering the compatibility between PVA and the liquid metal, and the composite theory was applied to determine the component proportion. The developed composites improved the surface wettability of the liquid metal on diverse substrates, and three-dimensional (3D) printing technology was chosen to maximize the use of this material. Moreover, the PVA-LM ink showed excellent conductivity of about 1.3 × 105 S/m after being turned on, which favored the designing of alarm systems and object locators. The flexible sensors produced with this ink have broad application, high sensitivity, and superstable signal generation even after 200 cycles. When acting as strain sensors, the constructed composites had high sensitivity for monitoring the human movements. Furthermore, liquid metals in printed products can be recycled under alkaline conditions. This study opens a new direction for the next generation of environmentally friendly flexible devices.
Abstract To elucidate the distribution law of the multiphase coupling slag discharge flow field in gas-lift reverse circulation during drilling shaft sinking, a numerical analysis model of ...gas–liquid–solid multiphase coupling slag discharge was established by CFD–DEM (Coupling of computational fluid dynamics and discrete element method) method, taking the drilling of North Wind well in Taohutu Coal Mine as an example. This model presented the distribution of the multiphase flow field in the slag discharge pipe and at the bottom hole, and was validated through experimentation and theoretical analysis. Finally, the impact of factors, including bit rotation speed, gas injection rate, air duct submergence ratio, and mud viscosity on the slag discharge flow field was clarified. The results indicated that the migration of rock slag at the bottom of the well was characterized by “slip, convergence, suspension, adsorption, and lifting”. The slag flow in the discharge pipe exhibited the states of “high density, low flow rate” and “low density, high flow rate”, respectively. The multiphase fluid flow patterns in the well bottom and slag discharge pipe were horizontal and axial flows, respectively. The model test of the gas lift reversed circulation slag discharge and the theoretical model of the bottom hole fluid velocity distribution confirmed the accuracy of the multiphase coupling slag discharge flow field distribution model. The rotation speed of the drill bit had the most significant impact on the bottom hole flow field. Increasing the rotation speed of the drill bit can significantly enhance the tangential velocity of the bottom hole fluid, increase the pressure difference between the bottom hole and annular mud column, and improve the adsorption capacity of the slag suction port. These findings can provide valuable insights for gas lift reverse circulation well washing in western drilling shaft sinking.