Tissue & cell最新文献

Urinary bladder cancer (UBC) is the ninth most common cancer worldwide. The intra-tumor heterogeneity of the UBC microenvironment explains the variances in response to therapy among patients. Tumor immune microenvironment (TIME) is based on the balance between anti-tumor and pro-tumorigenic immunity that eventually determines the tumor fate. This review addresses the recent insights of the cytokines, immune checkpoints, receptors, enzymes, proteins, RNAs, cancer stem cells (CSCs), tissue-resident cells, growth factors, epithelial-mesenchymal transition, microbiological cofactor, and paracrine action of cancer cells that mutually cross-talk within the TIME. In-depth balance and alteration of these factors influence the TIME and the overall tumor progression. This, in turn, highlights the prospects of the new era of manipulating these co-factors for improving the diagnosis, prognosis, and treatment of UBC. CONCLUSION: The heterogenic architecture of the TIME orchestrates the fate of the tumor. Nevertheless, recognizing the mutual cross-talk between these key players seems useful in prognostic and therapeutic approaches.

Diabetic foot ulcers (DFUs) pose a significant clinical challenge due to their slow healing and high risk of complications, which severely affect patient quality of life. Central to the delayed healing observed in DFUs is mitochondrial dysfunction, a critical factor impairing cellular repair processes. Phosphocreatine (PCr), a vital molecule involved in cellular energy buffering and ATP regeneration, has recently emerged as a promising therapeutic candidate for ameliorating mitochondrial dysfunction and enhancing tissue repair. This study explores the novel therapeutic potential of PCr in restoring mitochondrial function and accelerating wound healing in DFUs through both in vitro and in vivo models. Using hyperglycemic human umbilical vein endothelial cells (HUVECs) as an in vitro model and a streptozotocin (STZ)-induced diabetic rat model as an in vivo, we evaluated the impact of PCr treatment on mitochondrial activity and wound repair. PCr treatment notably upregulated key mitochondrial biogenesis markers, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1), indicating a restoration of mitochondrial function. In vivo, PCr-treated diabetic rats demonstrated significantly accelerated wound closure, enhanced granulation tissue formation, and reduced inflammatory cell infiltration. These findings underscore PCr's potential to address mitochondrial dysfunction and expedite wound healing in DFUs. This study offers promising new insights into PCr as a targeted therapeutic intervention, paving the way for improved patient outcomes in managing diabetic foot ulcers.

Obesity is a major worldwide health problem affecting one billion people. The purported cardioprotective benefits of hawthorn against cardiovascular diseases (CVDs) are controversial and may be attributed to its antioxidant and anti-inflammatory properties. The current study explored the underlying protective mechanisms of hawthorn berry extract (HBE) against obesity-induced cardiac injury in rats. The control group (G1) was fed a regular rat diet ad libitum. An obesity-induced cardiac injury model was established by feeding a high-fat diet (HFD) to rats of group 2 (G2) and group 3 (G3), while rats of G3 and group 4 (G4) received oral doses of HBE (100 mg/kg) for ten weeks. A light microscope was used to estimate the morphological changes in cardiac tissues. The apoptosis and ROS values of cardiomyocytes were estimated using flow cytometry. Also, the antioxidant enzymes, lipid profile, proinflammatory cytokines, and cardiac enzymes were assessed. Feeding of G2 with HFD significantly increased rats' body weight, cardiac inflammation, apoptosis, and fibrosis compared to G1. As well, significant oxidative stress was observed by reducing GPx1, SOD3, CAT, and HDL-C with a substantial increase of TG, TC, LDL-C, IL-1β, IL-6, TNF-α, cTnI, cTnT, and CK-MB serum levels. On the contrary, supplementation of G3 with HBE significantly protected rats against all mentioned changes compared to G2. The current study confirmed several mechanisms of obesity-induced cardiac injury and the tremendous cardioprotective antioxidant, hypolipidemic, anti-inflammatory, antiapoptotic, and antifibrotic impact of HBE against obesity-induced cardiac injury. Therefore, hawthorn could provide a novel dietary supplement against obesity-induced cardiac injury.

Testosterone signaling mediates diseases such as androgenetic alopecia and prostate cancer and is controlled by the activation of the androgen receptor (AR) and nuclear translocation of the ligand-receptor complex. This study established an immortalized dermal papilla cell line that stably expresses the AR labeled with a monomeric green fluorescence marker. The cells expressed the histone H2B protein as visualized using a red fluorescence marker, enabling the Detection of nuclear translocation under live cell conditions using image analysis. The AR was observed to be translocated from the cytoplasm to the nucleus of cells after stimulation with dihydrotestosterone (DHT). The signal intensity of the nuclear/cytoplasm ratio was analyzed using automatic image analysis and a newly developed algorithm. The quantitation method to detect nuclear translocation revealed that the AR nuclear signal plateaued approximately 20 min after DHT exposure. Our developed method has the potential to save human labor by the automatic process of the image.

Diabetic liver injury (DLI) refers to liver injury resulting from prolonged chronic hyperglycemia and represents a significant complication associated with diabetes, The specific pathogenic mechanism of DLI remains incompletely understood. Tumor necrosis factor α (TNF-α) has been demonstrated to play a crucial role in diabetic complications through intricate signalling pathways, including pyroptosis. However, it remains uncertain whether TNF-α mediates pyroptosis in DLI, we initially established an in vitro model of DLI and confirmed the presence of an inflammatory state characterized by TNF-α in DLI. Furthermore, evidence of gasdermin E (GSDME)-mediated pyroptosis and the activation of cysteinyl aspartate specific proteinase (caspase)-8 was observed in AML-12 cell exposed to high glucose concentrations. We subsequently demonstrated that TNF-α can trigger caspase-8 activation, leading to GSDME-mediated cellular pyroptosis. Furthermore, treatment with ghrelin effectively suppressed hepatic cell pyroptosis induced by high glucose concentrations and provided protection against liver injury. Therefore, we propose that the TNF-α/caspase-8/caspase-3/GSDME pathway represents a novel mechanism underlying pyrodeath in DLI cells and to explore the protective role and molecular mechanisms underlying the effects of ghrelin on DLI by this special pathway, These findings may present potential therapeutic implications for the management of DLI.

Bone formation is a complex multi-factor process of bone defect healing. Oxidative stress (OS) is predisposed to induce regulatory cell death (RCD), such as ferroptosis. At present, the antioxidant effects of Crocin on erastin induced oxidative damage were studied. The activity of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) was detected by CCK-8 and EdU staining. The production of reactive oxygen species (ROS), MDA, SOD and GSH were evaluated. Western blotting assay was used to detect ferroptosis-related proteins. The osteogenic function of BMSCs was determined by alkaline phosphatase (ALP) activity, ALP staining and alizarin red S (ARS) staining. Western blotting and RT-PCR assays were used to detect the expression of osteogenic proteins and genes. Angiogenesis of HUVECs was evaluated by tube formation, RT-PCR, scratch test and Transwell assay. The results showed that Crocin can promote the osteogenic function of BMSCs and angiogenesis of HUVECs. In addition, Crocin protects cells from erastin-induced oxidative injury and inhibits ferroptosis via the Nrf2/GPX4 pathway. These findings suggest that Crocin can promote bone defect healing by regulating OS and inhibiting ferroptosis through the Nrf2/GPX4 pathway.

Introduction: Chronic kidney disease (CKD) has long represented a substantial global health challenge. Regrettably, current therapeutic interventions exhibit limited efficacy in halting the progression of CKD. Ferroptosis may play a crucial role in CKD, as indicated by substantial evidence. Dental pulp stem cell-derived exosomes (DPSC-Exos) possess advantages such as abundant sources and low immunogenicity, holding promising prospects in CKD treatment.

Methods: This study constructed a mouse CKD model to investigate the therapeutic effects of DPSC-Exos. First, we successfully extracted and identified DPSC-Exos. Then, mice were randomly divided into sham, PBS, CKD, and CKD+Exos groups. Our study determined the expression of ferroptosis-related pathway molecules Nrf2, GPX4, Keap1, and HO-1 in each group. Finally, we detected the expression levels of inflammatory factors, TNF-α, IL-1β, and IL-6, at the injury site.

Results: Mice treated with DPSC-Exos showed increased expression of the ferroptosis inhibitory factor Nrf2 and its downstream regulatory factors GPX4 and HO-1, while the expression of Keap1 decreased. The expression of TNF-α, IL-1β, and IL-6 also decreased.

Conclusion: DPSC-Exos may help inhibit ferroptosis through the Keap1-Nrf2/GPX4 pathway and reduce the inflammatory response at the injury site, revealing their potential therapeutic effects on CKD.

Background: Diabetic keratopathy is a prevalent but sometimes ignored visual condition in diabetic patients, which significantly affects patients with diabetes mellitus (DM) in terms of their visual acuity. Exosomes regulate diabetes-related conditions like diabetic keratopathy (DK) by secreting their components into the body.

Objective: Aim to investigate the effect and mechanism of mesenchymal stem cell (MSC)-derived exosome miR-125a-5p on DK.

Methods: Transmission electron microscopy, along with nanoparticle tracking analysis, was used to determine the morphology and size of exosomes. To evaluate cell viability, proliferation, and migration, Western blotting and RT-qPCR methods were used. CCK-8, cell cloning, and scratch assays were used to measure protein levels and mRNA expression.

Results: High glucose treatment of corneal epithelial cells weakened cell viability, proliferation and migration, and the level of miR-125a-5p was significantly reduced. It has been proposed that elevated levels of miR-125a-5p could enhance cell viability, proliferation, and migration, can inhibit endoplasmic reticulum stress induced by high glucose, which is the same as the effect of endoplasmic reticulum stress inhibitors.

Conclusion: Mouse bone marrow MSC-derived exosome miR-125a-5p repairs corneal epithelial cell viability and proliferation as well as migration ability to improve DK by inhibiting high glucose-induced endoplasmic reticulum stress.

Background: The objective of the present study was to assess potential immunotoxic effects of aspartame in BALB/c mice.

Methods: Aspartame was administered orally at 400 and 2000 mg/kg for two weeks (five days per week). Specific parameters of humoral and cellular immune responses including hemagglutinating antibody (HA) titer, cytokine production (IFN-γ and IL-4 levels), delayed type hypersensitivity (DTH) response to SRBCs, histopathological examination of spleen and bone marrow, and T-lymphocyte proliferation in response to phytohemagglutinin-A (PHA) were evaluated.

Results and conclusion: Aspartame at 400 and 2000 mg/kg did not significantly change hematological and histopathological parameters, HA titer, IFN-γ and IL-4 levels, DTH, and lymphoproliferation responses (p > 0.05). Aspartame at 400 and 2000 mg/kg did not induce any noticeable effects in immune system parameters of mice after a 14-day feeding. Aspartame was found to be safe to BALB/c mice immune system.