Tissue & cell最新文献

Netrin-1, an essential extracellular protein, has gained significant attention due to its pivotal role in guiding axon and cell migration during embryonic development. The fundamental significance of netrin-1 in developmental biology is reflected in its high conservation across different species as a part of the netrin family. The bifunctional nature of netrin-1 demonstrates its functional versatility, as it can function as either a repellent or an attractant according to the context and the expressed receptors on the target cells including the deleted in colorectal cancer (DCC), the uncoordinated-5 (UNC5), DSCAM, Neogenin-1, Adenosine A2b and Draxin receptors. By directing axonal growth cones toward the appropriate targets, netrin-1 is a critical actor in the formation of the intricate architecture of the nervous system. Netrin-1 is believed to be involved in additional biological and pathological processes in addition to its traditional function in neural development. The behavior of a diverse array of cell types is influenced by controlling cell adhesion and movement, which is impacted by netrin-1. It is a molecule of interest in both developmental biology and clinical research because of its involvement in angiogenesis, tumorigenesis, inflammation, and tissue regeneration, as confirmed by recent studies. The therapeutic capability of netrin-1 in disorders such as cancer, neurodegenerative disorders, and cardiovascular diseases warrants significant attention.

Myricetin, a flavonoid present in numerous fruits, vegetables, and medicinal plants, is recognized for its potent antioxidant, anti-inflammatory, and anti-cancer activities. Nevertheless, its involvement in mitigating inflammation caused by the endocrine-disrupting chemical Di(2-ethylhexyl) phthalate (DEHP), commonly used in polyvinyl chloride (PVC) manufacturing to improve flexibility, has not been investigated. Here, we found that DEHP markedly increased IL-1β production through inflammatory pathways in RAW 264.7 murine macrophages. Treatment with myricetin at a concentration of 10 μM significantly reduced the elevated IL-1β levels. Myricetin achieves this by inhibiting the activation of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK), which are driven by reactive oxygen species (ROS), thereby suppressing IL-1β transcription via nuclear factor-kappa B (NF-κB). Additionally, myricetin prevents ROS-induced activation of the NLRP3 inflammasome and subsequent caspase-1 activation, further decreasing IL-1β production. These dual actions highlight myricetin's therapeutic potential in countering the oxidative stress-mediated inflammatory pathways triggered by environmental toxins like DEHP.

Background: In recent years, the fasciae of the human body have received significant attention because of their crucial role in the transmission of muscle force. However, studies on the development of the fasciae, particularly the cervical fascia, remain scarce.

Purpose: This study was performed to examine the development of the fascia of the infrahyoid strap muscles, also known as the middle layer of the deep cervical fascia (MDCF), in 17 human embryos aged 6-8 weeks and 20 human foetuses aged 9-14 weeks.

Methods: Histological examination of serial sections was performed using conventional light microscopy.

Results: Three stages in the development of the MDCF were identified: the initial, formation, and maturation stages. In the initial stage (week 6 of development, Carnegie stages 18-19), the mesenchymal primordium of the epimysium of the infrahyoid muscles was observed and found to be continuous with the mesenchymal primordium of the MDCF. The infrahyoid muscles already exhibited intramuscular fibres, the primordium of the perimysium, and the endomysium. In the formation stage (weeks 7-8 of development, Carnegie stages 20-23), fibroblast-like cells and collagen fibres appeared in the primordium of the muscle epimysium and in the MDCF. Intramuscular fibres had become very evident. In the maturation stage (from week 9 of development onward), further development and organisation of the fascial structures occurred.

Conclusion: Our results suggest that the MDCF of the neck develops in parallel with the mechanical activity of this region. The relationship between the MDCF and the lymphatic and venous structures of this region suggests that the MDCF may facilitate venous and lymphatic circulation.

Damage to nerves negatively impacts quality of life and causes considerable morbidity. Self-regeneration is a special characteristic of the nervous system, yet how successful regeneration is accomplished remains unclear. Research on nerve regeneration is advancing and accelerating successful nerve recovery with potential new approaches. Eukaryote cells release extracellular vesicles (EVs), which control intercellular communication in both health and disease. More and more, EVs such as microvesicles and exosomes (EXOs) are being recognized as viable options for cell-free therapies that address complex tissue regeneration. The present study highlights the functional relevance of EVs in regenerative medicine for nerve-related regeneration. A subclass of EVs, EXOs were first identified as a way for cells to expel undesirable cell products. These nanovesicles have a diameter of 30-150 nm and are secreted by a variety of cells in conditions of both health and illness. Their benefits include the ability to promote endothelial cell growth, inhibit inflammation, encourage cell proliferation, and regulate cell differentiation. They are also known to transport functional proteins, metabolites, and nucleic acids to recipient cells, thus playing a significant role in cellular communication. EXOs impact an extensive array of physiological functions, including immunological responses, tissue regeneration, stem cell conservation, communication within the central nervous system, and pathological processes involving cardiovascular disorders, neurodegeneration, cancer, and inflammation. Their biocompatibility and bi-layered lipid structure (which shields the genetic consignment from deterioration and reduces immunogenicity) make them appealing as therapeutic vectors. They can pass through the blood brain barrier and other major biological membranes because of their small size and membrane composition. The creation of modified EXOs is a dynamic area of research that supports the evaluation of diverse therapeutic freights, improvement of target selectivity, and manufacturing optimization.

Introduction: The phenotypic transition of vascular smooth muscle cells (VSMCs) from a quiescent, contractile type to a secretory phenotype with high proliferation and mobility is a key event in vascular remodeling. PF-477736 is an ATP-competitive inhibitor of Chk1 which induces the accumulation of DNA damage by increasing the level of replicative stress, and ultimately inhibiting cell proliferation or causing cell death. Although this compound has been utilized as an anti-tumor drug, its role in vascular remodeling remains unclear.

Methods: In vitro, Human aortic smooth muscle cell line (HAVSMC) and primary rat aortic smooth muscle cells were used to establish phenotype transformation model with PDGF-bb; Western blot was used to detect the expression of VSMCs phenotype marker α-SMA, Vimentin; MTT and EdU assays were used to evaluate the proliferation ability of VSMCs; wound healing assay was used to evaluate the migration ability of VSMCs. In vivo, we established ballon injury of carotid artery in rats, and the function of the PF-477736 was evaluated by several histological stainings.

Results: The results exhibit that PF-477736 effectively inhibited VSMCs phenotypic transition, resulting in G1/S phase arrest and decreased proliferation and migration ability of VSMCs. Furthermore, while PDGF-bb down-regulated p53 protein and up-regulated CD44 expression, PF-477736 significantly countered these effects. Pretreatment of VSMCs with p53 siRNA blocked the effect of PF-477736, up-regulated the expression of CD44, and promoted VSMCs' proliferation and migration. Conversely, CD44 silencing through siRNA mitigated the phenotypic transition of VSMCs. In addition, the H&E, Masson' staining and the immunohistochemistry of PCNA, p53 and CD44 showed that PF-477736 substantially inhibits vascular remodeling in the balloon injury model.

Conclusion: Our findings show that PF-477736 exerts anti-vascular remodeling effect by inhibiting phenotypic transition through the Chk1/p53/CD44 pathway in VSMCs, providing novel therapeutic strategies for preventing and treating vascular remodeling.

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.

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.