Tissue & cell最新文献

Introduction: Pressure Injury (PI) is a complex disease process which is influenced by multiple factors, among which ischemia-reperfusion (I/R) injury is closely related to the progression of PI. But its biomarkers are still unclearly. Understanding its physiological mechanisms and related molecular biomarkers is a key to developing effective prevention and therapeutic strategies.

Methods: This study through obtained the candidate genes of the differentially expressed genes (DEGs) from the PI rat model by transcriptome sequencing, PI single-cell sequencing database, and genes related to I/R injury from GeneCards database to analyze and screen prognostic related target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway analysis were performed using clusterProfiler package, and a protein-protein interaction (PPI) network was constructed to identify hub genes. The genes related to I/R injury were identified and analyzed using three machine learning algorithms. Then, the hub genes were evaluated using nomogram and receiver operating characteristic (ROC) curves, and validated using immunohistochemistry in the PI rat model.

Results: There were finally 7 candidate genes obtained from the intersection of the three datasets. GO and KEGG pathway analysis revealed that the DEGs were enriched in complement and coagulation cascades, and the keratinocyte differentiation is a significant factor. Then, two hub genes Serine protease inhibitor clade E member 1 (SERPINE1) and Cathepsin L (CTSL) were identified through three machine learning algorithms. The two hub genes were indicated had a high prognosis value by nomogram and ROC curves. SERPINE1 and CTSL both play crucial roles in vasculogenesis, coagulation and degradation of the extracellular matrix, which is essential for wound healing. The results of immunohistochemistry demonstrated that SERPINE1 and CTSL are significantly upregulated in skin tissue from PI caused by I/R injury, and their mRNA expression levels significantly correlate with PI outcomes.

Conclusion: According to our research we referred that the SERPINE1 and CTSL might be the potential biomarkers of PI.

Objective: Cancer cells undergo adaptive processes that favor their survival and proliferation when subjected to different types of cellular stress. These changes are linked to oncogenic processes such as genetic instability, tumor proliferation, therapy resistance, and invasion. Therefore, this study aimed to review studies that discuss possible morphological and genetic changes acquired by neoplastic cells under stressful conditions.

Methods: The articles used in this integrative review were searched on PubMed, Web of Science, CAPES, BVS and Scopus. Studies that discussed how cells undergo morphogenetic changes as an adaptive response to stress in cancer were included.

Results: This article reviewed 82 studies that highlighted multiple types of stress to which cancer can be subjected, such as oxidative, thermal and mechanical stress; glucose and other nutrients deficiency; hypoxia and chemotherapy. Neoplastic cells under stress can undergo adaptive changes that make it possible to overcome this obstacle. In this adaptive process, the acquisition of certain mutations implies cellular morphological changes such as Epithelial-Mesenchymal Transition, polyploidy, mitochondrial and cytoskeletal changes. These adaptive changes occur concomitantly with processes related to oncogenesis such as gene instability, tumor proliferation, resistance to therapy and invasion.

Conclusions: This study reveals that adaptations to cellular stress promote morphological and functional changes that accompany or accelerate oncogenesis. It has been revised how epithelial-mesenchymal transition, polyploidy and mitochondrial dysfunctions not only reinforce the survival of tumor cells in adverse environments, but also increase therapeutic resistance and invasive capacity. Also noteworthy are the contributions on genomic instability associated with stress and the potential of senescent cells in tumor heterogeneity, both as factors of tumor resistance and progression. These insights suggest new therapeutic targets and prognostic biomarkers, expanding the possibilities for more effective strategies to combat cancer.

Background: Cigarette smoking is known to induce various cellular changes and proliferative activities within the oral mucosa. This study compares the effects of smoking on cellular proliferation and cytological alterations using the AgNORs and Pap staining methods.

Methods: We performed statistical analyses to evaluate the mean AgNORs count in smokers and non- smokers. Additionally, we assessed the presence of reactive cellular changes in smokers using the Pap staining method. Cytological alterations, including inflammatory changes, were documented in both groups, and we focused on the prevalence of such changes in smokers.

Results: The mean AgNORs count was found to be 3.68 in smokers, which is consistent with marked reactive cellular changes. Inflammatory changes and reactive cellular changes, observed in 33.3 % and 59.3 % of cases, respectively, were significantly more prevalent in smokers. These findings suggest that smoking induces epithelial alterations, even in the absence of clinical symptoms, due to the physiochemical environment created by the elements in tobacco. This study also supports previous research indicating that cigarette smoking modifies cell growth control processes and increases cell proliferation in the oral mucosa.

Conclusion: Cigarette smoking significantly elevates cellular proliferation, as indicated by the increased AgNORs counts in smokers. The combined use of Pap staining and AgNORs counting proved effective at detecting cellular proliferation before clinical symptoms appeared in smokers. Additional research is recommended to assess the impact of factors such as age, sex, and daily cigarette consumption on different oral regions. Comparative studies involving other proliferation indicators, such as Ki-67 or molecular testing, are also advised.

Introduction: Human amniotic membrane (hAM) has a highly biocompatible natural scaffold that is abundant in several extracellular matrix (ECM) components, including but not limited to platelet-derived growth factor (PDGF), transforming growth factor (TGF), and fibroblast growth factor (FGF). In our study, we have focused on a mixture of hAM and demineralized bone matrix (DBM) as an allo-hybrid graft to deliver it into the site of bone defect to decrease bone remodeling time.

Methods: Allo-hybrid grafts were prepared by coating the jelly made of decellularized and lyophilized hAM (AMJ) on the surface of DBM and subsequently underwent in vitro studies, such as alkaline phosphatase activity, MTT assay, and SEM analysis. Twenty-four male rats were included in the study, and after creating calvarial defects, rats were divided into four groups: DBM implanted, allo-hybrid implanted, AMJ injection, and a negative control (NC). Bone regeneration was assessed using computed tomography (CT scan) and histological analysis at 1, 2, and 3 months after surgery.

Results: CT scan analysis clearly showed improved new bone growth in the allo-hybrid group compared to the NC group. Also, the Hounsfield unit of the allo-hybrid group (774.91 ± 47.8) after 90 days confirms CT scans. Histological staining revealed immature bone in allo-hybrid and DBM groups, along with the creation of a medullary cavity and bone marrow two months after surgery. Three months after surgery, the allo-hybrid group showed signs of new, mature bone, while no sign of healing could be seen in the NC group at any time points. Over a 90-day period, the allo-hybrid group recovered the bone defect area near 90 %. It is relatively twice as much as AMJ group.

Conclusion: Histological properties of bone defects and bone regeneration can both be improved by allo-hybrid grafts coated with AMJ.

Background: Skin melanoma is a highly metastatic cancer with an increasing global incidence. Despite advancements in immunotherapy, new treatment strategies based on tumor biology are essential for improving outcomes and developing novel therapies. Autophagy plays a critical role in melanoma cell metabolism and affects the tumor microenvironment (TME). This study aims to evaluate the impact of autophagy-modifying drugs on extracellular matrix (ECM) remodeling and changes in the TME cytokine profile.

Methods: Immunohistochemical analysis was performed using paraffin-embedded tumor samples of B16-bearing C57BL/6 mice to assess the effects of autophagy-modifying drugs, lithium or chloroquine, on the matrix degradation proteins, their main substrates, lysyl oxidase and collagen fibril formation-associated proteins. The cytokine profile of the tumor was defined to estimate the effect of autophagy-modifying drugs on the TME.

Results: Chloroquine and lithium administration caused a decrease in the expression of matrix metalloproteinases, and chloroquine contributed to the accumulation of collagen type I. Moreover, chloroquine dramatically decreased LOX levels. Decorin expression levels were reduced in tumors of mice treated with chloroquine or lithium. Significant changes in the cytokine profile were detected after chloroquine treatment, with increased expression of IL1, IL4, IL6, M-CSF, TGFβ2 and TNF-α genes observed in the tumors.

Conclusion: Autophagy-modifying drugs affect the TME, in particular, chloroquine promotes ECM remodeling, accumulation of collagen type I deposits and probably the formation of abnormal collagen fibril structures. In addition, chloroquine-treated mice showed high expression of pro-tumorigenic cytokines and growth factors, such as IL1, IL4, IL6, M-CSF, TGFβ2 and TNF-α in the TME.

Introduction: Mesenchymal stem cells possess the capability to proliferate and differentiate into diverse lineages. Their beneficial properties have been explored widely to treat various disorders. Phytochemicals like curcumin, catechin and resveratrol have been evaluated for their medicinal values and have promising potential in treating numerous diseases. In this study, we have elucidated the in vitro survival, proliferative and cytotoxic effects of these phytochemicals at selected range of concentrations on human umbilical cord derived Wharton's jelly mesenchymal stem cells (WJ-MSCs).

Methods: The human WJ-MSCs were extracted using explant culture method and characterized as per International Society for Cellular Therapy (ISCT) guidelines. To analyse the effect of different phytochemicals, the WJ-MSCs were treated with various concentrations ranging from 0.1 to 1000 µM and the viability, proliferative and toxicity effects were assayed using (3-(4,5-dimethylthioazolyl-2,5-diphenyltetrozolium bromide) MTT.

Results: Curcumin and catechin elicited no cytotoxic effect on WJ-MSCs after 48 hours of treatment between the concentrations ranging from 0.1 to 10 µM and the viability was maintained above 80 %. For both the phytochemicals, there was a significant decrease in the viability of WJ-MSCs after 50 µM. Resveratrol was well tolerated at higher doses till 100 µM with a viability above 90 % and cytotoxic effect was observed above 250 µM.

Conclusion: Curcumin, catechin and resveratrol, affect the viability and proliferation of WJ-MSCs differently at varying concentrations. This data will be useful in deciding the dose of phytochemicals when employed concomitantly with stem cells to increase their efficiency.

Osteosarcoma is the most common primary bone cancer, accounting for approximately 5 % of new cancer cases globally. In contrast, breast cancer remains the most prevalent malignancy and a leading cause of cancer-related mortality among women. Given the limitations of current therapies, novel treatment strategies are urgently needed. This study evaluates the effects of diapocynin, a derivative of apocynin, on osteosarcoma (UMR-106) and breast cancer (MDA-MB-231) cell lines. Our results demonstrate a dose-dependent cytotoxicity of diapocynin in both cell types, with UMR-106 cells showing higher sensitivity than MDA-MB-231 cells. Notably, treatment with diapocynin induced significant morphological changes in both cell lines, and both IC25 and IC50 concentrations effectively inhibited cell migration, particularly in osteosarcoma cells. However, no significant changes were detected in matrix metalloproteinases -2 and -9 activity following treatment, suggesting that diapocynin may exert its effects through alternative pathways. These results highlight diapocynin as a promising candidate for cancer therapy, warranting further investigation into its mechanisms of action and potential clinical applications.

The research sought to assess the therapeutic impact of resveratrol by biochemical, immunohistochemical, and histopathological analyses in a TiO₂-induced liver fibrosis model. Titanium dioxide (100 mg/kg body weight) was delivered for 15 days to induce liver fibrosis, either alone or in conjunction with resveratrol (30 mg/kg body weight) therapy for the same duration. Resveratrol has been identified as a crucial therapeutic drug that provides an alternative treatment method for TiO₂-induced liver fibrosis by mitigating inflammation, oxidative stress, and the expressions of α-SMA and 8-OHdG. Resveratrol treatment mitigated TiO₂-induced liver fibrosis by repairing hepatocellular injury and decreasing plasma AST, ALT, and ALP levels. Resveratrol improves the activity of superoxide dismutase (SOD) and catalase (CAT), crucial enzymes for antioxidant defense, and elevates glutathione peroxidase (GSH-Px) levels, so augmenting antioxidant function. Furthermore, resveratrol decreased hepatic inflammation (IL-6 and IL-1β) and oxidative stress markers. Furthermore, histological alterations and immunohistochemistry expression of α-SMA and 8-OhdG were reinstated after resveratrol administration in the TiO₂-induced liver fibrosis model. Our research indicates that resveratrol administration effectively protects against liver fibrosis produced by TiO₂.

Mesua ferrea L. was commonly used in Uyghur medicine, and the flowering buds of M. ferrea extract exhibited significant inhibitory effects on the proliferation of breast cancer cells in our preliminary research; however, the underlying active components remain to be elucidated. In this study, firstly, we extracted the flowering buds of M. ferrea with methanol and obtained eleven bioactive sub-fractions (MF-P-1-MF-P-11), and MF-P-5 showed the strongest inhibitory activity against MDA-MB-231 and 4T1 cells. Subsequently, 52 compounds from MF-P-5 were identified by UPLC Q-TOF MS/MS. In addition, ten compounds (MF1-MF10) from MF-P-5 were separated and identified, and MF5 could inhibit MDA-MB-231 and 4T1 cells proliferation as MTT and colony formation assay, suppress the migration of MDA-MB-231 and 4T1 cells by means of wound healing assay, reduce the expression level of E-cadherin, and induce MDA-MB-231 and 4T1 cells apoptosis by Annexin V-FITC/PI double staining assay and up-regulate the expression of Bax and down-regulate the expression of PARP. Ultimately, we evaluated the effects of MF-P-5 on breast cancer via MDA-MB-231 cell xenograft in nude mice. The results of tumor volume and weight and immunohistochemistry revealed that MF-P-5 could significantly inhibit the growth of MDA-MB-231 cells in vivo. Besides, the expression levels of E-cadherin significantly increased and MMP-2 decreased. The above results suggested that MF-P-5 could suppress the invasion of breast cancer cells in vivo. Furthermore, the expression level of Bcl-2 was prominently reduced which revealed that MF-P-5 stimulated the mitochondrial apoptosis pathway in vivo. As a result, MF5 could inhibit MDA-MB-231 and 4T1 cells proliferation, migration and tumor growth in vitro and MF-P-5 could suppress tumor growth in vivo which had laid a theoretical foundation for further clinical application.

Background: Motile sperm domain containing 1 (MOSPD1) is overexpressed in colorectal, prostate, and breast cancers, but its role in gastric cancer (GC) progression remains unclear.

Methods: The effect of MOSPD1 was evaluated using cell viability, colony formation, wound healing, and Transwell assays. Triglyceride and lipid levels were measured in GC cells. Western blotting was used to examine protein expression. A mouse model of subcutaneous tumor xenotransplantation was used to evaluate the effects of MOSPD1 knockdown on GC cells.

Results: MOSPD1 expression in GC tissues and cells was higher than in normal tissues and cells. MOSPD1 knockdown decreased the proliferation, migration, and invasion of GC cells and the growth of subcutaneous tumors. MOSPD1 overexpression increased the proliferation, migration, and invasion of GC cells. Levels of triglyceride, lipid, and fatty acid synthesis-related enzymes (ACLY, ACC1, and FASN) were downregulated in MOSPD1 knockdown cells and upregulated in MOSPD1 overexpressed cells. MOSPD1 knockdown inhibited the phosphorylation of ERK, JNK, and P38 in GC cells and subcutaneous tumors. MOSPD1 overexpression promoted the phosphorylation of ERK, JNK, and P38 in GC cells.

Conclusions: High MOSPD1 expression facilitates fatty acid metabolism and GC progression by activating the MAPK pathway. Thus, MOSPD1 may be a potential therapeutic target for GC.