Tissue & cell最新文献

Cervical cancer (CCA) is the predominant cause of fatalities from gynecologic malignancies, with metastasis responsible for 80 % of cancer-related mortalities. This study preliminarily examined the involvement of Sialic Acid Binding Ig Like Lectin 15 (Siglec-15) in the development of CCA and its probable mechanisms. We assessed the capacity of Siglec-15 to modulate CCA progression by establishing knockdown and overexpression Siglec-15 cell lines, supplemented with animal models, using both in vivo and in vitro dual investigations. Our findings indicate that Siglec-15 is significantly expressed in CCA cell lines and is intimately associated with the proliferation, migration, and invasion capabilities of CCA cells, as well as mitochondrial ROS homeostasis. The suppression of Siglec-15 expression markedly reduced tumor growth in mice, potentially due to Siglec-15's role in regulating the Mitogen-Activated Protein Kinase (MAPK) signaling pathway, which mediates the retrograde regulation of mitochondrial ROS homeostasis. Siglec-15 may emerge as a novel therapeutic target and prognostic marker for patients with CCA.

Background: Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Current solutions for SNHL, including hearing aids, cochlear implants, and hearing assistive devices, do not provide consistent results and fail to address the underlying pathology of hair cell and ganglion cell damage. Stem cell therapy is a cornerstone in regenerative medicine. It provides new hope to treat SNHL by replacing/regenerating damaged hair cells and ganglion cells. Mesenchymal stem cells are an interesting choice in stem cell therapy.

Aim of the work: Evaluation of bone marrow derived mesenchymal stem cell (BM-MSC) transplantation to improve SNHL management.

Methods: An experimental study was conducted using 40 recipient guinea pigs, randomly divided into four groups, along with 4 donor guinea pigs for bone marrow harvesting to isolate BM-MSC. Group I (12 animals) served as the control, receiving neither ototoxic drugs nor stem cell treatment. Group II (12 animals) received intraperitoneal cisplatin (1.5 mg/kg/day for 8 days) to induce sensorineural hearing loss, but no stem cell treatment. Group III (12 animals) received IP cisplatin to induce SNHL, followed by BM-MSC transplantation via round window injection one week later. Groups I, II, and III were euthanized 5 weeks after the last cisplatin injection, and their cochleae were examined using light microscopy, scanning electron microscopy, and fluorescent light microscopy to assess the effect of stem cell transplantation on the recovery of neurosensory tissue in the cochlea after cisplatin treatment. Group IV (4 animals) received IP cisplatin to induce SNHL, followed by transplantation of fluorescein-labeled BM-MSC (FLBM-MSC) via round window injection one week later and were euthanized after one week to study stem cell migration and homing.

Results: Light Microscopy: Group I exhibited a normal structure in the organ of Corti, spiral ganglion, and stria vascularis. In contrast, Group II demonstrated degeneration in these areas. Group III showed a preserved structure in the organ of Corti, spiral ganglion, and stria vascularis, with statistically significant differences compared to Group II (p < .05). Scanning Electron Microscopy: Group I displayed normal ultrastructure of the organ of Corti, while Group II showed a loss of outer hair cells. Group III demonstrated preserved ultrastructure of the organ of Corti. Fluorescent Light Microscopy: In Group IV, transplanted cells were observed to home into the cochlear lateral wall, organ of Corti, and spiral ganglion.

Conclusion: The study showed that BM-MSCs, delivered via round window injection, can migrate to cochlear regions and protect key structures after cisplatin-induced SNHL in guinea pigs, suggesting their potential as a treatment for SNHL.

Thyroid gland which is responsible for the maintenance of metabolism and growth is derived from thyroglossal duct, an outpocketing of foregut. The microscopic study of thyroid gland during development in first, second and third trimesters has utmost significance to understand the several developmental thyroid disorders metabolically and structurally. This study is descriptive observational study carried in tissue sections taken from thyroid gland of still birth and spontaneously aborted human fetuses of first, second and third trimester. The processed thyroid gland tissues were sectioned and conventional haematoxylin and eosin stain was used to study the detail histomorphology of this gland during these trimesters. Multiple shapes (round, oval and irregular) of thyroid follicles with variation in vascularity and fibrous capsule were observed in human fetuses during their development. Dimensions of epithelial cells (height and weight), outer and inner boundaries of thyroid follicles and number of parafollicular cells were increased as age progresses from first to third trimester whereas diameters, radius, perimeter, area and colloid volume of follicles were decreased as age progresses from first to third trimester. But the area of cytoplasm with nuclei (A_nc), cytoplasmic area (A_c) and nuclear-to-cytoplasmic (N/C) ratio were increased from first to second trimester thereafter decreased in third trimester. This study can act as baseline study to understand histomorphological differences in developing human fetal thyroid gland and to understand associated thyroid gland related disorders during its development.

Histocompatibility minor 13 (HM13) is a signal sequence stubbed intramembrane cleavage catalytic protein. Increasing evidence supports the association among HM13 expression, tumor-infiltrating immune cells (TIICs), and cancer. However, its role on formation and progression of colorectal cancer (CRC) has not been explored. In this study, we aim to identify the role and function of HM13 on the progression of CRC and explore the possible mechanism. The findings of our study indicate that HM13 is significantly upregulated in colorectal cancer (CRC) compared to normal colorectal tissues (P< 0.001). Moreover, the elevated expression of HM13 is associated with unfavorable prognosis in CRC patients. Furthermore, our results demonstrate that the overexpression of HM13 contributes to enhanced proliferation and migration, as well as suppressed apoptosis, in SM480 and HCT116 cell lines (P<0.001). Conversely, the downregulation of HM13 (shHM13) yields opposite effects. Additionally, the administration of LY294003 and nutlin-3 effectively inhibits proliferation and migration, while promoting apoptosis in HCT116 cells (P<0.001). However, the presence of HM13 counteracts these changes. In an in vivo study, the knockdown of HM13 (shHM13) significantly reduces tumor growth and the proportion of Ki-67 positive cells, while increasing the percentage of tunel-positive cells (P<0.001). Also, shHM13 decreased the level of p-PI3K/PI3K and p-AKT/AKT, upregulated p53 and p21 activities. It can thus be concluded that HM13 might be a novel oncogene in CRC and regulates proliferation, migration and apoptosis by modulating the PI3K/Akt and p53 signaling pathways.

Age-related diseases are often linked to chronic inflammation. Senescent cells secrete inflammatory cytokines, chemokines and matrix metalloproteinases, collectively referred to as the senescence-associated secretory phenotype (SASP). The current study discovered that aging leads to the accumulation of senescent tendon stem/progenitor cells (TSPCs) in tendon tissue, resulting in the development of a SASP. Conditioned medium from aged TSPCs induced cellular inflammation in young TSPCs. In addition, we found that Canopy homolog 2 (CNPY2) expression is reduced during tendon aging. CNPY2 deficiency causes TSPCs senescence and SASP. Our findings showed that the NF-κB signaling pathway is activated in CNPY2 knockdown TSPCs, pharmacological inhibition of NF-κB signaling pathway with BMS-345541 attenuated SASP of senescent TSPCs, which indicated that CNPY2 regulates TSPCs SASP might through NF-κB signaling pathway. Our findings suggested that CNPY2 plays an important role in TSPCs senescence and SASP, CNPY2 could be a promising target for age-related tendon disorders.

Chronic obstructive pulmonary disease (COPD) poses global health challenges owing to limited treatment options and high rates of morbidity and mortality. Airway organoids have recently become a valuable resource for the investigation of respiratory diseases. However, limited access to clinical tissue samples hinders the use of airway organoids to study COPD. Therefore, alternative models that can mimic human airway pathology without relying on human tissues are needed. In this study, airway organoids were developed from tracheal epithelial cells obtained from 8-week-old Sprague-Dawley rats and exposed to lipopolysaccharide (LPS) to induce COPD-like characteristics. Exposure to LPS leads to structural changes in organoids, including an increase in goblet cells, a decrease in ciliated cells, increased mucin production, and elevated levels of pro-inflammatory cytokines. The COPD drugs erdosteine and R-HP210 effectively reduced mucin secretion, although none was able to restore the function of ciliated cells. Inflammatory markers responded differently, with ensifentrine and erdosteine significantly reducing cytokine levels. These results demonstrate that rat airway organoids replicate important aspects of human COPD pathology, thus providing an accessible, ethical, and clinically relevant alternative to human tissues and traditional animal models to enhance our understanding of COPD pathogenesis and evaluate potential treatments.

Urolithin A (URA), a product of the gut microflora from foods rich in ellagitannins found in berries and nuts, has demonstrated anti-inflammatory and antioxidative stress properties in various disease models. Ferroptosis, an iron-dependent form of cell death, is considered a pathogenic cause of tendinopathy. However, the effects of URA on hyperlipidemic tenocytes and the related molecular mechanisms for the treatment of tendinopathy have not been elucidated. The expression of various proteins in human primary tenocytes was assessed via Western blot analysis. Tenocyte reactive oxygen species (ROS) were detected via DCFDA staining. Apoptotic tenocytes were visualized via TUNEL staining. The activities of antioxidant enzymes and caspase 3 were measured via activity assays. Cell viability was examined via the MTT assay. In this study, we found that URA treatment blocked ferroptosis and apoptosis and improved oxidative stress in palmitate-treated tenocytes. Moreover, URA treatment reversed the changes in the expression of extracellular matrix (ECM) markers and impaired cell migration. siRNA targeting PPARδ or ALDH2 abrogated the effects of URA on tenocytes treated with palmitate. Additionally, treatment of tenocytes with URA increased SOD and catalase activities. These results suggest that URA ameliorates tenocyte ferroptosis and apoptosis through PPARδ/ALDH2 signaling-mediated suppression of oxidative stress. By utilizing natural bioactive compounds derived from renewable dietary sources, this study highlights a potential therapeutic avenue for treating obesity-related tendinopathy while emphasizing the importance of sustainable, health-promoting interventions.

Background: Several studies have evaluated different cell cycle synchronization methods to improve reprogramming efficiency aimed at wild species conservation. The six-banded armadillo is one of the wild mammals with significant ecological and biomedical interests but has not yet been evaluated for reprogramming purposes.

Objective: We investigated the effects in a time-dependent manner of serum starvation (SS; 0.5 % serum), contact inhibition (CI), and roscovitine (RSV 15 and 30 µM) on the cycle synchronization at G₀/G₁ phase of six-banded armadillo fibroblasts by flow cytometric analysis.

Methods: The morphology, viability, and apoptosis levels were determined by microscopic analysis.

Results: The results showed that SS significantly increased the percentage of cells arrested in the G₀/G₁ phase in a time-dependent manner, where SS for 72 h (90.5 % ± 0.8) and 120 h (90.1 % ± 0.9) showed the highest value compared to SS for 24 h (86.1 % ± 0.9) and control group (69.7 % ± 0.8; P<0.05). However, neither CI nor RSV exposure significantly increased the arrest of fibroblasts at the G₀/G₁ phase under any of the evaluated conditions (P>0.05). In contrast to SS and RSV, CI significantly induced necrosis, as evidenced by an increase in dead cells (P < 0.05) over the evaluated periods, thereby disrupting the synchronization efforts. Moreover, all methods demonstrated similar morphology and cell viability rates over the evaluated times, as assessed by the trypan blue exclusion assay.

Conclusion: These results indicated that SS was the most suitable method for cell cycle modulation in G₀/G₁ of six-banded armadillo fibroblasts, especially after 72-120 h of treatment. This finding has significant implications for future reprogramming efforts and conservation strategies for this unique species, as effective cell cycle synchronization can enhance the success of techniques, such as cloning and generation of induced cells to pluripotency.

Addressing mandibular defects poses a significant challenge in maxillofacial surgery. Recent advancements have led to the development of various biomimetic composite scaffolds aimed at facilitating mandibular defect reconstruction. This study aimed to assess the regenerative potential of a novel composite scaffold consisting of polylactic acid (PLA), hydroxyapatite nanoparticles (n-HA), gelatin, hesperidin, and human dental pulp stem cells (DPSCs) in a rat model of mandibular bone defect. The PLA-HA-GLA composite was synthesized using solvent casting-leaching and freeze-drying methods and subsequently treated with 11 mg of hesperidin. The physicochemical properties of the PLA-HA-GLA and PLA-HA-GLA-HIS composites were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA). Additionally, the mechanical properties and cytotoxicity of DPSCs were assessed. Subsequently, PLA-HA-GLA and PLA-HA-GLA-HIS scaffolds with or without DPSCs were implanted into mandibular bone defects in rats, followed by histopathological, histomorphometric, and cone-beam computed tomography (CBCT) evaluations after eight weeks. SEM analysis revealed the porous structure of the fabricated PLA-HA-GLA and PLA-HA-GLA-HIS composites without aggregation. FTIR and XRD analyses confirmed the presence of functional groups and elements associated with PLA, HA, GLA, and hesperidin in the composites. Although the PLA-HA-GLA-HIS composite exhibited good thermal stability, its mechanical properties decreased after the addition of hesperidin. The cell viability of DPSCs on the surface of the PLA-HA-GLA-HIS scaffolds was statistically significant compared to that of the control group. Furthermore, histopathological, histomorphometric, and radiological evaluations demonstrated that the implantation of the DPSC-loaded PLA-HA-GLA-HIS scaffold had a beneficial effect on bone tissue reconstruction in rats with mandibular defects. These findings highlight the potential of DPSC-loaded PLA-HA-GLA-HIS composite scaffolds for spongy bone tissue engineering and mandibular defect repair.

Rotavirus is the most important cause of severe gastroenteritis in infants and children worldwide. This virus causes an increase in inflammatory responses by increasing cellular oxidative stress and the expression and activity of the transcription factor NF-κB and COX-2. As a result of NF-κB activation, the expression of inflammatory cytokines also increases. So, there is a need to control pathogenic inflammatory responses mediated by rotavirus. Mesenchymal stem cells (MSCs) have confirmed immunomodulatory characteristics. The present study aims to investigate the effects of MSCs conditioned media (MSCs-CM) in reducing the inflammatory response of Caco-2 cells when exposed to rotavirus. 72 h After rotavirus-infected Caco-2 cell of treatment with MSCs-CM, virus replication (CCID50), secretion of IL-6, and IL-8 (ELISA), COX-2 and NF-κB genes expression (q-PCR), apoptosis (Annexin V-PI), and nitric oxide (NO) level (Gries's reagent) are investigated. Based on the results, virus replication was reduced by Log1 in the CM-treated groups. Also, treating Caco-2 cells with MSCs-CM led to decreased IL-6 and NO and increased IL-8 production. Evaluation of apoptosis in MSCs-CM-treated rotavirus-exposed Caco-2 cells showed a significant reduction in their apoptosis. Also, the expression of COX-2 is increased significantly. However, the expression of NF-κB decreased significantly after treatment with MSCs-CM. The results show that inflammatory responses, oxidative stress, and apoptosis in rotavirus-infected cells have decreased after treatment with MSC-CM.