Advances in medical sciences最新文献

Hypoxia in the tumor core negatively affects the outcome of patients with head and neck squamous cell carcinoma (HNSCC). Nevertheless, its role in predicting treatment response requires further exploration. Typically, reduced oxygen levels in the tumor core correlate with diminished efficacy of radiotherapy, chemotherapy, and immunotherapy, which are commonly used for HNSCC patients' treatment. Understanding the mechanistic underpinnings of these varied treatment responses in HNSCC is crucial for enhancing therapeutic outcomes and extending patients’ overall survival (OS) rates. Standard monolayer cell culture conditions have major limitations in mimicking tumor physiological features and the complexity of the tumor microenvironment. Three-dimensional (3D) cell cultures enable the recreation of the in vivo tumor attributes, encompassing oxygen and nutrient gradients, cellular morphology, and intracellular connections. It is vital to use the 3D model in treatment response studies to mimic the tumor microenvironment, as evidenced by the decreased sensitivity of 3D structures to anticancer therapy. Accordingly, the aim of the study was to delineate the utility of the 3D models of hypoxic head and neck tumors in drug screening and treatment response studies.

Purpose

Breast cancer is a complex disease with several molecular subtypes that respond differently to therapy. This paper describes liposomes loaded with gold nanoparticles as a targeted drug delivery method in the rapidly developing precision breast cancer treatment area. The aim was to investigate the cytotoxicity level and cellular uptake using several breast cancer cell lines and a normal breast cell line.

Materials and methods

We synthesized gold nanoparticles incorporated in liposomes. Nanostructures were incubated with breast cancer cell lines of different subtypes. The analysis included MTT assay, flow cytometry and immunofluorescence.

Results

Cell viability varied among different cancer cells. Moreover, the time- and concentration-dependent manner of viability change was observed. The internalization of liposomes with gold nanoparticles and nanoparticles alone determined different results depending on molecular breast cancer subtypes. The luminal B and triple-negative breast cancer cells demonstrated the highest resistance and sensitivity, respectively. The intensity of cells’ interaction with the proposed nanostructures was observed in both cell lines. In this study, we compare the molecular subtypes of breast cancer and discuss how this novel method might improve the therapy success.

Conclusions

Our research sheds light on the possibility of new individualized treatments for breast cancer patients, opening the path for better results and a more detailed cancer therapy strategy.

Purpose

Strenuous running triggers the coordination of pro- and anti-inflammatory, as well as immunoregulatory cytokines, which are upregulated in response to inflammatory stimulus and thus considered a precursor to overuse injury. The aim of this study was to correlate injury risk to footwear stiffness normalized against each runner's weight, i.e. the midsole's ability to resist deformation in response to the applied force.

Materials and methods

Experienced runners participated in a 2h 15 ​min intensity-controlled run, averaging 85 ​% of their threshold heart rate. Venous blood, collected in the field prior to and immediately after the race, was subjected to multi-parameter flow cytometry, to monitor the plasma levels of interleukin (IL)-2, IL-6 and tumor necrosis factor alpha (TNFα). Footwear stiffness was determined utilizing an automated drop test, recreating footfall pattern, impact speed and weight of each runner. Plasma level increase was analyzed for each cytokine, using one-way ANOVA and the data associated to footwear stiffness through the calculation of Pearson correlation coefficient.

Results

Only IL-6 levels exhibited a statistical significant increase pre-to post-race, corresponding to F (1,8) ​= ​24.0417 with a critical value of 4.4139. The increase in IL-6 levels was also found to produce a strong correlation to footwear stiffness, expressed in a Pearson coefficient of r (8) ​= ​0.79 ​at ρ ​= ​0.0063 (P ​< ​0.05).

Conclusion

The significant increase in pro-inflammatory markers, such as IL-6 which are associated with injury, would suggest that runners using compliant footwear are at lower risk of overuse injury than the ones running on stiffer midsoles.

Purpose

The process of osteogenic differentiation hinges upon the pivotal role of mechanical signals. Previous studies found that mechanical tensile strain of 2500 microstrain (με) at a frequency of 0.5 ​Hz promoted osteogenesis in vitro. However, the mechanism of the mechanical strain influencing osteogenesis at the cellular and molecular levels are not yet fully understood. This study aimed to explore the mechanism of mechanical strain on osteogenic differentiation of MC3T3-E1 cells.

Materials and methods

Proteomics analysis was conducted to explore the mechanical strain that significantly impacted the protein expression. Bioinformatics identified important mechanosensitive proteins and the expression of genes was investigated using real-time PCR. The dual-luciferase assay revealed the relationship between the miRNA and its target gene. Overexpression and downexpression of the gene, to explore its role in mechanically induced osteogenic differentiation and transcriptomics, revealed further mechanisms in this process.

Results

Proteomics and bioinformatics identified an important mechanosensitive lowexpression protein ATP13A3, and the expression of Atp13a3 gene was also reduced. The dual-luciferase assay revealed that microRNA-3070–3p (miR-3070–3p) targeted the Atp13a3 gene. Furthermore, the downexpression of Atp13a3 promoted the expression levels of osteogenic differentiation-related genes and proteins, and this process was probably mediated by the tumor necrosis factor (TNF) signaling pathway.

Conclusion

Atp13a3 responded to mechanical tensile strain to regulate osteogenic differentiation, and the TNF signaling pathway regulated by Atp13a3 was probably involved in this process. These novel insights suggested that Atp13a3 was probably a potential osteogenesis and bone formation regulator.

Purpose

Idiopathic pulmonary fibrosis (IPF), a chronic and progressively worsening condition characterized by interstitial lung inflammation and fibrosis of unknown etiology, has a grim prognosis. The treatment options for IPF are limited and new therapeutic strategies are urgently needed. Dietary restriction can improve various inflammatory diseases, but its therapeutic effect on bleomycin (BLM)-induced pulmonary fibrosis mouse model remains unclear. This study aims to investigate whether intermittent fasting (IF) can alleviate BLM-induced pulmonary inflammation and fibrosis.

Methods

Pulmonary fibrosis mouse models were induced by BLM. The IF group underwent 24-h fasting cycles for one week prior and three weeks following BLM administration. Meanwhile, the ad libitum feeding group had unrestricted access to food throughout the experiment. The evaluation focused on lung pathology via histological staining, qPCR analysis of collagen markers, and immune cell profiling through flow cytometry.

Results

IF group significantly reduced inflammation and fibrosis in lung tissues of BLM-induced mice compared to ad libitum feeding group. qPCR results showed IF remarkably decreased the mRNA expression of Col 1a and Col 3a in the lungs of BLM-induced mouse models. IF also reduced the numbers of regulatory T cells (Tregs), T helper 17 (Th17) cells, monocytes, and monocyte-derived alveolar macrophages (MoAMs) in the lung tissues.

Conclusions

IF may improve BLM-induced pulmonary fibrosis by decreasing numbers of immune cells including Treg cells, Th17 ​cells, monocytes, and MoAMs in the lungs. This study offers experimental validation for dietary intervention as a viable treatment modality in IPF management.

Purpose

This review aimed to evaluate the significance of assessing radial peripheral capillary (RPC) network parameters by optical coherence tomography angiography (OCTA) in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confirmed by polymerase chain reaction.

Methods

A literature search was conducted in the PubMed database to select high-quality reviews and original articles on the use of OCTA for visualizing the RPC network and calculating RPC parameters.

Results

The study revealed that systemic hypoxia, hypercoagulable state, and inflammation affect the RPC network in patients with coronavirus disease 2019 (COVID-19). Reduced RPC parameters were observed early in the course of SARS-CoV-2 infection and after several months of follow-up. Additionally, there was a correlation between reduced RPC parameters and subsequent thinning of the retinal nerve fiber layer.

Conclusions

The OCTA examination of the retina and optic disc should be considered in patients with a history of COVID-19 to assess the impact of systemic hypoxia and inflammation on ocular function. Follow-up assessment of these patients is also necessary to understand the potential consequences of ischemia affecting the optic nerve, retina, and choroid.

Purpose

Polycyclic aromatic hydrocarbons (PAHs), present in air and food, generated during energy production and waste incineration, are known for health toxicity. PAHs may activate the aryl hydrocarbon receptor, which could in turn modify estrogen-dependent inflammatory pathways in endometriosis. The possible role of PAHs in the pathogenesis of endometriosis remains unclear. The study aimed to evaluate the potential link between exposure to PAHs and the occurrence of peritoneal and ovarian endometriosis.

Methods

A prospective case-control tertiary-center study included 46 women aged 22–45 undergoing laparoscopy due to pelvic endometriosis (n ​= ​32; arm 1) and idiopathic infertility (n ​= ​14; arm 2). A sample of the greater omentum was collected intraoperatively for detection of 16 standard PAHs by gas chromatography-isotope dilution mass spectrometry method. PAHs concentrations were compared in both study arms. The associations between PAHs concentrations and selected variables were investigated.

Results

There were no significant differences between both arms in terms of reference PAHs concentrations, nor correlations between PAHs concentrations and the stage of endometriosis. However, notable differences were observed in specific PAHs concentrations related to certain conditions. The concentrations of acenaphthene (p ​= ​0.016) and fluorene (p ​= ​0.013) were significantly lower in women with peritoneal adhesions, while the concentrations of benz[a]anthracene, benzo[k]fluoranthene and indeno[1,2,3-cd]pyrene [ng/g] were higher in cigarette smokers.

Conclusions

The study showed no differences in exposure to PAHs between women with and without pelvic endometriosis. Determining the toxicity of PAHs in endometriosis requires further research.

Purpose

The imbalance of thyroid hormones affects the metabolic activity of various tissues, including periodontium. Also, autoimmune diseases present an increased tendency to suffer from periodontal disease. Therefore, our systematic review was designed to answer the question "Is there a relationship between thyroid diseases and periodontal disease?".

Materials and methods

Following the inclusion and exclusion criteria, 10 studies were included in this systematic review using the databases PubMed, Scopus and Web of Science (according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines).

Results

Based on the meta-analysis, patients with thyroid diseases (especially with hypothyroidism) demonstrated significantly worse periodontal status than systemically healthy controls. Moreover, according to the cross-sectional studies, 5.74 ​% of periodontitis patients reported the concomitance of thyroid diseases.

Conclusions

In summary, the included studies suggest a potential relationship between thyroid diseases and periodontal disease. However, further research is necessary to reliably assess the oral health in patients with hypothyroidism and hyperthyroidism.

Purpose

Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator in neural stem cells. However, its function is still not clear in hepatocytes. This study aimed to clarify the effects of Nr2e1-deficiency in hepatocytes in lipotoxic conditions.

Materials/methods

Nr2e1-knockdown AML12 ​cells were generated by lentiviral vector transfection. The influences of Nr2e1-deficiency on hepatocyte survival were determined by cell cycle progression and cell apoptosis rate using flow cytometry. Real-time quantitative PCR and Western blot were used to examine the genes and protein expression related to apoptosis, lipid metabolism, and oxidative stress. Meanwhile, RNA sequencing was adopted in liver samples from Nr2e1-knockout (Nr2e1-KO) mice.

Results

Nr2e1 expression was observed with a significant decrease in AML12 ​cells after palmitic acid-stimulation. Knockdown of Nr2e1 in AML12 ​cells resulted in increased sensitivity to lipotoxicity, evidenced by a partial G0/G1 cell-cycle arrest and higher rates of cell apoptosis. Moreover, Nr2e1-knockdown AML12 ​cells presented increased gene expressions relative to lipid synthesis but decreased levels of β-oxidation related genes. Lack of Nr2e1 augmented palmitate-induced oxidative stress in hepatocytes. In vivo, differential genes in Nr2e1-KO mice liver were enriched in pathways associated with liver regeneration and cell proliferation.

Conclusions

This study indicated that hepatocytes lacking Nr2e1 were more susceptible to lipotoxic-mediated damage. Nr2e1 may serve as a potential target for the development of novel therapies for lipotoxicity-induced liver injury.

Purpose

Static magnetic fields (SMFs) induce various biological reactions and have been applied in the biological therapy of diseases, especially in combination with mesenchymal stem cells (MSCs) and tissue engineering. However, the underlying influence of SMFs on MSCs gene expression remains largely unclear. In this study, we aim to investigate the effects of SMFs on gene expression of human MSCs.

Materials and methods

We exposed human MSCs to two different intensities (0.35 ​T and 1.0 ​T) of SMFs and observed the effects of SMFs on cell morphology. Subsequently, RNA-sequencing was performed to explore the gene expression changes.

Results

Compared with control group cells, no significant differences in cell morphology were observed under a phase contrast inverted microscope, but the transcriptome of SMF-exposed MSCs were significantly changed in both 0.35 ​T and 1.0 ​T groups and the differential expressed genes are involved in multiple pathways, such as ubiquitin mediated proteolysis, TNF signaling pathway, NF-kappa B signaling pathway, TGF-beta signaling pathway, metabolic pathways, and apoptosis, which regulate the biological functions of MSCs.

Conclusions

SMFs stimulation could affect the gene expression of human MSCs and the biological effects vary by the different intensities of SMFs. These data offer the molecular foundation for future application of SMFs in stem cell technology as well as tissue engineering medicine.