Advances in medical sciences最新文献

Purpose

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by a range of symptoms, including sleep disturbances. The present study aimed to investigate the prevalence of sleep disorders and the associations between sleep disorders and clinical outcomes in PBC.

Patients and methods

We enrolled 177 patients with PBC and 165 healthy controls (age- and sex-matched). Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Demographic and clinical data were collected from comprehensive clinical records to investigate whether sleep disorder was correlated with disease severity, therapeutic response and liver cirrhosis.

Results

The prevalence of sleep disorders in patients with PBC (50.8 ​%) was significantly higher than healthy controls (18.2 ​%). Patients with sleep disorders presented with higher levels of laboratory parameters including globulin (GLO), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL) and immunoglobulin M (IgM), as well as higher ratio of poor therapeutic response and liver cirrhosis (p ​< ​0.05). There was a positive correlation between global PSQI score and AST, ALP, GGT, TBIL, DBIL and IgM in patients with PBC. Patients with poor therapeutic response and liver cirrhosis in PBC had a higher proportion of sleep disorders and more chaotic sleep patterns, whereas a stronger correlation between sleep quality and laboratory parameters was found in patients with liver cirrhosis.

Conclusions

Sleep disorders were prevalent and manifested as adverse effects in PBC. Assessment of sleep quality and intervention were essential to the overall clinical management of patients with PBC.

Purpose

Materials and methods

Results

Conclusions

Purpose

Materials/methods

Results

Conclusions

Purpose

The evolution of splenomegaly in patients with liver cirrhosis remains largely unknown. In this study, we followed the changes in splenic volume and established the natural course of splenomegaly. We developed an electronic circuit that simulated splenoportal circulation and identified the underlying hemodynamic mechanisms.

Materials and methods

This retrospective observational study included 93 patients with cirrhosis. Splenic volumes were measured in imaging studies at 6-month intervals and normalized by the ratio of each patient's maximum volume during follow-up (%Vmax). An electronic simulation model was constructed using software and realized on a breadboard.

Results

Overall, the %Vmax increased from 0.77 ​± ​0.21 to a maximum of 1.00 ​± ​0.00 (p ​< ​0.001) during a median follow-up of 23 (3–162) months and then decreased to 0.84 ​± ​0.18 (p ​< ​0.001) during the next 9 (3–132) months. No interventional radiology procedure was performed to improve hepatic fibrosis and portal hypertension. The evolution of %Vmax showed single-peaked symmetry. An electronic simulation model showed that the upslope of the evolution curve was dependent on the increased intrahepatic vascular resistance and portal hypertension, whereas the downslope was dependent on the decreased portosystemic shunt (PSS) resistance.

Conclusions

Splenomegaly in cirrhotic patients aggravated over a period of 23 months and then regressed spontaneously to its initial volume. Electronic simulation of splenoportal circulation showed that splenic enlargement was due to the advancement of liver cirrhosis and portal hypertension, whereas its regression was due to the development of a PSS.

Purpose

Matrix metalloproteinases (MMPs) catalyze degradation of extracellular matrix proteins. The activity of MMPs is controlled by tissue inhibitors of metalloproteinases (TIMPs). An imbalance in the MMP-9/TIMP-1 ratio has been linked with chronic periodontitis (CP). Photodynamic therapy (PDT) uses visible light, photosensitizer and oxygen to eradicate pathogens. The aim of the study was to evaluate the presence of MMP-9 and TIMP-1 in gingival crevicular fluid (GCF) in chronic periodontitis patients before and after nonsurgical periodontal therapy with additional PDT.

Methods

Nineteen patients, each with CP, were included in the study. After periodontal examination one site with a probing depth (PD) ​≥ ​4 ​mm was selected. The patients received scaling and root planing (SRP) with additional PDT by means of HELBO® diode minilaser. Prior to treatment, and after 3 and 6 months, the following parameters were estimated from the same site: PD, gingival recession (GR), clinical attachment level (CAL), plaque index (PI), bleeding on probing (BOP) and sulcus fluid flow rate (SFFR). The levels of MMP-9 and TIMP-1 in GCF were determined.

Results

Compared to baseline, the levels of MMP-9 and TIMP-1 did not show statistically significant differences after 3 and 6 months. According to Spearman's rank correlations, MMP-9 was positively correlated with SFFR at all time points. PD, CAL and PI showed a statistically significant decrease compared to baseline (p ​< ​0.001). SFFR decreased but not significantly.

Conclusion

Nonsurgical periodontal therapy in conjunction with PDT was clinically effective but it had no effect on the levels of MMP-9 and TIMP-1 in GCF.

Purpose

The excessive fructose intake including high-fructose corn syrup (HFCS) may be responsible for increase of obesity occurrence. This study was designed to find potential differences in duodenal fructose transporters on mRNA and protein levels between obese and normal weight children and adolescents.

Materials/methods

We performed a cross-sectional study on a group of 106 hospitalized patients aged 12 to 18. Glucose transporter 2 (GLUT2) and glucose transporter 5 (GLUT5) mRNA as well as protein levels (ELISA and Western blot methods) were assessed in duodenal mucosa biopsies of the patients categorized as obese or normal weight. Additionally, the expression of the aforementioned transporters was analyzed in patients based on the presence of insulin resistance (IR) and metabolic syndrome (MS).

Results

In children with obesity, increased duodenal protein levels of GLUT5 (Relative protein GLUT5 expression/ACTB) (0.027 ​± ​0.009 vs. 0.011 ​± ​0.006, p ​< ​0.05) but not GLUT2 as compared with the normal weight group, were revealed. No significant differences in duodenal relative GLUT2 and GLUT5 genes expression between the studied groups were found. There was no relationship between the presence of IR or MS and intestinal mRNA GLUT2 and GLUT5 as well as GLUT2 protein expression.

Conclusion

The upregulation of the duodenal GLUT5 may contribute to obesity occurrence in children and adolescents.

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.