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Foot ulceration is a major complication of diabetes mellitus, which results in significant human suffering and a major burden on healthcare systems. Mesenchymal stromal cells (MSCs) emerged as a promising therapeutic agent for treatment of diabetic wound healing because of their paracrine properties, including the secretion of angiogenic, immunomodulatory and anti-inflammatory factors. However, topical administration of MSCs via direct injection result in low cell viability and poor cell localization at the wound bed, which hinder the efficacy and clinical translation of a MSC therapy product. Here in, we used macromolecular crowding (MMC) concept to develop a MSC-scaffold bio-complex containing the native extracellular matrix (ECM) and investigated its therapeutic effect in a diabetic wound model. Firstly, we investigated the optimal MMC agent in human umbilical cord derived MSC (hUC-MSC) cultures. Seven types of carrageenan at five different concentrations were supplemented to MSC medium. 50 μg/ml l-MV carrageenan was identified to be the optimal cell culture condition, as it did not adversely affect (p > 0.05) cell viability, metabolic activity, proliferation, and the expression of MSC surface markers and immune phenotype markers, whereas it significantly increased (p < 0.05) the deposition of collagen types I, III and IV, fibronectin and laminin. The shortest cell culture time was 4 days. These data highlight the potential of l-MV carrageenan as crowding agents for developing ECM-rich cell therapy product and describes the optimal conditions for use. Secondly, as hUC-MSCs grown under the optimum MMC conditions, can only develop a thin cell layer, which was not suitable for transfer from the tissue culture dish directly to the wound. A collagen porous scaffold was utilised to deliver this ECM-rich MSC layer. Scaffolds were fabricated using either neutralised or non-neutralised collagen. Compared to neutralized scaffold, the non-neutralized scaffold is pliable, thicker and has significantly (p < 0.05) smaller pore size, which is suitable for pre-clinical wound healing studies. hUC-MSCs grown on the non-neutralized scaffold under MMC conditions maintained the cell viability and proliferation at three cell doses (150k, 300k, 600k) groups. hUC-MSCs deposited significantly higher (p < 0.05) fibronectin in the presence of 50 μg/ml l-MV carrageenan at 300k and 600k cell dose groups and no significant difference was observed between the two groups. These data suggest this MSC-scaffold bio-complex at 300k cell dose may have augmented therapeutic potential for the treatment of diabetic wounds. Thirdly, to evaluate the therapeutic effect of this MSC-scaffold bio-complex, we developed a diabetic model using immunodeficient mice, and reproduced the excisional splinting wound model to avoid the confounding effect of wound contraction. Diabetes was induced in animals using low-dose streptozotocin. Wounds were treated as per groups: Sham (no treatment control), SC (scaffold only), SC+MSC (MSC grown on scaffold), and SC+MSC+MMC (MSC grown on scaffold under MMC conditions). 60% of mice successfully developed diabetes and exhibited mild diabetic signs (polydipsia and polyuria) with no loss of body weight and fatality. Gross view of wounds on day 7 showed no significant difference in wound closure rate. Histology and immunohistochemistry analysis revealed no significant difference in re-epithelialization, granulation tissue area, blood vessel density and ECM deposition between the four groups. Donor comparison analysis revealed no significant difference in therapeutic effects between MSCs from 3 different donors. Correlation analysis revealed no correlation between wound gap and blood glucose level, and each group had similar blood glucose levels. Although current pre-clinical data did not support this MSC-scaffold bio-complex to improve diabetic wound healing, these results direct investigation of alternative scaffolds and cell doses as a next step. Collectively, this study provides a new method for the development of a novel MSC therapy product with augmented therapeutic potential. Further improvement of the wound model and optimization of this MSC therapy product are needed for future study. 2026-08-23

To investigate the degree of fusion in sutures of the skull, the authors analyzed cranial computed tomography (CT) data using digital technologies to obtain the density values of coronal, sagittal, and lambdoid sutures in Chinese Han adolescents.The authors selected 80 patients who had undergone maxillofacial surgery. They were divided by age into a 9- to 12-year-old group and a 13 to 15-year-old group. The grayscale value of the cranial CT suture was segmented and measured using Mimics 20.0 software. The Mimics software measurement data were imported into SPSS 21.0 for data comparison and analysis.The mean grayscale value of coronal sutures was 1203.25 and the standard deviation was 220.48, while the mean grayscale value of sagittal sutures was 1113.76 and the standard deviation was 197.83. The mean grayscale value of lambdoid sutures was 1106.37, and the standard deviation was 200.01. The grayscale values of coronal sutures were higher than those of sagittal sutures or lambdoid sutures. Further paired sample t tests were performed on the 3 types of cranial sutures. The differences between coronal and sagittal sutures and between coronal and lambdoid sutures were both substantial with statistical significance. Nevertheless, the difference between sagittal and lambdoid sutures was not significant. Further, an independent sample t-test, showed the grayscale values of coronal, sagittal and lambdoid sutures in the 9-12-year)ear-old group were significantly lower than those in the 13 to 15-year-old group (P

Oxaliplatin (L-OHP) has been widely used in the treatment of various tumors, especially in colorectal cancer. The mechanism of peripheral neurotoxicity induced by L-OHP (OIPN) is unclear and current therapeutic options only serve to alleviate the symptoms rather than prevent OIPN. To observe the effects of electroacupuncture (EA) stimulation on OIPN in rats, rats were randomly divided into the control group, OIPN model group, and OIPN + EA group. To establish OIPN rat models, a single intraperitoneal injection with 10 mg/kg L-OHP in the OIPN model rats. Rats in the control group received a single intraperitoneal injection with 0.9% lactose. From the third day after establishing OIPN models, the rats were treated with EA. Cold allodynia and heat sensitivity were assessed using the acetone drop and the Hargreaves method, respectively. Pathological changes in nerves were detected using hematoxylin and eosin (H&E) staining and transmission electron microscopy. Related mRNA and protein expression levels were measured by real-time polymerase chain reaction (PCR) and western blotting from 14 days after establishing OIPN models. Our results showed that L-OHP significantly increased the sensitivity to cold allodynia and nervous injury, which were ameliorated after EA treatment. The expression of glucocorticoid receptor alpha (GR-α) and B-cell lymphoma 2 (Bcl-2) was significantly decreased and that of Bax was significantly increased in sciatic nerve of OIPN model rats compared with control rats. However, EA treatment significantly inhibited L-OHP-induced protein expressions in rats. Moreover, compared with the control rats, the nucleus NF-κBp65 levels were significantly increased, while the cytoplasm NF-κBp65 levels were significantly decreased, which were reversed by EA treatment. In conclusion, EA treatment may reduce peripheral neurotoxicity induced by L-OHP through regulating related protein expression.

Objective: To investigate the relationship of interleukin (IL)-35 with sarcoidosis. Methods: We enrolled 114 inpatients and outpatients with sarcoidosis at the Shanghai Pulmonary Hospital, and 24 healthy controls between March 2015 and December 2017. Serum and whole blood were collected during the follow-up period. Serum IL-35 levels were detected by ELISA. Proportions of Breg, Tfh, and Treg cells in the peripheral blood were detected using flow cytometry (FCM). The mRNA levels of p35, EBI3, and GAPDH in CD19+ cells and CD4+ cells were detected by real-time PCR. Sarcoidosis granuloma mice models were established with Propionibacterium acnes (PA) and one group was treated with IL-35 antibodies. Proportions of Breg, Tfh, and Treg cells in the peripheral blood and bronchoalveolar lavage fluid (BALF) were detected by FCM. Results: The IL-35 levels and the proportions of Breg and Tfh cells in the peripheral blood of patients with active sarcoidosis were significantly higher compared to patients with stable sarcoidosis and healthy controls. Moreover, the IL-35 level in patients with progressive disease was lower than that found at the initial visit. EBI3 and p35 mRNA levels in CD19+ cells for patients with active sarcoidosis were significantly higher as compared to patients with stable sarcoidosis and healthy controls, while there were no significant differences in p35 and EBI3 mRNA levels in CD4+ cells between the three groups. In the mouse model of sarcoidosis, there were loose granulomata (macrophage accumulation in the bronchial areas and immature granuloma) after intervention with IL-35 antibodies. Meanwhile, the proportions of Breg cells in the peripheral blood and BALF of the model were significantly increased, while the proportion of Treg cells declined significantly. After intervention with IL-35 antibodies, the proportion of Breg cells in the peripheral blood of mice decreased significantly as compared to the mice not exposed to anti-IL-35 antibodies. Conclusion: IL-35 levels increased significantly in the serum of patients with active sarcoidosis, and lower IL-35 levels were correlated with persistent disease. Serum IL-35 levels might be better correlated with Breg cell functions.

Computer-aided diagnosis has been extensively investigated for more rapid and accurate screening during the outbreak of COVID-19 epidemic. However, the challenge remains to distinguish COVID-19 in the complex scenario of multi-type pneumonia classification and improve the overall diagnostic performance. In this paper, we propose a novel periphery-aware COVID-19 diagnosis approach with contrastive representation enhancement to identify COVID-19 from influenza-A (H1N1) viral pneumonia, community acquired pneumonia (CAP), and healthy subjects using chest CT images. Our key contributions include: 1) an unsupervised Periphery-aware Spatial Prediction (PSP) task which is designed to introduce important spatial patterns into deep networks; 2) an adaptive Contrastive Repre-sentation Enhancement (CRE) mechanism which can effectively capture the intra-class similarity and inter-class difference of various types of pneumonia. We integrate PSP and CRE to obtain the representations which are highly discriminative in COVID-19 screening. We evaluate our approach comprehensively on our constructed large-scale dataset and two public datasets. Extensive experiments on both volume-level and slice-level CT images demonstrate the effectiveness of our proposed approach with PSP and CRE for COVID-19 diagnosis.

The antioxidant and emulsifying properties of flaxseed gum-whey protein isolate (FSG-WPI) conjugates prepared by Maillard reaction via controlled dry-heating were investigated. The reaction was carried out using a ratio of FSG to WPI of 1:3 at 60 °C and 79% relative humidity for different incubation times. The reaction was confirmed by analysis of the browning index, free amino content and soluble sulfhydryl content, as well as by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, ultraviolet-visible spectroscopy, and Fourier transform infrared spectroscopy. We found that nearly 35% of the protein participated in conjugation with FSG after 48 h of incubation. The antioxidant activity of the conjugates improved markedly after 48 and 72 h incubation time. Differential scanning calorimetry results indicated that the denaturation temperature of the conjugates increased. The FSG-WPI conjugate prepared by 72 h incubation had the best emulsifying properties in stabilizing an oil-in-water emulsion. This research provides significant knowledge for the potential applications of FSG in food industry.

In recent years, the perpendicular plate of the ethmoid (PPE) has emerged as a new autogenous grafting material in rhinoplasty and septoplasty of nasal deviation. However, no studies have outlined the precise size, shape, and morphologic features of the PPE. Therefore, this study aimed to provide detailed information on the anatomical and morphologic characteristics of the PPE to assist surgeons in performing surgeries that are more precise. About 104 Chinese patients who underwent paranasal computed tomography were assessed in this study. By analyzing the features of the PPE reconstructed with 3-dimensional models, the characteristics of the PPE at different stages of development and according to sex were observed. The PPE had a flat shape, and its lower part was relatively thin. It usually developed horizontally with age, which contributed to expansion of the PPE area. The dimensions of the PPE were significantly larger in male patients than in female patients. Through the reconstruction and measurement of Chinese patients' PPE, the authors have established precise information about the PPE's anatomical and morphologic features. The flat shape and proper size, which are similar to those of nasal septum cartilage, make the PPE an ideal alternative to conventional autogenous grafting materials. The findings might be useful to surgeons in helping them perform surgeries that are more precise.

Aim This study was conducted to evaluate the influence of decorin on apoptosis and oxidative stress response upon exposure of human lens epithelial (HLE) cells to high levels of glucose. Methods The HLE cell line (HLEB3) was cultured under various conditions, including normal (5.5 mM) or high glucose (60 mM) medium. Next, 50 nM Decorin was added two hours prior to the addition of high glucose medium. Apoptosis detection was carried out by Western blotting and flow cytometry. Oxidative stress levels were determined by quantifying reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GSH) levels. P38 mitogen-activated protein kinase (MAPK) phosphorylation and rac1 in HLE cells and human lens anterior capsules were evaluated using Western blotting. Knockdown of rac1 and p38 MAPK in HLEB3 cells was achieved using transfection of small-interfering RNAs. Results HLE cells exposed to high levels of glucose underwent oxidative stress and apoptosis, leading to higher proportion of apoptotic cells, ROS generation and a reduction in the bcl/bax ratio, GSH/GSSG ratio, and SOD activity. Additionally, HLEB3 cells exposed to high levels of glucose were found to have increased rac1 and phospho-p38 MAPK. Next, we found that siRNA-mediated knockdown of rac1 or p38 led to a reduction in high-glucose-stimulated cellular apoptosis and oxidative stress. Furthermore, knockdown of rac1 led to a downregulation of p38 MAPK. Interestingly, addition of decorin to HLEB3 cells led to a decrease in apoptosis, oxidative stress, and high-glucose-stimulated induction of rac1 and phospho-p38. Finally, rac1 and p38 levels of capsules were detected to be significantly upregulated in patients with diabetes in comparison to age-matched patients with cataracts. Conclusion The findings indicate that the rac1-p38 pathway plays a role in causing high-glucose-induced injury to the lens epithelial cells. Additionally, these data indicate that decorin can suppress high glucose-stimulated cellular apoptosis and oxidative stress, in part through suppression of the rac1-p38 pathway.

Prostate cancer is the second most common disease of the male reproductive system. Berberine is a quaternary ammonium salt that is extracted from plants. The aim of the current study was to explore the antitumor activity of berberine in prostate cancer cells and identify the underlying mechanism of its effects. PC3 human and RM‑1 mouse prostate cancer cells were treated with increasing concentrations of berberine, followed by analysis of the cell viability with an MTT assay. The results demonstrated that berberine markedly inhibited the proliferation of PC3 and RM‑1 cells, and that the inhibitory effects to PC3 and RM‑1 were enhanced in a concentration‑ and time‑dependent manner. Flow cytometry was used to analyze the cell cycle of PC3 human prostate cancer cells, and the results demonstrated that G0/G1 phase arrest was induced following treatment with 10 µM berberine (P