Detecting Nanotopography Induced Changes in Cell Migration Directions Using Oxygen Sensors.

This study investigates the oxygen (O2) consumption of single cells during changes in their migration direction. This is the first integration of nanotopographies with an O2 biosensor in a platform, allowing the real-time monitoring of O2 consumption in cells and the ability to distinguish cells migrating in the same direction from those migrating in the opposite direction. Advanced nanofabrication technologies were used to pattern nanoholes or nanopillars on grating ridges, and their effects were evaluated using fluorescence microscopy, cell migration assays, and O2 consumption analysis. The results revealed that cells on the nanopillars over grating ridges exhibited an enhanced migration motility and more frequent directional changes. Additionally, these cells showed an increased number of protrusions and filopodia with denser F-actin areas and an increased number of dotted F-actin structures around the nanopillars. Dynamic metabolic responses were also evident, as indicated by the fluorescence intensity peaks of platinum octaethylporphyrin ketone dye, reflecting an increased O2 consumption and higher mitochondria activities, due to the higher energy required in response to directional changes. The study emphasizes the complex interplay between O2 consumption and cell migration directional changes, providing insights into biomaterial science and regenerative medicine. It suggests innovative designs for biomaterials that guide cell migration and metabolism, advocating nanoengineered platforms to harness the intricate relationships between cells and their microenvironments for therapeutic applications.

Association between a family history of cancer and multiple primary lung cancer risks: a population-based analysis from China.

OBJECTIVES: The incidence of multiple primary lung cancer (MPLC) has increased in recent years. The risk factors of MPLC are not well studied, especially in the Asian population. This case-control study investigated the association between a family history of cancer and MPLC risk. METHODS: We used data from people who surgically confirmed MPLC with at least 2 nodes of Fujian Medical University Union Hospital and matched 1:2 normal individuals as controls between 2016 and 2017. Information on age, sex, lifestyle, personal history, and family history of cancer was collected using a self-administered questionnaire, and odds ratios (OR) were estimated using unconditional logistic regression. RESULTS: We included 2 104 patients. In total, 321 patients with histologically confirmed MPLC and 642 healthy controls were studied. The significantly higher ratio of current smokers was observed for the cases than the controls (54.1% vs. 30.0%). A family history of LC in first-degree relatives of the cases reported a significantly higher proportion than in the controls (15.3% vs. 8.6%). Family history of all cancers and LC significantly increased the risk of MPLC (OR = 1.64, P = 0.009 and OR = 2.59, P = 0.000, respectively). The multivariate analysis identified a significantly increased risk of MPLC (OR = 2.45, P = 0.000) associated with parents and siblings influenced by LC history. The younger age (aged < 55 years) of LC cases at diagnosis exhibited a significantly increased risk of MPLC (OR = 2.39, P = 0.000). A significant association with a family history of LC was found for male squamous carcinoma and male adenocarcinoma (OR = 1.59, p = 0.037 and OR = 1.64, p = 0.032, respectively). A positive association with LC history was only observed for female adenocarcinoma (OR = 2.23, p = 0.028). The risk of MPLC was not significantly associated with A family history of cancers in non-smokers (OR = 0.91, P = 0.236). Ever-smokers with a positive family history of cancer or LC had a significantly elevated risk of MPLC (OR = 4.01, P = 0.000 and OR = 6.49, P = 0.000, respectively). We also observed a very elevated risk for smokers with no family history (OR = 3.49, P = 0.000). Such a positive association was also observed in ever-smokers with no family history of LC (OR = 3.55, P = 0.000). Adenocarcinoma in females was prevalent and significantly associated with a family history of LC in risk of MPLC compared with other histologic subtypes. CONCLUSIONS: Our findings suggest an association between a family history of LC and MPLC risk among an Asian population. Smoking status and family history of LC have a synergistic effect on MPLC. These findings indicate that MPLC exhibits familiar aggregation and that inherited genetic susceptibility may contribute to the development of MPLC.

Estimating the Neovascularity of Human Finger Tendon Through High-Frequency Ultrasound Micro-Doppler Imaging.

OBJECTIVE: Neovascularization of injured tendons prolongs the proliferative phase of healing, but prolonged neovascularization may cause improper healing and pain. Currently, ultrasound Doppler imaging is used for measuring the neovascularization of injured tendons (e.g., Achilles tendon). However, the resolution of state-of-the-art clinical ultrasound machines is insufficient for visualizing the neovascularization in finger tendons. In this study, a high-frequency micro-Doppler imaging (HFµDI) based on 40-MHz ultrafast ultrasound imaging was proposed for visualizing the neovascularization in injured finger tendons during multiple rehabilitation phases. METHOD: The vessel visibility was enhanced through a block-wise singular value decomposition filter and several curvilinear structure enhancement strategies, including the bowler-hat transform and Hessian-based vessel enhancement filtering. HFµDI was verified through small animal kidney and spleen imaging because the related vessel structure patterns of mice are well studied. Five patients with finger tendon injuries underwent HFµDI examination at various rehabilitation phases after surgery (weeks 11-56), and finger function evaluations were performed for comparisons. RESULTS: The results of small animal experiments revealed that the proposed HFµDI provides excellent microvasculature imaging performance; the contrast-to-noise ratio of HFµDI was approximately 15 dB higher than that of the conventional singular value decomposition filter, and the minimum detectable vessel size for mouse kidney was 35 µm without the use of contrast agent. In the human study, neovascularization was clearly observed in injured finger tendons during the early phase of healing (weeks 11-21), but it regressed from week 52 to 56. Finger rehabilitation appears to help reduce neovascularization; neovascular density decreased by approximately 1.8%-8.0% in participants after 4 weeks of rehabilitation. CONCLUSION: The experimental results verified the performance of HFµDI for microvasculature imaging and its potential for injured finger tendon evaluations.

Cell Signaling Pathway in 12-O-Tetradecanoylphorbol-13-acetate-Induced LCN2 Gene Transcription in Esophageal Squamous Cell Carcinoma.

LCN2 is involved in various cellular functions, including transport of small hydrophobic molecules, protection of MMP9 from proteolytic degradation, and regulating innate immunity. LCN2 is elevated in multiple human cancers, frequently being associated with tumor size, stage, and invasiveness. Our previous studies have shown that LCN2 expression could be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in esophageal squamous cell carcinoma (ESCC) by the binding of five nucleoproteins (MISP, KLF10, KLF15, PPP1R18, and RXRß) at a novel TPA-responsive element (TRE), at -152~-60 bp of the 5' flanking region of the LCN2 promoter. However, much is unknown about whether these proteins can respond to TPA stimulation to regulate LCN2 transactivation and which cell signaling pathways mediate this process. In this study, expression plasmids encoding these five nucleoproteins were stably transfected into EC109 cells. Then, stable transfectant was characterized by a Dual-Luciferase Reporter Assay System. RT-PCR, real-time PCR, western blotting, specific kinase inhibitor treatment, and bioinformatics analyses were applied in this study. We found that MISP, KLF10, KLF15, PPP1R18, and RXRß proteins could strongly respond to TPA stimulation and activate LCN2 transcriptional expression. MEK, ERK, JNK, and P38 kinases were involved in the LCN2 transactivation. Furthermore, the MEK-ERK signal pathway plays a major role in this biological process but does not involve PKCα signaling.

Establishment of an animal model of vascular restenosis with bilateral carotid artery grafting.

BACKGROUND: Vascular restenosis occurring after CABG is a major clinical problem that needs to be addressed. Vein grafts are associated with a higher degree of stenosis than artery grafts. However, the mechanism responsible for this effect has not been elucidated. We aimed to establish a rabbit model of vascular restenosis after bilateral carotid artery grafting, and to investigate the associated spatiotemporal changes of intimal hyperplasia in carotid artery and jugular vein grafts after surgery. MATERIAL AND METHODS: Twenty adult New Zealand white rabbits (10 males; 10 females), weighing 2.0-2.5 kg, were obtained from the Experimental Animal Center of Southern Medical University, Guangzhou, China (License No.: scxk-Guangdong-2006-0015). We quantitatively analyzed intimal thickness, area, and degree of stenosis in carotid artery and jugular vein bridges. RESULTS: After 8 weeks of a high-fat diet, rabbit carotid arteries showed early atherosclerotic lesions. With increasing time after surgery, carotid artery and jugular vein grafts showed histopathological and morphological changes, including smooth muscle cell migration, lipid deposition, intimal hyperplasia, and vascular stenosis. The degree of vascular stenosis was significantly higher in vein grafts than in artery grafts at all time points - 35.1±6.7% vs. 16.1±2.6% at Week 12, 56.2±8.5% vs. 23.4±3.4% at Week 16, and 71.2±1.3% vs. 25.2±5.3% at Week 20. CONCLUSIONS: Rabbit bilateral carotid arteries were grafted with carotid artery and jugular vein bridges to simulate pathophysiological processes that occur in people after CABG surgery.

[Comparative study on the quality of life in patients with prevertebral or retrosternal reconstruction after cervical tubular gastroesophagostomy].

OBJECTIVE: To compare the quality of life in patients with prevertebral or retrosternal reconstruction after cervical tubular gastroesophagostomy. METHODS: A total of 167 patients enrolled in this prospective study from July 2008 to June 2012 in Shantou Central Hospital, and divided into prevertebral route group(85 cases) and retrosternal route group(82 cases) according to the random number table method. Quality of life questionnaire was investigated 1, 3, 6, 9, and 12 months after operation respectively. RESULTS: The incidence of anastomotic stenosis was lower in the prevertebral route group (P<0.05). However, the differences in perioperative general conditions between the two groups were not statistically significant(all P>0.05). One hundred and forty-nine patients completed the postoperative quality of life questionnaire. Dysphagia and swallowing retching symptom were better, while acid reflux and heartburn symptom were more serious in prevertebral route group as compared to retrosternal route group(all P<0.05). Overall quality of life score difference between the two groups was not statistically significant(P>0.05). CONCLUSIONS: For digestive tract reconstruction after resection of esophageal cancer, tubular gastroesophagostomy by prevertebral or retrosternal route both can obtain better quality of life after surgery. Swallowing function after surgery of the former is superior to the latter, but the reflux symptoms is more serious. Therefore the two mehods have their own advantages and disadvantages, and the choice of route should be depended on clinical experience and patient condition.