The distribution and structural fingerprints of metals from particulate matters (PM) deposited in human lungs.

This work investigated the distribution and chemical fingerprints of 24 metals in particulate matter (PM) deposited in nonoccupational human lungs. Metals in the pulmonary PM can be grouped by the mean concentration as > 5 × 103 µg/g (Al/Fe/Ca/Mg/Zn), 1-5 × 103 µg/g (Ti/Ba/Pb/Mn), 0.2-1 × 103 µg/g (Cu/Cr/As/V) and < 100 µg/g (Ni/Sn/Cd/Sb). Three parameters (LFL, LR, EFP) were defined to predict different metal leaching behaviors. The leaching factor (LFL) of metals was 10-60 for Pb/Sb/Cd/Co/Cu and decreased to 1-2 for Ni/Cr/Mg/Al/Fe. Metals showed a divergent extent of lung retention (LR), including high retention (LR>10, Al/Cd/Cr/Ba/Ni/Ti/Sn/V/Sb), moderate retention (2 

First-Line Contact Aspiration vs Stent Retriever for Proximal Occlusion in Acute Ischemic Stroke: A Systemic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to compare the performance of first-line contact aspiration (ASP) and stent retriever (SR) in acute ischemic stroke caused by proximal large vessel occlusion. METHODS: Cochrane databases, MEDLINE and EMBASE were systematically searched for literatures reporting outcomes on thrombectomy with both first-line aspiration and first-line stent retriever in proximal occlusion. RESULTS: Thirteen studies with a total of 1614 patients were included. No differences were identified between the SR and ASP groups in terms of final reperfusion rate (modified thrombolysis in cerebral infarction 2b/3) (OR: 1.54, 95% CI: 0.88-2.70), complete recanalization rate (modified thrombolysis in cerebral infarction 3) (OR: 1.78, 95% CI: 0.58-5.44), and favorable outcomes (modified Rankin scale ≤2) (OR: 1.02, 95% CI: 0.79-1.32). With regard to adverse events, emboli to new territories (OR: 0.81, 95% CI: 0.31-2.14), intracranial hemorrhage (OR: 0.71, 95% CI: 0.40-1.28), 90-days mortality (OR: 1.02, 95% CI: 0.71-1.47) were similar between groups, while symptomatic intracerebral hemorrhage (OR: 0.43 95% CI: 0.21-0.86) was less seen in ASP. Subgroup analysis indicated that ASP was comparable to stent retriever with local aspiration (SRLA) (OR: 1.25 95% CI: 0.25-6.22) and superior to stent retriever alone (OR: 1.85 95% CI: 1.22-2.81). Moreover, in posterior circulation, contact aspiration achieved a significantly higher reperfusion (OR: 1.97 95% CI: 1.03-3.76) compared to stent retriever, and needed relatively less rescue therapies (21.5% vs 29.6%, p < 0.05). CONCLUSION: Our study suggested that contact aspiration might be advantageous over stent retriever alone and more suitable in posterior circulation. While ASP and SRLA thrombectomy were equally effective in achieving good clinical outcomes. However, further studies are needed to confirm these results.

Epigenetic roles in the malignant transformation of gastric mucosal cells.

Gastric carcinogenesis occurs when gastric epithelial cells transition through the initial, immortal, premalignant, and malignant stages of transformation. Epigenetic regulations contribute to this multistep process. Due to the critical role of epigenetic modifications , these changes are highly likely to be of clinical use in the future as new biomarkers and therapeutic targets for the early detection and treatment of cancers. Here, we summarize the recent findings on how epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, regulate gastric carcinogenesis, and we discuss potential new strategies for the diagnosis and treatments of gastric cancer. The strategies may be helpful in the further understanding of epigenetic regulation in human diseases.

Optimization and quality control of genome-wide Hi-C library preparation.

Highest-throughput chromosome conformation capture (Hi-C) is one of the key assays for genome- wide chromatin interaction studies. It is a time-consuming process that involves many steps and many different kinds of reagents, consumables, and equipments. At present, the reproducibility is unsatisfactory. By optimizing the key steps of the Hi-C experiment, such as crosslinking, pretreatment of digestion, inactivation of restriction enzyme, and in situ ligation etc., we established a robust Hi-C procedure and prepared two biological replicates of Hi-C libraries from the GM12878 cells. After preliminary quality control by Sanger sequencing, the two replicates were high-throughput sequenced. The bioinformatics analysis of the raw sequencing data revealed the mapping-ability and pair-mate rate of the raw data were around 90% and 72%, respectively. Additionally, after removal of self-circular ligations and dangling-end products, more than 96% of the valid pairs were reached. Genome-wide interactome profiling shows clear topological associated domains (TADs), which is consistent with previous reports. Further correlation analysis showed that the two biological replicates strongly correlate with each other in terms of both bin coverage and all bin pairs. All these results indicated that the optimized Hi-C procedure is robust and stable, which will be very helpful for the wide applications of the Hi-C assay.

POU2F2-oriented network promotes human gastric cancer metastasis.

BACKGROUND AND AIMS: Aberrant upregulation of POU2F2 expression has been discovered in metastatic gastric cancer (GC). However, the mechanisms underlying the aberrant upregulation and the potential functions of POU2F2 remain uncertain. DESIGN: The role and mechanism of POU2F2 in GC metastasis were investigated in gastric epithelial cells, GC cell lines and an experimental metastasis animal model by gain of function and loss of function. Upstream and downstream targets of POU2F2 were selected by bioinformatics and identified by luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation PCR. The influence of miR-218 on its putative target genes (POU2F2, ROBO1 and IKK-ß) and GC metastasis was further explored via in vitro and in vivo approaches. RESULTS: Increased POU2F2 expression was detected in metastatic GC cell lines and patient samples. POU2F2 was induced by the activation of nuclear factor (NF)-κB and, in turn, regulated ROBO1 transcription, thus functionally contributing to GC metastasis. Finally, miR-218 was found to suppress GC metastasis by simultaneously mediating multiple molecules in the POU2F2-oriented network. CONCLUSIONS: This study demonstrated that NF-κB and the SLIT2/ROBO1 interaction network with POU2F2 as the central part may exert critical effects on tumour metastasis. Blocking the activation of the POU2F2-oriented metastasis network using miR-218 precursors exemplified a promising approach that sheds light on new strategies for GC treatment.

Construction of CTCF degradation cell line by CRISPR/Cas9 mediated genome editing.

The CCCTC-binding factor (CTCF) is the main insulator protein described in vertebrates. It plays fundamental roles during diverse cellular processes. CTCF gene knockout mice led to death during embryonic development. To further explore the functions of CTCF, we employed a CRISPR/Cas9-based genome engineering strategy to in-frame insert the mitosis-special degradation domain (MD) of cyclin B into the upstream open reading frame of CTCF gene. Fusion protein is designed to degrade during mitosis leaded by MD. As a control group, mutation of a single arginine (R42A) within the destruction box inactivates the MD leading to constitutive expression of MD*-CTCF. The homozygous clones were obtained via the screening by puromycin when coexpressed with puromycin resistence gene. The protein level of CTCF in MD-CTCF cell line was about 10% of wild-type cells throughout cell cycles by the analyses of Western blotting and immunofluorescence. There was no significant difference between MD*-CTCF cell line and wild type. Flow cytometry results showed prolonged G1 phase in MD-CTCF cell line. Taken together, we demonstrated the feasibility of efficiently inserting MD domain into genome with the CRISPR/Cas9 technology and reported the first CTCF-specific degradation human cell line.

A wide survey of heavy metals-induced in-vitro DNA replication stress characterized by rate-limited replication.

Heavy metals (HMs) are environmental pollutants that pose a threat to human health and have been accepted to cause various diseases, including cancer and developmental disorders. DNA replication stress has been identified to be associated with such diseases. However, the effect of HMs exclusively on DNA replication stress is still not well understood. In this study, DNA replication stress induced by thirteen HMs was assessed using a simplified in-vitro DNA replication model. Two parameters, Cte/Ctc reflecting the cycle threshold value alteration and Ke/Kc reflecting the linear phase slope change, were calculated based on the DNA replication amplification curve to evaluate the rate of exponential and linear phases. These parameters were used to detect the replication rate reflecting in-vitro DNA replication stress induced by tested HMs. According to the effective concentrations and rate-limiting degree, HMs were ranked as follows: Hg, Ce > Pb > Zn > Cr > Cd > Co > Fe > Mn, Cu, Bi, Sr, Ni. Additionally, EDTA could relieve the DNA replication stress induced by some HMs. In conclusion, this study highlights the potential danger of HMs themselves on DNA replication and provides new insight into the possible links between HMs and DNA replication-related diseases.

A new strategy to stabilize the heavy metals in carbonized MSWI-fly ash using an acid-resistant oligomeric dithiocarbamate chelator.

Fly ash (FA) derived from municipal solid waste incineration (MSWI) requires safe handling before landfilling due to its extremely high salt content and the risk of leaching heavy metals (HMs) under acidic conditions. Herein, aimed at improving the acid stability of dithiocarbamates, a cost-effective oligomeric dithiocarbamate (ODTC) was developed to stabilize HMs from carbonated MSWI-FA. Spiking of 3.6 wt% ODTC reduced the HM leaching below landfill standards in China, even across the pH range of 2.0-13.0 or 8-week exposure to the natural environment. Stabilization decreased the acid-soluble/exchangeable fractions of Cd, Pb, and Zn from 22.2%, 4.49%, and 21.9% to 0.14%, 0.11%, and 12.2%, respectively, resulting in safe levels for Pb and Cd with risk assessments. Compared to DDTC and SDD, ODTC exhibited higher stability under acidic conditions after chelation with the HMs, minimized the risk of HM leaching, and significantly reduced stabilization costs. In-depth studies proved that the stabilization mechanism involved the ability of ODTC to chelate HMs strongly and form acid-resistant ODTC-HM complexes, agglomeration of the MSWI-FA grains to encapsulate the ODTC-HM complexes, transformations of the HMs from acid-soluble species to stable oxidizable and residual species, and specifically ODTC reducing high-valent Pb to more stable Pb(II) species.

Effect of replacement therapy (CRRT) and hemodialysis (IHD) on severe acute renal failure.

Hyperkalemia, metabolic acidosis, and acute uremia are the main symptoms in patients with severe acute renal failure (SARF). Its clinical symptoms are obvious, and it is extremely harmful. It needs to take active and effective measures for treatment. CRRT refers to any extracorporeal blood purification treatment technique designed to replace impaired renal function for 24 h or nearly 24 h. Hemodialysis treatment is a treatment process in which the patient's blood is discharged from the body, passes through the dialysis membrane and dialysis machine, removes excess toxins and water in the body, corrects electrolyte and acid-base disorders, and then returns the blood to the body. In order to explore the efficacy of replacement therapy and hemodialysis in the treatment of severe acute renal failure, the data samples were randomly divided into observation group and control group, who were given conventional treatment, hemodialysis and replacement therapy, respectively. Clinical data show that after replacement therapy and hemodialysis in patients with severe acute renal failure in the observation group, the levels of parathyroid hormone, renin, and quality of life were all improved, with an improvement rate of 9.47%, which has certain promotional value.

Is non-alcoholic fatty liver disease a sign of left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus? A systematic review and meta-analysis.

Recent studies have associated non-alcoholic fatty liver disease (NAFLD) with impaired cardiac function. However, patients with type 2 diabetes mellitus (T2DM), a high-risk group for left ventricular diastolic dysfunction (LVDD), were not analyzed as an independent study population. A systematic review was conducted to identify all published clinical trials using the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases from inception to September 14, 2022. Observational studies that reported echocardiographic parameters in T2DM patients with NAFLD compared with those without NAFLD were included for further selection. The Agency for Healthcare Research and Quality checklist was used to appraise the study quality. Ten observational studies (all cross-sectional in design) comprising 1800 T2DM patients (1124 with NAFLD, 62.4%) were included. We found that T2DM patients with NAFLD had a significantly lower E/A ratio, higher peak A velocity, higher E/e' ratio, lower e' velocity, greater left atrial maximum volume index, and greater left ventricular mass index than non-NAFLD patients. These findings reinforced the importance of NAFLD being associated with an increased risk of LVDD in the T2DM population, and NAFLD may be a sign of LVDD in patients with T2DM.PROSPERO registration numberCRD42022355844.

A new approach to predict microhardness of two-phase in cutting S32760 duplex stainless steel.

The uneven distribution of microhardness in the two-phase structure of S32760 duplex stainless steel after cutting is attributed to variations in the crystal structure, which significantly impact the material's performance. This paper presents a new approach to predict the microhardness of two-phase based on the flow stresses in the austenitic and ferrite. The effect of strain, strain rate, and temperature on the flow stress in the shear plane of orthogonal cutting S32760 was analyzed, and the prediction model for microhardness of two-phase considering the two-phase flow stress was established to obtain a mapping relationship between the two-phase flow stress and the two-phase microhardness of S32760. The impact of cutting dosages on shear strain, strain rate, and temperature in the shear plane was investigated. A function relationship between cutting dosages and microhardness of austenite and ferrite in the shear plane was established, two-phase microhardness experiments were conducted, and the model's accuracy was validated with a prediction error of less than 6%. This study provided insights into the impact of strain, strain rate, and temperature in the shear plane on the microhardness of the two-phase, thus contributing to the theoretical foundation of processing techniques in duplex stainless steel.

Comparison of the effects of different percentages of soy protein in the diet on patients with type 2 diabetic nephropathy: systematic reviews and network meta-analysis.

Background: Dietary soy protein (SP) is a potential intervention for protecting the kidneys and improving glucose and lipid metabolism. However, whether this effect is related to the percentage of SP intake remains unclear. Objective: This study aims to review and analyze the results of randomized clinical trials (RCTs) in patients with type 2 diabetic nephropathy (T2DN) who received diets with different percentages of SP. Methods: The databases: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), WanFang, Weipu (VIP), and ClinicalTrials.gov were searched until February 2023, for RCTs on T2DN and SP. Results: A total of six studies comprising 116 participants were included. The interventions were classified as 0% SP, 35% SP, and 100% SP. To improve serum creatinine (Scr), blood urea nitrogen (BUN), 24-h urine total protein (24hUTP), and glomerular filtration rate (GFR), a 35% SP diet was the most effective, compared to a 0% SP diet, which showed a mean difference of -154.00 (95% confidence interval: -266.69, -41.31) for 24hUTP. Although it had significant benefits for 24hUTP, great heterogeneity was observed. To improve the glycolipid metabolism-related markers such as cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FPG), and weight, the 35% SP diet demonstrated superior efficacy compared to the 0% SP diet. Specifically, the mean difference for CHO was -0.55 (95% confidence interval: -1.08, -0.03), and for LDL-C, it was -17.71 (95% confidence interval: -39.67, -4.24). The other indicators were not statistically significant. Most studies had concerns regarding the risk of bias. Conclusion: The findings of this study demonstrate that both 35% and 100% SP diets are more effective than a diet with no SP in improving renal function and glucolipid metabolism in patients with T2DN. As a result, a diet incorporating 35% SP may be the optimal choice for individuals with T2DN. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=352638, identifier CRD42022352638.

Natural compounds efficacy in complicated diabetes: A new twist impacting ferroptosis.

Ferroptosis, as a way of cell death, participates in the body's normal physiological and pathological regulation. Recent studies have shown that ferroptosis may damage glucose-stimulated islets ß Insulin secretion and programmed cell death of T2DM target organs are involved in the pathogenesis of T2DM and its complications. Targeting suppression of ferroptosis with specific inhibitors may provide new therapeutic opportunities for previously untreated T2DM and its target organs. Current studies suggest that natural bioactive compounds, which are abundantly available in drugs, foods, and medicinal plants for the treatment of T2DM and its target organs, have recently received significant attention for their various biological activities and minimal toxicity, and that many natural compounds appear to have a significant role in the regulation of ferroptosis in T2DM and its target organs. Therefore, this review summarized the potential treatment strategies of natural compounds as ferroptosis inhibitors to treat T2DM and its complications, providing potential lead compounds and natural phytochemical molecular nuclei for future drug research and development to intervene in ferroptosis in T2DM.

Chemical fingerprints and implicated cancer risks of Polycyclic aromatic hydrocarbons (PAHs) from fine particulate matter deposited in human lungs.

Exposure to fine particles (PM2.5) and associated PAHs are frequently linked with lung cancer, which makes the understanding of their occurrence and health risk in human lungs urgently important. Using the ultrasonic treatment and sequencing centrifugation (USC) extraction method coupled with gas chromatography-tandem mass spectrometry (GC - MS/MS) analysis, we revealed the molecular fingerprints of PM-accumulated PAHs in human lungs from a cohort of 68 patients with lung cancer in a typical air-polluted region, China. Sixteen priority PAHs can be grouped by concentrations as âˆ¼ 1 × 104 ng/g (ANT/BkF/ACE/DBA/BgP/PHN/PYR), 2-5 × 103 ng/g (BaP/FLE/NaP/BbF), and âˆ¼ 1 × 103 ng/g (IND/Acy/CHR/FLT/BaA). The sum concentration of 16 PAHs was approximately equaled to 13% of those in atmospheric PM2.5, suggesting significant pulmonary leaching of PAHs deposited in lungs. Low- and high-molecular weight PAHs accounted for âˆ¼ 41.8% and âˆ¼ 45.1% of the total PAHs, respectively, which indicated that atmospheric PM2.5, tobacco and cooking smoke were likely to be important sources of pulmonary PAHs. The evident increasing concentrations of NaP and FLE in pulmonary PM were significantly correlated with smoking history among smokers. The implicated carcinogenic potency of PM-accumulated PAHs among the participants aged 70-80 was 17 times that among participants aged 40-50 on the basis of BaP equivalent concentration (BaPeq) evaluation. The particulate enrichment factor (EFP), the PAH content in pulmonary PM relative to the bulk lung tissue, was equaled to 54 âˆ¼ 835 and averaged at 436. The high value of EFP suggested that PAHs were essentially accumulated in pulmonary PM and exhibited a pattern of "hotspot" distribution in the lungs, which would likely increase the risk of monoclonal tumorigenesis. The chemical characteristics of PM-accumulated PAHs in human lungs together with their implicated lung cancer risks could provide significant information for understanding health effects of particulate pollution in the human body.

Herbal tea, a novel adjuvant therapy for treating type 2 diabetes mellitus: A review.

Type 2 diabetes mellitus (T2DM) is a metabolic, endocrine disease characterized by persistent hyperglycemia. Several studies have shown that herbal tea improves glucose metabolism disorders in patients with T2DM. This study summarizes the published randomized controlled trials (RCTs) on herbal tea as a adjuvant therapy for treating T2DM and found that herbal teas have potential add-on effects in lowering blood glucose levels. In addition, we discussed the polyphenol contents in common herbal teas and their possible adverse effects. To better guide the application of herbal teas, we further summarized the hypoglycemic mechanisms of common herbal teas, which mainly involve: 1) improving insulin resistance, 2) protecting islet ß-cells, 3) anti-inflammation and anti-oxidation, 4) inhibition of glucose absorption, and 5) suppression of gluconeogenesis. In conclusion, herbal tea, as a novel adjuvant therapy for treating T2DM, has the potential for further in-depth research and product development.

The FENDRR/FOXC2 Axis Contributes to Multidrug Resistance in Gastric Cancer and Correlates With Poor Prognosis.

The dysregulation of long non-coding RNAs (lncRNAs) and transcription factors (TFs) is closely related to the development and progression of drug resistance in cancer chemotherapy. However, their regulatory interactions in the multidrug resistance (MDR) of gastric cancer (GC) has largely remained unknown. In this study, we report a novel oncogenic role of lncRNA FENDRR in conferring MDR in GC by coordinated regulation of FOXC2 expression at the transcriptional and posttranscriptional levels. In vitro and in vivo experiments demonstrated that downregulation of FENDRR expression remarkably decreased drug resistant ability of GC MDR cells while upregulation of FENDRR expression produced the opposite effect. FENDRR overexpression was observed in MDR GC cell lines, patient-derived xenografts, and clinical samples. And the high levels of FENDRR expression were correlated with poor prognosis in GC patients. Regarding the mechanism, FENDRR was revealed to increase proto-oncogene FOXC2 transcription by performing an enhancer-like role in the nucleus and by sponging miR-4700-3p in the cytoplasm. Both FOXC2 and miR-4700-3p were shown to be functionally involved in the FENDRR-induced chemoresistance. In addition, there is a positive correlation between FENDRR and FOXC2 expression in clinic and the overexpressed FOXC2 indicated a poor prognosis in GC patients. Collectively, our findings provide a new perspective for the lncRNA-TF regulatory interaction involved in MDR, suggesting that targeting the FENDRR/FOXC2 axis may be an effective approach to circumvent GC chemoresistance.

[(99m)Tc-MDP wholebody bone imaging in evaluation of the characteristics of bone metastasis of primary lung cancer].

OBJECTIVE: To explore the image characteristics of bone metastasis of primary lung carcinoma. METHODS: Whole-body bone imaging ((99)Tc(m)-MDP) was performed in 258 patients with pathologically proven lung carcinoma. The rate of bone metastasis, distribution of the metastatic lesions and their characteristics were analyzed. RESULTS: Among the 258 cases, 142 patients developed bone metastasis. The overall rate of bone metastasis was 55.0%. The metastases located in axial skeleton were 49.6%, appendicular skeleton 36.0%, trunk bones of the axial skeleton 48.4%, and appendicular girdle skeleton 31.4%. Ribs, thoracic vertebrae, ilium and lumbar vertebrae had a higher rate of bone metastasis, higher than 20%, respectively. 1252 lesions were detected including 406 at the left side of the body, 387 in the axial skeleton and 459 at the right side of the body. There was no significant difference in terms of number of lesions between left side and right side (chi(2) = 3.3, P = 0.072). 1224 bone metastatic foci (97.8%) were presented as strong radioactive, 26 (2.1%) mixed lesion, and 2 (0.2%) low radioactive. According to the shape of the lesions, there were 810 punctate lesions (71.5%), 159 (14.0%) lump form, 108 (9.5%) strip form and 56 (4.9%) lamellar form. The accumulative bone metastasis rate was 28.7% for the patients with one to three lesions. The metastasis rate decreased gradually with the increasing number of metastatic lesions. CONCLUSION: Bone metastasis is very common in patients with lung cancer. Most bone metastases are characterized by strong radioactive and earlier punctate form, often occurs in the trunk bones of axial skeleton or appendicular girdles. The distribution of earlier metastases has not obvious regularity, and advanced bone metastases are often concurrent, multiple and multiform, widely and randomly distributed in the body.

Epigenetics recording varied environment and complex cell events represents the origin of cellular aging.

Although a relationship between epigenetics and aging phenotypic changes has been established, a theoretical explanation of the intrinsic connection between the epigenetics and aging is lacking. In this essay, we propose that epigenetic recording of varied cell environment and complex history could be an origin of cellular aging. Through epigenetic modifications, the environment and historical events can induce the chromatin template into an activated or repressive accessible structure, thereby shaping the DNA template into a spectrum of chromatin states. The inner nature of diversity and conflicts born by the cell environment and its historical events are hence recorded into the chromatin template. This could result in a dissipated spectrum of the chromatin state and chaos in overall gene expression. An unavoidable degradation of epigenome entropy, similar to Shannon entropy, would be consequently induced. The resultant disorder in epigenome, characterized by corrosion of epigenome entropy as reflected in chromatin template, can be stably memorized and propagated through cell division. Furthermore, the hysteretic nature of epigenetics responding to the emerging environment could exacerbate the degradation of epigenome entropy. As well as stochastic errors, we propose that outside entropy (or chaos) derived from the varied environment and complex cell history, gradually input and imprinted into the chromatin via epigenetic modifications, would lead inevitably to cellular aging, the extent of which could be aggravated by hysteresis of epigenetics without error erasing and correction.

Roles of bone scintigraphy and resonance frequency analysis in evaluating osseointegration of endosseous implant.

The purpose of this study is to analyze the roles of two non-invasive techniques, bone scintigraphy and resonance frequency analysis (RFA), in the osseointegration assessment. Sixty implants with sandblasted/acid-etched (SA) or machined (MA) surface were placed into the distal femur condyles of 30 rabbits. At 1, 2, 4, 6, 8, and 12 weeks postsurgery, they were subjected to bone scintigraphy, digital radiographic examination, histological and histomorphometric analysis. RFA was performed on each implant both at the time of implant placement and animal sacrifice. The results showed that variation of Tc-99m-MDP uptake (bone scintigraphy value) coincided with that of new bone formation activity and accumulation of osteoblasts. Bone scintigraphy was more sensitive to the change of peri-implant bone than the digital radiographic examination. But it did not correlate with histomorphometric data and failed to detect the difference between SA and MA implants. It was found that RFA value increased with the bone-to-implant contact during the healing phase and correlated with the histomorphometric data. Moreover, RFA distinguished between the SA and MA implants. It is concluded, therefore, that bone scintigraphy may be a dynamic method on peri-implant bone healing, while RFA may be a reliable biomechanical technique that can monitor the osseointegration at macro level. We propose that the combination of these non-destructive techniques may facilitate the identification of the nature of osseointegration.

miR-218 inhibited tumor angiogenesis by targeting ROBO1 in gastric cancer.

Aberrant expression of miRNAs is involved in several carcinogenic processes, including tumor growth, metastasis and angiogenesis. The aim of this study was to determine the role of miR-218 in gastric cancer angiogenesis. In situ hybridization was performed on a set of tissue microarray samples to assess the difference in miR-218 expression in vessels between tumor tissues and normal gastric mucosa. In vitro, ectopic expression of miR-218 disturbed the tubular structure and inhibited the migration of endothelial cells. Motility and tube formation were rescued when miR-218 was downregulated. Moreover, miR-218 suppressed endothelial cell sprouting in a fibrin bead sprouting assay. Subsequently, we identified ROBO1 as a target of miR-218 in endothelial cells and determined it was responsible for the effect of miR-218 on tumor angiogenesis. In vivo, local injection of mature miR-218 in xenografted tumors disrupted the vessel plexus and thus inhibited tumor growth. Taken together, our study demonstrated an anti-angiogenic role of miR-218 in gastric cancer and indicated that delivery of miR-218 may be a potential therapeutic strategy to inhibit tumor angiogenesis.