The Expression Levels of XLF and Mutant P53 Are Inversely Correlated in Head and Neck Cancer Cells.

XRCC4-like factor (XLF), also known as Cernunnos, is a protein encoded by the human NHEJ1 gene and an important repair factor for DNA double-strand breaks. In this study, we have found that XLF is over-expressed in HPV(+) versus HPV(-) head and neck squamous cell carcinoma (HNSCC) and significantly down-regulated in the HNSCC cell lines expressing high level of mutant p53 protein versus those cell lines harboring wild-type TP53 gene with low p53 protein expression. We have also demonstrated that Werner syndrome protein (WRN), a member of the NHEJ repair pathway, binds to both mutant p53 protein and NHEJ1 gene promoter, and siRNA knockdown of WRN leads to the inhibition of XLF expression in the HNSCC cells. Collectively, these findings suggest that WRN and p53 are involved in the regulation of XLF expression and the activity of WRN might be affected by mutant p53 protein in the HNSCC cells with aberrant TP53 gene mutations, due to the interaction of mutant p53 with WRN. As a result, the expression of XLF in these cancer cells is significantly suppressed. Our study also suggests that XLF is over-expressed in HPV(+) HNSCC with low expression of wild type p53, and might serve as a potential biomarker for HPV(+) HNSCC. Further studies are warranted to investigate the mechanisms underlying the interactive role of WRN and XLF in NHEJ repair pathway

Delayed bilateral spontaneous renal rupture after surgery for unilateral upper ureteral calculi: a case report

Spontaneous renal rupture is a rare clinical condition characterized by spontaneous bleeding in the renal subcapsular and perinephric spaces in patients without a history of trauma. It occurs mainly in pathologic kidneys and after some renal surgeries. We report a 40-year-old male patient admitted with a diagnosis of gallstones with cholecystitis due to fever and abdominal pain after unilateral ureteral calculi. The patient developed delayed right renal rupture hemorrhage during treatment, controlled after selective arterial embolization (SAE). Still, the patient developed spontaneous left renal rupture due to a systemic inflammatory response. Finally, the patient’s life was saved after several selective embolizations of the renal artery. We retrospectively analyzed this case to improve our understanding of the disease

Geology, U-Pb geochronology and stable isotope geochemistry of the Heihaibei gold deposit in the southern part of the Eastern Kunlun Orogenic Belt, China : A granitic intrusion-related gold deposit?

The Heihaibei gold deposit is a newly discovered gold deposit in the southern part of the Eastern Kunlun Orogenic Belt. Its most distinctive features are that the gold mineralization is hosted in monzogranite, and that the presence of pre-ore (possibly syn-ore) monzogranite and post-ore gabbro allows to constrain the minerali-zation's formation age. Zircons from the monzogranites yield U-Pb ages of 454 +/- 3 Ma, while zircons separated from the gabbro dikes cutting the monzogranites and gold mineralized body yield U-Pb ages of 439 +/- 3 Ma, which is interpreted to be the minimum age of the Au mineralizing event. Combined with the regional geological background, we proposed that the Heihaibei Au mineralization occurred during the subduction stage of the Early Paleozoic Proto-Tethys ocean. The ore assemblage is dominated by pyrite, arsenopyrite and native gold. The hydrothermal alteration that has led to the peculiar enrichment of Au is not systematically distributed and displays no clear concentric zoning pattern. The main mineralization formed during three stages: the K-feldspar-quartz-pyrite (Py1)-arsenopyrite-sericite-epidote stage (I), the quartz-pyrite (Py2)-native gold-chlorite stage (II), and the quartz-carbonate stage (III). The main gold mineralization occurred during stage II. Fluid inclusion homogenization temperature and salinities decrease from stage I (Th., 268-412 C; W., 6.87-16.63 wt% NaCl equiv.) to stage II (Th., 183-288 C; W., 3.69-14.84 wt% NaCl equiv.). The 818O and 8D values (818OH2O = 4.9 to 9.7%o; 8DV-SMOW =-84.1%o to -81.1%o) of quartz samples from stage I and stage II are comparable to a magmatic-hydrothermal ore-forming fluid that possibly underwent fluid-rock interaction with the Nachitai Group metamorphic rocks during the early ore-forming stage. The relatively uniform 834S values (834SV-CDT = 7.7 to 8.5%o) are slightly elevated compared to magmatic 834S values, but could be derived from a magma if a significant crustal melt component is present. Moreover, the 834S values are within the S isotopic composition range of a granitic reservoir, suggesting that they are probably inherited from the Heihaibei monzogranites. The Pb and Hf isotope compositions imply a close genetic association between the gold mineralization and granitic magmatism, which are both the products of the mixing of crustal and mantle sources. The trace element compositions of pyrite provide additional evidence that the gold mineralization in the Heihaibei deposit was related to the magmatism. Compared with the typical characteristics of orogenic gold and intrusion-related gold systems (IRGS) deposits, the Heihaibei gold deposit may instead be classified as a granitic intrusion-related gold deposit.Peer reviewe

High-altitude cerebral hypoxia promotes mitochondrial dysfunction and apoptosis of mouse neurons

IntroductionNeuronal cell death is an important factor in the pathogenesis of acute high-altitude cerebral hypoxia; however, the underlying molecular mechanism remains unclear. In this study, we tested if high-altitude hypoxia (HAH) causes neuronal death and mitochondrial dysfunction using various in vivo and in vitro approaches.MethodsAcute high-altitude cerebral hypoxia was induced by hypobaric hypoxia chamber in male mice. we explored the mechanisms of neuronal cell death using immunofluorescence, western blotting, transmission electron microscopy, and flow cytometry. Next, mitochondrial function and morphology were observed using Jc-1 staining, seahorse assay, western blotting, MitoTracker staining, and transmission electron microscopy. Moreover, open field test, elevated plus test, and Morris water maze were applied for animal behavior.ResultsResults revealed that HAH disrupted mitochondrial function and promoted neuronal apoptosis and necroptosis both in HT-22 cells and in mouse hippocampal neurons. Moreover, the mitochondrial membrane potential and adenosine triphosphate production decreased in neurons after HAH, while oxidative stress and mitochondrial fission increased. Behavioral studies suggested that HAH induced anxiety-like behavior and impaired spatial memory, while it had no effect on athletic ability.DiscussionThese findings demonstrated that HAH promotes mitochondrial dysfunction and apoptosis of mouse neurons, thus providing new insights into the role of mitochondrial function and neuronal cell death in acute high-altitude cerebral hypoxia

Chitosan-salvianolic acid B coating on the surface of nickel-titanium alloy inhibits proliferation of smooth muscle cells and promote endothelialization

Introduction: Intracranial stents are of paramount importance in managing cerebrovascular disorders. Nevertheless, the currently employed drug-eluting stents, although effective in decreasing in-stent restenosis, might impede the re-endothelialization process within blood vessels, potentially leading to prolonged thrombosis development and restenosis over time.Methods: This study aims to construct a multifunctional bioactive coating to enhance the biocompatibility of the stents. Salvianolic acid B (SALB), a bioactive compound extracted from Salvia miltiorrhiza, exhibits potential for improving cardiovascular health. We utilized dopamine as the base and adhered chitosan-coated SALB microspheres onto nickel-titanium alloy flat plates, resulting in a multifunctional drug coating.Results: By encapsulating SALB within chitosan, the release period of SALB was effectively prolonged, as evidenced by the in vitro drug release curve showing sustained release over 28 days. The interaction between the drug coating and blood was examined through experiments on water contact angle, clotting time, and protein adsorption. Cellular experiments showed that the drug coating stimulates the proliferation, adhesion, and migration of human umbilical vein endothelial cells.Discussion: These findings indicate its potential to promote re-endothelialization. In addition, the bioactive coating effectively suppressed smooth muscle cells proliferation, adhesion, and migration, potentially reducing the occurrence of neointimal hyperplasia and restenosis. These findings emphasize the exceptional biocompatibility of the newly developed bioactive coating and demonstrate its potential clinical application as an innovative strategy to improve stent therapy efficacy. Thus, this coating holds great promise for the treatment of cerebrovascular disease

Neuroform stent-assisted coiling of large and giant intracranial aneurysms: Angiographic and clinical outcomes in 71 consecutive patients

Background: Large and giant aneurysms still remain a therapeutic challenge both surgically and endovascularly. Objective: The authors report their clinical experience and follow-up results using Neuroform stent, as an adjunct in the treatment of large and giant aneurysms. Materials and Methods: A total of 71 consecutive patients with 72 large or giant intracranial aneurysms were treated with the Neuroform stent-assisted coiling. Both sequential technique and parallel technique were used. In all cases, embolization was completed by packing the aneurysm sac with a variety of commercially available coils. The technical feasibility of the procedure, procedure-related complications, angiographic results, clinical outcome, and follow-up angiography were evaluated. Results: In all the patients, the Neuroform stent system was delivered and deployed accurately, and occlusion was achieved. Immediate angiography demonstrated complete occlusion of the aneurysm in 59.7% of the patients, neck remnant in 26.4%, and incomplete occlusion in 13.9%. Procedure-related complication, morbidity, and mortality were 15.3, 4.2, and 1.4%, respectively. Favorable clinical outcome (modified Rankin Scale score 0-2) was observed in 83.3% of the patients (average follow-up time: 37.1 months). None of the treated aneurysm had rebleeding. Angiography follow-up was obtained in 81.7% (58/71 patients; 59/72 aneurysms; average follow-up time, 43.2 months). The overall recanalization rate was 28.8%. No delayed coil or stent migration was found. In-stent stenosis occurred as a delayed complication in one patient. Conclusions: The Neuroform stent-assisted coiling for large and giant intracranial aneurysms is safe and feasible with comparable incidences of morbidity and mortality