Species,tissue and gender-related metal and element accumulation in fish species in a large reservoir (Turkey) and health risks and nutritional benefits for consumers

Concentrations of 18 metals and elements (MEs) in the gills, skin, muscle and liver of Carasobarbus luteus and Cyprinus carpio from the Atatürk Reservoir in Turkey were investigated. The results revealed that variations in the ME contents between fish species can be attributed to different diets. The highest contents of most MEs were recorded in the gills. Gender had no significant effect on the contents of most MEs in the tissues of fish species investigated. The relations between MEs in tissues and fish size were not clear and consistent. Health risk assessment methods indicated that consumption of the studied fish species is safe. It was estimated that daily consumption of 140 g of C. carpio or 170 g of C. luteus would not be expected to cause any health risks. Furthermore, it was found that fish species would provide significant benefits in terms of intake of essential MEs.     

The Role of Oral Health in the Acquisition and Severity of SARS-CoV-2: A Retrospective Chart Review

ObjectiveStudies have shown that gingival crevices may be a significant route for SARS-CoV-2 entry. However, the role of oral health in the acquisition and severity of COVID-19 is not known.DesignA retrospective analysis was performed using electronic health record data from a large urban academic medical center between 12/1/2019 and 8/24/2020. A total of 387 COVID-19 positive cases were identified and matched 1:1 by age, sex, and race to 387 controls without COVID-19 diagnoses. Demographics, number of missing teeth and alveolar crestal height were determined from radiographs and medical/dental charts. In a subgroup of 107 cases and controls, we also examined the rate of change in alveolar crestal height. A conditional logistic regression model was utilized to assess association between alveolar crestal height and missing teeth with COVID-19 status and with hospitalization status among COVID-19 cases.ResultsIncreased alveolar bone loss, OR = 4.302 (2.510 – 7.376), fewer missing teeth, OR = 0.897 (0.835–0.965) and lack of smoking history distinguished COVID-19 cases from controls. After adjusting for time between examinations, cases with COVID-19 had greater alveolar bone loss compared to controls (0.641 ± 0.613 mm vs 0.260 ± 0.631 mm, p < 0.01.) Among cases with COVID-19, increased number of missing teeth OR = 2.1871 (1.146– 4.174) was significantly associated with hospitalization.ConclusionsAlveolar bone loss and missing teeth are positively associated with the acquisition and severity of COVID-19 disease, respectively.     

新型肝癌组织的体外三维培养模型

目的:利用肝癌组织进行体外的三维（three-dimension，3D）组织块培养，通过添加PD98059和霍乱毒素（cholera toxin，CT）优化培养条件，建立一种高活性的肝癌组织体外培养模型。方法:收集中山大学肿瘤防治中心肝胆科的肝癌组织标本，经清洗、冻存、复苏等处理后分为对照组、PD组、CT组、PD+CT组，同时进行体外的二维（two-dimension，2D）和三维培养。各组组织采用DNA断裂的原位末端标记法（TUNEL）检测组织细胞凋亡情况，qRT-PCR检测BCL-2、BID、Caspase 3、Cyclin D1、CDK2、ELK-1、C-FOS、C-MYC、C-JUN等相关基因的mRNA表达水平，免疫荧光染色检测BCL-2和cleaved caspase-3蛋白表达情况，筛选并确定最优的体外培养方法。结果:3D培养组的组织细胞凋亡均少于2D培养组；PD98059通过上调BCL-2蛋白的表达，下调cleaved caspase-3蛋白的表达，激活MEK/ERK下游基因，从而减少体外培养的组织细胞凋亡，增强其抗凋亡能力；霍乱毒素通过上调Cyclin D1、CDK2的基因表达，促进其增殖。结论:我们开发了一种新型肝癌组织的体外三维培养模型，它可以作为进一步的药物试验和人源性异种移植(PDX)模型的工具。     

Design,synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure–activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.     

A perivascular niche in the bone marrow hosts quiescent and proliferating tumorigenic colorectal cancer cells

Disseminated tumor cells (dTCs) can frequently be detected in the bone marrow (BM) of colorectal cancer (CRC) patients, raising the possibility that the BM serves as a reservoir for metastatic tumor cells. Identification of dTCs in BM aspirates harbors the potential of assessing therapeutic outcome and directing therapy intensity with limited risk and effort. Still, the functional and prognostic relevance of dTCs is not fully established. We have previously shown that CRC cell clones can be traced to the BM of mice carrying patient-derived xenografts. However, cellular interactions, proliferative state and tumorigenicity of dTCs remain largely unknown. Here, we applied a coculture system modeling the microvascular niche and used immunofluorescence imaging of the murine BM to show that primary CRC cells migrate toward endothelial tubes. dTCs in the BM were rare, but detectable in mice with xenografts from most patient samples (8/10) predominantly at perivascular sites. Comparable to primary tumors, a substantial fraction of proliferating dTCs was detected in the BM. However, most dTCs were found as isolated cells, indicating that dividing dTCs rather separate than aggregate to metastatic clones—a phenomenon frequently observed in the microvascular niche model. Clonal tracking identified subsets of self-renewing tumor-initiating cells in the BM that formed tumors out of BM transplants, including one subset that did not drive primary tumor growth. Our results indicate an important role of the perivascular BM niche for CRC cell dissemination and show that dTCs can be a potential source for tumor relapse and tumor heterogeneity.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

Peritonitis esclerosante encapsulante: hallazgos en imágenes de una entidad poco frecuente

ObjectivesTo describe the most characteristic imaging findings for sclerosing encapsulating peritonitis, with an emphasis on the computed tomography findings.ConclusionThe incidence of sclerosing encapsulating peritonitis is low. The pathophysiology of this condition is unclear. Two types are recognized: idiopathic and secondary; the secondary type is generally a complication of peritoneal dialysis. Its nonspecific clinical presentation and the absence of blood markers mean that sclerosing encapsulating peritonitis is usually diagnosed late. Thus, it is important to know the imaging signs; these include thickening and calcification of the peritoneum and dilation of bowel loops with thickening and calcification of bowel walls, whether in isolation or in association with loculated ascites. Although ultrasonography allows the complexity of the collections to be evaluated, computed tomography is the most useful technique for the general assessment of the signs mentioned above.     

Soft tissue foreign bodies: A training manual for sonographic diagnosis and guided removal

Sonography provides excellent detection, localization, and characterization of soft-tissue foreign bodies. Ultrasound guided foreign body removal is a safe and highly successful minimally invasive procedure that facilitates effective treatment and avoidance of complications in patients with soft tissue foreign bodies. Focused laboratory training is critical to successful implementation of a sonographic foreign body management practice.