Regulation of Hook1-mediated endosomal sorting of clathrin-independent cargo by γ-taxilin

In clathrin-independent endocytosis, Hook1, a microtubule- and cargo-tethering protein, participates in sorting of cargo proteins such as CD98 and CD147 into recycling endosomes. However, the molecular mechanism that regulates Hook1-mediated endosomal sorting is not fully understood. Here, we found that γ-taxilin is a novel regulator of Hook1-mediated endosomal sorting. γ-Taxilin depletion promoted both CD98-positive tubular formation and CD98 recycling. Conversely, overexpression of γ-taxilin inhibited the CD98-positive tubular formation. Depletion of Hook1, or Rab10 or Rab22a (which are both involved in Hook1-mediated endosomal sorting), attenuated the effect of γ-taxilin depletion on the CD98-positive tubular formation. γ-Taxilin depletion promoted CD147-mediated spreading of HeLa cells, suggesting that γ-taxilin may be a pivotal player in various cellular functions in which Hook1-mediated cargo proteins are involved. γ-Taxilin bound to the C-terminal region of Hook1 and inhibited its interaction with CD98; the latter interaction is necessary for sorting CD98. We suggest that γ-taxilin negatively regulates the sorting of Hook1-mediated cargo proteins into recycling endosomes by interfering with the interactions between Hook1 and the cargo proteins.

INFECTED URACHAL CYST IN AN ADULT

Urachus is a tubular formation originating from the top of the urinary bladder and directed to the umbilicus between the peritoneum and the transverse fascia of the abdomen. In an embryo, it serves to divert primary urine to the amniotic fluid. In case, if obliteration of the duct does not occur until the birth, various pathological processes can develop in it. The most common abnomalies of urachus reported in adults are an infected urachal cyst and urachal carcinoma. These diagnoses are not always easy to make due to atypical symptoms of their manifestation and the rarity of these diseases - just two cases per 100,000 hospitalizations of adults. A 22-year-old man with a subcutaneous abscess and anexternal fistula located in theumbilical region with redness of the surrounding skin. 16 hours after dissection and drainaging of the abscess, the patient’s condition worsened, pain in the lower parts of the abdomen began, muscle tension of the anterior abdominal wall and inflammatory changes in blood tests were revealed. The patient was operated on for peritonitis. A two-chambered urachus cyst of the «hourglass» type, with the formation of a dense consistency calculus in one of the cavities, which perforated into the abdominal cavity This clinical case is of the great interest from the point of view of the atypical course and the treatment of a rather rare anomaly in adults. The publication will remind emergency medicine physicians about the possibility of infected urachus in patients with symptoms of acute abdomen.

Exosomal miR-130b-3p Promotes Progression and Tubular Formation Through Targeting PTEN in Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC), accounting for two-thirds of head and neck cancer, is characterized by poor prognosis and a high rate of mortality. Exosomes have emerged as potential molecule-shuttle in intercellular communication, thereby regulating the physiological processes of recipient cells. To date, the effect of exosomal microRNAs (miRNAs) on the progression of OSCC has not been fully investigated. In this study, we found that the protein, but not mRNA expression of Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was decreased in OSCC. The results revealed that miR-130b-3p was an important negative regulator for PTEN expression. Additionally, overexpression and knockdown of miR-130b-3p enhanced and inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs), respectively. Also, miR-130b-3p was transferred by exosomes to HUVECs and then promoted angiogenesis and inhibit the expression of PTEN. Furthermore, exosomal miR-130b-3p derived from OSCC cells promoted tumor growth and blood vessel formation in the xenograft mice model. Taken together, we demonstrated that exosome-mediated miR-130b-3p promoted progression and tubular formation in OSCC in vitro and in vivo. These results would provide new insight into exploring biomarkers and effective therapeutic strategies for OSCC.

Characteristics and Histopathological Grading of Malignant Spiculated Mass in regards to Histopathological Grading of Breast Cancer Based on The Nottingham Grading System

Introduction: Spiculation in mammography is a typical finding for invading breast cancer and is an important criterion in diagnosis and in predicting prognostic and plays an important role in management. The purpose of this research is to determine the characteristics of malignant spiculating mass in mammography in regards to histopathological grading using The Nottingham Grading System.Methods: Patients whom had spiculation in mammography was reviewed using medical record data by two breast imaging consultants and then combined with The Nottingham Grading System criteria obtained from histopathological examination results of core biopsy and surgery specimen. There was 29 cases that met the inclusion criteria.Results: Of the 29 patients that met the inclusion, the spiculated masses grade I, II has mitotic index of 0-12, grade III has mitotic index of 13-25. Histopathologic grade II, III has the most tubular formation of <10%, grade I has 10-75%. Grade I, II has moderate nuclear pleomorphism, grade III has severe nuclear pleomorphism. Most were grade III (44.8%), followed by grade II (37.9%), and minimally grade I (17.2%). Most patients are in stage 3 breast cancer.Conclusion: Malignant spiculated mass with grade I, II has low proliferation index (mitotic index 0-12), histopathological grade II, III had worse cellular differentiation (tubular formation <10%), histopathological grade II, III has moderate to severe nuclear pleomorphism.

Unexpected formation of a tubular architecture by optically active pure organic calixsalen

Herein, an unusual tubular formation of a supramolecular organic framework by optically active macrocyclic calixsalen is shown via single crystal X-ray diffraction.

Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.

Automated Classification of Glandular Tissue by Statistical Proximity Sampling

Due to the complexity of biological tissue and variations in staining procedures, features that are based on the explicit extraction of properties from subglandular structures in tissue images may have difficulty generalizing well over an unrestricted set of images and staining variations. We circumvent this problem by an implicit representation that is both robust and highly descriptive, especially when combined with a multiple instance learning approach to image classification. The new feature method is able to describe tissue architecture based on glandular structure. It is based on statistically representing the relative distribution of tissue components around lumen regions, while preserving spatial and quantitative information, as a basis for diagnosing and analyzing different areas within an image. We demonstrate the efficacy of the method in extracting discriminative features for obtaining high classification rates for tubular formation in both healthy and cancerous tissue, which is an important component in Gleason and tubule-based Elston grading. The proposed method may be used for glandular classification, also in other tissue types, in addition to general applicability as a region-based feature descriptor in image analysis where the image represents a bag with a certain label (or grade) and the region-based feature vectors represent instances.