F-box protein FBXO16 functions as a tumor suppressor by attenuating nuclear β-catenin function

Aberrant activation of β-catenin has been implicated in a variety of human diseases, including cancer. In spite of significant progress, the regulation of active Wnt/β-catenin-signaling pathways is still poorly understood. In this study, we show that F-box protein 16 (FBXO16) is a putative tumor suppressor. It is a component of the SCF (SKP1-Cullin1-F-box protein) complex, which targets the nuclear β-catenin protein to facilitate proteasomal degradation through the 26S proteasome. FBXO16 interacts physically with the C-terminal domain of β-catenin and promotes its lysine 48-linked polyubiquitination. In addition, it inhibits epithelial-to-mesenchymal transition (EMT) by attenuating the level of β-catenin. Therefore, depletion of FBXO16 leads to increased levels of β-catenin, which then promotes cell invasion, tumor growth, and EMT of cancer cells. Furthermore, FBXO16 and β-catenin share an inverse correlation of cellular expression in clinical breast cancer patient samples. In summary, we propose that FBXO16 functions as a putative tumor suppressor by forming an SCF^FBXO16 complex that targets nuclear β-catenin in a unique manner for ubiquitination and subsequent proteasomal degradation to prevent malignancy. This work suggests a novel therapeutic strategy against human cancers related to aberrant β-catenin activation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Comparison of radiorespirometric Budemeyer assay with ATP assay and mouse foot pad test in detecting viable Mycobacterium leprae from clinical samples

PURPOSE: This study compares the results of radiorespirometric Buddemeyer assay with adenosine triphosphate (ATP) assay and mouse foot pad (MFP) test to validate the sensitivity of Buddemeyer assay in detecting viable M. leprae in clinical samples. METHODS: Viability was assessed using all the three methods in 60 skin biopsy specimens, including 20 untreated lepromatous leprosy (BL-LL), 13 treated BL-LL, 12 untreated borderline tuberculoid to mid borderline (BT-BB) and 15 treated BT-BB cases. RESULTS: Of the 20 untreated BL-LL cases tested, positivity indicating the presence of viable M. leprae was detected in 85, 60 and 85% with Buddemeyer, ATP and MFP test, respectively. Among the 13 treated BL-LL cases, scores were 61, 54 and 0%; among the 12 untreated BT-BB cases, the scores were 58, 16 and 16% and among the 15 treated BT-BB cases, the scores were 46, 20, 0%, respectively. CONCLUSION: The detection sensitivity (positive scores) with three tests were closely comparable in the two untreated groups of cases. On the other hand, in the two treated groups, a good proportion of cases scored positive in the in vitro tests but none in the MFP test. Among the two in vitro methods, the Buddemeyer assay emerged as a better test, in terms of sensitivity and specificity.     

Primary spinal paragangliomas: a clinicopathological and immunohistochemical study of six cases

Spinal paragangliomas are uncommon neoplasms and subject of much debate regarding the factors governing their biological behaviour. We describe the clinicopathological and immunohistochemical (IHC) features of six cases of spinal paraganglioma. The mean age of patients was 40 years (range 20-60 years) with a male to female ratio of (2:1). Majority presented with low backache, sphincter disturbances and sensory symptoms. All tumors were intradural in the cauda region one of them extending to the filum. Only one showed focal extradural extension on microscopy. Gross total resection of tumors was possible in all cases. Histologically four showed classical 'zell-ballen' pattern and two revealed an ependymal morphology. On immunohistochemistry, in all the six cases the chief cells were intensely labeled by antibody to chromogranin but not for GFAP while staining for synaptophysin was less intense and variable in five. Sustentacular cells in all cases showed strong expression for S-100 protein and chief cells were stained light in three cases. Low MIB-1 labeling index of 0.01-2% was noted in five cases and in the sixth it was 5%. None of the tumours recurred. Immunohistochemistry assisted in differentiating these relatively benign neural crest tumours from the more aggressive spinal ependymomas.     

Endobronchial metastasis from renal cell carcinoma: a case report

A 46-year-old man had primary pulmonary symptoms of intermittent fever, cough and dyspnoea. Radiological investigations revealed a mass at right hilum with right upper lobe collapse. Bronchoscopy showed a luminal mass of which the biopsy showed a tumour with predominantly clear cell change. Subsequent investigations revealed primary renal adenocarcinoma. The differential diagnosis of clear cell lung tumour is discussed. This case of endobronchial metastasis from renal cell carcinoma is being presented because of its rarity.     

Assessment of preclinical effect of (+)-catechin hydrate on sexual function: An in silico and in vivo study

Considering dopamine-enhancing effect of (+)-catechin, the present study was designed to evaluate dopamine-2 (D2) receptor agonistic and phosphodiesterase-5 (PDE5) enzyme inhibitory effects in in silico and effect on male sexual function of Sprague Dawley rats in vivo. (+)-Catechin and standard (sildenafil and bromocriptine) were docked using Autodock Vina 1.1.2 and visualised by UCSF Chimera 1.14. Significant interactions in terms of binding energies were observed for catechin with both proteins. In in vivo study, the rats were dosed orally for 54 days with (+)-catechin hydrate (50 mg/kg), sildenafil citrate (standard, 4 mg/kg) and carboxymethylcellulose (vehicle, 0.25% w/v). The aphrodisiac effects were evaluated on the day 14, 28, 42 and 54 using the behavioural parameters of mounting and intromission. After the study, animals were sacrificed and testes and spermatozoa were assessed for safety profile. Results showed a significant increase in mount and intromission frequencies and a significant reduction in mount and intromission latencies in the catechin group on all tested days when compared to vehicle control. (+)-Catechin was found to be safe on histology of testes, sperm count, sperm motility and sperm morphology parameters. In conclusion, catechin demonstrated an enhancement in sexual behaviour without eliciting toxicity on the male reproductive system in rats.     

Relevance of IgE,allergy and eye rubbing in the pathogenesis and management of Keratoconus

Keratoconus (KC) is an ectatic disease of the cornea characterized by localized thinning and protrusion causing irregular astigmatism, which can lead to significant visual impairment. KC has often been associated with allergy and/or atopy, which are immune-mediated inflammatory reactions primarily driven by IgE. A higher proportion of KC patients were reported to have history or suffer from systemic and/or ocular allergy with elevated allergen-specific IgE and/or total serum IgE. Eye rubbing, one of the risk factors for worsening of the disease and developing related complications in KC, is associated with IgE driven conditions. The current review enumerates and contextualizes the evidence related to IgE in mediating KC pathogenesis, including aberrant extra-cellular matrix remodeling. This review also discusses clinical strategies directed at modulating IgE-mediated responses in the management of KC, and the emerging academic and plausible clinical relevance of assessing serum and tear IgE (allergen-specific and total) status in improving the understanding of disease pathobiology, treatment planning, and prognosis.     

ABCD: A new classification for keratoconus

Recent advances in the diagnosis and treatment of ectatic corneal disease have mandated a more modern staging system. The new Belin ABCD keratoconus staging system incorporates anterior and posterior curvature centered on the thinnest point of the cornea, thinnest pachymetry values and distance visual acuity in grades from 0-4. By including posterior curvature and thickness measurements based on the thinnest point, as opposed to apical, the new staging system better reflects anatomical changes seen in keratoconus and other ectatic diseases.     

Study of tear film optics and its impact on quality of vision

Purpose:To evaluate the relation of the tear film on the quality of vision comparing parameters in normal patients to those having dry eye disease.Methods:50 normal and 50 eyes with dry eye disease (DED) were included in the study. Patients were screened for dry eye with Schirmer''s test, tear break up time, ocular surface staining, and assessment of meibomian gland disease. Their quality of vision was assessed using the Optical quality analysis system (OQAS). The results of dry eye evaluation were correlated with the parameters on the OQAS especially the mean objective scatter index (OSI).Results:Patients with dry eye and unstable tear film were found to have a significantly worse quality of vision and optical scatter (P < 0.05). They were also noted to have fluctuation of vision between blinks.Conclusion:Tear film optics can have an important bearing on the quality of vision and quality of life. A detailed assessment preoperatively will help improve surgical outcomes and patient satisfaction.