MicroRNAs in HBV-related hepatocellular carcinoma: functions and potential clinical applications.

Hepatitis B virus (HBV) infection is still a relevant problem worldwide and many cases of hepatocellular carcinoma (HCC) are related to HBV. The prognosis of HBV-related HCC is poor, particularly for advanced stage diagnosis. Although follow-up strategies were adopted for patients at risk, there is need for an optimal early biomarker for the screening purpose. MicroRNAs (miRNAs) are small non-coding RNAs, tightly connected to cell type and differentiation status and act as genetic regulator which can be involved in oncogenic processes. The alteration in miRNA expression pattern may represent a new opportunity for HBV-related HCC diagnosis and therapies. Some studies focused on miRNA polymorphism responsible for HCC susceptibility; others found several miRNAs deregulated by HBV X protein as well as miRNAs altered in HBV-related HCC tissue and cells. A high variability among results emerged, probably due to different techniques employed, biological substrates, experimental procedures, criteria of miRNAs selection and ethnic provenience of the included patients. Interestingly, circulating miRNAs have been studied as potential HCC-biomarkers but the reported accuracy is still not convincing, particularly in distinguishing patients with HCC from patients with cirrhosis. Hence, the use of miRNAs remains in an experimental phase and more studies are required to define their role in the clinical practice.

Allosteric interaction of zinc with recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) GABA(A) receptors.

In a recent study we have provided evidence that inhibition of native GABA(A) receptors by zinc depends primarily on the allosteric modulation of receptor gating. Both the kinetics and the sensitivity of the GABA(A) receptor to zinc depend on subunit composition, especially on the presence of the gamma(2) subunit. To analyze the mechanism of action of zinc its effects have been tested on recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors expressed in HEK 293 cells. The currents produced by ultrafast application of GABA have been measured to assess the impact of zinc ions on GABA(A) receptor gating with resolution corresponding to the time scale of synaptic currents. While, as expected, zinc markedly reduced the peak amplitude of alpha(1)beta(2)-mediated currents, its effect on kinetics was significantly different from that observed for alpha(1)beta(2)gamma(2). In particular, unlike alpha(1)beta(2)gamma(2), zinc did not affect the onset of alpha(1)beta(2)-mediated responses. Moreover, zinc increased the extent of desensitisation of alpha(1)beta(2)gamma(2) receptors and reduced desensitisation of alpha(1)beta(2) ones. Quantitative analysis suggests that zinc exerts an allosteric modulation on both alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors. Zinc effects on alpha(1)beta(2)gamma(2) were qualitatively similar to those reported for native receptors.

[Initial observations on the organization of the testis of Trisopterus minutus capelanus]. / Prime osservazioni sulla organizzazione del testicolo di Trisopterus minutus capelanus.

Testis of the Teleostean fish Trisopterus minutus capelanus has been examined to study the organization of the seminiferous tubules and the ultrastructural features of the germ cells. The testis is shown to be composed of seminiferous tubules full of cells: only few of them have just a very narrow lumen. Each tubule is divided by thin septa of connective tissue in zones containing homogeneous cells; such an organization is confirmed by ultrastructural images showing groups of synchronously developing germ cells. By morphological characterization of the germ cells found in each zone, 6 maturation stages have been identified. During spermiogenesis, a progressive shrinkage of germ cells and a nuclear chromatin condensation have been observed. Intercellular bridges, homogeneously dispersed granules of glycogen and groups of mitochondria associated with dense granular material have been described. Such features are present in the earlier stages of spermiogenesis and are retained until the later stages of spermatid differentiation. The spermatozoon shows a lack of acrosome as in many other teleosts previously studied.

Particular ultrastructural aspects of cryptorchid testis in adult and advanced age.

The authors have observed with E.M. Philips 301 some biopsies obtained from testes of cryptorchid patients aged between 38 and 72 to study the ultrastructural aspects of seminiferous tubules in this age. Tissues were fixed in 2% phosphate-buffered solution of glutaraldehyde and then postfixed in 1% osmium tetroxide, processed for routine electron microscopy. The seminiferous tubules appear strongly damaged and we have observed numerous Sertoli cells and only few dark spermatogonia. The Sertoli cells appear either normal and mature or with a cytoplasm filled with big lipid droplets and large amounts of glycogen. The basal membrane of the seminiferous tubules is thickened. Leydig cells are characterized by dilated smooth endoplasmic reticulum and numerous nuclear bodies.

Particular aspects of seminiferous tubules at early puberty.

In the seminiferous tubules of patients at early puberty we have observed Sertoli cells showing an homogeneous aspect. In the cytoplasm of some of these elements dense bodies, which present a particular structure and shape, have been recognized. As far as the germ cells, we can find spermatogonia, spermatocytes and spermatids at various developmental stages. The presence of intercellular bridges among the germ cells and of binucleated spermatids with only one acrosome is a characteristic and fairly frequent finding in our specimens, obtained from normal patients.

Further contributions about the use of the horseradish peroxidase (HRP) in the ultrastructural study of the olivary neurons of cat.

In order to recognize with E.M. the specific aspect of HRP in olivary neurons of cat, we have used newborn animals twenty-four, forty-eight hours old. The observation of these neurons has allowed us to see a numerous series of dense bodies various in size and density; these bodies have never been found in similar neurons from adult cats or from newborn cats not treated with HRP. These structures could represent the equivalent of an intraneuronal storage of enzyme, whose presence had been confirmed by O.M.

Ultrastructural aspects of Sertoli cells in infancy.

In the present study some aspects of Sertoli cells of testicular-biopsy specimens of children from 0 to 8 years old are examined. We can distinguish two main morphological situations. In the first one, Sertoli cells with monomorphic aspect can be seen; in the second can be shown Sertoli cells with various aspects. In this polimorphic situation we can distinguish three Sertoli cell types differing in cellular shape, cytoplasme electron-density and amount of RER and Golgi complex.

[Problems in perfusion and preservation of the rat kidney isolated for the purpose of transplantation]. / Problemi di perfusione e conservazione di rene di ratto isolato a scopo di trapianto.

AA. performed an experimental trial on rats in order to demonstrate damages derived from organ perfusion (kidney) with endo- and extracellular electrolitic solutions. M/E values of structural alterations of the cells allowed the standardisation of renal perfusion methods for transplantation.