Viral-mediated activation and inhibition of programmed cell death.

Viruses are ubiquitous intracellular genetic parasites that heavily rely on the infected cell to complete their replication life cycle. This dependency on the host machinery forces viruses to modulate a variety of cellular processes including cell survival and cell death. Viruses are known to activate and block almost all types of programmed cell death (PCD) known so far. Modulating PCD in infected hosts has a variety of direct and indirect effects on viral pathogenesis and antiviral immunity. The mechanisms leading to apoptosis following virus infection is widely studied, but several modalities of PCD, including necroptosis, pyroptosis, ferroptosis, and paraptosis, are relatively understudied. In this review, we cover the mechanisms by which viruses activate and inhibit PCDs and suggest perspectives on how these affect viral pathogenesis and immunity.

Valsartan reduced the vulnerability to atrial fibrillation by preventing action potential prolongation and conduction slowing in castrated male mice.

INTRODUCTION: Deficiency of testosterone was associated with the susceptibility of atrial fibrillation (AF). Angiotensin-II (AngII) receptor antagonists were shown to reduce AF by improving atrial electrical remodeling. This study investigated the effects and mechanism of valsartan, an AngII receptor antagonist, on the susceptibility to AF with testosterone deficiency. METHODS AND RESULTS: Five-week-old male ICR mice were castrated and valsartan was administered orally (50 mg/kg/d). High-frequency electrical stimulation method was used to induce atrial arrhythmia. Patch-clamp technique was used for recording action potential duration (APD), transient outward potassium current ( I to ), sustained outward potassium current ( I ksus ), and late sodium current ( I Na-L ). Optical mapping technique was used to examine atrial conduction velocity (CV). The expression of connexin40 (Cx40) and Cx43 were detected by Western blot analysis. The occurrence rate of AF was significantly increased in castrated mice and APDs measured at 50% and 90% repolarization were markedly prolonged in castrated mice than controls, which were alleviated by the administration of valsartan. Valsartan suppressed the increase of INa-L and rescued the reduction of Ito and Iksus in castrated mice. The left atrial CV in castrated mice was decreased and the expression of Cx43 reduced than controls, which were restored after valsartan treatment. CONCLUSIONS: Valsartan reduced the susceptibility of AF in castrated mice, which may be related to the inhibition of action potential prolongation and improvement of atrial conduction impairment. This study indicates that valsartan may represent a useful agent for the prevention of AF pathogenesis in elderly male patients.

Dry environment on the expression of lacrimal gland S100A9, Anxa1, and Clu in rats via proteomics.

AIM: To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats. METHODS: Twenty Sprague-Dawley rats were randomly divided into two groups. The rats were fed in specific pathogen free environment as the control group (n=10), and the rats fed in dry environment as the dryness group (n=10). After 24d, lacrimal glands were collected from the rats. The tissues morphology was observed by hematoxylin-eosin (HE) staining. Tandem mass tags (TMT) quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups, then bioinformatics analysis was performed. Further, the immunohistochemical (IHC) method was used to verify the target proteins. RESULTS: In dryness group, the lacrimal glands lobule atrophied, the glandular cavities enlarged, the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed. The proteomics exhibited that a total of 195 up-regulated and 236 down-regulated differential expressed proteins screened from the lacrimal glands of rats. It was indicated that the biological processes (BP) of differential expressed proteins mainly included cell processes and single BP. The cellular compositions of differential expressed proteins mainly located in cells, organelles. The molecular functions of differential expressed proteins mainly included binding, catalytic activity. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential expressed proteins mainly involved lysosome, complement and coagulation cascade, and ribosome pathway. The IHC result verified that the up-regulated expression proteins of Protein S100A9 (S100A9), Annexin A1 (Anxa1), and Clusterin (Clu) in lacrimal glands of rats in dryness group were higher than control group. CONCLUSION: The up-regulated expression proteins of S100A9, Anxa1, and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment. This study provides clues of dry environments causing eye-related diseases for further studies.

The incidence of cerebral amyloid angiopathy in surgically treated intracranial hemorrhage in the Chinese population.

Despite being widely accepted as an important cause of spontaneous intracranial hemorrhage (ICH), cerebral amyloid angiopathy (CAA) has seldom been studied in the Chinese population. The current study aims to investigate the incidence and features of CAA in surgically treated ICH patients in China. From May 2006 to April 2011, 974 patients admitted to 71 hospitals throughout China for acute spontaneous ICH were studied. Craniotomy for hematoma evacuation was performed. Brain tissue from the superficial side of the suspected residual hematoma cavity, as well as from the cortex and subcortex, was obtained. Congo Red stain and ß-amyloid immunohistochemistry were used for the diagnosis. Each case was assigned a pathological severity score. Of the 974 involved patients, 37.7% were identified with CAA of different degrees. CAA had positive correlation with age and was independent of sex. Most patients had mild CAA with only the superficial vessels involved in lobes instead of the basal ganglia; the patients ≥65 years had more severe pathological score of CAA than those <65 years and had more lobes and cerebellum involved than the latter. More than one third of the surgically treated Chinese ICH patients may have CAA of different degrees.

Upconversion nanoparticles/carbon dots (UCNPs@CDs) composite for simultaneous detection and speciation of divalent and trivalent iron ions.

In this study, the application of carbon dots (CDs) modified NaYF4:Yb, Er nanoparticles (UCNPs@CDs) as the fluorescent nanoprobe for simultaneous detection of Fe2+ and Fe3+ was investigated. Fe3+ quantification (5-80 µmol L-1) was achieved, as a result of Fe3+ induced fluorescence quenching of UCNPs@CDs at 434 nm (under the 336 nm excitation). The chelate (Fe2+-phen) formed by Fe2+ and 1,10-phenanthroline had a broad absorption centered at 510 nm, due to inner filter effect (IFE), Fe2+ quantification (4-120 µmol L-1) was achieved as a result of (Fe2+-phen) induced fluorescence quenching of UCNPs@CDs at 545 nm (under the 980 nm excitation). The resultant UCNPs@CDs probe, with excellent anti-interference capability, favorable fluorescence stability, and convincing performance in real sample analysis, showed promising application in simultaneous detection of Fe2+ and Fe3+.

[The study of association between spontaneous intracranial hemorrhage and cerebral amyloid angiopathy].

OBJECTIVE: To get the general situation of the cerebral amyloid angiopathy (CAA) incidence in spontaneous intracranial hemorrhage (SICH) patients receiving surgical treatment in Chinese people. METHODS: During the period May 2008 and March 2009, 105 patients admitted to 30 hospitals throughout China for acute SICH were studied, including 68 male and 37 female mean aged (55 +/- 13). The patients were suffered from SICH proved by computed tomography scan (CT). Emergent craniotomies for hemorrhage evacuation were performed for these patients within 72 h after hemorrhage onset and brain tissue of the cortex was also obtained meanwhile. A further histological study, Congo red stained and Abeta immunochemistry included was followed to verify the existence of CAA. RESULT: Fifteen out of the 105 cases is identified as CAA positive, and the total ratio is 14.29%. As to age groups, about 20.83% (5/24) of the cases of the 40-49 years old group have been diagnosed as CAA, 17.14% (6/35) of the 50-59 years old group, 4.17% (1/24) of the 60-69 group, and for those older than 70 years, the ratio is 8.00% (2/25). CONCLUSION: We come to the conclusion that 14.29% of the surgically treated SICH events might be closely related to CAA.

GSK­3 inhibitor CHIR99021 enriches glioma stem­like cells.

Glioblastoma (GBM) is the most prevalent and lethal primary intrinsic brain cancer. The disease is essentially incurable, with glioblastomas characterized by resistance to both chemotherapy and radiotherapy, as well as by rapid tumor progression, all of which are mainly ascribed to glioma stem­like cells (GSLCs). In the present study, an improved model that is more similar to clinical GBM was constructed. Twenty clinical glioma samples were collected to obtain primary low­grade tumor cells. The cells were either maintained in serum­free medium as primary glioma­based cells (PGBCs) or cultured in the same medium with CHIR99021 as GSLCs. Then, the molecular and ultrastructural differences between the two cell groups were determined. Furthermore, the proliferation and migration of the GSLCs were examined and the potential mechanisms were investigated. Finally, temozolomide resistance in vitro and in the mouse model was assessed to study the properties of the induced GSLCs. The primary low­grade tumor cells extracted from surgical samples were enriched with GSLC properties, with high expression levels of CD133 and Nestin in 100 nM CHIR99021. The GSLCs exhibited high proliferation and migration. Furthermore, the expression of the PI3K/AKT signaling pathway and that of related genes and proteins were significantly enhanced by CHIR99021. The animal study also revealed high levels of STAT3, mTOR, NF­κB, and VEGF in the GSLC­transplanted mice. CHIR99021 could stably enhance GSLC properties in patient­derived glioma samples. It may provide a useful model for further study, helping to understand the pathogenesis of therapeutic resistance and to screen drug candidates.

[Clinical characteristics and ultra-structural features of skeletal muscle in mitochondrial cytopathies].

OBJECTIVE: To investigate the ultrastructural features of mitochondrial cytopathies and its diagnostic value. METHODS: Muscle biopsy specimens from 33 cases of mitochondrial cytopathies were examined by routine pathological and electron microscopic examinations. RESULTS: The main pathologic changes included ragged red fibers in modified Gomori staining, hyper-intense staining myofibers in SDH, COX-negative fibers while dark counterstaining with SDH in COX/SDH double staining technique. Ultrastructural findings included subsarcolemmal and intramyofibrillar proliferation of mitochondria and the appearance of abnormal mitochondria, paracrystalline inclusions, concentric dystrophic cristae and excessive subsarcolemmal glycolipid compounds in subsarcolemmal. CONCLUSION: The presence of proliferation and abnormality of mitochondria, electro-dense granule and paracrystalline inclusions in mitochondria provide key diagnostic evidence for the diagnosis of this disease.

Hybrid graphene/cadmium-free ZnSe/ZnS quantum dots phototransistors for UV detection.

Graphene-based optoelectronic devices have attracted much attention due to their broadband photon responsivity and fast response time. However, the performance of such graphene-based photodetectors is greatly limited by weak light absorption and low responsivity induced by the gapless nature of graphene. Here, we achieved a high responsivity above 103 AW-1 for Ultraviolet (UV) light in a hybrid structure based phototransistor, which consists of CVD-grown monolayer graphene and ZnSe/ZnS core/shell quantum dots. The photodetectors exhibit a selective photo responsivity for the UV light with the wavelength of 405 nm, confirming the main light absorption from QDs. The photo-generated charges have been found to transfer from QDs to graphene channel, leading to a gate-tunable photo responsivity with the maximum value obtained at V G about 15V. A recirculate 100 times behavior with a good stability of 21 days is demonstrated for our devices and another flexible graphene/QDs based photoconductors have been found to be functional after 1000 bending cycles. Such UV photodetectors based on graphene decorated with cadmium-free ZnSe/ZnS quantum dots offer a new way to build environmental friendly optoelectronics.

Ultrastructure of Pericystic or Intracystic Blood Vessels in Epidermoid Cysts-A Transmission Electron Microscopy Study: Laboratory Investigation.

OBJECTIVES: Recently, we reported a tendency toward spontaneous hemorrhage in both the preoperative and postoperative periods in patients with intracranial epidermoid cyst (EC). According to our experience, this tendency for spontaneous hemorrhage was partly caused by the pathologic blood vessels adjacent to the EC. This study was designed to testify this hypothesis. METHODS: Twenty-three removable pericystic or intracystic blood vessels from 17 patients with EC were collected during surgery and were then examined by transmission electron microscopy. The microvascular structure in gliomas was chosen as the control. RESULTS: Under electron microscopy, variant pathologic changes of vessels were found in all patients with EC. In the tunicae intima, we found vacuolization, apoptosis, necrosis, and intralumenal protrusion of endothelial cells, as well as swollen basement and highly flexed and discontinued elastic plate. In the tunicae media, vacuolization and swollen mitochondria were found in muscular cells. In the tunicae adventitia, extravascular erythrocytes, edema or apoptosis of pericytes, collagen predominance, and inflammatory cell infiltration and destruction were found. Neuron denature and necrosis were found in the peripheral brain tissue. In the microvascular structure of 5 glioma specimens, we found enlargement and hyperplasia of endothelial cells, swollen basement membrane, swollen pericytes, and astrocytic hyperplasia and neuron denature in adjacent brain tissues. CONCLUSIONS: Our findings provide strong evidence for the hypothesis that intracystic or pericystic vascular degeneration or destruction accounts for the spontaneous hemorrhage tendency before and after surgical resection of ECs.

Efficient and Reversible Electron Doping of Semiconductor-Enriched Single-Walled Carbon Nanotubes by Using Decamethylcobaltocene.

Single-walled carbon nanotubes (SWCNTs) offer great potential for field-effect transistors and integrated circuit applications due to their extraordinary electrical properties. To date, as-made SWCNT transistors are usually p-type in air, and it still remains challenging for realizing n-type devices. Herein, we present efficient and reversible electron doping of semiconductor-enriched single-walled carbon nanotubes (s-SWCNTs) by firstly utilizing decamethylcobaltocene (DMC) deposited by a simple spin-coating process at room temperature as an electron donor. A n-type transistor behavior with high on current, large I on /I off ratio and excellent uniformity is obtained by surface charge transfer from the electron donor DMC to acceptor s-SWCNTs, which is further corroborated by the Raman spectra and the ab initio simulation results. The DMC dopant molecules could be reversibly removed by immersion in N, N-Dimethylformamide solvent, indicating its reversibility and providing another way to control the carrier concentration effectively as well as selective removal of surface dopants on demand. Furthermore, the n-type behaviors including threshold voltage, on current, field-effect mobility, contact resistances, etc. are well controllable by adjusting the surface doping concentration. This work paves the way to explore and obtain high-performance n-type nanotubes for future complementary CMOS circuit and system applications.

Short-term Preoperative Octreotide for Thyrotropin-secreting Pituitary Adenoma.

BACKGROUND: Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism. Somatostatin (SST) analogs work by interacting with somatostatin receptors (SSTRs). This study aimed to evaluate short-term preoperative octreotide (OCT) use in TSHoma patients and to investigate SSTR2 and SSTR5 expression and observe structural changes in tumor tissue. METHODS: We reviewed records and samples from eight TSHoma patients treated between July 2012 and July 2015. We tested immunohistochemically for SSTR2/5 expression and examined TSHoma cells for morphological changes. Signed rank sum test was used to compare the efficacy of short-term preoperative OCT treatment. RESULTS: OCT treatment (median time: 7.9 days, range: 3-16 days; median total dose: 1.8 mg, range: 0.9-4.2 mg) led to significant decrease in all patients' thyroid hormone levels (FT3 [nmol/L]: 8.33 [7.02, 12.29] to 4.67 [3.52, 5.37] [P = 0.008]; FT4 [pmol/L]: 25.36 [21.34, 28.99] to 16.66 [14.88, 21.49] [P = 0.016]; and TSH [µU/ml]: 5.80 [4.37, 6.78] to 0.57 [0.19, 1.24] [P = 0.008]). All the eight tumor specimens expressed high SSTR2 protein levels; 5/8 expressed high SSTR5, but 3/8 that expressed low SSTR5 presented a significantly higher TSH suppression rate (P = 0.036). Electron microscopy showed subcellular level impairments, including clumped nuclear chromatin and reduced cytoplasmic volume. Golgi complexes were observed in the OCT-treated TSHoma specimens. CONCLUSIONS: OCT can control hormone levels and damage the ultrastructure of tumor cells and organelles. Short-term response to OCT may be related to SSTR5 expression. Preoperative SST analog treatment for TSHoma could be considered as a combination therapy.

Increment of late sodium currents in the left atrial myocytes and its potential contribution to increased susceptibility of atrial fibrillation in castrated male mice.

BACKGROUND: The incidence of atrial fibrillation (AF) is correlated with decreased levels of testosterone in elderly men. Late sodium current may exert a role in AF pathogenesis. OBJECTIVE: The purpose of this study was to explore the effect of testosterone deficiency on AF susceptibility and the therapeutic effect of late sodium current inhibitors in mice. METHODS: Male ICR mice (5 weeks old) were castrated to establish a testosterone deficiency model. One month after castration, dihydrotestosterone 5 mg/kg was administered subcutaneously for 2 months. Serum total testosterone level was assessed by enzyme-linked immunosorbent assay. High-frequency electrical stimulation was used to induce atrial arrhythmias. Whole-cell patch-clamp technique was used to for single-cell electrophysiologic study. RESULTS: Serum dihydrotestosterone levels of castration mice declined significantly but recovered with administration of exogenous dihydrotestosterone. In comparison with sham mice, the number of AF episodes significantly increased by 13.5-fold, AF rate increased by 3.75-fold, and AF duration prolonged in castrated mice. Dihydrotestosterone administration alleviated the occurrence of AF. Action potential duration at both 50% and 90% repolarization were markedly increased in castrated mice compared to sham controls. The late sodium current was enhanced in castrated male mice. These alterations were alleviated by treatment with dihydrotestosterone. Systemic application of the INa-L inhibitors ranolazine, eleclazine, and GS967 inhibited the occurrence of AF in castrated mice. CONCLUSION: Testosterone deficiency contributed to the increased late sodium current, prolonged action potential repolarization, and increased susceptibility to AF. Blocking of late sodium current is beneficial against the occurrence of AF in castrated mice.

[Function magnetic resonance imaging and diffusion tensor tractography in patients with brain gliomas involving motor areas: clinical application and outcome].

OBJECTIVE: To explore the role of preoperative blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTT) to identify the relationship between motor cortical area, pyramidal tracts with brain gliomas in neurosurgical treatment of intraoperative electrical stimulation for gliomas involving motor areas at 3T. METHODS: Twenty-eight patients with brain gliomas involving motor areas were included. They underwent MRI examination, which included conventional T1WI, T2WI, BOLD-fMRI of bilateral hands movement paradigm and diffusion tensor imaging (DTI). The data of BOLD-fMRI and DTI were transferred to the workstation (Leonardo syngo 2003A, Siemens) and analyzed. Activation mapping of hands movement, fractional Anisotropy (FA) Color and three dimensional pyramidal tracts were produced. The relationship between motor cortical area, pyramidal tracts and brain gliomas was demonstrated, which was used to optimize the pre-surgical planning. With guidance of the result of BOLD-fMRI and DTT, all patients received microsurgery under anaesthesia retaining consciousness using intraoperative motor functional brain mapping with the method of direct electrical stimulations. The brain lesions were removed as far as possible in the case of eloquent areas and sub-cortical important white matters preservation. The preoperative and postoperative KPS of all patients were operated to evaluate the state of patients. RESULTS: BOLD-fMRI, DTI were performed successfully in 28 patients. The relationship between the primary motor cortex, premotor area, supplementary motor area, pyramidal tracts and brain gliomas localized by preoperative fMRI and DTI. Under anaesthesia retaining consciousness, the primary motor area was monitored by the method of direct electrical stimulations with the guidance of preoperative BOLD-fMRI. There was good correlation between preoperative fMRI and intraoperative cortical stimulation. Furthermore, the preoperative mappings and DTT could make up for the un-monitored motor areas and pyramidal tracts during operative cortical stimulation. Comparing the preoperative KPS, the postoperative KPS was advanced. CONCLUSIONS: BOLD-fMRI and DTT could non-invasively localize the relationship between brain motor cortex, pyramidal tracts and brain gliomas in vivo to optimize the surgical planning, guide the microsurgery under anaesthesia retaining consciousness using intraoperative motor functional brain mapping with the method of direct electrical stimulations and remove brain tumors as far as possible in the case of eloquent areas and sub-cortical important white matters preservation.

Organic Dye-Sensitized CH3NH3PbI3 Hybrid Flexible Photodetector with Bulk Heterojunction Architectures.

A flexible photodetector based on the bulk heterojunction of an organometallic halide perovskites CH3NH3PbI3 and an organic dye Rhodamine B (RhB) has been fabricated via a solution casting process. It showed a high responsivity (Rmax = 43.6 mA/W) to visible lights, short response time (tr ≈ 60 ms, td ≈ 40 ms), high on-off ratio (Ion/Ioff ≈ 287) and satisfactory stability because of its Schottky barrier structure and the dye enhanced light absorption.

Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

BACKGROUND: Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma. METHODS: Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis. RESULTS: Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1ß and TNF-α levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05). CONCLUSION: SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH.

Controllable Hysteresis and Threshold Voltage of Single-Walled Carbon Nano-tube Transistors with Ferroelectric Polymer Top-Gate Insulators.

Double-gated field effect transistors have been fabricated using the SWCNT networks as channel layer and the organic ferroelectric P(VDF-TrFE) film spin-coated as top gate insulators. Standard photolithography process has been adopted to achieve the patterning of organic P(VDF-TrFE) films and top-gate electrodes, which is compatible with conventional CMOS process technology. An effective way for modulating the threshold voltage in the channel of P(VDF-TrFE) top-gate transistors under polarization has been reported. The introduction of functional P(VDF-TrFE) gate dielectric also provides us an alternative method to suppress the initial hysteresis of SWCNT networks and obtain a controllable ferroelectric hysteresis behavior. Applied bottom gate voltage has been found to be another effective way to highly control the threshold voltage of the networked SWCNTs based FETs by electrostatic doping effect.

Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFß1 and miR-29 pathways.

Interleukin 6 (IL-6) has been shown to be an important regulator of cardiac interstitial fibrosis. In this study, we explored the role of interleukin-6 in the development of diabetic cardiomyopathy and the underlying mechanisms. Cardiac function of IL-6 knockout mice was significantly improved and interstitial fibrosis was apparently alleviated in comparison with wildtype (WT) diabetic mice induced by streptozotocin (STZ). Treatment with IL-6 significantly promoted the proliferation and collagen production of cultured cardiac fibroblasts (CFs). High glucose treatment increased collagen production, which were mitigated in CFs from IL-6 KO mice. Moreover, IL-6 knockout alleviated the up-regulation of TGFß1 in diabetic hearts of mice and cultured CFs treated with high glucose or IL-6. Furthermore, the expression of miR-29 reduced upon IL-6 treatment, while increased in IL-6 KO hearts. Overexpression of miR-29 blocked the pro-fibrotic effects of IL-6 on cultured CFs. In summary, deletion of IL-6 is able to mitigate myocardial fibrosis and improve cardiac function of diabetic mice. The mechanism involves the regulation of IL-6 on TGFß1 and miR-29 pathway. This study indicates the therapeutic potential of IL-6 suppression on diabetic cardiomyopathy disease associated with fibrosis.

Morphological characteristics of submandibular glands of miniature pig.

BACKGROUND: Miniature pig (minipig) is increasingly used as a large animal model for a variety of biomedical studies. Little information is available in the literature on anatomy, histology and sialograghy of the submandibular gland of the minipig. The purpose of this study was to characterize the morphology of a miniature pig's (minipig) submandibular gland as a large animal model for further biomedical studies. METHODS: Five minipigs were subjected to sialographic, anatomic, histologic, histochemical and ultrastructural evaluations for submandibular glands. RESULTS: Sialograms showed a long, horizontal main excretory duct and a pear-shaped gland located inferoposterior to the angle of the mandible. The submandibular glands lied superficial to the suprahyoid, and infrahyoid muscle groups, and were covered by the inferior portion of the parotid gland. The submandibular glands were characterized by a mixed parenchyma of mucous and serous secretory acini. Alcian blue (AB) staining and periodic acid-Schiff (PAS) reactions demonstrated that minipig submandibular glands synthesized and secreted acid mucous substances by serous cells and polysaccharide, and neutral mucous substances, by mucous cells. CONCLUSION: The submandibular gland of the minipig is considered a useful large salivary gland animal model for biomedical studies.

[In vitro study on inhibition of human choroidal melanoma OCM-1 cell line by arsenic trioxide].

OBJECTIVE: To investigate the effects and mechanisms of arsenic trioxide (ATO) on human choroidal melanoma cell line OCM-1. METHODS: OCM-1 cells were cultured with 0.75 to 24.00 micromol/L arsenic trioxide for various durations, then cell viability was measured by MTT assay. The cell necrosis and apoptosis rates were observed by flow cytometry. The morphological changes of the cells were examined by electron microscopy. Glutathione peroxidase (GSH-Px) activities were tested. Mitochondrial membrane potential (MMP) was detected by confocal microscopy. RESULTS: Growth of OCM-1 cells was inhibited by ATO at concentrations of (1.5 to 24.0) micromol/L. However, there was no effect of 0.75 micromol/L ATO on the growth of OCM-1 cells. The inhibition showed both dose and time dependent effects (P < 0.05). The IC(50) was 16.8 micromol/L at 24 h. Flow cytometry analysis showed a positive correlation between the rate of cell necrosis and apoptosis and the concentration of ATO. The cell necrosis rates were higher than the cell apoptosis rates at various concentrations of ATO. OCM-1 cells cultured with ATO showed the classic morphologic characteristics of necrosis and apoptosis. GSH-Px activities and MMP decreased in a dose dependent manner. CONCLUSION: ATO inhibits the growth of OCM-1 cells. The mechanism of this effect is that ATO inhibits the GSH-Px activities, decreases the MMP and impairs mitochondrial energy synthesis, which induces necrosis and apoptosis of human choroidal melanoma COM-1 cells eventually.