FBW7 regulates HIF-1α/VEGF pathway in the IL-1ß induced chondrocytes degeneration.

OBJECTIVE: The aim of the study was to observe the effect of F-box/WD repeat-containing protein 7 (FBW7) on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in chondrocytes (CHs) under IL-1ß induced degeneration. PATIENTS AND METHODS: We explored the levels of FBW7, HIF-1α, and VEGF in degenerated cartilage from osteoarthritis (OA) and chondrocytes (CHs) treated by IL-1ß. Meanwhile, we regulated HIF-1α and FBW7 expression in IL-1ß treated CHs and observed the effects FBW7 of the HIF-1α/VEGF pathway. RESULTS: FBW7 expression was significantly decreased along with the increased HIF-1α and VEGF expression both in OA cartilage and IL-1ß induced degenerated CHs. Additionally, suppression of HIF-1α decreased VEGF level, which contributed to the production of collagen II, aggrecan and SOX-9, and inhibited collagen I and Runx-2 expression. Furthermore, FBW7 suppressed HIF-1α/VEGF pathway and promoted the integration of collagen II, aggrecan, and SOX-9, but inhibited the collagen I and Runx-2 expression. CONCLUSIONS: FBW7 negatively regulates HIF-1α/VEGF pathway and plays a protective role in the IL-1ß induced CHs degeneration.

Anomalous Rabi Oscillations in Multilevel Quantum Systems.

We show that the excitation probability of a state within a manifold of levels undergoes Rabi oscillations with the frequency determined by the energy difference between the states and not by the pulse area, for sufficiently strong pulses. The population and coherence remains in the two-level subsystem formed by the initial and target state even at Rabi frequencies exceeding the energy difference. The observed dynamics can be useful in nonlinear spectroscopy and quantum state preparation.

[Radiofrequency ablation combined with systemic chemotherapy in the management of nasopharyngeal carcinoma with liver metastasis].

Objective: To determine the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (chemo-RFA) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Methods: A total of 427 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center between January 2000 and December 2013 were enrolled. Of the patients, 340 cases were male, 87 cases were female, the median age was 45 years (range 18-80 years), all patients received systemic chemotherapy and part of them also received RFA treatment. Patients were evaluated for response every two cycles during systemic chemotherapy and then every three months until death. One-to-one matched pairs between chemo-RFA group with chemo-only group were generated using propensity score matching; survival analysis was further conducted. Results: Of all the enrolled patients, 56 patients (13.1%) received combined treatment, 371 patients (86.9%)received chemotherapy alone. After propensity score matching, 56 pairs of well-matched liver metastatic NPC patients were selected from different treatment groups. The 1-, 3-, 5- year overall survival (OS) rates for chemo-RFA group were 89.2%, 45.5% and 32.5% and chemo-only group were 77.1%, 27.5% and 4.8% respectively; the 1-, 3-, 5- year progression-free survival (PFS) rates for chemo-RFA group were 64.0%, 25.4% and 10.7% and chemo-only group were 44.1%, 5.5% and 5.5% respectively.The adjusted hazard ratio in OS and PFS of the choice for chemo-RFA approach to chemo-only was HR 0.43, 95% CI 0.25-0.73 and HR 0.44, 95% CI 0.28-0.71 respectively. Conclusion: CT-guided RFA combined with chemotherapy approach could improve the survival rate for NPC patients with liver metastasis.

BTK inhibition results in impaired CXCR4 chemokine receptor surface expression, signaling and function in chronic lymphocytic leukemia.

Bruton's tyrosine kinase (BTK) is involved in the regulation of B-cell growth, migration and adhesion. The importance of BTK in cell trafficking is emphasized by the clonal contraction proceeded by lymphocytosis typical for the enzyme inhibitor, ibrutinib, in B-cell malignancies, including chronic lymphocytic leukemia (CLL). Here, we investigated BTK regulation of leukemic B-cell trafficking in a mouse model of aggressive TCL1 CLL-like disease. Inhibiting BTK by ibrutinib reduced surface membrane (sm) levels of CXCR4 but not CXCR5, CD49d and other adhesion/homing receptors. Decreased smCXCR4 levels resulted from blocking receptor signal transduction, which in turn aborted cycling from and to the membrane. This resulted in rapid re-distribution of CLL cells from spleens and lymph nodes into the circulation. CLL cells with impaired smCXCR4 from BTK inhibition failed to home to spleens. These functional changes mainly resulted from inhibition of CXCR4 phosphorylation at Ser339, mediated directly by blocking BTK enzymatic activity and indirectly by affecting the function of downstream targets PLCγ2 and PKCµ, and eventually synthesis of PIM-1 and BTK itself. Our data identify CXCR4 as a key regulator in BTK-mediated CLL-cell retention and have elucidated a complex set of not previously described mechanisms responsible for these effects.

External dacryocystorhinostomy in consultants and fellows - a comparison of the causes of failure.

PURPOSE: Failure of primary dacryocystorhinostomy (DCR) often requires revision surgery to inspect the cause of failure and re-establish anatomic patency. This study aims to specifcally compare the anatomical causes of failure noted during revision DCR of primary external DCR (EX-DCR) and compare the difference between consultants and fellows. METHODS: A retrospective review of 37 patients who underwent revision of a primary external approach DCR over a 7-year-period in a University Hospital. All primary surgery was performed by either a consultant surgeon or senior oculoplastic fellow. Details of the initial pathology prior to primary DCR and grade of operating surgeon were collected along with perioperative surgical findings. The cause of failure of the initial surgery was classified according to perioperative findings. Failure was classified as either inappropriately sized/located ostium or fibrous/membranous soft tissue obstruction of the newly created ostium. RESULTS: The cause of failure of the initial surgery was soft tissue obstruction in 43.3% and an inappropriately sized/located ostium in 56.7%. In those patients whose primary surgery was performed by a consultant, 73.3% were found to have a soft tissue obstruction and 26.7% were found to have an inappropriately sized/ located ostium. In contrast, if initial surgery was performed by a fellow, 22.7% were found to have a soft tissue obstruction and 77.3% an inappropriately sized/ located ostium (p =0.002). CONCLUSIONS: Where the primary surgeon has been a trainee there is a trend toward inadequately sized or located ostium being the most likely causative factor in failure of primary EX-DCR.  Hippokratia 2015; 19 (3): 216-218.

Prevalence of ocular and orbital injuries in polytrauma patients.

INTRODUCTION: Polytrauma patients usually suffer from both life-threatening injuries, where early intervention is mandatory in order to prevent mortality from uncontrollable haemorrhage-especially during the "golden hour", and secondary injuries of lower priority which receive delayed referral or treatment. Non-life-threatening injuries can sometimes be overlooked and so remain untreated until a much later stage. The aim of this study was to investigate the incidence of eye (ocular and orbital) injuries in polytrauma (injury severity score >15) patients and describe their complexities and outcomes. MATERIALS AND METHODS: Over a 10-year period (1991-2001), all polytrauma patients admitted in our institution were evaluated. Patients with ocular and orbital injuries were identified and their records were retrospectively analyzed. RESULTS: Out of a total of 2,985 polytrauma patients, 222 (7.5%) met the inclusion criteria. Forty-one case notes were not retraceable. The files of 181 patients were therefore available for review. The mean age of this group of patients was 33 years (3-84) with a sex ratio (male: female ratio) 5:1. The types of eye injuries encountered were orbital wall fractures (61%), periorbital swelling or hematoma (46%), sub-conjunctival hemorrhage (23%), periorbital lacerations (22%), optic nerve trauma (11%) and penetrating eye injuries (6%). Visual impairment resulted in about 67% of survivors, including loss of eye in 24%. Diplopia requiring intervention was seen in 24% of the cases. CONCLUSIONS: Polytrauma patients are at high risk for vision-threatening injuries, and an early multidisciplinary approach is essential for early detection and treatment.

Ternary mixed monolayers for simultaneous DNA orientation control and surface passivation for label free DNA hybridization electrochemical sensing.

Target recognizing ternary mixed monolayer is constructed by simple sequential adsorption of thiol caped single stranded DNA (HS-ssDNA), 6-mercapto-1-hexanol (MCH) and 3-mercaptopropionic acid (MPA) diluents (abbreviated as HS-ssDNA/MPA/MCH) and applied for detection of DNA hybridization sequence by electrochemical method. The method is more reliable and reproducible on both conventional wire electrode and 100 nm scale gold-coated silicon chips. Detection limit of 10 pM is observed constantly on all types of electrodes. This ternary layer approach provides 60-80% discrimination effect between the hybridized and un-hybridized surfaces compared to the binary mixed monolayers HS-ssDNA/MCH and HS-ssDNA/MPA that showed 20-30% only. Characterization by impedance spectroscopy, X-ray photoelectron spectroscopy and surface Fourier Transform Infrared (FT-IR) techniques reveals 'head-to-head' anisotropic hydrogen bonding between MPA and MCH diluents that controls the HS-ssDNA orientation and enhancing the electrostatic blockade for K3[Fe(CN)6]. This is the first report characterizing the ternary layer for DNA molecular affinity sensing. Results provided unprecedented insight onto the label free electrochemical sensing and understanding of the complex sensing mechanism to develop sensors that is more reliable.

Simultaneous determination of salbutamol, ractopamine, and clenbuterol in animal feeds by SPE and LC-MS.

A liquid chromatography-mass spectrometry (LC-MS) method for the simultaneous determination of salbutamol, ractopamine, and clenbuterol in commercial feeds was developed. Samples were extracted with phosphoric acid-methanol solution, and further clean-up was achieved with a C18 cation exchange mixed mode cartridge. Separation of analytes was developed on a C18 column with 0.01 M aqueous ammonium formate solution (pH 3.8)-acetonitrile by gradient program, and characterized by LC-MS on a quadrupole detector, in electrospray positive ion mode. This method provides average recoveries for salbutamol, ractopamine, and clenbuterol of 83-110% and coefficients of variation of 1.5-11% in feeds spiked in the range of 0.5-500 mg/kg. The limits of detection and quantification in feeds were 0.01 mg/kg and 0.05 mg/kg, respectively. Such limits are well below the dose of 2-25 mg/kg feed proposed as effective.

Is this really a capillary haemangioma?

Periocular tumours in newborn babies are not uncommon and their diagnosis and management can be challenging. Capillary haemangioma is the most common of them and superficial ones are easy to recognise. Deep-seated (orbital) lesions can mimic various other orbital mass lesions - dermoid cysts, cellulitis, lymphangioma and the more serious rhabdomyosarcoma and neuroblastoma. A careful elicitation of history, physical examination, and appropriate orbital imaging (ultrasound for superficial ones and magnetic resonance imaging/angiography for deep-seated lesions) helps in the diagnosis. This is a brief report of a very large vascular lesion involving the lower lid with very atypical clinical features. The approach to diagnosis and successful treatment and the histological features are discussed.

Twenty year review of histopathological findings in enucleated/eviscerated eyes.

BACKGROUND/AIMS: To evaluate the need for routine histopathological analysis of enucleated/eviscerated eyes and changes in indications for eye removal. METHODS: Retrospective review of all enucleation/evisceration histopathology reports over 20 years. Clinical history was correlated with pathological findings. Two 10 year periods (1984-93, 1994-2003) were compared to detect changes in indications for eye removal. RESULTS: In total, 285 histopathology results were traced from 1984 to 2003; 161 and 124 were evisceration and enucleation specimens, respectively. Glaucoma, malignant melanoma, trauma, and retinal detachment were the most frequent diagnoses 1984-1993. Ocular trauma was the most frequent diagnosis 1994-2003, followed by phthisis bulbi and endophthalmitis. Three cases were diagnosed as metastatic carcinoma; all were suspected preoperatively. A fourth case was a diagnostic surprise: adenocarcinoma found in an eye removed for pain and phthisis. Comparison of two 10 year periods showed a decrease in the number of enucleations/eviscerations, perhaps reflecting a decrease in the number of specimens sent. A preference for eviscerations was evident over the 20 years. CONCLUSION: The number of eyes removed and histologically analysed decreased in the period 1994 to 2003, perhaps because of better treatment options, allowing globe preservation. There was a significant shift in the diagnosis in the two time periods, and a preference for evisceration in both. Only one diagnostic surprise was discovered (0.35%). This study does not support the need to send all globes/contents for histopathological examination. However, because of the one unexpected finding, it is recommended where the examination is incomplete or the history of visual loss is unclear.

Biological functions of the cytoplasmic TGBp1 inclusions of bamboo mosaic potexvirus.

The TGBp1 protein encoded by the first open reading frame of the triple-gene-block (TGB) of bamboo mosaic potexvirus (BaMV) plays important roles in virus movement; one of them is to shape the viral RNA before its being transported from cell to cell. However, TGBp1 mainly forms cytoplasmic inclusions which are devoid of the RNA-binding activity. With the purified TGBp1 inclusions of BaMV, we analyzed the possibility of dissociation of functional TGBp1 from the inclusions. Our data showed that the cytoplasmic inclusions were able to dissociate continuously functional TGBp1, which possessed ATP-binding, ATPase, and RNA-binding activities. Moreover, the dissociation of TGBp1 was significantly enhanced by the presence of viral RNA and capsid protein (CP), consistent with the finding that TGBp1 are able to form ribonucleoprotein complex with viral RNA and CP. Taken together, these results support the idea that the cytoplasmic TGBp1 inclusions are active pools of TGBp1, upon which viral RNA can be shaped into a transferable form.

Effects of lentinan on broiler splenocyte proliferation, interleukin-2 production, and signal transduction.

Lentinan (LEN) is an intensively studied beta-glucan that has been shown to have immunostimulating and antitumor functions. However, it currently is not used in veterinary practice and animal production. This study was conducted to investigate the impacts of LEN on broiler splenocyte proliferation, interleukin-2 (IL-2) production, and to explore its effects on receptor signal transduction by determining signaling molecules, including nitric oxide (NO), cytosolic-free Ca2+, cytosolic cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP). The results showed that compared to the control all three measured doses, including 40, 80, and 160 microg/mL LEN, increased splenocyte proliferation and IL-2 production (P < 0.05). Lentinan increased splenocyte NO production and cytosolic-free calcium concentration in a dose-dependent manner (P < 0.001). After incubating splenocytes for 20 min, LEN increased intracellular cAMP and cGMP concentrations at a dose of 80 and 160 microg/mL, respectively. However, after incubating the splenocytes for 60 min, LEN had no effect on cytosolic cAMP and cGMP concentration irrespective of the LEN dosage. Those results indicated that LEN had immunostimulatory effects on splenocytes by increasing splenocyte proliferation and IL-2 production and by activating splenocyte receptor signal transduction.

Effects of Chinese herbal polysaccharides on the immunity and growth performance of young broilers.

Two trials were conducted to study the effects of two Chinese herbal polysaccharides [achyranthan (ACH), a low-molecular-weight polysaccharide, and astragalan (APS), a high-molecular-weight polysaccaride] on the immunity and growth performance of young broilers. Trial 1 was a 28-d growth assay, in which 7-d-old broilers (n = 240) were randomly allotted to one of three dietary treatments, with eight replicate pens per treatment and ten chickens per pen. Dietary treatments included a control corn-soy-fishmeal (Treatment 1), a diet with 200 mg/kg APS (Treatment 2), and a diet with 200 mg/kg ACH (Treatment 3). Blood samples were collected by cardiac puncture on Days 7, 14, 21, and 28 for determination of serum parameters, and chickens were killed on Day 28 to measure immune organ indexes. Trial 2 was an in vitro trial to study the effects of different concentrations of polysaccharides on broiler splenocyte functions. In Trial 1, feeding either APS or ACH had no significant effects on growth performance of broilers relative to the control. However, compared to the control, feeding ACH significantly increased microhemagglutination inhibition (HI) antibody titers, bursa of Fabricius index, serum albumin, serum calcium, and nitric oxide (NO) concentrations at Day 28 (P < or = 0.05). In Trial 2, both polysaccharides showed significant immunostimulating effects. They increased NO and interleukin-2 (IL-2) production of splenocytes and enhanced splenocyte proliferation in a dose-dependent manner (P < 0.05). Those results indicate that the immunostimulating effects of APS are not as pronounced as those of ACH. Achyranthan showed immunostimulating effects in both the growth assay and in vitro studies. Therefore, ACH may be a Chinese herbal polysaccharide that has the potential to be used as a feed additive to improve broilers' immunity.