Previous studies from our own and other labs reported the surprising finding that the soluble V domain of the herpes simplex virus type 1 (HSV-1) entry receptor nectin-1 can both block HSV infection of receptor-bearing cells and mediate infection of receptor-deficient cells. Here we show that this property is not unique to nectin-1. We generated a pair of truncated, soluble forms of the other major HSV-1 entry receptor, herpes virus entry mediator (HVEM or HveA), and examined its effects on HSV-1 infection of receptor-deficient cells.

A nephropathogenic K2/01 strain of infectious bronchitis virus (IBV) was attenuated by 170 serial passages in embryonated chicken eggs for possible use as a future IBV vaccine strain. High-growth properties and narrow tissue tropisms (limited replication in respiratory tracts) were achieved by the adaptation process. Unlike the parent strain, the attenuated strain (K2p170) was safe in day-old specific-pathogen-free chicks since replication of the virus did not induce mortality and nephritis, and rarely induced histological changes in the trachea and kidney after intraocular administration. In day-old broilers, even though coarse spray administration of K2p170 induced clinical signs, ciliostasis, and histopathological lesions in the trachea and the kidney, they were all comparable to birds vaccinated with commercial H120 vaccine. Despite restriction of viral replication in the respiratory tract, K2p170 elicited the production of antiserum with a neutralization index of 4.5. K2p170 provided almost complete protection against both two distinct subgroups of Korean nephropathogenic strain (KM91-like and QX-like subgroup). Furthermore, K2p170 provided significantly greater cross-protection against two heterologous strains (Massachusetts and Korean respiratory strain) than those conferred by the commercial H120 vaccine. K2p170 also had no virulence reversion after five back passages in chickens. In conclusion, K2p170 exhibits a fine balance between attenuation and immunogenicity, possesses cross-protective efficacy, and merits further investigation as a potential live vaccine as an alternative means of protection against the recently emergent nephropathogenic IBV infection in many Eurasian countries.

Lung cancer is one of the deadliest malignant tumors with limited treatment options. Although targeted therapy, using tyrosine-kinase inhibitors such as erlotinib (Erlo), has shown therapeutic benefit, only 15 % patients with mutated epidermal growth factor receptor (EGFR) in lung cancer cells are sensitive. Therefore, additional therapeutic strategy should be developed. In this study, we found that metformin (Met), which is widely used for the treatment of type 2 diabetes (T2D), sensitized lung cancer cells bearing wild-type EGFR to Erlo treatment by enriching cancer cells expressing higher levels of EGFR with persistent phosphorylation. As a consequence, combination of Met and Erlo more efficiently inhibited the growth of lung cancer cells both in vitro and in mice with xenografted tumors. Our results suggest a novel approach to treating lung cancer cases which are originally resistant to Erlo.

Coffee has been shown to attenuate sarcopenia, the age-associated muscle atrophy. Myostatin (MSTN), a member of the TGF-β growth/differentiation factor superfamily, is a potent negative regulator of skeletal muscle mass, and MSTN-inhibition increases muscle mass or prevents muscle atrophy. This study, thus, investigated the presence of MSTN-inhibitory capacity in coffee extracts. The ethanol-extract of coffee silverskin (CSE) but not other extracts demonstrated anti-MSTN activity in a pGL3-(CAGA)12-luciferase reporter gene assay. CSE also blocked Smad3 phosphorylation induced by MSTN but not by GDF11 or Activin A in Western blot analysis, demonstrating its capacity to block the binding of MSTN to its receptor. Oral administration of CSE significantly increased forelimb muscle mass and grip strength in mice. Using solvent partitioning, solid-phase chromatography, and reverse-phase HPLC, two peaks having MSTN-inhibitory capacity were purified from CSE. The two peaks were identified as βN-arachinoyl-5-hydroxytryptamide (C20-5HT) and βN-behenoyl-5-hydroxytryptamide (C22-5HT) using mass spectrometry and NMR analysis. In summary, the results show that CSE has the MSTN-inhibitory capacity, and C20-5HT and C22-5HT are active components of CSE-suppressing MSTN activity, suggesting the potential of CSE, C20-5HT, and C22-5HT being developed as agents to combat muscle atrophy and metabolic syndrome.

Bioactive glass-ceramic (BGC) cage is a substitute for polyether ether ketone (PEEK) cages in anterior cervical discectomy and fusion (ACDF). Only a few comparative studies exist using PEEK and non-window-type BGC cages (CaO-SiO2-P2O5-B2O3) in single-level ACDF. This study compared PEEK cages filled with autologous iliac bone grafts and BGC cages regarding clinical safety and effectiveness. A retrospective case series was performed on 40 patients who underwent single-level ACDF between October 2020 and July 2021 by a single orthopedic spine surgeon. The spacers used in each ACDF were a PEEK cage with a void filled with an autologous iliac bone graft and a non-window-type BGC cage in 20 cases. The grafts were compared pre-operatively and post-operatively at 6 weeks and 3, 6, and 12 months. Post-operative complications were investigated in each group. Clinical outcome was measured, including Visual Analog Scale (VAS) scores of neck and arm pains, Japanese Orthopedic Association score (JOA), and Neck Disability Index (NDI). Dynamic lateral radiographs were used to assess the inter-spinous motion (ISM) between the fusion segment and subsidence. The fusion status was evaluated using a computed tomography (CT) scan. Overall, 39 patients (19 and 20 patients in the PEEK and BGC groups, respectively) were recruited. Eighteen (94.7%) and 19 (95.0%) patients in the PEEK and BGC groups, respectively, were fused 12 months post-operatively, as assessed by ISM in dynamic lateral radiograph and bone bridging formation proven in CT scan. The PEEK and BGC groups showed substantial improvement in neck and arm VAS, JOA, and NDI scores. No substantial difference was found in clinical and radiological outcomes between the PEEK and BGC groups. However, the operation time was considerably shorter in the BGC group than in the PEEK group. In conclusion, a non-window-type BCG cage is a feasible substitute for a PEEK cage with an autologous iliac bone graft in single-level ACDF.