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Nonalcoholic steatohepatitis (NASH) is characterized by hepatocyte injury and inflammatory cell infiltration, which has been linked to peripheral insulin resistance and increased levels of triglycerides in the liver. The purposes of this study were to establish a mouse model of NASH by feeding mice a 60% high-fat diet (HFD) and to demonstrate the anti-fibrotic effects of oleuropein, which has been shown to have anti-oxidant and anti-inflammatory properties, in this HFD-induced mouse model of NASH. C57BL/6 mice were divided into three groups: a regular diet group (Chow), a HFD group and an oleuropein-supplemented HFD group (OSD), which was fed a 0.05% OSD for 6 months. The effects of oleuropein in this model were evaluated using biochemical, histological and molecular markers. The expression levels of alpha-smooth muscle actin (α-SMA)and collagen type I in the HFD and OSD groups were evaluated using real-time PCR and western blotting. The body weight, biochemical marker levels, nonalcoholic fatty liver disease activity score, homeostasis model of assessment-insulin resistance (HOMA-IR) and leptin levels observed in the HFD group at 9 and 12 months were higher than those observed in the Chow group. The HOMA-IR and leptin levels in the OSD group were decreased compared with the HFD group. In addition, α-SMA and collagen type I expression were decreased by oleuropein treatment. We established a NASH model induced by HFD and demonstrated that this model exhibits the histopathological features of NASH progressing to fibrosis. Our results suggest that oleuropein may be pharmacologically useful in preventing the progression of steatohepatitis and fibrosis and may be a promising agent for the treatment of NASH in humans.

Patients with recent pandemic coronavirus disease 19 (COVID-19) complain of neurological abnormalities in sensory functions such as smell and taste in the early stages of infection. Determining the cellular and molecular mechanism of sensory impairment is critical to understand the pathogenesis of clinical manifestations, as well as in setting therapeutic targets for sequelae and recurrence. The absence of studies utilizing proper models of human peripheral nerve hampers an understanding of COVID-19 pathogenesis. Here, we report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly infects human peripheral sensory neurons, leading to molecular pathogenesis for chemosensory impairments. An in vitro system utilizing human embryonic stem cell (hESC)-derived peripheral neurons was used to model the cellular and molecular pathologies responsible for symptoms that most COVID-19 patients experience early in infection or may develop as sequelae. Peripheral neurons differentiated from hESCs expressed viral entry factor ACE2, and were directly infected with SARS-CoV-2 via ACE2. Human peripheral neurons infected with SARS-CoV-2 exhibited impaired molecular features of chemosensory function associated with abnormalities in sensory neurons of the olfactory or gustatory organs. Our results provide new insights into the pathogenesis of chemosensory dysfunction in patients with COVID-19.

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The recent emergence of Staphylococcus schleiferi in dogs with otitis externa or skin and soft tissue infections has become a significant zoonotic issues. In the current study, we investigated 1) the carriage rates of S. schleiferi among major staphylococci in healthy dogs and dogs with otitis externa, 2) antibiotic susceptibility profiles of S. schleiferi, particularly methicillin resistance (MR), and 3) virulence factors associated with skin and soft tissue infections such as ability to form biofilm, resistance to cationic antimicrobial peptides (CAMPs), and carriage of staphylococcal enterotoxin genes. Among the 21 S. schleiferi isolates, 5 isolates (24%) were determined to be methicillin-resistant (MRSS). Staphylococcal cassette chromosome mec (SCC mec ) typing revealed the presence of SCC mec type V in 4 MRSS isolates and type VII in one MRSS. Higher levels of antibiotic resistance, especially multidrug resistance, were observed in MRSS isolates compared to the methicillin-susceptible S. schleiferi (MSSS) isolates. In addition, MRSS isolates exhibited enhanced ability to form biofilm under static condition and all the 5 MRSS isolates carried three or more enterotoxin genes. However, there were no significant differences in resistance to CAMPs between MRSS and MSSS isolates. These findings suggest that coagulase-negative S. schleiferi is becoming more prevalent in canine otitis externa cases. Our results also highlight the presence of multidrug-resistant MRSS isolates with enhanced biofilm production and carriage of multiple enterotoxins.