Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease (almost 25% of the general population). Autoimmune hepatitis (AIH) is a relatively rare liver disease of unknown aetiology characterized by female predominance and large heterogeneity regarding epidemiology, clinical manifestations, genetics, serology and liver pathology. The potential NAFLD/AIH coincidence or an AIH diagnosis alone instead of NAFLD represent a challenge for clinicians, both in making a correct and timely diagnosis but also in the management of these diseases. The diagnosis of both diseases can be challenging as (a) reliable laboratory tests to confidently diagnose or exclude NAFLD or AIH are missing; (b) physicians and pathologists are much more familiar with a very common disease like NAFLD so, they do not consider an alternative or additional diagnosis; (c) most NAFLD studies do not investigate the patients for all autoantibodies involved in AIH diagnosis, apply the diagnostic scoring systems for AIH or address the possibility of AIH features on liver histology and (d) the recent European and American practice guidelines for NAFLD do not mention clearly the importance of IgG determination and liver autoimmune serology according to the AIH guidelines. Patients with NAFLD/AIH coincidence have significantly more frequently hypertension, diabetes, obesity, older age, lower transaminases, bilirubin and simplified score for AIH diagnosis but no female predominance compared to AIH patients only. The true outcome of NAFLD/AIH patients is practically unknown while their management is quite problematic because official clinical practice guidelines for this condition are missing. BACKGROUND Piper nigrum L. (Piperaceae) is commonly used as a spice and traditional medicine in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. SB431542 order However, the protective role of P. nigrum on epithelial function of upper respiratory tract injury in an allergic rhinitis (AR) mouse model has been unclear. This study aims to investigate the effects of P. nigrum fruit extract (PNE) on the nasal epithelial barrier function of the upper respiratory tract in an ovalbumin (OVA)-induced AR model. METHODS AR mouse model was established by intraperitoneal injection with 200 µL saline containing 50 µg OVA adsorbed to 1 mg aluminum hydroxide, and intranasal challenge with 20 µL per nostril of 1 mg/ml OVA. Besides, mice were orally administrated once daily with PNE and dexamethasone (Dex) in 13 days. The nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokines, nasal histopathology, and immunohistochemistflammation enzyme HO-1. CONCLUSIONS These obtained results suggest that PNE has a promising strategy for epithelial barrier stabilization in allergic rhinitis treatment. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neuroprotective factor produced in response to endoplasmic reticulum (ER) stress induced by various stressors, but its involvement in the radioresistance of tumor cells is unknown. Here, we found that MANF is released after γ-irradiation (2 Gy and 4 Gy) of B16 melanoma cells, and its release was suppressed by 4-phenylbutyric acid, an ER stress inhibitor. MANF was not released after low-dose (1 Gy) γ-irradiation, but pretreatment of 1 Gy-irradiated cells with recombinant MANF enhanced the cellular DNA damage response and attenuated reproductive cell death. In MANF-knockdown cells, the DNA damage response and p53 activation by γ-irradiation (2 Gy) were suppressed, and reproductive cell death was increased. MANF also activated the ERK signaling pathway. Our findings raise the possibility that MANF could be a new target for overcoming radioresistance. S-Nitrosylation of protein cysteine thiol is a post-translational modification mediated by nitric oxide (NO). The overproduction of NO causes nitrosative stress, which is known to induce endoplasmic reticulum (ER) stress. We previously reported that S-nitrosylation of protein disulfide isomerase (PDI) and the ER stress sensor inositol-requiring enzyme 1 (IRE1) decreases their enzymatic activities. However, it remains unclear whether nitrosative stress affects ER-associated degradation (ERAD), a separate ER stress regulatory system responsible for the degradation of substrates via the ubiquitin-proteasomal pathway. In the present study, we found that the ubiquitination of a known ERAD substrate, serine/threonine-protein kinase 1 (SGK1), is attenuated by nitrosative stress. C-terminus of Hsc70-interacting protein (CHIP) together with ubiquitin-conjugating enzyme E2 D1 (UBE2D1) are involved in this modification. We detected that UBE2D1 is S-nitrosylated at its active site, Cys85 by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, in vitro and cell-based experiments revealed that S-nitrosylated UBE2D1 has decreased ubiquitin-conjugating activity. Our results suggested that nitrosative stress interferes with ERAD, leading to prolongation of ER stress by co-disruption of various pathways, including the molecular chaperone and ER stress sensor pathways. Given that nitrosative stress and ER stress are upregulated in the brains of patient with Parkinson’s disease (PD) and of those with Alzheimer’s disease (AD), our findings may provide further insights into the pathogenesis of these neurodegenerative disorders. Ectopic implantation of donor testis cell aggregates in recipient mice results in de novo formation or regeneration of testis tissue and, as such, provides a unique invivo model for the study of testis development. However, currently the results are inconsistent and the efficiency of the model remains low. This study was designed to (1) examine several factors that can potentially improve the consistency and efficiency of this model and (2) explore the use of ultrasound biomicroscopy (UBM) for the non-invasive invivo evaluation of implants. Testis cell aggregates, containing ~40% gonocytes, from 1-week-old donor piglets were implanted under the back skin of immunodeficient mice through skin incisions using gel matrices or through subcutaneous injection without using gel matrices. The addition of gel matrices led to inconsistent tissue development; gelatin had the greatest development, followed by collagen, whereas agarose resulted in poor development. The results also depended on the implanted cell numbers since implants with 100×106 cells were larger than those with 50×106 cells.