Neuropeptide hormone oxytocin has roles in social bonding, energy metabolism, and wound healing contributing to good physical, mental and social health. It was previously shown that feeding of a human commensal microbe Lactobacillus reuteri (L. reuteri) is sufficient to up-regulate endogenous oxytocin levels and improve wound healing capacity in mice. Here we show that oral L. reuteri-induced skin wound repair benefits extend to human subjects. Further, dietary supplementation with a sterile lysate of this microbe alone is sufficient to boost systemic oxytocin levels and improve wound repair capacity. Oxytocin-producing cells were found to be increased in the caudal paraventricular nucleus [PVN] of the hypothalamus after feeding of a sterile lysed preparation of L. reuteri, coincident with lowered blood levels of stress hormone corticosterone and more rapid epidermal closure, in mouse models. We conclude that microbe viability is not essential for regulating host oxytocin levels. The results suggest that a peptide or metabolite produced by bacteria may modulate host oxytocin secretion for potential public or personalized health goals.

1. The study aimed to investigate the effect of lysolecithin supplementation in low-energy diets on growth, nutrient digestibility and intestinal mucosa characteristics of broilers. 2. A total of 800 one-d-old Ross 308 broiler chickens were assigned to 4 dietary treatments consisting of 10 replicates of 20 broilers each. Broilers were fed with 4 different diets: (i) HE: positive control group broilers received a diet with unaltered energy; (ii) LE: negative control group broilers received a diet with lower energy of about 0.27 MJ/kg; (iii) LElys500: broilers received a diet similar to LE supplemented with 500 g/tn lysolecithin product (Lysoforte Booster Dry); and (iv) LElys300: broilers received a diet similar to LE supplemented with 300 g/tn lysolecithin product. The experimental period was 42 d. 3. Body weight gain in treatments HE was higher than LE during the overall experimental period, while LElys500 and LElys300 had intermediate values. Feed conversion ratio was lower in HE and LElys500 than LE group, while the LElys300 had intermediate values. Fat digestibility was improved in both LElys 500 and LElys300 compared to the HE group. Apparent metabolisable energy (AMEn) was higher in HE, LElys500 and LElys300 than LE. Ileum viscosity at 42 d was also affected, being higher in LE group compared to HE. At 28 d mucosal thickness was lower both in LElys500 and LElys300 compared to HE and LE, while no difference occurred between treatment proliferation patterns of duodenal epithelial cells. 4. These findings indicated that lysolecithin supplementation at 500 g/tn of feed in low-energy diets maintained broiler performance. Supplementation of reformulated low-energy diets induced an increase in digesta viscosity. Lysolecithin supplementation resulted in variable alterations in the duodenum mucosal morphology.

Background: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection and aggressive intervention. Based on the knowledge that hepatocarcinogenesis is significantly influenced by histone acetylation, we directed our search for novel HCC therapeutics among histone deacetylation inhibitors (HDACi). The aim of the present study was to investigate the effect of HDAC1/2 inhibitor Romidepsin in the well-established mouse model of diethylnitrosamine (DEN)-induced HCC. Materials and Methods: C56BL/6 mice were treated with Romidepsin at the critical point of 10 months after DEN challenge and their livers were examined 2 months later using histopathology and morphometry. Protein levels were assessed in serum using ELISA and in liver tissues using Western blot and immunohistochemistry (in-situ detection). Gene expression was quantified using real-time PCR. Results: Romidepsin suppressed cancer progression. This effect was associated with decreased proliferation and increased apoptosis of cancer cells. The cell cycle regulator CK2a, the anti-inflammatory molecule PPAR-γ, and the tumor suppressors PTEN and CYLD were upregulated in treated HCC. By contrast, the expression of PI3K, NF-κB p65 and c-Jun was reduced. In line with this result, the levels of two major apoptosis regulators, ie, BAD and the multifunctional protein c-Met, were lower in the blood serum of treated mice compared to the untreated mice with HCC. Conclusion: These findings suggest that Romidepsin, a drug currently used in the treatment of lymphoma, could also be considered in the management of early-stage HCC.

Objectives To summarise the clinical presentation and outcomes in a series of miniature schnauzers diagnosed with histiocytic sarcoma. Materials and Methods Retrospective review of medical records of miniature schnauzers diagnosed with histiocytic sarcoma between 2008 and 2019 at two referral centres in the UK. Signalment, clinical signs at initial presentation, imaging results and clinico‐ and histopathological findings, treatment type and outcome were recorded. Progression‐free survival and overall survival time were calculated. Results Thirty dogs were included. Twenty‐four of 29 dogs undergoing imaging of the thorax had lung and/or mediastinal involvement. The median overall survival time for dogs that were not euthanased within 3 days of diagnosis was 117 days (range 10 to 790). Three dogs underwent surgery; 13 received treatment with lomustine as a sole therapy ‐ with partial responses documented on imaging in five of six dogs and 11 of 13 showing clinical improvement. Clinical Significance Histiocytic sarcoma should be considered as a differential diagnosis for miniature schnauzers with pulmonary masses. Although responses to treatment were common, they were usually short‐lived because of the aggressive nature of the disease.

Abstract. Recent evidence has suggested that downregulation of the Wnt/β-catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti-HCC. Thus, the present study sought to examine the effects of Wnt-1 blockade using the classical diethylnitrosamine (DEN)-induced chemical carcinogenesis mouse model of HCC. The depletion of Wnt-1 using neutralizing antisera was done for ten consecutive days at the age of 9 months and mice were examined for the following 20 days. At that time, DEN-treated mice had multiple variably-sized hepatic cell adenomas. Anti-Wnt-1 was particularly potent in suppressing the expression of critical elements of the Wnt/β-catenin signaling pathway, such as β-catenin and Frizzled-1 receptor, however, not Dickkopf-related protein 1. This effect co-existed with the suppression of Cyclin D1, FOXM1, NF-κΒ and c-Jun commensurate with proliferation and apoptosis blockade in hepatocellular adenomas, and reduced Bcl-2 and c-Met in the serum of mice. Nonetheless, tumor size and multiplicity were found to be unaffected, suggesting that apoptosis may be equally important to proliferation in the context of counteracting DEN induced hepatocellular adenomas of mice.

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Downregulation of the cylindromatosis (CYLD) tumor suppressor has been associated with breast cancer development and progression. Here, we report a critical role for CYLD in maintaining the phenotype of mammary epithelial cells in vitro and in vivo. CYLD downregulation or inactivation induced an epithelial to mesenchymal transition of mammary epithelial cells that was dependent on the concomitant activation of the transcription factors Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) and transforming growth factor beta (TGFβ)signaling. CYLD inactivation enhanced the nuclear localization of YAP/TAZ and the phosphorylation of Small Mothers Against Decapentaplegic (SMAD)2/3 proteins in confluent cell culture conditions. Consistent with these findings were the hyperplastic alterations of CYLD-deficient mouse mammary epithelia, which were associated with enhanced nuclear expression of the YAP/TAZ transcription factors. Furthermore, in human breast cancer samples, downregulation of CYLD expression correlates with enhanced YAP/TAZ-regulated target gene expression. Our results identify CYLD as a critical regulator of a signaling node that prevents the coordinated activation of YAP/TAZ and the TGFβ pathway in mammary epithelial cells, in order to maintain their phenotypic identity and homeostasis. Consequently, they provide a novel conceptual framework that supports and explains a causal implication of deficient CYLD expression in aggressive human breast cancers.

Background: To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice.Methods: Thirty mice C56Bl6 were randomly divided into Group A or control, Group B animals who underwent experimental hepatocarcinogenesis with diethylnitrosamine (DEN), and Group C animals with DEN-induced hepatocarcinogenenesis that treated with pan-aurora kinase inhibitor Danusertib. Primary antibodies for immunochistochemistry (IHC) included rabbit antibodies against Ki-67, DKK1, INCENP, cleaved caspase-3, NF-κB p65, c-Jun, β-catenin. Hepatocyte growth factor receptor (C-MET/HGFR) and Bcl-2 antagonist of cell death (BAD) serum levels were determined using a quantitative sandwich enzyme immunoassay technique.Results: Inhibition of AURK reduced the number of DEN-induced liver tumours. Apoptosis and proliferation was very low in both DEN-induced and anti- AURK groups respectively. The hepatocellular adenoma cells of DEN-treated mice uniformly had ample nuclear INCENP whereas in anti- AURK markedly decreased. Expression of β-catenin, NF-kB and c-Jun did not differ in liver tumors of both AURK -depleted and non-depleted mice.Conclusions: Depletion of AURK reduced the number of DEN-induced hepatic tumours. However, their size did not differ significantly between the groups.