Background CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor whose high expression in human cancers is associated with tumour aggressiveness and poor outcomes. Most advanced cancer patients will develop cachexia, characterized by loss of skeletal muscle mass. In response to secreted factors from cachexia-inducing tumours, C/EBPβ is stimulated in muscle, leading to both myofibre atrophy and the inhibition of muscle regeneration. Involved in the regulation of immune responses, C/EBPβ induces the expression of many secreted factors, including cytokines. Because tumour-secreted factors drive cachexia and aggressive tumours have higher expression of C/EBPβ, we examined a potential role for C/EBPβ in the expression of tumour-derived cachexia-inducing factors. Methods We used gain-of-function and loss-of-function approaches in vitro and in vivo to evaluate the role of tumour C/EBPβ expression on the secretion of cachexia-inducing factors. ResultsWe report that C/EBPβ overexpression up-regulates the expression of 260 secreted protein genes, resulting in a secretome that inhibits myogenic differentiation (À31%, P < 0.05) and myotube maturation [À38% (fusion index) and À25% (myotube diameter), P < 0.05]. We find that knockdown of C/EBPβ in cachexia-inducing Lewis lung carcinoma cells restores myogenic differentiation (+25%, P < 0.0001) and myotube diameter (+90%, P < 0.0001) in conditioned medium experiments and, in vivo, prevents muscle wasting (À51% for small myofibres vs. controls, P < 0.01; +140% for large myofibres, P < 0.01). Conversely, overexpression of C/EBPβ in non-cachectic tumours converts their secretome into a cachexia-inducing one, resulting in reduced myotube diameter (À41%, P < 0.0001, EL4 model) and inhibition of differentiation in culture (À26%, P < 0.01, EL4 model) and muscle wasting in vivo (+98% small fibres, P < 0.001; À76% large fibres, P < 0.001). Comparison of the differently expressed transcripts coding for secreted proteins in C/EBPβ-overexpressing myoblasts with the secretome from 27 different types of human cancers revealed ~18% similarity between C/EBPβ-regulated secreted proteins and those secreted by highly cachectic tumours (brain, pancreatic, and stomach cancers). At the protein level, we identified 16 novel secreted factors that are present in human cancer secretomes and are up-regulated by C/EBPβ. Of these, we tested the effect of three factors (SERPINF1, TNFRSF11B, and CD93) on myotubes and found that all had atrophic potential (À33 to À36% for myotube diameter, P < 0.01). Conclusions We find that C/EBPβ is necessary and sufficient to induce the secretion of cachexia-inducing factors by cancer cells and loss of C/EBPβ in tumours attenuates muscle atrophy in an animal model of cancer cachexia. Our findings establish C/EBPβ as a central regulator of cancer cachexia and an important therapeutic target.

Satellite cells are required for muscle regeneration, remodeling, and repair through their activation, proliferation, and differentiation; however, how dietary factors regulate this process remains poorly understood. The L-Type amino acid transporter 1 (LAT1) transports amino acids, such as leucine, into mature myofibers, which then stimulates protein synthesis and anabolic signaling. However, whether LAT1 is expressed on myoblasts and is involved in regulating myogenesis is unknown. The aim of this study was to characterize the expression and functional relevance of LAT1 during different stages of myogenesis and in response to growth and atrophic conditions in vitro. We determined that LAT1 is expressed by C2C12 and human primary myoblasts, and its gene expression is lower during differentiation (p<0.05). Pharmacological inhibition and genetic knockdown of LAT1 impaired myoblast viability, differentiation, and fusion (all p<0.05). LAT1 protein content in C2C12 myoblasts was not significantly altered in response to different leucine concentrations in cell culture media or in two in vitro atrophy models. However, LAT1 content was decreased in myotubes under atrophic conditions in vitro (p<0.05). These findings indicate that LAT1 is stable throughout myogenesis and in response to several in vitro conditions that induce muscle remodeling. Further, amino acid transport through LAT1 is required for normal myogenesis in vitro.

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Human infection by Helicobacter pylori is a great public health hazard because they colonize the stomach of approximately half world’s population. The current work tries to detect and assess the association between salty foods and the prevalence of H. Pylori in Benghazi outpatients who attending Benghazi Medical Centre. It is retrospective cohort study on 293 patients in Benghazi Medical Center Gastroenterological Unit. The study includes all adult patients, a confirmed H. Pylori immunity test, a body weight records, and twenty four dietary recalls. Exclusion criteria; this work does not involve study of peptic ulcer and or any other gastric diseases. (69.7%) of the subjects prefer eating salty foods. (72.2%) of the subjects prefer pickled foods; and (83%) of the subjects prefer canning foods. Age, sex, body mass index, nutritional supplement intake were the variables associated with high salt intake among H. pylori patients. All patients in Benghazi Medical Center should be routinely screened for H. Pylori due to their health and financial consequences. Early nutritional intervention strategies including nutrition education should be implemented with an appropriate follow up.

Administration of an anti-inflammatory steroidal drug-Prednisolone-(0.85 mg/kg body weight, daily for 10 days) to adult toads Bufo tibamicus resulted in suppression of the function of the adrenal gland, as shown by a significant increase in the lipid droplets, autolysis of mitochondria and disorganization and degranulation of rER in the steriodogenic cells. Furthermore, chromaffin cells (catecholamines secreting cells), showed a marked decrease in the number of chromaffin granules and degenerative changes in the nuclei. These serious side effects should be taken into consideration when using this drug.