Short bowel syndrome (SBS) is a particularly serious condition in which the small intestine does not absorb sufficient nutrients for biological needs, resulting in severe illness and potentially death if not treated. Given the important role of the gut in many signaling cascades throughout the body, SBS results in disruption of many pathways and imbalances in various hormones. Due to the inability to meet sufficient nutritional needs, an intravenous form of nutrition, total parental nutrition (TPN), is administered. However, TPN presents difficulties such as severe liver injury and altered signaling secondary to the continued lack of luminal contents. This manuscript aims to summarize relevant studies into the systemic effects of TPN on systems such as the gut–brain, gut-lung, and gut-liver axis, as well as present novel therapeutics currently under use or investigation as mitigation strategies for TPN induced injury.

Background Parenteral nutrition (PN) remains a critical therapeutic option in patients who cannot tolerate enteral feeding. However, although lifesaving, PN is associated with significant side effects, including liver injury, the etiology of which is multifactorial. Carbamazepine (CBZ), an antiepileptic medication, is known to modulate hepatic fibrosis and hepatocellular injury in a variety of liver diseases. We hypothesized that CBZ could prevent PN‐associated liver disease (PNALD), which we tested by using our novel ambulatory PN piglet model. Methods Piglets were fitted with jugular catheters and infusion pumps for PN and randomized to enteral nutrition (n = 7), PN (n = 6), or PN with parenteral CBZ (n = 6) for 2 weeks. Serum and liver tissue were analyzed via light microscopy, quantification of serum liver injury markers, Ki67 and cytokeratin‐7 indexing, and real‐time quantitative polymerase chain reaction. Results PN‐fed piglets in our model developed manifestations of PNALD—particularly, increased serum bilirubin, gamma‐glutamyltransferase, liver cholestasis, and Ki67 expression compared with that of EN‐fed animals (P < 0.03). CBZ therapy in PN‐fed animals led to a significant reduction in these markers of injury (P < 0.05). Investigation into the mechanism of these therapeutic effects revealed increased expression of sterol regulatory element‐binding protein 1 (SREBP‐1), peroxisome proliferator‐activated receptor alpha (PPAR‐α), and fatty acid binding protein (FABP) in PN‐fed animals receiving CBZ (P < 0.03). Further investigation revealed increased LC3 expression and decreased lysosomal‐associated membrane protein (LAMP1) expression with CBZ (P < 0.03). Conclusion CBZ administration mitigates PNALD severity, suggesting a novel therapeutic strategy targeting PN‐associated side effects, and may present a paradigm change to current treatment options.

In 2020, the Department of Energy established the National Virtual Biotechnology Laboratory (NVBL) to address key challenges associated with COVID-19. As part of that effort, Pacific Northwest National Laboratory (PNNL) established a capability to collect and analyze specimens from employees who self-reported symptoms consistent with the disease. During the spring and fall of 2021, 688 specimens were screened for SARS-CoV-2, with 64 (9.3%) testing positive using reverse-transcriptase quantitative PCR (RT-qPCR). Of these, 36 samples were released for research. All 36 positive samples released for research were sequenced and genotyped. Here, the relationship between patient age and viral load as measured by Ct values was measured and determined to be only weakly significant. Consensus sequences for each sample were placed into a global phylogeny and transmission dynamics were investigated, revealing that the closest relative for many samples was from outside of Washington state, indicating mixing of viral pools within geographic regions.

mTOR is an established anabolic signaling that leads to skeletal muscle hypertrophy when activated. Hippo signaling is an emerging pathway that involves the muscle size change in response to resistance-type exercise. However, whether the Hippo signaling response differs in muscle-wasting conditions is unknown. PURPOSE: The purpose of this study was to determine whether repeated muscle contractions would induce different Hippo signaling responses in cachectic mice. METHODS: Male ApcMin/+ (Min, n=5) mice and age-matched Wild-type (WT, n=5) mice were used. A single bout of high-frequency electric stimulations (HFES, ten sets of six repetitions, ~18 min) was applied to both groups' tibialis anterior (TA) muscles. This intervention caused eccentric contraction on the left TA muscle, while the right TA muscle served as internal control. Both TA muscles were exercised and snap-frozen in the liquid nitrogen for further analysis after 30 min following the HFES. Routine western blotting was performed using approximately 60~120 µg of the total protein. Body and muscle weights were analyzed by a Student's t-test. Western blot data were analyzed by a two-way ANOVA with repeated measures (genotype x HFES). Post-hoc analyses were performed with the Bonferroni test when appropriate. RESULTS: Min mice lost approximately 17.6% of body weight (BW) than their peak BW at HFES, confirming that the Min mice had developed a cachectic condition. Min mice had a smaller TA weight than WT mice regardless of HFES (52.4±1.0 mg vs. 35.1±1.9 mg, p<0.01). Western blot analysis showed that HFES increased the phosphorylated state of p70S6K regardless of genotype (p<0.01). However, the p70S6K response to HFES was higher in WT mice than Min mice (2.5 folds vs. 1.5 folds, p<0.01). HFES decreased the activity levels of MOB1, a molecule of Hippo signaling, regardless of genotype (p<0.05), yet the Min mice maintained higher levels of MOB1 activity irrespective of HFES (p<0.05). The Hippo signaling effector YAP activity increased in response to HFES in WT mice, but not in Min mice (14.7% vs. 0.0%, p<0.05). CONCLUSION: These results suggest that the Hippo signaling response to muscle contractions differs between healthy and cachectic muscles in mice. Supported by the Louisiana Board of Regents Support Fund (LEQSF(2017-20)-RD-A-22).

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