Ubiquitin: Not just a one-way ticket to the proteasome, but a therapeutic dial to fine-tune the molecular landscape of disease.

Recently, there is a rise in studies that recognize the importance of targeting ubiquitin and related molecular machinery in various therapeutic contexts. Here we briefly discuss the history of ubiquitin, its biological roles in protein degradation and beyond, as well as the current state of ubiquitin-targeting therapeutics across diseases. We conclude that targeting ubiquitin machinery is approaching a renaissance, and tapping its full potential will require embracing a wholistic perspective of ubiquitin's multifaceted roles.

The effects of inspiratory muscle training with pulmonary rehabilitation on NSCLC patients during radiation therapy: A pilot clinical study.

BACKGROUND: The effects of inspiratory muscle training (IMT) with pulmonary rehabilitation (PR) on patients with non-small cell lung cancer (NSCLC) receiving radiotherapy (RT) have not previously been reported. This pilot study aimed to determine the effectiveness of IMT with PR on respiratory muscles and exercise capacity of NSCLC patients receiving RT. METHODS: We retrospectively analyzed 20 patients who underwent RT for NSCLC. The rehabilitation included IMT, stretching, strengthening, and aerobic exercises three times a week for 4 weeks with concurrent RT. IMT training lasted 10 min, consisting of one cycle of 30 breaths using the Powerbreathe KH1 device in the hospital by a physical therapist. Patients underwent two IMT sessions at home daily at an intensity of approximately 30%-50% of the participant's maximum inspiratory muscle pressure (MIP) using the threshold IMT tool. We analyzed the results from the respiratory muscle strength test, pulmonary function test, 6-min walk test (6MWT), cardiopulmonary function test, cycle endurance test (CET), Inbody test, grip measurement, knee extensor/flexor strength measurement, Cancer Core Quality of Life Questionnaire (EORTCQ-C30), and NSCLC 13 (EORTC-LC13). RESULTS: There were no adverse events during evaluation and IMT with PR. MIP (60.1 ± 25.1 vs. 72.5 ± 31.9, p = 0.005), 6MWT (439.2 ± 97.1 vs. 60.7 ± 97.8, p = 0.002), CET (181.39 ± 193.12 vs. 123.6 ± 87.6, p = 0.001), knee extensor (14.4 ± 5.3 vs. 17.4 ± 5, p = 0.012), and knee flexor (14.0 ± 5.2 vs. 16.9 ± 5.5, p = 0.004) significantly improved after IMT with PR. CONCLUSION: IMT with PR appears effective on respiratory muscles and exercise capacity without adverse events in NSCLC patients who underwent RT.

Physical limits on galvanotaxis.

Eukaryotic cells can polarize and migrate in response to electric fields via "galvanotaxis," which aids wound healing. Experimental evidence suggests cells sense electric fields via molecules on the cell's surface redistributing via electrophoresis and electroosmosis, though the sensing species has not yet been conclusively identified. We develop a model that links sensor redistribution and galvanotaxis using maximum likelihood estimation. Our model predicts a single universal curve for how galvanotactic directionality depends on field strength. We can collapse measurements of galvanotaxis in keratocytes, neural crest cells, and granulocytes to this curve, suggesting that stochasticity due to the finite number of sensors may limit galvanotactic accuracy. We find cells can achieve experimentally observed directionalities with either a few (∼100) highly polarized sensors or many (∼10^{4}) sensors with an ∼6-10% change in concentration across the cell. We also identify additional signatures of galvanotaxis via sensor redistribution, including the presence of a tradeoff between accuracy and variance in cells being controlled by rapidly switching fields. Our approach shows how the physics of noise at the molecular scale can limit cell-scale galvanotaxis, providing important constraints on sensor properties and allowing for new tests to determine the specific molecules underlying galvanotaxis.

Feasibility of an outpatient-based pulmonary rehabilitation program for lung cancer patients during radiation therapy.

PURPOSE: Data are lacking regarding pulmonary rehabilitation (PR) programs in patients with lung cancer receiving radiation therapy. This study aimed to confirm the feasibility of an outpatient-based PR program in lung cancer patients during radiation therapy. METHODS: A retrospective chart review was performed of 40 patients with lung cancer who had undergone radiation therapy between July and December 2019. The patients received an outpatient-based PR program for a total of eight sessions two times weekly comprising 60 min per session. Feasibility was assessed based on the completion rate, adverse events, and satisfaction with the PR program. Functional evaluations using 6-min walk and grip strength tests were conducted before and after PR. Patient quality of life was assessed by the EORTC QLQ-C30 questionnaire before and after PR. RESULTS: The completion rate for the PR program was 72.5% among the 40 patients. No adverse events related to PR were reported. The overall satisfaction was 5.7 ± 1.1 on a seven-point Likert scale in all participants. The mean 6-min walk test distance increased significantly from 419.1 to 446.2 m. The improvement in grip strength in the dominant hand after PR was not significant. The social functioning score in the EORTC QLQ-C30 improved significantly. CONCLUSION: The results of this study showed the feasibility without serious adverse effects of a 4-week outpatient-based PR program for lung cancer patients undergoing outpatient-based radiation therapy. This program might improve patient physical function and quality of life.

Anti-inflammatory effects of isoacteoside from Abeliophyllum distichum.

Isoacteoside, a dihydroxypheynylethyl glycoside, is a major bioactive component of Abeliophyllum distichum (White Forsythia) which is a deciduous shrub native to the south and central areas of Korea. The present study is designed to evaluate the anti-inflammatory activities and underlying mechanisms of isoacteoside in human mast cell line, HMC-1 cells. We isolated isoacteoside from A. distichum. The anti-inflammatory effect of isoacteoside was investigated in HMC-1 cells by studying the following markers: phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) secretion and mRNA expression by ELISA and RT-PCR, respectively. In addition, mechanism related to anti-inflammatory was investigated by Western blotting. Isoacteoside significantly suppressed the production and mRNA expression of proinflammatory cytokines including IL-1ß, IL-6, IL-8 and TNF-α in PMACI-stimulated HMC-1 cells without cytotoxicity. It was found that anti-inflammatory effects of isoacteoside are mediated by action on caspase-1, mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, extracellular signal-regulated protein kinase) and nuclear factor-kappa B pathways. Taken together, the present findings provide new insights that isoacteoside may be a promising anti-inflammatory agent for inflammatory disorders.