Combined Effects of Continuous Positive Airway Pressure and Cycle Ergometer in Early Rehabilitation of Coronary Artery Bypass Surgery Patients.

OBJECTIVE: To determine the combined effects of continuous positive airway pressure (C-PAP) and physical exercise rehabilitation on a cycle ergometer on postcoronary artery bypass surgery patients. STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Rawalpindi Institute of Cardiology, from December 2020 to May 2021. METHODOLOGY: Patients, who underwent coronary artery bypass graft surgery, were divided into two equal groups of each 51. The control group received standard physiotherapy from the 1st postoperative day which included breathing exercises, passive mobilisation in the sitting position, and ambulation. The interventional group also had standard physiotherapy from 1st postoperative day; but also the 2nd to 4th postoperative day had additional dynamic exercises on cycle ergometry in combination with CPAP (continuous positive airway pressure). RESULTS: There was a significant improvement in functional capacity measured by 6-minute walk test in the interventional group (p<0.001). Length of hospital and ICU stay mean rank (68.88 and 58) were also significantly decreased in the interventional group (p<0.001). There was no improvement in maximum inspiratory pressure and maximum expiratory pressure. One-minute sit-to-stand test was increased on 4th postoperative day in the interventional group. There was no significant difference observed in arterial blood gases between these two groups. CONCLUSION: Cycle ergometry combined with continuous positive airway pressure (C-PAP) applied earlier on patients undergoing coronary artery bypass grafting improves the functional capacity, decreases the ICU and hospital length of stay and also improves lower limb muscle strength. But no difference in respiratory muscle strength and arterial blood gases was observed between the control and interventional groups. KEY WORDS: Aerobic exercise, Coronary artery bypass graft surgery, Continuous positive airway pressure.

Association of MARCH7 with tumor progression and T-cell infiltration in esophageal cancer.

MARCH7 is an E3 ubiquitin ligase known to regulate neuronal development,T-cell proliferation, and cell and tissue differentiation. But, the altered expression of MARCH7 has been observed in various malignancies. Herein, the cellular localization and role of MARCH7 have been elucidated in esophageal squamous cell carcinoma (ESCC), the information regarding which is currently limited. To check the expression of MARCH7 and its correlation with immune cells infiltration in ESCC, immunohistochemical analysis was performed. RNAi approach was used to investigate the role of MARCH7 in esophageal cancer cells. Interestingly, we found a significantly higher expression of MARCH7 protein in 84% of ESCC tissues than in distant matched non-malignant tissues (p ≤ 0.001). In addition to this, immunohistochemistry results have shown a negative correlation between MARCH7 protein expression and tumor-infiltrating immune cells such as CD8 + T cells (r = - 0.633, p = 0.001) and PD1 + T cells (r = - 0.560, p = 0.005). Furthermore, MARCH7 silencing inhibited the ESCC cell growth and reduced the clonogenic and invasion/migration potential of ESCC cells. MARCH7 silencing also significantly increased E-cadherin protein levels in ESCC cells relative to those in negative control cells (p < 0.05). Thus, MARCH7 is oncogenic and might have a possible role in esophageal carcinogenesis. Moreover, E-cadherin may be a downstream target of MARCH7 in ESCC.

iTRAQ-based analysis for the identification of MARCH8 targets in human esophageal squamous cell carcinoma.

MARCH8 is an E3 ligase, primarily involved in immune-modulation. Recently, we reported its aberrant expression in human esophageal squamous cell carcinoma. However, exact mechanisms by which it regulates cancer have been poorly understood. We applied high-throughput quantitative proteomics approach to identify downstream protein targets of MARCH8. Silencing of endogenous MARCH8 in ESCC cells followed by LC-MS/MS analysis led to identification of 1,029 unique proteins showing altered expression post MARCH8 knockdown. Several previously reported MARCH8 target proteins viz. TFR1, syntaxin-4, e-cadherin and CD44 were found to be upregulated. Furthermore, new putative targets of MARCH8, including ß2M, were identified in the present study. We demonstrated that MARCH8 interacts with and ubiquitinates CDH1 and ß2M. Inhibiting proteasome activity with MG132 prevented CDH1 and ß2M degradation, indicating that MARCH8 might be targeting CDH1 and ß2M for proteasomal degradation. Further, loss of ß2M and CDH1 expression significantly and inversely correlated with MARCH8 expression in ESCC tissues (r =  -0.737 and  - 0.651, respectively; p < 0.01). In conclusion, our present study has led to identification of new targets of MARCH8 and suggests the role of MARCH8 in regulating CDH1 and ß2M turnover in esophageal cancer cells. SIGNIFICANCE: The use of quantitative proteomics carried out has led to the recognition of new targets of MARCH8. The present study gives a broad understanding of the molecular remodeling arising in the ESCC after MARCH8 knockdown. The study also solidifies the idea that role of MARCH8 is not just limited to immunomodulation as silencing of MARCH8 affects various other processes such as protein processing and localization. This study might help in understanding the regulation of MARCH8 in ESCCs and the mechanism by which MARCH8 might be facilitating cancer cells to evade immune surveillance.