In the classic paradigm of mammalian cell cycle control, Rb functions to restrict cells from entering S phase by sequestering E2F activators (E2f1, E2f2 and E2f3), which are invariably portrayed as the ultimate effectors of a transcriptional program that commit cells to enter and progress through S phase1, 2. Using a panel of tissue-specific cre-transgenic mice and conditional E2f alleles we examine the effects of E2f1, E2f2 and E2f3 triple deficiency in murine ES cells, embryos and small intestines. We show that in normal dividing progenitor cells E2F1-3 function as transcriptional activators, but contrary to current dogma, are dispensable for cell division and instead are necessary for cell survival. In differentiating cells they function in complex with Rb as repressors to silence E2F targets and facilitate exit from the cell cycle. The inactivation of Rb in differentiating cells resulted in a switch of E2F1-3 from repressors to activators, leading to the superactivation of E2F responsive targets and ectopic cell divisions, and loss of E2f1-3 completely suppressed these phenotypes. This work contextualizes the activator versus repressor functions of E2F1-3 in vivo, revealing distinct roles in dividing versus differentiating cells and in normal versus cancer-like cell cycles in vivo.
Objective
Ozone therapy has tremendous therapeutic potential owing to its antiviral, anti-inflammatory and antioxidant properties, and potential to improve oxygenation. A pilot clinical trial was conducted to evaluate the safety and efficacy of intravenous ozonised saline treatment in patients with moderate COVID-19 pneumonia.
Patients and Methods
10 patients were administered 200 ml freshly prepared ozonised saline intravenously over 1 hour once a day for 8 days along with standard medical treatment. Clinical symptoms were monitored everyday and laboratory biomarkers, radiological findings at 1,3,6,10 days. Telephonic follow up was done for all after discharge till Day 14. 7 out of 10 patients required oxygen supplementation at recruitment.
Results
There was severe adverse event recorded in the study group. All patients improved from moderate to mild category in average 8 days and were discharged in average 9.7 days. None deteriorated to severe stage. All clinical symptoms resolved within 6 days and oxygen supplementation requirement reduced to none within 4.1 days. There was statistically significant reduction in CRP (p=0.003), D-Dimer (p=0.049), IL6 (p=0.002) and statistically significant improvement (p=0.001) in SpO2/FiO2 ratio. Change in LDH was borderline statistically not significant (p=0.058). All patients showed significant resolution of bilateral interstitial infiltrates at the end of 10 days.
Conclusion
Resolved clinical symptoms, improved oxygenation, clearance of infiltrates on Chest X-ray and improvement in biomarkers in a short period with non-progression of the disease showed that IV ozonised saline therapy was safe and effective to prevent disease progression in COVID-19, making it an effective novel therapeutic tool.
The Indian generic molecule of IM is effective in the treatment of CML-CP. The cost of Indian generic molecule is less than Rs. 10,000 per month there by making this affordable for large number of CML-CP patients in India.
The study compares potential of transcript signature and IGRA to diagnose LTBI. It is first of its kind study to screen household contacts (HHCs) in high TB burden area of India. A transcript signature (
FCGR1B, GBP1
, &
GBP5
) is identified as potential biomarker for LTBI. These results can lead to development of point-of-care (POC) like device for LTBI screening in a high TB burdened area.
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