Regulatory circuit of p300 and DNA Methylation in cancer

p300 is a Histone acetyltransferase which mainly acts as a global transcriptional coactivator and plays important roles in various biological processes including cell proliferation, differentiation, and apoptosis. DNMTs faithfully replicate the existing methylation marks and propagate the methylation pattern across successive cell generations. Since p300 is an acetyltransferase it activates many genes to express, thus encouraging transcriptional activity whereas DNA methylation represses the expression of the genome leading to silencing of genes. Therefore, a homeostatic balance between the two transcriptional states is maintained by a co-ordinated and concerted interplay between these two opposing epigenomic manipulations. Hence, the aberrant activity of both p300 and DNMTs may be cause malignant transformation leading to cancer. The present study was carried out to investigate the relationship between p300 and DNMTs so as to find a correlation between their expression and activity in cancer tissues. The mechanisms by which the inactivation of p300 contributes to carcinogenesis have not been fully revealed. Normally, the expression of p300 should remain at base levels in normal tissues. In cancer cells its expression is likely to be higher since it is a transcriptional coactivator. The results that are obtained might be because of the activation of the promoter regions of p300 by some other epigenetic mechanisms such as DNA methylation. Further studies in this area might provide an in-depth knowledge regarding the above two phenomena and provide ideas about novel networking between the various epigenetic modifications

Differential expression of selected Arabidopsis resistant genes under abiotic stress conditions

The plant immune system is equipped with several defensive layers to evade pathogen attack. One of the primary defense includes plasma membrane-localized receptors explicitly detect conserved pathogen-associated molecular patterns. Transcriptional reprogramming of resistant genes confers PAMP-triggered immunity. Consequently basal immunity is triggered which is primarily mediated by several intracellular nucleotide-binding leucine rich repeat receptors. Subsequently, nucleotide-binding leucine rich repeat receptors sense pathogens and activate another defense response known as effector triggered immunity. Both the PTI and ETI are mediated by resistant genes. Interestingly, the detailed molecular function of resistant genes is not yet fully revealed. Resistant genes are also well involved in non pathophysiological conditions such as during cold stress, heat stress, duration of exposure of light and drought stress. Here, we have reported that the Arabidopsis resistant genes AT1G17600, AT4G14368, AT4G16860, AT5G40910 and AT5G45050 are temperature regulated. We found that the transcript levels of AT1G58400, AT2G14080, AT2G17055, AT3G51560, AT4G16950, AT5G40910 and AT5G45050 were significantly raised for the plant samples grown under short-day conditions. The transcript levels of AT1G17600, AT1G27180, AT1G33560, AT2G14080, AT3G51560, AT4G16860 and AT4G16950 were upregulated for plants grown under drought stress conditions. In Arabidopsis, the transcriptional reprogramming is modulated by decapping protein factors. There was no significant change in the protein level of DCPs. Our results suggest that under abiotic stress conditions, the resistant genes differentially express independent of the decapping event

In silico ANALYSIS OF EFFECT OF PHYTOCHEMICALS FROM Pavonia odorata AGAINST Epidermophyton floccosum CAUSING ATHLETES FOOT DISEASE

Epidermophyton floccosum causes athletes foot disease. Strikingly, athlete’s foot disease rises primarily during specific molecular events, thus acting as a potential clinical biomarker. Further, athlete’s foot disease may also activate further downstream events, supporting the detrimental phase. To restrict the activity of athletes foot disease, several bio molecules can be deployed, of which the phytochemicals can be the best alternative. Molecular docking-based screening of a few phytochemicals revealed that the phytochemicals effectively associate with the active site of the protein and hence bears diagnostic and therapeutic potentials against athletes’ foot disease

Locoregional recurrence after cystectomy in muscle invasive bladder cancer:Implications for adjuvant radiotherapy

Purpose We report the patterns of locoregional recurrence (LRR) in muscle invasive bladder cancer (MIBC), and propose a risk stratification to predict LRR for optimizing the indication for adjuvant radiotherapy.Materials and Methods The study included patients of urothelial MIBC who underwent radical cystectomy with standard perioperative chemotherapy between 2013 and 2019. Recurrences were classified into local and/or cystectomy bed, regional, systemic, or mixed. For risk stratification modelling, T stage (T2, T3, T4), N stage (N0, N1/2, N3) and lymphovascular invasion (LVI positive or negative) were given differential weightage for each patient. The cohort was divided into low risk (LR), intermediate risk (IR) and high risk (HR) groups based on the cumulative score.Results Of the 317 patients screened, 188 were eligible for the study. Seventy patients (37.2%) received neoadjuvant chemotherapy (NACT) while 128 patients (68.1%) had T3/4 disease and 66 patients (35.1%) had N+ disease. Of the 55 patients (29%) who had a recurrence, 31 (16%) patients had a component of LRR (4% cystectomy bed, 11.5% regional 0.5% locoregional). The median time to LRR was 8.2 (IQR 3.3–18.8) months. The LR, IR and HR groups for LRR based on T, N and LVI had a cumulative incidence of 7.1%, 21.6%, and 35% LRR, respectively. The HR group was defined as T3, N3, LVI positive; T4 N1/2, LVI positive; and T4, N3, any LVI. The odds ratio for LRR was 3.37 (95% CI 1.16–9.73, P = 0.02) and 5.27 (95% CI 1.87–14.84, P = 0.002) for IR and HR respectively, with LR as reference.Conclusion LRR is a significant problem post radical cystectomy with a cumulative incidence of 35% in the HR group. The proposed risk stratification model in our study can guide in tailoring adjuvant radiotherapy in MIBC

Locoregional recurrence after cystectomy in muscle invasive bladder cancer:Implications for adjuvant radiotherapy

Purpose We report the patterns of locoregional recurrence (LRR) in muscle invasive bladder cancer (MIBC), and propose a risk stratification to predict LRR for optimizing the indication for adjuvant radiotherapy.Materials and Methods The study included patients of urothelial MIBC who underwent radical cystectomy with standard perioperative chemotherapy between 2013 and 2019. Recurrences were classified into local and/or cystectomy bed, regional, systemic, or mixed. For risk stratification modelling, T stage (T2, T3, T4), N stage (N0, N1/2, N3) and lymphovascular invasion (LVI positive or negative) were given differential weightage for each patient. The cohort was divided into low risk (LR), intermediate risk (IR) and high risk (HR) groups based on the cumulative score.Results Of the 317 patients screened, 188 were eligible for the study. Seventy patients (37.2%) received neoadjuvant chemotherapy (NACT) while 128 patients (68.1%) had T3/4 disease and 66 patients (35.1%) had N+ disease. Of the 55 patients (29%) who had a recurrence, 31 (16%) patients had a component of LRR (4% cystectomy bed, 11.5% regional 0.5% locoregional). The median time to LRR was 8.2 (IQR 3.3–18.8) months. The LR, IR and HR groups for LRR based on T, N and LVI had a cumulative incidence of 7.1%, 21.6%, and 35% LRR, respectively. The HR group was defined as T3, N3, LVI positive; T4 N1/2, LVI positive; and T4, N3, any LVI. The odds ratio for LRR was 3.37 (95% CI 1.16–9.73, P = 0.02) and 5.27 (95% CI 1.87–14.84, P = 0.002) for IR and HR respectively, with LR as reference.Conclusion LRR is a significant problem post radical cystectomy with a cumulative incidence of 35% in the HR group. The proposed risk stratification model in our study can guide in tailoring adjuvant radiotherapy in MIBC

Tissue- and age-specific DNA replication patterns at the CTG/CAG-expanded human myotonic dystrophy type 1 locus

International audienceMyotonic dystrophy, caused by DM1 CTG/CAG repeat expansions, shows varying instability levels between tissues and across ages within patients. We determined DNA replication profiles at the DM1 locus in patient fibroblasts and tissues from DM1 transgenic mice of various ages showing different instability. In patient cells, the repeat is flanked by two replication origins demarcated by CTCF sites, with replication diminished at the expansion. In mice, the expansion replicated from only the downstream origin (CAG as lagging template). In testes from mice of three different ages, replication toward the repeat paused at the earliest age and was relieved at later ages-coinciding with increased instability. Brain, pancreas and thymus replication varied with CpG methylation at DM1 CTCF sites. CTCF sites between progressing forks and repeats reduced replication depending on chromatin. Thus, varying replication progression may affect tissue- and age-specific repeat instability