Targeting DNA methylation in diabetic kidney disease: A new perspective.

Diabetic kidney disease (DKD) is a leading diabetic complication causing significant mortality among people around the globe. People with poor glycemic control accompanied by hyperinsulinemia, dyslipidemia, hypertension, and obesity develop diabetic complications. These diabetic patients develop epigenetic changes and suffer from diabetic kidney complications even after subsequent glucose control, the phenomenon that is recognized as metabolic memory. DNA methylation is an essential epigenetic modification that contributes to the development and progression of several diabetic complications, including DKD. The aberrant DNA methylation pattern at CpGs sites within several genes, such as mTOR, RPTOR, IRS2, GRK5, SLC27A3, LCAT, and SLC1A5, associated with the accompanying risk factors exacerbate the DKD progression. Although drugs such as azacytidine and decitabine have been approved to target DNA methylation for diseases such as hematological malignancies, none have been approved for the treatment of DKD. More importantly, no DNA hypomethylation-targeting drugs have been approved for any disease conditions. Understanding the alteration in DNA methylation and its association with the disease risk factors is essential to target DKD effectively. This review has discussed the abnormal DNA methylation pattern and the kidney tissue-specific expression of critical genes involved in DKD onset and progression. Moreover, we also discuss the new possible therapeutic approach that can be exploited for treating DNA methylation aberrancy in a site-specific manner against DKD.

Arsenic exposure in Indo Gangetic plains of Bihar causing increased cancer risk.

Reportedly, 300 million people worldwide are affected by the consumption of arsenic contaminated groundwater. India prominently figures amongst them and the state of Bihar has shown an upsurge in cases affected by arsenic poisoning. Escalated arsenic content in blood, leaves 1 in every 100 human being highly vulnerable to being affected by the disease. Uncontrolled intake may lead to skin, kidney, liver, bladder, or lung related cancer but even indirect forms of cancer are showing up on a regular basis with abnormal arsenic levels as the probable cause. But despite the apparent relation, the etiology has not been understood clearly. Blood samples of 2000 confirmed cancer patients were collected from pathology department of our institute. For cross-sectional design, 200 blood samples of subjects free from cancer from arsenic free pockets of Patna urban agglomeration, were collected. Blood arsenic levels in carcinoma patients as compared to sarcomas, lymphomas and leukemia were found to be higher. The geospatial map correlates the blood arsenic with cancer types and the demographic area of Gangetic plains. Most of the cancer patients with high blood arsenic concentration were from the districts near the river Ganges. The raised blood arsenic concentration in the 2000 cancer patients strongly correlates the relationship of arsenic with cancer especially the carcinoma type which is more vulnerable. The average arsenic concentration in blood of the cancer patients in the Gangetic plains denotes the significant role of arsenic which is present in endemic proportions. Thus, the study significantly correlates and advocates a strong relation of the deleterious element with the disease. It also underlines the need to address the problem by deciphering the root cause of the elevated cancer incidences in the Gangetic basin of Bihar and its association with arsenic poisoning.

Therapeutic effect of Aegle marmelos fruit extract against DMBA induced breast cancer in rats.

Breast cancer is among most common form of cancer worldwide. It is also the major cause of death in female cancer patient around the world. Despite various therapeutic measures, it remains associated with high mortality rate. Aegle marmelos (L.) Correa has been extensively used in Indian medicine system Ayurveda, due to its various medicinal properties. However, there are very limited reports regarding its anticancer activity. Thus, the present research work has been aimed to study the anticancer activity of Aegle marmelos fruit extract on 7,12-dimethylbenz(a)anthracene (DMBA) induced breast cancer in rats. Female Charles Foster rats, 55-60 days old weighing around (150 ± 10 g) were used for the study and were induced DMBA (20 mg/mL dissolved in Olive oil) orally. After the development of breast tumors (about 0.5 cm), the rats were treated with Aegle marmelos ethanolic fruit pulp extract (200 mg/kg b.w./day) orally for 5 weeks and then volume of tumor was measured. Aegle marmelos treatment showed significantly reduced mammary tumor volume (P < 0.05), along with significant reduction (P < 0.0001) in the different serum biomarkers such as TNF-α level, serum malondialdehyde (MDA) level and glucose levels. Significant (P < 0.0001) improvement in both, the kidney and liver serum biomarker parameters were also observed after the treatment with Aegle marmelos ethanolic fruit pulp extract. From the entire study, taking everything into account it can be interpreted that Aegle marmelos ethanolic fruit pulp extract possesses anti-proliferative activity by suppressing the progression of breast tumors in rat model. The plant extract also possesses hepato-renal protective effect. Hence, it can be targeted as novel and safe anti-cancer drug against breast cancer.

Antitumour Property of Pterocarpus santalinus Seeds Against DMBA-Induced Breast Cancer in Rats.

Breast cancer has been one of the most common form of malignancy globally among women, for more than a decade. Despite various preventive and treatment measures, it remains associated with high incidence and mortality rate. Pterocarpus santalinus Linn. f. has been extensively used in Indian medicine system Ayurveda, due to its various medicinal properties. However, despite various research works on the anticancer activity of P santalinus, no studies have been reported on animal model. Therefore, this study was aimed to decipher the antitumour activity of ethanolic seeds extract of P santalinus on DMBA (7,12-dimethylbenz(a)-anthracene)-induced breast cancer in rats. Fifty-five-days-old weighed (150 ± 10 g) female Charles Foster rats (12 females) were used for the study. The rats were divided into 3 groups of 4 rats each. 7,12-Dimethylbenz(a)-anthracene (single dose of 20 mg/mL dissolved in olive oil) was induced orally, to develop breast tumour. After the development of breast tumours (about 0.5 cm), the rats were treated with P santalinus ethanolic seeds extract (300 mg/kg body weight/day) orally for 5 weeks and then volume of tumour was measured. Oral administration of P santalinus extract resulted in about 49.5% tumour growth inhibition in the final week of treatment in DMBA + P santalinus group as compared with the DMBA group. Pterocarpus santalinus administration also significantly reduced (P < .0001) the serum malondialdehyde level from 58.81 ± 4.09 nmol/mL in DMBA group to 10.87 ± 1.20 nmol/mL in the DMBA + P santalinus group. Serum tumour necrosis factor-α level reduced significantly (P < .0001) from 80.43 ± 2.45 pg/mL in DMBA group to 28.30 ± 3.24 pg/mL in the DMBA + P santalinus group. The blood serum glucose level also reduced significantly (P < .0001) from 205.9 ± 22.22 mg/dL in DMBA group to 86.44 ± 8.36 in DMBA + P santalinus group. There was significant (P < .0001) improvement in the both the liver and kidney serum biomarkers level after P santalinus administration. The histological study of mammary tissues of rats shows that, in the DMBA group immature fibrocytes are completely replacing the normal adipocytes suggestive of fibroma molle, whereas in the DMBA + P santalinus group mature fibrocytes with multilayer glandular cells were seen denoting fibroadenoma. Thus, the P santalinus ethanolic seed extract possesses antitumorigenic, antioxidant and hypoglycaemic properties as well as hepato-renal protective effect. Hence, it may be concluded that P santalinus has therapeutic role against DMBA-induced breast cancer in rats and has a greater potential to develop as a chemotherapeutic agent in breast cancer treatment.