No abstract

The study was designed to collect water samples over two seasons-wet-monsoon season (n = 96) (March-April) and dry-monsoon season (n = 44) (September-October)-to understand the seasonal variation in anion and cation hydrochemistry of the coastal rivers and estuaries contributing in the spatial trend in salinity. Hydrochemical examination of wet-monsoon season primarily revealed Ca-Mg-HCO type (66%) and followed by Na-Cl type (17.70%) water. In the dry-monsoon season, the scenario reversed with primary water being Na-Cl type (52.27%) followed by Ca-Mg-HCO type (31.81%). Analysis of Cl/Br molar ratio vs. Cl (mg/L) depicted sampling area affected by seawater intrusion (SWI). Spatial analysis by ordinary kriging method confirmed approximately 77% sample in the dry-monsoon, and 34% of the wet-monsoon season had shown SWI. The most saline-intruded areas in the wet-monsoon seasons were extreme south-west coastal zone of Bangladesh, lower Meghna River floodplain and Meghna estuarine floodplain and south-eastern part of Chittagong coastal plains containing the districts of Chittagong and Cox's Bazar adjacent to Bay of Bengal. In addition, mid-south zone is also affected slightly in the dry-monsoon season. From the analyses of data, this study could further help to comprehend seasonal trends in the hydrochemistry and water quality of the coastal and estuarine rivers. In addition, it can help policy makers to obligate some important implications for the future initiatives taken for the management of land, water, fishery, agriculture and environment of coastal rivers and estuaries of Bangladesh.

No abstract

BackgroundOxaliplatin belongs to the platinum-based drug family and has shown promise in treating cancer by binding to DNA to induce cytotoxicity. However, individual patients show diverse therapeutic responses toward oxaliplatin due to yet-unknown underlying mechanisms. We recently established that oxaliplatin also exert its anti-cancer activity in gastric cancer cell lines by targeting tumor-associated NADH oxidase (tNOX), attenuate NAD+ generation and reduce NAD+-dependent sirtuin 1 (SIRT1) deacetylase activity, which in turn enhances p53 acetylation and apoptosis.MethodsIn this study, differential cellular outcomes in response to oxaliplatin exposure of p53-wild-type versus p53-null HCT116 human colon cancer cells were examined. Cell growth profile was determined by cell impedance measurements and apoptosis was analyzed by flow cytometry. The engagement between oxaliplatin and tNOX protein was studied by cellular thermal shift assay. Furthermore, western blot analysis revealed that p53 was important in regulating tNOX expression in these cell lines.ResultsIn p53-wild-type cells, we found that oxaliplatin inhibited cell growth by inducing apoptosis and concurrently down-regulating tNOX at both the transcriptional and translational levels. In p53-null cells, in contrast, oxaliplatin moderately up-regulated tNOX expression and yielded no apoptosis and much less cytotoxicity. Further experiments revealed that in p53-wild-type cells, oxaliplatin enhanced ROS generation and p53 transcriptional activation, leading to down-regulation of the transcriptional factor, POU3F2, which enhances the expression of tNOX. Moreover, the addition of a ROS scavenger reversed the p53 activation, POU3F2 down-regulation, and apoptosis induced by oxaliplatin in p53-wild-type cells. In the p53-null line, on the other hand, oxaliplatin treatment triggered less ROS generation and no p53 protein, such that POU3F2 and tNOX were not down-regulated and oxaliplatin-mediated cytotoxicity was attenuated.ConclusionOur results show that oxaliplatin mediates differential cellular responses in colon cancer cells depending on their p53 status, and demonstrate that the ROS-p53 axis is important for regulating POU3F2 and its downstream target, tNOX. Notably, the depletion of tNOX sensitizes p53-null cells to both spontaneous and oxaliplatin-induced apoptosis. Our work thus clearly shows a scenario in which targeting of tNOX may be a potential strategy for cancer therapy in a p53-inactivated system.

No abstract

Capsaicin (8-methyl-N-vanillyl-6-noneamide), which is an active component in red chili peppers, is used as a chemopreventive agent that shows favorable cytotoxicity against cancer cells. Accumulating evidence indicates that capsaicin preferentially inhibits a tumor-associated NADH oxidase (tNOX, ENOX2) that is ubiquitously expressed in cancer but not in non-transformed cells. This attenuates cancer cell growth by inducing apoptosis. The capsaicin-mediated inhibition of tNOX was recently shown to prolong the cell cycle. However, the molecular events underlying this regulation have not yet been investigated. In the present study, we used a cellular thermal shift assay (CETSA) to detect “target engagement” of capsaicin and its consequent impact on cell cycle progression. Our results indicated that capsaicin engaged with tNOX and triggered the proteasomal degradation of tNOX, which leads to the inhibition of NAD+-dependent SIRT1 deacetylase. Ultimately, the acetylation levels of c-Myc and p53 were enhanced, which suppressed the activation of G1 cyclin/Cyclin-dependent kinase complexes and triggered cell cycle arrest in cancer cells. The results obtained when tNOX was overexpressed in non-cancer cells validated its importance in cell cycle progression. These findings provide the first molecular insights into the regulatory role of tNOX and the anti-proliferative property of capsaicin in regulating the cell cycle of bladder cancer cells.

Background: Although considered a rare form of skin cancer, malignant melanoma has steadily increased internationally and is a main cause of cancer-associated death worldwide. The treatment options for malignant melanoma are very limited. Accumulating data suggest that the natural compound, capsaicin, exhibits preferential anticancer properties to act as a nutraceutical agent. Here, we explored the underlying molecular events involved in the inhibitory effects of capsaicin on the growth of melanoma cells.Methods: The cellular thermal shift assay (CETSA) and isothermal dose response fingerprint (ITDRFCETSA) were utilized to validate the binding of capsaicin with the tumor-associated NADH oxidase, tNOX (ENOX2) in melanoma cells. We also assessed the cellular impact of capsaicin-targeting of tNOX on A375 cells by flow cytometry and protein analysis. The essential role of tNOX in tumor- and melanoma-growth limiting abilities of capsaicin was evaluated in C57BL/6 mice.Results: Our data show that capsaicin directly targets cellular tNOX to inhibit its enzymatic activity and enhance protein degradation capacity. The inhibition of tNOX by capsaicin is accompanied by the attenuation of SIRT1, a NAD+-dependent deacetylase that enhances ULK1 acetylation to induce ROS-dependent autophagy in melanoma cells. Capsaicin treatment of mice implanted with melanoma cancer cells suppressed tumor growth by down-regulating tNOX and SIRT1, which was also seen in an in vivo xenograft study with tNOX-depleted melanoma cells. Conclusions: Together, our findings suggest that tNOX expression is important for the growth of melanoma cancer cells both in vitro and in vivo, and that inhibition of the tNOX-SIRT1 axis contributes to inducting cytotoxic ROS-dependent autophagy in melanoma cells.

To examine the groundwater quality a total of 120 groundwater samples were collected from two southern districts; Barguna (27 points) and Patuakali (33 points) of Bangladesh in two seasons viz., pre-monsoon (60 samples) and post-monsoon (60 samples) in 2012. A comprehensive analysis has been conducted to explore the groundwater hydrochemistry and effects of major ions on the suitability for potable water and agricultural uses. Geochemical analyses have clearly shown that the seasonal effect does change the order of abundance of major ions in the groundwater, while principal component analysis confirmed the reasons of extreme salinity and hardness. Piper diagram showed that the predominant hydrochemical facies for the groundwater were Na ? -Cl --SO 4 2-and Na ? -K ? -HCO 3 -types. The chloroalkaline index confirmed that the ion exchange was governed mainly in water phase. Equiline diagram explained the relationship among the alkali with total cations and anions where cations were more dominant than anions at 1:1 ratio. The Gibb's diagram illustrated the chemical composition of water mainly influenced by precipitation from the water sources. The molar ratio Cl -/Ranions and Na ? /Na ? ?Cl -indicated that the groundwater of the study area was affected by seawater intrusion. In addition to unsuitable salinity ([5000 ls/cm), Kelly's ratio, total hardness, sodium absorption ratio, residual Sodium carbonate, and Na % clearly indicated that the groundwater in the study area were not suitable for drinking, irrigation, and domestic uses. Moreover, the spatial distribution maps were drawn to observe the spatial extent of EC, TDS, SAR, and SSP using IDW technique. Thus, considering all the above findings this area needs special attention to ensure the supply of potable water and to maintain sustainable agricultural activities.