Ovarian cancer is one of the most common cancers in women and even with the currently available treatment options, including surgery, radiation, and chemotherapy, it caused 13,940 deaths in US alone in 2020. Thus, there is a continuous need for developing novel approaches for the treatment of ovarian cancer, particularly drug resistant ovarian cancer, as ovarian cancer most adversely affects the lives patients. Here in, we have designed seleno-biotin derivatives as potential therapeutics for ovarian cancer. The rational for designing these hybrid small molecules is two fold: (i) The biotin receptors are up-regulated in various carcinomas including ovarian cancer cells while being expressed at low levels in normal cells. Due to the high affinity of biotin towards BR, biotin has been used as a conjugate for several targeted imaging, sensing, and delivery in vitro and in vivo. (ii) Organoselenium compounds with appropriate selenium moieties have shown therapeutic efficacy in several pre-clinical cancer models. Therefore, we designed several analogs of biotin by conjugating selenium moieties connected through ester, selenoester, or amide functionalities and their cytotoxicities were assessed using four different ovarian cancer cell lines. Ester-linked biotin-selenocyanate compound 2, out of the other analogs, in direct comparison to biotin alone, more effectively reduced the cell viability (IC50 9.8-18.5 µM against all the tested cell lines) and induced apoptosis in ovarian cancer cells in dose dependent manner as demonstrated by the cell viability assay. It showed three times more potency (IC50 14.08 µM) than standard drugs 5-FU (IC50 48.4 µM) and cisplatin (IC50 41.0 µM) against drug-resistant Hey A8 cancer cells and three times more activity with an IC50 value of 9.8 µM as compared to 5-FU (IC50 25.92 µM) against ES-2 cells. The above findings were supported by trypan blue dye exclusion assay, Annexin V/7-AAD, Caspase 3/7 apoptosis assays and Western blotting of apoptotic proteins. Compound 2 effectively caused cell cycle arrest of the treated OVCAR-3 cells in S-phase of the cell cycle, thus causing regulatory changes in the cell cycle proteins, as evident by Western blotting. In addition, compound 2 redox cycles was demonstrated by DCFDA based reactive oxygen species estimation. These experiments demonstrate that selenium modified biotin which contains a covalently attached redox cycling selenide group has the potential for human therapeutic applications against ovarian and other cancers over-expressing biotin receptors. Citation Format: Asif Raza, Amandeep Singh, Amin Shantu, L. Mallory Boylan, Julian E. Spallholz, Arun Sharma. Novel seleno-biotin compound inhibits viability of and induces reactive oxygen species (ROS)-mediated apoptosis in ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5449.

The primary objective of this study was to determine the intralaboratory performance of a cholesterol determination method that combines direct saponification of a 1 g meat or poultry sample and GC quantification of liberated cholesterol without derivatization. Cholesterol was detected at 11.96 min using a GC-flame ionization detector (FID) system. With a 0.005 mg/mL 5alpha-cholestane internal standard and 0.008 to 0.020 mg/mL cholesterol standard series, the FID response was linearly correlated to standard concentrations with a coefficient of determination of 0.995 and a response factor of 0.66. The LOD and LOQ were 1.24 and 4.00 mg/100 g, respectively. Cholesterol could be analyzed within 6 days of preparation with high precision (CV of 0.92 to 2.69%) and accuracy (recovery of 93.24 to 100.56%). This simplified procedure allows for decreased errors and increased productivity, and the method proved to be reliable and able to withstand practical variation in procedural application. The method has been applied routinely with excellent precision to update data on the cholesterol content of beef, pork, and chicken in the U.S. Department of Agriculture National Nutrient Database for Standard Reference.

Objective To explore depressed mood in the breastfeeding dyad. Method N = 50 mothers of 12-day-olds reported depressed mood (EPDS) and anxiety (STAI), then were videotaped while breastfeeding. Infants were weighed before and after breastfeeding. Results An ANCOVA on weight gain, which controlled for infant age and birth weight, found EPDS inversely related to weight gain. Following a significant MANCOVA on infant biobehavioral measures, ANCOVAs which controlled for birth weight, age, hunger at time of testing, and degree of exclusivity in breastfeeding, found EPDS inversely related to infants' milk intake and latch quality. Following a significant MANOVA on maternal behaviors, ANOVAs revealed EPDS inversely related to mothers' sensitive positioning and touch frequency. Contrastingly, anxiety was associated with increased touch. Conclusion In the breastfed newborn, mothers' depressed mood is associated with lesser weight gain, lower milk intake, poorer latch to the breast, and receiving less frequent touch and less-sensitive positioning at the breast by mother.

Available data for cholesterol content of beef, pork, poultry, and processed meat products were reported. Although the cholesterol concentration in meat and poultry can be influenced by various factors, effects of animal species, muscle fiber type, and muscle fat content are focused on in this review. Oxidative red muscles tend to have greater total lipid and cholesterol contents, although differences in the same types of muscles or cuts have been reported. Moreover, contradictory results among various studies suggest that unless there are pronounced changes in muscle structure and composition, cholesterol content is unlikely to be affected. Second, multiple issues in cholesterol analysis, including sample preparation, detection, and quantification, were evaluated. Cholesterol content of meat and poultry has been determined mostly by colorimetry and chromatography, although the latter has become predominant because of technological advances and method performance. Direct saponification has been the preferred method for hydrolyzing samples because of cost- and time-effectiveness. The extraction solvent varies, but toluene seems to provide sufficient recovery in a single extraction, although the possible formation of an emulsion associated with using toluene requires experience in postsaponification manipulation. The most commonly used internal standard is 5 alpha-cholestane, although its behavior is not identical to that of cholesterol. Cholesterol can be analyzed routinely by gas chromatography (GC)-flame ionization detector without derivatization; however, other methods, especially high-performance liquid chromatography (HPLC) coupled with different detectors, can also be used. For research purposes, HPLC-ultraviolet/Visible/photodiode array detector with nondestructiveness is preferred, especially when cholesterol must be separated from other coexisting compounds such as tocopherols. More advanced methods, such as GC/HPLC-isotope dilution/mass spectrometry, are primarily used for quality control purposes.

Arsenic (As) contamination of the available domestic drinking water from shallow aquifers to villagers in Bangladesh often exceeds the newest WHO standard of <10 µg As L−1 and the older Bangladeshi standard of <50 µg As L−1. An estimated 9.2 million shallow tube wells in Bangladesh deliver water to 97% of the rural population, placing an estimated 57 million people at risk for arsenicosis. The contamination of drinking water by As extends to W. Bengal, India and Nepal. The same shallow aquifers used for domestic water are also used to irrigate food crops, particularly rice. Irrigation adds As to soils and increases exposure of the population to additional As via foods consumed. Selenium (Se), an essential trace mineral found in soils, is absorbed by plants, entering the human food chain. It was suggested that a low dietary intake of Se may be contributing to the problem of human arsenicosis in Bangladesh. Dietary Se acts as a natural antidote to As by (1) accelerating As excretion, (2) sequestering As by ...

Selenium (Se), an essential trace mineral, is obtained by individuals from foods ingested and is necessary for 25 human proteins including the antioxidant family of glutathione peroxidases. Since plants are not known to require Se for growth, the quantity of this mineral in plant foods depends on the soluble Se in soils that is passively accumulated by plants. As all animals require Se, it is usually stored more uniformly and to a greater degree in animal than plant protein foods. Owing to the alluvial origin, high rainfall and flooding upon the soils of Bangladesh these soils appear to be low in measured soluble Se. These low levels of soluble Se in Bangladeshi soils reflect the low levels of Se in plant foods, rice and vegetables, staples of the rural and poor Bangladeshi's diet. This study reports on the dry-weight content of Se found in samples of rice, other plant foods and fish from Bangladesh. Rice grain averaged 0.105 µg Se g−1 from Jessore and 0.212 µg Se g−1 from 5 other districts of Bangladesh. Gourds and potatoes from Jessore averaged 0.471 and 0.181 µg Se g−1 respectively. All other district plant foods averaged 0.26 µg Se g−1. All 7 different but unidentified species of fish sampled in Jessore and quantitated fluorimetrically averaged 1.318 µg Se g−1. Fish was the single highest food source of dietary Se per unit dry weight. Fish in particular, but also other animal foods, are likely to serve as better dietary sources of Se for the people of Bangladesh.

The carcinostatic activities of selenium (Se) compounds have been shown to be composition and concentration dependent. Several studies have indicated that the ratios between glutathione (GSH) and Se may play an important role in Se catalysis and toxicity. The present study examined the catalytic effect of three selenium compounds on GSH oxidation using lucigenin-dependent chemiluminescence (CL) as an indirect measure of superoxide generation. Various GSH:Se ratios were assayed for the glutathione oxidase activity of selenite, selenocystamine and diselenodipropionic acid. CL emitted from the reaction of selenite with GSH increased more rapidly and was greater than those from the diselenides, but the diselenide CL reactions were sustainable. Both selenite- and diselenide-induced CL were markedly suppressed by superoxide dismutase (SOD). Iodoacetic acid (IAc) effectively inhibited CL generated from selenite-, selenocystamine- and diselenodipropionic acid-catalyzed GSH oxidation. These results suggest that GSH oxidation catalyzed by selenite, and the diselenides selenocystamine and diselenodipropionic acid, generated the superoxide radical in which the CL was inhibited by SOD. Furthermore, CL inhibition by IAc suggests that the catalytic species producing superoxide were the GSSe(-) or RSe(-) anion. This redox chemistry may be responsible for selenite and organoselenium toxicity and apoptosis, making possible the design and synthesis of organoselenium-containing pharmaceuticals.

The selenium (Se) content of the diet and/or selenium supplements might have an ameliorating effect on arsenic (As) toxicity as recently shown by Wang et al. (1), Yang et al. (2), and as reviewed by Spallholz et al. (3). The underlying principles of the ameliorating effect is the complexation of Se with As forming the seleno-bis (S-glutathionyl) arsinium ion (4) excreted in bile and the complexation of Se with As in tissues forming nontoxic insoluble selenides (5,6). Addition protection afforded by Se supplementation from arsenicosis could be the elevation of glutathione peroxidase activity reducing the oxidative stress induced by As (7,8). The present study assessed the status of Se and As in hair by neutron activation analysis (NAA). Human hair samples were collected from the United States, Canada, The People's Republic of China (PRC), Bangladesh, and Nepal, the latter two countries now engaged in a struggle to find relief from human arsenicosis resulting from extensive domestic groundwater contamination by As. No statistically significant differences were observed in the samples between the Se and As content of hair from, Lubbock, Texas (USA) or Winnipeg, Canada. The concentration of As in all hair samples analyzed correlated (r=0.960, p<0.001) with the amount of As in the drinking water. Selenium levels in hair were highest from Nepal. The results demonstrate the viability of hair as a noninvasive biomonitor in assessing aspects of dietary Se and environmental As exposure. The hair data confirmed the known low intake of Se in the Keshan disease area of the PRC, the very high accumulation in hair of As from subjects consuming contaminated ground waters, and an adequate Se status in subjects from North America consuming municipal water of low As content. The high As content of hair from people in Bangladesh is the result of a high As consumption from contaminated water compounded by a less than desirable intake of Se (9). From Nepal, the As content of hair corresponded to the known low and high intake of As from contaminated groundwater. The very high Se content found in all hair samples from Nepal might be the result of the use of henna.