BNCT pancreatic cancer treatment strategy with glucose-conjugated boron drug.

Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.

Secondary metabolite pathway of SDG (secoisolariciresinol) was observed to trigger ROS scavenging system in response to Ca2+ stress in cotton.

Ca2+ is an essential nutrient for plants and animals which plays an important role in plant signal transduction. Although the function and regulation of mechanism of Ca2+ in alleviating various biotic and abiotic stresses in plants have been studied deeply, the molecular mechanism to adapt high Ca2+ stress is still unclear in cotton. In this study, 103 cotton accessions were germinated under 200 mM CaCl2 stress, and two extremely Ca2+-resistant (Zhong 9807, R) and Ca2+-sensitive (CRI 50, S) genotypes were selected from 103 cotton accessions. The two accessions were then germinated for 5 days in 0 mM CaCl2 and 200 mM CaCl2 respectively, after which they were sampled for transcriptome sequencing. Morphological and physiological analyses suggested that PLR2 specifically expressed in R may enhance the ability of cotton to scavenge ROS by promoting the synthesis of SDG. In conclusion, this study proposed the adaptation mechanisms to response to the high Ca2+ stress in cotton which can contribute to improve the stress resistance of cotton.

Microstructure and Properties of Mg-Al-Ca-Mn Alloy with High Ca/Al Ratio Fabricated by Hot Extrusion.

Mg-Al-Ca-Mn alloys with Ca/Al ≥ 1 of AX33, AX44, and AX55 were prepared by combining three processes of water-cooling semi-continuous cast, homogenization heat treatment, and hot extrusion. The as-fabricated alloys translated into composites consisting of α-Mg solid solution + granular Al2Ca. These alloys exhibited some favourable properties such as a tensile strength of 324~350 MPa at room temperature and 187~210 MPa at elevated temperature of 423 K, an ignition temperature of 1292~1344 K, and so on. Variation trend between performance and content of Al and Ca is given in this paper. The result indicated that the emerged second-phase Al2Ca in the alloys was beneficial to the improvement in mechanical properties, heat resistance, flame retardation, and corrosion resistance.

Biochemical and molecular investigation of oxidative stress associated with urolithiasis induced by increased dietary calcium or protein in chickens.

This study was carried out to evaluate the effects of induced urolithiasis by high dietary calcium (Ca) or protein levels on biochemical analyte levels, redox status, selected inflammatory cytokines and histopathology in chickens. A total of 90 one-day-old white Hy-Line chicks were fed basal control diets containing 20% crude protein (CP) and 1% Ca until they reached 44 days of age. After that, the birds were divided into three groups (30 birds per group). All management factors (light, temperature, ventilation, stock density and diet) were identical among the three groups throughout the study except for the dietary Ca and protein percentages. Group I was fed a control diet containing 20% CP and 1% Ca, group II was fed a high-Ca diet containing 5% Ca, and group III was fed a high-protein diet containing 25% CP. Our findings clearly demonstrated that dietary imbalance (caused by high-Ca or high-CP levels) per se in chickens was physiologically harmful, as it was accompanied by post-mortem lesions; biochemical, redox status and histopathological alterations; and upregulation of inflammatory cytokines (interleukin (IL)-1ß and IL-6). In particular, the birds fed the high-Ca diet clearly exhibited the most obvious alterations in most of the endpoints. In conclusion, this study constitutes the first extensive investigation of the effects of high-Ca or high-protein diets induced urolithiasis on growth performance, redox status, inflammatory cytokine levels and pathological characterization in chickens.

Inhibitory effect of high calcium concentration on municipal solid waste leachate treatment by the activated sludge process.

This research focused on the inhibitory effects of Ca on the aerobic biological treatment of landfill leachate containing extremely high Ca concentrations. When the Ca concentration in leachate to be treated was more than 4500 mg l-1, the total organic carbon removal rate was significantly reduced and the processing time to achieve the same removal efficiency was 1.4 times that in the control treatment without added Ca. In contrast, the total nitrogen and ammonia nitrogen (NH4+-N) removal efficiencies were positively related to the Ca concentration, increasing from 65.2% to 81.2% and from 69.2% to 83.7%, respectively, when the dosage of added Ca increased from zero to 8000 mg l-1. During aerobic treatment, the reductions of solution Ca concentration were in the range of 1003-2274 mg l-1 and were matched with increases in the Ca content in the residual sludge. The inhibition threshold of Ca in the leachate treated by the activated sludge process appeared to be 4500 mg l-1, which could be realized by controlling the influent Ca concentration and using an appropriate sludge return ratio in the activated sludge process.

Inhibition effects of high calcium concentration on anaerobic biological treatment of MSW leachate.

With the increasing use of municipal solid waste incineration (MSWI) and more stringent limits on landfilling of organic waste, more MSWI bottom ash is being landfilled, and the proportion of inorganic wastes in landfills is increasing, causing the increased Ca concentrations in landfill leachate. In this research, the inhibition effect of Ca concentration on the anaerobic treatment of landfill leachate was studied using a biochemical methane potential experiment. Slight inhibition of methane production occurred when the addition of Ca concentration was less than 2000 mg/L. When the addition of Ca concentration was between 6000 and 8000 mg/L, methane production was significantly reduced (to 29.4-34.8 % of that produced by the BLK reactor), and the lag phase was increased from 8.55 to 16.32 d. Moreover, when the dosage of Ca concentration increased from zero to 8000 mg/L, reductions in solution Ca concentration increased from 929 to 2611 mg/L, and the proportion of Ca in the residual sludge increased from 22.58 to 46.87 %. Based on the results, when the dosage of Ca concentration was less than 4000 mg/L, the formation of Ca precipitates on the surface of sludge appeared to prevent mass transfer and was the dominant reason for the reduction in methane production and sludge biomass. At higher Ca concentrations (6000-8000 mg/L), the severe inhibition of methane production appeared to be caused by the toxic effect of highly concentrated Ca on sludge as well as mass transfer blockage.

The Preventive Effect of Calcium Supplementation on Weak Bones Caused by the Interaction of Exercise and Food Restriction in Young Female Rats During the Period from Acquiring Bone Mass to Maintaining Bone Mass.

Increasing calcium (Ca) intake is important for female athletes with a risk of weak bone caused by inadequate food intake. The aim of the present study was to examine the preventive effect of Ca supplementation on low bone strength in young female athletes with inadequate food intake, using the rats as an experimental model. Seven-week-old female Sprague-Dawley rats were divided into four groups: the sedentary and ad libitum feeding group (SED), voluntary running exercise and ad libitum feeding group (EX), voluntary running exercise and 30% food restriction group (EX-FR), and a voluntary running exercise, 30% food-restricted and high-Ca diet group (EX-FR+Ca). To Ca supplementation, we used 1.2% Ca diet as "high-Ca diet" that contains two-fold Ca of normal Ca diet. The experiment lasted for 12 weeks. As a result, the energy availability, internal organ weight, bone strength, bone mineral density, and Ca absorption in the EX-FR group were significantly lower than those in the EX group. The bone strength and Ca absorption in the EX-FR+Ca group were significantly higher than those in the EX-FR group. However, the bone strength in the EX-FR+Ca group did not reach that in the EX group. These results suggested that Ca supplementation had a positive effect on bone strength, but the effect was not sufficient to prevent lower bone strength caused by food restriction in young female athletes.

A comparative study on Ca content and distribution in two Gesneriaceae species reveals distinctive mechanisms to cope with high rhizospheric soluble calcium.

Excessive Ca is toxic to plants thus significantly affects plant growth and species distribution in Ca-rich karst areas. To understand how plants survive high Ca soil, laboratory experiments were established to compare the physiological responses and internal Ca distribution in organ, tissue, cell, and intracellular levels under different Ca levels for Lysionotus pauciflorus and Boea hygrometrica, two karst habitant Gesneriaceae species in Southwest China. In the controlled condition, L. pauciflorus could survive as high as 200 mM rhizospheric soluble Ca, attributed to a series of physiological responses and preferential storage that limited Ca accumulation in chloroplasts of palisade cells. In contrast, B. hygrometrica could survive only 20 mM rhizospheric soluble Ca, but accumulated a high level of internal Ca in both palisade and spongy cells without disturbance on photosynthetic activity. By phenotype screening of transgenic plants expressing high Ca-inducible genes from B. hygrometrica, the expression of BhDNAJC2 in A. thaliana was found to enhance plant growth and photosynthesis under high soluble Ca stress. BhDNAJC2 encodes a recently reported heat shock protein (HSP) 40 family DnaJ-domain protein. The Ca-resistant phenotype of BhDNAJC2 highlights the important role of chaperone-mediated protein quality control in Ca tolerance in B. hygrometrica. Taken together, our results revealed that distinctive mechanisms were employed in the two Gesneriaceae karst habitants to cope with a high Ca environment.

Estrogen deficiency-induced Ca balance impairment is associated with decrease in expression of epithelial Ca transport proteins in aged female rats.

AIMS: The study is designed to determine whether estrogen and vitamin D endocrine systems interact to regulate calcium (Ca) balance as well as changes in mRNA expression of epithelial Ca transport proteins involved in intestinal and renal Ca transport in aging animals in response to ovariectomy and low dietary Ca intake. MAIN METHODS: Eleven-month-old female sham or ovariectomized (OVX) rats were divided into four groups and fed with either a low-Ca (LCD; 0.1% Ca, 0.65% P) or a high-Ca (HCD; 1.2% Ca, 0.65% P) diet for 12weeks. Ca balance and mRNA expression of Ca transport proteins in the intestine and kidney from rats were systematically studied. KEY FINDINGS: OVX rats fed with LCD resulted in a negative Ca balance. LCD suppressed serum Ca in OVX but not sham rats, resulting in an induction of serum PTH and 1,25(OH)2D3 levels. The surge in serum 1,25(OH)2D3 levels in LCD-fed OVX rats was associated with an increase in mRNA expression of intestinal transient receptor potential cation channel (TRPV6) and calbindin D9k (CaBP9k) as well as renal vitamin D receptor (VDR), but such an induction was unable to restore Ca balance in vivo. In contrast, the negative Ca balance was associated with suppression of intestinal plasma membrane Ca pump (PMCA1b) and renal transient receptor potential cation channel (TRPV5), calbindin D28k (CaBP28k) and PMCA1b mRNA expression in aged OVX rats. SIGNIFICANCE: Negative Ca balance in aged female OVX rats is associated with estrogen-dependent and vitamin D-independent downregulation of epithelial Ca transport protein mRNA expression.

Myxedema ascites with high CA-125: Case and a review of literature.

Ascites appearing in a previously healthy female patient is usually ascribed to a variety of causes, among which, is a cancerous process, especially if it comes with a raised CA-125 level. Although the CA-125 antigen is present on more than 80% of malignant epithelial ovarian tissue of non-mucinous type, it is also found on both healthy and malignant cells of mesothelial and non-mesothelial origin. Myxedema ascites which is caused by hypothyroidism is a rare entity, but on the other hand is easy to treat. It is one of the differential diagnoses when the ascites is refractory to treatment and no other obvious cause can be identified. If the diagnosis is delayed, patients will frequently receive unnecessary procedures, while treatment has very good response rates and ascites resolve with serum CA-125 normalization after adequate hormonal treatment.