Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin.

The oxidative pentose phosphate pathway (PPP) is crucial for cancer cell metabolism and tumor growth. We recently reported that targeting a key oxidative PPP enzyme, 6-phosphogluconate dehydrogenase (6PGD), using our novel small-molecule 6PGD inhibitors Physcion and its derivative S3, shows anticancer effects. Notably, humans with genetic deficiency of either 6PGD or another oxidative PPP enzyme, glucose-6-phosphate dehydrogenase, exhibit non-immune hemolytic anemia upon exposure to aspirin and various antimalarial drugs. Inspired by these clinical observations, we examined the anticancer potential of combined treatment with 6PGD inhibitors and antimalarial drugs. We found that stable knockdown of 6PGD sensitizes leukemia cells to antimalarial agent dihydroartemisinin (DHA). Combined treatment with DHA and Physcion activates AMP-activated protein kinase, leading to synergistic inhibition of human leukemia cell viability. Moreover, our combined therapy synergistically attenuates tumor growth in xenograft nude mice injected with human K562 leukemia cells and cell viability of primary leukemia cells from human patients, but shows minimal toxicity to normal hematopoietic cells in mice as well as red blood cells and mononucleocytes from healthy human donors. Our findings reveal the potential for combined therapy using optimized doses of Physcion and DHA as a novel antileukemia treatment without inducing hemolysis.

Calcium-binding protein expression in peritoneal endometriosis-associated nerve fibres.

BACKGROUND: Recent studies demonstrated the potential involvement of nerve fibres in the chronic inflammatory process of endometriosis. We aimed to characterize nerve fibres in the proximal and distal areas of the peritoneal endometriotic lesions in order to understand the chronic inflammatory process in endometriosis. METHODS: Peritoneal endometriotic lesions (proximal area) (n = 17), the matching unaffected peritoneum (distal area) and healthy peritoneum of patients without endometriosis (n = 15) were analysed with the neuronal markers PGP 9.5, calbindin, calretinin and parvalbumin. Peritoneal fluids of women with and without endometriosis were used for Western blot analysis and for the neuronal growth assay. The protein expression of neuronal PC-12 cells incubated with peritoneal fluids was analysed. RESULTS: The overall nerve fibre density was significantly reduced in the distal area of the lesion when compared with the proximal area or with healthy peritoneum. The density of calbindin-, calretinin- and parvalbumin-positive nerve fibres was significantly increased in the endometriosis group. Calretinin expression was elevated in the peritoneal fluid of women with symptomatic endometriosis when compared with women with asymptomatic endometriosis. Furthermore, PC-12 cells incubated with peritoneal fluid of women with endometriosis showed a higher proliferation rate and a stronger neurite outgrowth than the control group. PC-12 cells incubated in peritoneal fluids of women with endometriosis expressed less calretinin but more calbindin than the control group. CONCLUSIONS: Calcium-binding proteins seem to be increased in endometriosis-associated nerve fibres and might play an important role in the chronic inflammatory condition and the pain pathogenesis of endometriosis.

Lymphangiogenesis in deep infiltrating endometriosis.

BACKGROUND: In patients diagnosed with deep infiltrating endometriosis (DIE), foci of endometriosis are detected in mesorectal lymph nodes (LNs) after segmental bowel resection and in pelvic sentinel LNs. Lymph vessels (LVs) seem to be the possible routes for the dissemination of endometriotic cells from DIE-lesions to LN. Therefore, we conducted a study to investigate the occurrence and density of LV and lymphangiogenic growth factors in DIE. METHODS: Included in this study were 38 premenopausal women who underwent surgery due to symptomatic rectovaginal DIE. In order to identify LV, immunohistochemical analysis with anti-Podoplanin (D2-40), LYVE-1 and Prox-1 was performed. Furthermore, the expression of VEGF-C and VEGF-D in endometriotic tissue was investigated. RESULTS: LV density (LVD) of DIE lesions was significantly higher compared with healthy corresponding tissue. All LV makers could be detected, and the density of LYVE-1- or Prox-1-positive LV was significantly higher than that of D2-40-positive LV. Endometriotic epithelial cells and stromal cells showed a moderate to strong VEGF-C and VEDF-D expression. CONCLUSIONS: DIE lesions have lymphangiogenic properties, probably leading to endometriosis-like cells in lymphatic vessels and LNs featuring a loco-regional disease.

Comparison of the chemical composition and nutritional value of Amaranthus cruentus flour and its protein concentrate.

Plants constitute an alternative source of proteins in the human diet, with advantages over animal proteins because of their low content of saturated fats and absence of cholesterol. Within the framework of a wider research project on the role of Amaranthus cruentus (Ac) in lipid metabolism, in this work the chemical composition and biological value of the Ac flour and its protein concentrate were compared. Proximate chemical composition, amino acid and fatty acid profiles, some antinutrient factors, and biological values were determined for Ac seed flour and its protein concentrate obtained by extraction at pH 11 and precipitation at pH 4.5. The flour protein content was 16.6 g% while that of the concentrate was 52.56 g%. The content of the soluble dietary fiber with a hypolipemic function was notably higher in the protein concentrate (12.90 g%) than in the seed flour (4.29 g%). The protein concentrate also exhibited a higher content of insoluble dietary fiber. The Ac flour and the concentrate contain 75.44 and 56.95% unsaturated fatty acids, respectively. Squalene, which affects the biosynthesis of cholesterol, was detected both in the flour and the concentrate oils, with a higher content in the concentrate (9.53%) as compared to the flour (6.23%). Comparison of the amino acid composition with the FAO pattern protein indicated that the concentrate does not have limiting amino acids, while the flour has leucine, threonine, and valine. The content of lysine was high in both the flour and the concentrate, making these products particularly useful as a complement for cereal flour, which is deficient in this amino acid. The biological quality analysis demonstrated an improvement in the quality of the concentrate. The presence of saponins, phytic acid, and trypsin inhibitors in the concentrate, which favor the metabolism of lipids, suggests that consumption of the concentrate might reduce the risk of heart disease.

[Chemical-nutritional evaluation of Sorghum saccharatum var. sugar drip. A supplementation study with lactoserum proteins]. / Evaluación químico-nutricional de Sorghum saccharatum var. sugar drip. Estudio de complementación con proteína de lactosuero.

The chemical-nutritional composition and some indexes of biological quality of sorghum (Sorghum saccharum, var. sugar drip) unwashed whole flour were studied. The culture and selection of sorghum were assayed in the "San Roque" Experimental Station of the Agriculture Department, Undersecretary of Agricultural Affairs, San Luis, Argentina. The obtained protein content was 7.5% (Nx6.25). The values for net protein utilization (NPU); true digestibility (tD); net protein ratio (NPR) and and relative net protein ratio (RNPR) were 12.4 +/- 0.6, 22.0 +/- 0.2, 0.8 +/- 0.1 and 24%, respectively. Deficient nitrogen utilization constitutes a limitation for the use of sorghum. However, considering its abundance and low cost, sorghum could become a profitable feeding resource if conveniently supplemented without increasing costs. Sorghum flour was supplemented with protein recovered from ricotta serum (50:50), discarded as industrial waste, in order to compensate for lysine and threonine deficiency in this cereal. Studies performed on this mixture gave RNPR values of 85.7%. This might permit us to infer that despite its low biological value, sorghum can be used as food resource, potentially for poultry, with adequate supplementation.

[Protein concentrate from Amaranthus mantegazzianus. Physical, chemical and biological characterization]. / Concentrado proteico de Amaranthus mantegazzianus. Caracterización físico-químico-biológica.

The aim of this study was the obtainment of a protein concentrate (PC) from A. mantegazzianus seed powder and the evaluation of its percentual chemical composition, functional properties and biological protein quality. For this purpose, the optimal PC conditions assessed were: pH values for maximal and minimal solubility 11.5 and 5 respectively; flour/solvent ratio 1:20, stirring time 1.30 h at room temperature. A product exhibiting a protein content value of 55.3 g/ 100 g was obtained. The functional properties were evaluated by means of the following indexes Nitrogen Solubility Index (NSI) 94.9% at pH 11.5; emulsification activity (EA) 47 +/- 4.8; water absorption capacity (WAC) 2.1 +/- 0.3 and oil absorption capacity (AOAC) 0.8 +/- 0.1. The water and oil absorption index (WOAI) expressed as WAI/OAI was 2.6. These results render the product useful for bread baking due its high solubility, water absorption capacity and the OAI value which shows hydrophilic characteristics. The PC biological quality were calculated determining the net protein utilization (NPU): 64 +/- 7.4, true digestibility (tD): 88 +/- 7.6, biological value (BV): 73, intake: (I) 74 +/- 8.9 and weight gain (delta P) 23 +/- 4.5. The results of this study show a good nitrogen utilization, which plus the functional characterization let us infer that the A. mantegazzianus PC constitutes a good resource for the enrichment of bread baking products, preparing of diets for special regimens and protein complement for deficient foods.

Chemical and nutritional assessment of heifer's omasum flour.

The chemical and nutricional properties of flour from total calf omasum are assessed with the purpose of considering the utilization of a waste product from the meat industry as animal food. The results of the chemical percent analysis showed a high protein content of 78.6 g/100 g, a total lipid amount of 3.70 g/100 g and a cholesterol concentration of 0.14 g/100 g. From the study of the total saturated fatty acid composition it is deduced that palmitic acid prevails with a value of 28.4%. Unsaturated fatty acids show a value of 75% for oleic acid, this being the highest concentration. The values found for lipid composition are similar a fat bovine. Biological techniques were used to evaluate nitrogen utilization: Net Protein Utilization (NPU), true Digestibility (tD) and Biological Value (BV); a proof with casein as reference was simultaneously performed. The NPU, tD and the BV values found were: 58 +/- 7.0; 87 +/- 8.5 and 67 respectively. These results demonstrate that the assayed meat by-product had the adecuate nutritive elements for its industrialization as porcine balanced food.

Archives of Medical Research: an historical and subject coverage overview.

A bibliometric study about the subject content of the articles published in the Mexican scientific journal Archives of Medical Research is reported. The journal, published by the Mexican Institute of Social Security (IMSS), is comprised of 100 regular issues and 12 special supplements giving a total amount of 1,424 reports on medical research performed in Mexico during the last 25 years. According to the type of studies published during this period, we found that there is a similar percent of biomedical and clinical reports in the journal (47 and 42%, respectively) and a low proportion of epidemiological and medical educational reports (8 and 3%, respectively). Six thematic areas of research have been permanently published in this journal: investigations on infectious and neurological diseases being the areas mainly represented (34% of the total, corresponding to 17% in each area), followed by studies in reproductive biology (10%) and endocrine (7%), oncological (5%) and cardiovascular (3%) diseases. The tendency of the subjects covered by the journal during this period shows an increment in reports on infectious and parasitic disorders together with an increase in publications related to medicinal plant pharmacology; reproductive biology and endocrine studies show also an increasing tendency. On the other hand, a moderate decrease in studies related to neurological, oncological and cardiovascular diseases is observed. The origin of contributions during the last five years has balanced the proportion of papers published from IMSS scientists, other Mexican biomedical researchers and foreign contributions, thus reflecting favorably the recent changes in the journal's policies. This journal represents a clear example of a scientific publication edited in a developing country, originating as a national publication that evolved progressively into an international biomedical journal.

[Mountain chinchilla (Lagostomus maximus maximus Blainv) meat. Biological value]. / Carne de vizcacha (Lagostomus maximus maximus Blainv). Valor biológico.

In order to establish the vizcacha meat quality as food, the percentual chemical composition, cholesterol content and values of some fatty acids were determined. Assays were performed using Wistar rats for estimation of Net Protein Utilization (UPN), True Digestibility (TD) and Biological Value (BV). The results obtained were: protein, 23.87 g/100 g; total lipids, 3.74g/100g and a low content of cholesterol of 50 mg/100g. From the analysis of the fatty acids composition it is noticed a remarkable high proportion of insatured C18 fatty acids. The nitrogen availability calculated from UPN studies gave a value of 60.50 +/- 9.7, a TD of 85.00 +/- 13.20 and a BV of 70.60. Considering on the whole the results here obtained and the optimal approval of this product by man, it is inferred that vizcacha meat constitutes a good base for the production of foods suitable to be manufactured as can products. An adequate promotion of this product will be needed for its introduction in new markets.

[Chemical composition of 6 unconventional plants from Oaxaca State, Mexico, as potential resources for animal feed]. / Estudio de la composición química de 6 plantas no convencionales del Estado de Oaxaca, México, como recursos potenciales en la alimentación animal.

Characteristics and distribution of six plants are described. The chemical composition and in vitro digestibility of leaf and stem of Polymnia maculata, Trigonospermum annuum, Buddleia parviflora Kunt, Canna indica L, Gnaphalium oxyphyllum y Saurauia scabrida Hensl., selected for farmers information, were analysed as a potential resources in animal feeding. The results in dry matter: Crude protein (%): Go and Ss 10.9, Bp 16.7, Pm 11.7 and Ta 11.3. Cell wall (%): Go 54.1, Ss 52.3, Ci 54.4, Bp 68.3, Pm 27.8 and Ta 30.9. Lignin (%): Go and Ss 16.6, Ci 15.5, Bp 10.4, Pm 10.6 and Ta 13.3. IN vitro dry matter digestibility (%): Go 55.1, Ss 37.6, Ci 55.4, Bp 46.5, Pm 82.4 and Ta 81.4. Calcium and phosphorus (mg/100g) respectively: Go 1095 and 379, Ss 1132 and 387, Ci 600 and 421, Bp 800 and 855, Pm 1146 and 421 and Ta 905 and 480. Tannic acid (mg/100g): Go 1450, Ss 1480, Bp 575, Ci 518, Pm 3329 and Ta 2760. Trypsin inhibitor (UIT/g): Go 22264, Ss 29720, Bp 755, Ci 4228, Pm 931 and Ta 4412. Hemagglutinins were detected in Pm and Ta. Alkaloids were detected as scarce in Bp, Ci and Pm, moderate in Ta. Saponins and Cyanogenic glucosides were not detected. It is concluded that Pm and Ta could be considered as a forage for ruminants; Go, Bp and Ci as a complement; recommended the voluntary intake, in vivo digestibility and weight increase trials.

[Effects of treatment with polyvinylpyrrolidone on nutritional quality of sorghum]. / Efectos del tratamiento con polivinilpirrolidona (PVP) sobre la calidad nutricional del sorgo.

The purpose of this paper was to show that a high polyphenolic compound content in the sorghum grain (Sorghum saccharatum, var sugar drip) has an unfavorable influence on the nitrogen absorption. In order to arrive at this conclusion, the tannin content in sorghum flour was reduced by means of a treatment with polyvinylpyrrolidone (PVP) as a complexing agent. Several biological experiments were performed with non-treated flour (S) and with PVP-treated flour (S + PVP). Treatment improved true digestibility (D), having obtained the following values: for S = 31 +/- 2.67, and for S + PVP = 55.8 +/- 3.48 (significance P less than 0.001). The tannin evaluation yielded the following results: S = 1.90 g/100 g, and S + PVP = 0.85 g/100 g reported as tannic acid. The digestibility increase induced a better nitrogenous utilization, the net protein utilization (NPU) values being from 19 +/- 1.58 to 37 +/- 3.36 for S, and S + PVP, respectively.

[Obtaining flour and protein concentrate from seeds of Melilotus albus. Study of the protein quality]. / Obtención de harina y concentrado proteínico de semillas de Melilotus albus. Estudio de la calidad de la proteína.

The present research was carried out to determine the nutritive quality of the flour and protein concentrate from Melilotus albus (white clover) seeds. The flour was studied first. The protein analysis showed methionine to be the first limiting amino acid with a chemical score of 25, with threonine as the second. The biological value obtained was 27. Supplementation studies were performed with different levels of methionine and it was found that the 0.3% level resulted in the best net performance. The biological value obtained under these conditions was 60. The protein efficiency ratio (PER) was also determined, with a value of 1.40 after being corrected with respect to casein. The protein was isolated after studying the pH optimum solubility and precipitation conditions until the flour coumarin compounds were eliminated. Further biological experiments were carried out with the supplemented isolated protein. Under these conditions, a PER value of 2.4 and a biological value of 69 were obtained. No toxicity was observed in rats of both sexes by administration of the protein concentrate during 60 days, at least in the parameters studied during this period.

[Cassia aphylla flour. Study of its chemical composition and the biological quality of its proteins]. / Harina de Cassia aphylla. Estudio de la composición química y calidad biológica de la proteina.

The chemical and biological value of the flour from Cassia aphylla was determined. The chemical study showed that this flour contains a good amount of protein, calcium, phosphorus, iron, ascorbic acid, niacin and thiamine. It is also a good source of lysine and sulfur amino acids. Tests concerning nutritive value carried out were: net protein utilization (NPU), 54.7 +/- 2.45; digestibility, 71.00 +/- 0.30; biological value, 77.00, and protein efficiency ratio (PER) 1.74, corrected with respect to casein. Toxicological tests were performed with rats during a period of 30 days. The criteria used in these tests were: hematological data, organ weights, liver composition and histopathology of the liver and kidney. These tests revealed no signs of pathological damage under the experimental conditions used by us. Based on these results, it can be concluded that this product has a potential value as a feedstuff.

Harina de Cassia aphylla. Estudio de la composicion quimica y calidad biologica de la proteina. / Cassia aphylla flour.Study of the chemical composition and biological quality of the protein

El presente estudio se realizo con el objeto de establecer las caracteristicas quimicas y biologicas de la harina de Cassia aphylla. El estudio quimico porcentual evidencio un buen contenido proteinico, asi como de calcio, fosforo, hierro, acido ascorbico, niacina y tiamina. La determinacion de aminoacidos demostro que la harina en estudio es una fuente muy buena de lisina y aminoacidos azufrados.La utilizacion proteinica neta (NPU) encontrada fue de 54.70 mas o menos 2.45, la digestibilidade, de 71.00 mas o menos 0.3 y el valor biologico, de 77.00. La razon de eficiencia proteinica (PER) fue de 1.74 corregida con respecto a la caseina. Para determinar su inocuidad se realizaron ensayos toxicologicos en ratas durante un periodo de 30 dias.Los analisis hematologicos, peso de organos, composicion del higado y rinon, no mostraron dano patologico en las condiciones en que se realizo el ensayo. A partir de estos resultados, es posible concluir que el producto estudiado es un buen recurso para la alimentacion animal