The Determination of Efficacy of CircuCare on Blood Circulation and Metabolism: An Animal Model Study.

OBJECTIVES: To determine whether feeding CircuCare to rats improves blood circulation, metabolism, immune regulation, endocrine activity, and oxidative stress. METHODS: 28 eight-week-old male Sprague-Dawley rats were evenly randomized into control and experimental groups. The control group was fed with ordinary drinking water, while the experimental group was fed with CircuCare at a daily dose of 93.75 mg per 300 g of body weight over eight weeks. Both groups were subjected to a swimming test, and blood samples were taken to observe any variations in various biochemical parameters before and after the test. Key Findings. The experimental group's mean swimming exhaustion duration was 53.2% longer and had a significantly higher lactic acid removal ratio. Their mean prostaglandin E2 level and mean glucose, cortisol, and glutathione level (30 minutes after swimming test) were also significantly higher. No undesirable impacts from CircuCare relating to general blood biochemistry values and bone mineral density were reported. CONCLUSIONS: The present results show that CircuCare can be safely used to increase stamina and exercise capability, expedite the metabolism of lactic acid, accelerate muscle repair, and promote the antioxidant activity of cells in rats.

Glycerol Monocaprylate Modulates Gut Microbiota and Increases Short-Chain Fatty Acids Production without Adverse Effects on Metabolism and Inflammation.

Glycerol monocaprylate (GMC) is a glycerol derivative of medium-chain fatty acids (MCFAs) and is widely used as a preservative in food processing. However, GMC and its hydrolytic acid (octylic acid) have antibacterial properties that may affect the physiology and intestinal microecology of the human body. Therefore, in this study, the effects of two different dosages of GMC (150 and 1600 mg kg-1) on glucose, lipid metabolism, inflammation, and intestinal microecology of normal diet-fed C57BL/6 mice were comprehensively investigated. The obtained results showed that the level of triglycerides (TGs) in the low-dose group down-regulated significantly, and the anti-inflammatory cytokine interleukin 10 (IL-10) significantly increased, while the pro-inflammatory cytokines monocyte chemotactic protein 1 (MCP-1) and interleukin 1beta (IL-1ß) in the high-dose group were significantly decreased. Importantly, GMC promoted the α-diversity of gut microbiota in normal-diet-fed mice, regardless of dosages. Additionally, it was found that the low-dose treatment of GMC significantly increased the abundance of Lactobacillus, while the high-dose treatment of GMC significantly increased the abundance of SCFA-producers such as Clostridiales, Lachnospiraceae, and Ruminococcus. Moreover, the content of short-chain fatty acids (SCFAs) was significantly increased by GMC supplementation. Thus, our research provides a novel insight into the effects of GMC on gut microbiota and physiological characteristics.

Ninjin'yoeito modulates feeding and activity under negative energy balance conditions via the NPY system.

The central and peripheral neuropeptide Y (NPY) system is critically involved in feeding and energy homeostasis control. Disease conditions as well as aging can lead to reduced functionality of the NPY system and boosting it represents a promising option to improve health outcomes in these situations. Here we show that Ninjin-yoeito (NYT), a Japanese kampo medicine comprising twelve herbs, and known to be effective to treat anorexia and frailty, mediates part of its action via NPY/peptide YY (PYY) related pathways. Especially under negative energy homeostasis conditions NYT is able to promote feeding and reduces activity to conserve energy. These effects are in part mediated via signalling through the NPY system since lack of Y4 receptors or PYY leading to modification in these responses highlighting the possibility for combination treatment to improve aging related conditions on energy homeostasis control.

Aqueous extract of pomegranate enriched in ellagitannins prevents anxiety-like behavior and metabolic changes induced by cafeteria diet in an animal model of menopause.

Women around menopause are vulnerable to present psychiatric and metabolic disorders; thus, therapies that contribute to treat both pathologies are required. Previous reports showed that an aqueous extract of pomegranate (Punica granatum), enriched in ellagitannins, exerts an antidepressant-like effect in ovariectomized rats. We analyze whether this aqueous extract of P. granatum (AE-PG) prevents the anxiety-like behavior induced by a cafeteria diet (CAF) in middle-aged ovariectomized rats at the same time that it prevents an increase in body weight, glucose, lipids, and the changes on mRNA expression of the peroxisome proliferator-activated receptor-gamma (PPAR-γ) in the liver. Also, the effects of AE-PG on the protein levels of PPAR-γphospho-PPAR-γ, extracellular signal-regulated protein kinase (ERK1/2) and phospho-ERK1/2 were measured in the hippocampus and amygdala. CAF induced anxiety-like behavior, augmented lipids and glucose blood levels, body weight, visceral fat, insulin resistance, and decreased mRNA expression of PPAR-γ in the liver. In rats fed with the CAF, AE-PG prevented the anxiety-like behavior, reduced body weight, lowered lipid levels, reduced insulin resistance, and increased PPAR-γ mRNA expression in the liver. In the hippocampus, ERK1/2 but not PPAR-γ protein levels were decreased by CAF, while AE-PG prevented these effects. In the amygdala, CAF increased the phosphorylation of PPARγ, and AE-PG prevented it. In contrast, AE-PG rescued the decreased ERK1/2 protein level in the hippocampus caused by CAF. In conclusion, AE-PG treatment prevented anxiogenic and metabolic effects induced by CAF, and its effects appear to be mediated by ERK1/2 and PPARγ depending on the brain area studied.

Selenium supplementation during pregnancy and lactation promotes metabolic changes in Wistar rats' offspring.

Epidemiological and animal studies have demonstrated a strong association between selenium (Se) supplementation and metabolic disorders, we aimed to evaluate whether maternal Se supplementation was able to change metabolic parameters in rats' offspring. Moreover, as Se is a deiodinase (DIO) cofactor, we decided to investigate how thyroid hormones (THs) would be involved in such metabolic changes. Thereby, two groups (n = 6, ~250 g) of female Wistar rats underwent isotonic saline or sodium selenite (1 mg/kg, p.o.) treatments. Although there were no significant differences in body weight between groups, the Se treatment during pregnancy and lactation increased milk intake and the visceral white adipose tissue (WAT) in offspring. The rats whose mothers were treated with Se also presented an improvement in the glucose tolerance test and in the glucose-stimulated insulin secretion. Regarding the lipid metabolism, the Se group had a reduction of triglycerides in the liver and in WAT. These metabolic changes were accompanied by an increase in serum triiodothyronine (T3 ) and in DIO 2 expression in brown adipose tissue (BAT). We further demonstrate an increased expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) and nuclear respiratory factor-1 (NRF-1) mRNA in the liver. In adulthood offspring, Se supplementation programs thyroid function, glucose homeostasis, and feeding behaviour. Taken together, there is no indication that Se programming causes insulin resistance. Moreover, we conjecture that these metabolic responses are induced by increased thyroxine (T4 ) to T3 conversion by DIO2 in BAT and mediated by altered transcription factors expression associated with oxidative metabolism control in the liver.

A Compound Isolated from Phyllanthus tenellus Demonstrates Metabolic and Vascular Effects In Vitro.

Common chronic conditions such as metabolic syndrome and diabetes are increasingly associated to metabolic and cardiovascular complications. Although Phyllanthus tenellus leaves have been used in decoctions as a popular remedy to control blood glucose levels and hypertension, its use needs a scientific basis. This study was therefore undertaken to report a phytochemical analysis of P. tenellus leaves and to test if the main active compound has potential to simultaneously tackle several pathophysiological features of metabolic syndrome and diabetes-related metabolic and vascular disorders such as hyperglycaemia, increased platelet activation, and endothelial dysfunction. We performed a partition of the methanolic extract of P. tenellus leaves among different organic solvents followed by chromatographic separation guided by the rat liver microsomal glucose-6-phosphatase assay. Two known tannins were identified by spectroscopic methods as pinocembrin-7-O-[3″-O-galloyl-4″,6″-(S)-hexahydroxydiphenoyl]-α-D-glucose, named P7OG by us, and gemin D. The structural determination of the isolated compounds was based on spectral data. The ability of the main active component, P7OG, to inhibit human platelet aggregation and to modify vascular reactivity of rat aortic rings incubated with high glucose (D-glucose 55 mM) was then evaluated. P7OG was further able to inhibit platelet aggregation induced by adenosine 5'-diphosphate and collagen, showed vasorelaxant effects in arteries precontracted with phenylephrine, and reverted the endothelium-dependent impairment effect of high glucose in rat aortic rings. In conclusion, one tannin isolated from P. tenellus showed promising metabolic, antiaggregant, and vascular effects, which suggests the potential beneficial use of P. tenellus to tackle complex cardiometabolic diseases.

[Investigation of the metabolic effects of selenium-modified Essentuki mineral water in the experiment]. / Izuchenie metabolicheskikh éffektov modifitsirovannoi selenom mineral'noi vody Essentukskogo tipa v éksperimente.

BACKGROUND: The urgent tasks of experimental balneology are to design and investigate of the action of native mineral waters (MW) enriched with essential trace elements in order to improve their therapeutic and prophylactic effects. OBJECTIVE: To investigate the mechanisms of direct action of the cycle intake of Essentuki MWs modified with selenium (Essentuki Novaya - MW1, Essentuki No. 4 - MW2) on healthy animals. MATERIAL AND METHODS: According to the experimental conditions, 102 male albino rats were divided into 7 groups using a simple randomization method. Group 1 (n=15) received only drinking water (DW) (a control group); Group 2 (n=13) used native MW1; Group 3 (n=13) took native MW2; Group 4 (n=15) had MW1 with selenium (MW1Se1 - 3 mcg/kg); Group 5 (n=15) received MW1Se2; Group 6 (n=15) had MW2Se1 - 300 mcg/kg; and Group 7 (n=16) used MW2Se2. RESULTS: After cycle drinking, the body weight of the animals in the experimental groups did not significantly differ from that in the control group and was determined within the normal species range. X-ray densitometry showed that the body fat composition in the rats was lower than the control values only after MW1Se1, MW1Se2, and MW2Se1 cycles. The rat lipid spectrum in different groups displayed differences: the atherogenic index was low after MW1, MW1Se1, and MW1Se2 cycles. The blood glucose levels increased in the rats after drinking native MWs (F=2.7; p=0.01). After selenium-modified MW cycles, the blood glucose levels corresponded to the control values. The blood of experimental and control animals showed no differences in bone mineral density (BMD), levels of hormones (insulin, thyroxine, dehydroepiandrosterone (DHEA) and end products of protein metabolism. Selenium-modified Essentuki No. 4 changed the orientation of functional relationships from negative to positive ones between glucose and BMD. CONCLUSION: The findings suggest that cycle drinking with native and selenium-enriched Essentuki MWs differently affect the animals. The Essentuki Novaya MW (MW1, MW1Se1, and MW1Se2) drinking cycles predominantly affected in reducing blood atherogenic lipids. The volume of an animal fat component was lower after selenium-modified Essentuki Novaya and Essentuki No. 4 water (MW1Se1, MW1Se2, and MW2Se1) cycles. A direct relationship between DHEA and BMD was found in animals after using the selenium-enriched Essentuki No. 4 cycle.

DI/LC-MS/MS-Based Metabolome Analysis of Plasma Reveals the Effects of Sequestering Agents on the Metabolic Status of Dairy Cows Challenged with Aflatoxin B1.

The study applied a targeted metabolomics approach that uses a direct injection and tandem mass spectrometry (DI-MS/MS) coupled with a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics of plasma to evaluate the effects of supplementing clay with or without Saccharomyces cerevisiae fermentation product (SCFP) on the metabolic status of dairy cows challenged with aflatoxin B1. Eight healthy, lactating, multiparous Holstein cows in early lactation (64 ± 11 DIM) were randomly assigned to one of four treatments in a balanced 4 × 4 duplicated Latin square design with four 33 d periods. Treatments were control, toxin (T; 1725 µg aflatoxin B1 (AFB1)/head/day), T with clay (CL; 200 g/head/day), and CL with SCFP (YEA; 35 g of SCFP/head/day). Cows in T, CL, and YEA were dosed with aflatoxin B1 (AFB1) from days 26 to 30. The sequestering agents were top-dressed from day 1 to 33. On day 30 of each period, 15 mL of blood was taken from the coccygeal vessels and plasma samples were obtained from blood by centrifugation and analyzed for metabolites using a kit that combines DI-MS/MS with LC-MS/MS-based metabolomics. The data were analyzed using the GLIMMIX procedure of SAS. The model included the effects of treatment, period, and random effects of cow and square. Significance was declared at p ≤ 0.05. Biomarker profiles for aflatoxin ingestion in dairy cows fed no sequestering agents were determined using receiver-operator characteristic (ROC) curves, as calculated by the ROCCET web server. A total of 127 metabolites such as amino acids, biogenic amines, acylcarnitines, glycerophospholipids, and organic acids were quantified. Compared with the control, T decreased (p < 0.05) plasma concentrations of alanine, leucine, and arginine and tended to decrease that of citrulline. Treatment with CL had no effects on any of the metabolites relative to the control but increased (p ≤ 0.05) concentrations of alanine, leucine, arginine, and that of citrulline (p = 0.07) relative to T. Treatment with YEA resulted in greater (p ≤ 0.05) concentrations of aspartic acid and lysine relative to the control and the highest (p ≤ 0.05) plasma concentrations of alanine, valine, proline, threonine, leucine, isoleucine, glutamic acid, phenylalanine, and arginine compared with other treatments. The results of ROC analysis between C and T groups revealed that the combination of arginine, alanine, methylhistidine, and citrulline had sufficient specificity and sensitivity (area under the curve = 0.986) to be excellent potential biomarkers of aflatoxin ingestion in dairy cows fed no sequestering agents. This study confirmed the protective effects of sequestering agents in dairy cows challenged with aflatoxin B1.

Does cartilage ERα overexpression correlate with osteoarthritic chondrosenescence? Indications from Labisia pumila OA mitigation.

Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed after treatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterally ovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX+OA control, OVX+OA + diclofenac (5 mg/kg) (positive control), OVX+OA + LP leaf extract (150 and 300 mg/kg) and healthy sham control. After 8 weeks' treatment, their conditions were evaluated via serum biomarkers, knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilage erosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenac and the non-treated OA. The cartilage catabolic markers' (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa, CASP3 and HIF-2 alpha) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased by LP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilage protective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondral bone restoration. The cartilage ER alpha over-expression showed a strong positive correlation with MMP-13, COL10 alpha1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.

Formononetin Antagonizes the Interleukin-1ß-Induced Catabolic Effects Through Suppressing Inflammation in Primary Rat Chondrocytes.

In the present study, we demonstrated the anti-catabolic effects of formononetin, a phytoestrogen derived from herbal plants, against interleukin-1ß (IL-1ß)-induced severe catabolic effects in primary rat chondrocytes and articular cartilage. Formononetin did not affect the viability of primary rat chondrocytes in both short- (24 h) and long-term (21 days) treatment periods. Furthermore, formononetin effectively antagonized the IL-1ß-induced catabolic effects including the decrease in proteoglycan content, suppression of pericellular matrix formation, and loss of proteoglycan through the decreased expression of cartilage-degrading enzymes like matrix metalloproteinase (MMP)-13, MMP-1, and MMP-3 in primary rat chondrocytes. Moreover, catabolic oxidative stress mediators like nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin E2 were significantly downregulated by formononetin in primary rat chondrocytes treated with IL-1ß. Sequentially, the upregulation of pro-inflammatory cytokines (like IL-1α, IL-1ß, IL-6, and tumor necrosis factor α), chemokines (like fractalkine, monocyte chemoattractant protein-1, and macrophage inflammatory protein-3α), and vascular endothelial growth factor were significantly downregulated by formononetin in primary rat chondrocytes treated with IL-1ß. These data suggest that formononetin may suppress IL-1ß-induced severe catabolic effects and osteoarthritic condition. Furthermore, formononetin may be a promising candidate for the treatment and prevention of osteoarthritis.

Influence of Diet Enriched with Cocoa Bean Extracts on Physiological Indices of Laboratory Rats.

Cocoa bean is a rich source of polyphenols, mainly flavonoids which have a wide range of biological properties. The aim of the study was to determine the physiological indices of laboratory rats as a response to diets containing water extracts of raw or roasted cocoa beans of Forastero variety, as well as purified monomeric flavan-3-ols fraction isolated from them. The influence of these extracts on selected parameters was studied during 4 weeks feeding. The samples of rats feces were collected throughout the experiment and after its completion, biological samples (intestines content, blood, and organs) were retrieved individually from each rat and subjected to analyses. The observed changes in the gastrointestinal tract functioning indices and metabolism indicators, determined throughout the study and after its completion, confirm to some extent the biological activity of polyphenol extracts of cocoa beans. The differences in the results obtained for the analyzed parameters of the gastrointestinal tract revealed that the cocoa bean extracts differently affected the physicochemical properties of rats' intestines. The results indicate the beneficial effects of the applied nutrition treatment on the activity of cecal enzymes and the content of volatile fatty acids in the gut.

IL6 receptor blockade preserves articular cartilage and increases bone volume following ischemic osteonecrosis in immature mice.

OBJECTIVE: Juvenile ischemic osteonecrosis (JIO) of the femoral head is one of the most serious hip disorders causing a permanent deformity of the femoral head in childhood. We recently reported that interleukin 6 (IL6) is predominantly increased in the hip synovial fluid of patients with JIO and that articular chondrocytes are primary source of IL6. This study investigated whether an inhibition of IL6 receptor improves cartilage preservation and bone healing in JIO. METHOD: A small animal model (i.e., 6-week-old mouse) of JIO was treated with either saline or tocilizumab, an IL6 receptor blocker, for 6 weeks. RESULTS: TUNEL-positive chondrocytes in the articular cartilage were reduced by the tocilizumab treatment, concomitant with the increase in cartilage matrix. The levels of a cartilage anabolic marker Sox9 was significantly increased in the articular cartilage of mice treated with tocilizumab. Micro-CT assessment showed tocilizumab treatment significantly increased trabecular epiphyseal bone volume (P = 0.001, n = 10), thickness (P = 0.007) and number (P = 0.014) and decreased bone separation (P = 0.002) and its deformity (P = 0.003). A bone formation marker, BMP2, and an angiogenic marker, vascular endothelial growth factor (VEGF), were both significantly increased by tocilizumab treatment under hypoxia using human chondrocytes while the bone resorption marker, RANKL/OPG ratio, was reduced. CONCLUSION: Tocilizumab treatment following ischemic osteonecrosis has cartilage anabolic effect and increases bone volume in JIO mouse model. The findings lead to a possible application of tocilizumab for preclinical study using a large animal model of JIO and a clinical trial to validate this treatment.

Maternal and Postnatal Supplementation of Fish Oil Improves Metabolic Health of Mouse Male Offspring.

OBJECTIVE: Over half of American women of childbearing age have either obesity or overweight. Hence, maternal programming through diet is critical for prevention of diseases in the offspring. Clinical trials with fish oil (FO) report various health benefits; however, it remains unclear whether maternal and postnatal consumption of FO protects offspring from adverse effects of consuming a high-fat (HF) diet. METHODS: Female mice were fed HF diets supplemented without (HF) or with FO from 8 weeks before pregnancy through lactation. A low-fat (LF) diet was included as a control diet. After weaning, male offspring from HF or FO dams were either continued on their respective diet (HF-HF and FO-FO) or switched to the other diet (HF-FO and FO-HF) and compared with LF. Phenotypic and mechanistic studies were performed. RESULTS: FO-FO offspring demonstrated significantly higher glucose clearance and insulin sensitivity compared with other pups fed the HF diet (P < 0.05). Furthermore, FO-FO pups had lower adiposity, inflammation, and fat deposition in the liver, consistent with reduced markers of hepatic lipogenesis and increased hepatic lipid oxidation. CONCLUSIONS: Supplementation of FO during pregnancy and early life is more beneficial than treating with FO either during pregnancy or in pups.

Maternal consumption of green tea extract during pregnancy and lactation alters offspring's metabolism in rats.

INTRODUCTION: Green tea extract has anti-inflammatory and antioxidant effects which improve dyslipidemia and decrease adipose tissue depots associated with hyperlipidic diet consumption. OBJECTIVE: To evaluate the effect of green tea extract consumption by rats during pregnancy and lactation on the metabolism of their offspring that received control or high-fat diet with water during 10 weeks after weaning. METHODS: Wistar rats received water (W) or green tea extract diluted in water (G) (400 mg/kg body weight/day), and control diet (10 animals in W and G groups) during pregnancy and lactation. After weaning, offspring received water and a control (CW) or a high-fat diet (HW), for 10 weeks. One week before the end of treatment, oral glucose tolerance test was performed. The animals were euthanized and the samples were collected for biochemical, hormonal and antioxidant enzymes activity analyses. In addition, IL-10, TNF-α, IL-6, and IL-1ß were quantified by ELISA while p-NF-κBp50 was analyzed by Western Blotting. Repeated Measures ANOVA, followed by Tukey's test were used to find differences between data (p < 0.05). RESULTS: The consumption of high-fat diet by rats for 10 weeks after weaning promoted hyperglycemia and hyperinsulinemia, and increased fat depots. The ingestion of a high-fat diet by the offspring of mothers who consumed green tea extract during pregnancy and lactation decreased the inflammatory cytokines in adipose tissue, while the ingestion of a control diet increased the same cytokines. CONCLUSION: Our results demonstrate that prenatal consumption of green tea associated with consumption of high-fat diet by offspring after weaning prevented inflammation. However, maternal consumption of the green tea extract induced a proinflammatory status in the adipose tissue of the adult offspring that received the control diet after weaning.

Diverse antimalarials from whole-cell phenotypic screens disrupt malaria parasite ion and volume homeostasis.

Four hundred structurally diverse drug-like compounds comprising the Medicines for Malaria Venture's 'Pathogen Box' were screened for their effect on a range of physiological parameters in asexual blood-stage malaria (Plasmodium falciparum) parasites. Eleven of these compounds were found to perturb parasite Na+, pH and volume in a manner consistent with inhibition of the putative Na+ efflux P-type ATPase PfATP4. All eleven compounds fell within the subset of 125 compounds included in the Pathogen Box on the basis of their having been identified as potent inhibitors of the growth of asexual blood-stage P. falciparum parasites. All eleven compounds inhibited the Na+-dependent ATPase activity of parasite membranes and showed reduced efficacy against parasites carrying mutations in PfATP4. This study increases the number of chemically diverse structures known to show a 'PfATP4-associated' phenotype, and adds to emerging evidence that a high proportion (7-9%) of the structurally diverse antimalarial compounds identified in whole cell phenotypic screens share the same mechanism of action, exerting their antimalarial effect via an interaction with PfATP4.

Mapping metabolic changes by noninvasive, multiparametric, high-resolution imaging using endogenous contrast.

Monitoring subcellular functional and structural changes associated with metabolism is essential for understanding healthy tissue development and the progression of numerous diseases, including cancer, diabetes, and cardiovascular and neurodegenerative disorders. Unfortunately, established methods for this purpose either are destructive or require the use of exogenous agents. Recent work has highlighted the potential of endogenous two-photon excited fluorescence (TPEF) as a method to monitor subtle metabolic changes; however, mechanistic understanding of the connections between the detected optical signal and the underlying metabolic pathways has been lacking. We present a quantitative approach to detecting both functional and structural metabolic biomarkers noninvasively, relying on endogenous TPEF from two coenzymes, NADH (reduced form of nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide). We perform multiparametric analysis of three optical biomarkers within intact, living cells and three-dimensional tissues: cellular redox state, NADH fluorescence lifetime, and mitochondrial clustering. We monitor the biomarkers in cells and tissues subjected to metabolic perturbations that trigger changes in distinct metabolic processes, including glycolysis and glutaminolysis, extrinsic and intrinsic mitochondrial uncoupling, and fatty acid oxidation and synthesis. We demonstrate that these optical biomarkers provide complementary insights into the underlying biological mechanisms. Thus, when used in combination, these biomarkers can serve as a valuable tool for sensitive, label-free identification of changes in specific metabolic pathways and characterization of the heterogeneity of the elicited responses with single-cell resolution.

Restrained management of copper level enhances the antineoplastic activity of imatinib in vitro and in vivo.

The present study was designed to investigate if elevated copper level can be targeted to enhance the efficacy of a significant anticancer drug, imatinib (ITB). The antineoplastic activity of this drug was assessed in the HepG2, HEK-293, MCF-7 and MDA-MD-231 cells targeting elevated copper level as their common drug target. The cell lines were treated with the different doses of copper chloride (Cu II) and disulfiram (DSF) alone as well as in their combinations with the drug for 24 h in standard culture medium and conditions. The treated cells were subjected to various assays including MTT, PARP, p-53, caspase-7, caspase-3, LDH and single cell electrophoresis. The study shows that DSF and Cu (II) synergizes the anticancer activity of ITB to a significant extent in a dose-specific way as evidenced by the combinations treated groups. Furthermore, the same treatment strategy was employed in cancer-induced rats in which the combinations of ITB-DSF and ITB-Cu II showed enhanced antineoplastic activity as compared to ITB alone. However, DSF was more effective than Cu (II) as an adjuvant to the drug. Hence, restrained manipulation of copper level in tumor cells can orchestrate the redox and molecular dispositions inside the cells favoring the induction of apoptosis.

Physiometabolic effects of Agave salmiana fructans evaluated in Wistar rats.

A prospective completely randomized experimental study was conducted using 48 animals to evaluate the physiometabolic effects of Agave salmiana fructans as a dietary supplement in healthy Wistar rats. Five fructans concentrations from 5 to 20% (w/w) and one control were used in the rats' diet and were divided into six groups (n=8 rats/group). The treatments were carried out for 35days, during which glucose, cholesterol, triglycerides, body-weight gain, food intake, fecal excretion, organ weights, renal and hepatic functions and a histological analysis of the cecum were evaluated. Glucose, cholesterol, triglycerides, renal and hepatic functions were not significantly affected by any treatment. Body-weight gain and food intake were lower in the rat groups fed fructans than in the control group. Increased fecal excretion (p<0.05) was observed only in animals fed 12.5 and 20% fructans. Mice supplemented with fructans exhibited increased weight and length (p<0.05) in the cecum and colon. A histological analysis of the cecum showed cellular proliferation with a dose of 12.5% and membrane lysis at doses of 15 and 20%. In conclusion, the inclusion of 12.5% of Agave salmiana fructans in the animals' diets exerts beneficial physiometabolic effects after the seventh treatment day.

Cocos nucifera water improves metabolic functions in offspring of high fat diet fed Wistar rats.

BACKGROUND: Maternal high fat diet has been implicated in the aetiology of metabolic diseases in their offspring. The hypolipidaemic actions of Cocos nucifera water improve metabolic indices of dams consuming a high fat diet during gestation. This study investigated the effects of C. nucifera water on metabolism of offspring of dams exposed to high fat diet during gestation. METHODS: Four groups of pregnant Wistar rat dams (n=6) were treated orally from Gestation Day (GD) 1 to GD 21 as follows: standard rodent feed+10 mL/kg distilled water (Control), standard rodent feed+10 mL/kg C. nucifera water, high fat feed+10 mL/kg distilled water (high fat diet), and high fat feed+10 mL/kg C. nucifera water (high fat diet+C. nucifera water). The feeds were given ad libitum and all dams received standard rodent feed after parturition. Fasting blood glucose was measured in offspring before being euthanized on Postnatal Day (PND) 120. Serum insulin, leptin, lipid profile and liver enzymes were measured. RESULTS: Serum total cholesterol (TC), insulin, alanine transaminase (ALT) and alkaline phosphatase levels were significantly increased (p<0.05) in high fat diet offspring compared with controls. Similar changes were not observed in high fat diet+C. nucifera water offspring. CONCLUSIONS: Results suggest that the adverse effects of maternal high fat diet on offspring's metabolism can be ameliorated by C. nucifera water.

Folate dietary insufficiency and folic acid supplementation similarly impair metabolism and compromise hematopoiesis.

While dietary folate deficiency is associated with increased risk for birth defects and other diseases, evidence suggests that supplementation with folic acid can contribute to predisposition to some diseases, including immune dysfunction and cancer. Herein, we show that diets supplemented with folic acid both below and above the recommended levels led to significantly altered metabolism in multiple tissues in mice. Surprisingly, both low and excessive dietary folate induced similar metabolic changes, which were particularly evident for nucleotide biosynthetic pathways in B-progenitor cells. Diet-induced metabolic changes in these cells partially phenocopied those observed in mice treated with anti-folate drugs, suggesting that both deficiency and excessive levels of dietary folic acid compromise folate-dependent biosynthetic pathways. Both folate deficiency and excessive dietary folate levels compromise hematopoiesis, resulting in defective cell cycle progression, persistent DNA damage, and impaired production of lymphocytes. These defects reduce the reconstitution potential in transplantation settings and increase radiation-induced mortality. We conclude that excessive folic acid supplementation can metabolically mimic dietary folate insufficiency, leading to similar functional impairment of hematopoiesis.