New perspectives on the role of biological factors in anorexia nervosa: Brain volume reduction or oxidative stress, which came first?

Anorexia nervosa (AN) is an eating disorder (ED) that has seen an increase in its incidence in the last thirty years. Compared to other psychosomatic disorders, ED can be responsible for many major medical complications, moreover, in addition to the various systemic impairments, patients with AN undergo morphological and physiological changes affecting the cerebral cortex. Through immunohistochemical studies on portions of postmortem human brain of people affected by AN and healthy individuals, and western blot studies on leucocytes of young patients and healthy controls, this study investigated the role in the afore-mentioned processes of altered redox state. The results showed that the brain volume reduction in AN could be due to an increase in the rate of cell death, mainly by apoptosis, in which mitochondria, main cellular organelles affected by a decreased dietary intake, and a highly compromised intracellular redox balance, may play a pivotal role.

Chemotherapy-Induced Changes in Plasma Amino Acids and Lipid Oxidation of Resected Patients with Colorectal Cancer: A Background for Future Studies.

Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.

Inflammation, pressure ulcers and poor functional status predict negative rehabilitation outcomes in postacute geriatric patients.

The purposes of this retrospective study were to document the prevalence of serum C-reactive protein (CRP), a biomarker of inflammation, and its potential predictive value for Rehabilitation outcomes in post-acute elderly inpatients. The medical records of 304 elderly subjects admitted to our Rehabilitation Institute for any disease following an acute event were examined. High levels of CRP (> 0.5 mg/dl) were present in 100% of the subjects, and the value > 1.5 mg/dl (n = 86) predicted unfavourable outcomes (n = 28; 32.5% of the patients: death or transfer to other institutions). Among the patients with favourable outcomes (discharge home n = 255), 62.7% still exhibited severe disabilities. Pressure ulcers and low functional status also predicted unfavourable outcomes. The study highlights the need for future investigations into the possible reduction of CRP levels, after an intensive nutritional approach and combined physical interventions.

Long-term effects after treatment with platinum compounds, cisplatin and [Pt(O,O'-acac)(γ-acac)(DMS)]: Autophagy activation in rat B50 neuroblastoma cells.

Cisplatin (cisPt), among the best known components of multi-drug front-line therapies used for the treatments of solid tumors, such as the childhood neuroblastoma, acts through DNA linking. Nevertheless, the cisPt effectiveness is compromised by the onset of severe side effects, including neurotoxicity that results in neurodegeneration, cell death, and drug-resistance. In the field of experimental oncology, aimed at overcoming cytotoxicity and chemoresistance, great efforts are devoted to the synthesis of new platinum-based drugs, such as [Pt(O,O'-acac)(γ-acac)(DMS)] (PtAcacDMS), which shows a specific reactivity with sulfur residues of enzymes involved in apoptosis. Autophagy, an evolutionary conserved degradation pathway for recycling of cytoplasmic components, represents one of the mechanisms adopted by cancer cells which contribute to drug-resistance. In the present study, standard acute (48 h-exposure) and long-term effects (7 day-recovery after treatment or 7 day-recovery followed by reseeding and 96 h-growth), of cisPt and PtAcacDMS (40 and 10 µM, respectively) were investigated in vitro employing rat B50 neuroblastoma as a cancer model. Using fluorescence and electron microscopy, as well as biochemical techniques, our data highlight a key role of the autophagic process in B50 cells. Specifically, long-term effects caused by cisPt lead to inhibition of the apoptotic process and paralleled by the activation of autophagy, thus evidencing that autophagy has a protective role after cisPt exposure, allowing cells to survive. Whereas, long-term effects produced by PtAcacDMS lead toward both apoptosis and autophagy activation. In conclusion, autophagy may represents an alternative cell death pathway, circumventing drug-resistance strategies employed by cancer cells to survive chemoterapy.

Supplemented amino acids may enhance the walking recovery of elderly subjects after hip fracture surgery.

The purpose of this study was to investigate whether supplemented essential amino acids (EAAs) could enhance rehabilitation therapy (Rehab) for recovery of walking capacity in subjects after hip fracture surgery (HFS). Eighty-three elderly subjects with HFS (20 ± 11 days after acute trauma) were eligible for the study and randomized to receive Rehab only (Rehab; n = 27), Rehab + placebo (RP; n = 28) or Rehab + EAAs (RE 8 g/day; n = 28). The patients' walking capacity (m) was measured by 6-min walking distance (6MWD) at admission and at discharge (median 66 days after admission). All patient groups were treated with the same Rehab (2 sessions/day × 5 days/week). The results showed that the gain in 6MWD was higher in RE than in Rehab and RP (p = 0.034; p = 0.024). The study shows that EAA supplementation can enhance walking recovery rate in subjects with HFS.

Serenoa repens extracts: In vitro study of the 5α-reductase activity in a co-culture model for Benign Prostatic Hyperplasia.

OBJECTIVES: Benign Prostatic Hyperplasia (BPH) is a form of benign tumor that occurs in humans mainly with ageing. It affects more than 50% of over 50 years old males and it is characterized by an increased synthesis of dihydrotestosterone (DHT), due to the 5α-reductase activity. The BPH therapeutic approach mainly uses 5α-reductase inhibitors, such as the active compounds present in the extracts deriving from species Serenoa repens. Many lipidosterolic extracts are available on the market, which are obtained with different solvents, among them ethanol is recognized as non-toxic and has less handling risks than hexane. The purpose of the present experimental study was to investigate in-vitro the potency of an ethanol extract of S. repens comparing it with an n-hexane one. MATERIALS AND METHODS: Two different lipido-sterolic extracts of S. repens have been tested: ethanol extract and n-hexane extract, two batches for each one. The inhibitory action of the extract was evaluated estimating in-vitro the activity of enzyme 5α-reductase type I (5α-RI), which was mainly active under the experimental condition of pH 7.5. DHT amount, synthesized from testosterone (1 µM), was evaluated in a co-culture model of epithelial cells and fibroblasts resulting from prostatic biopsy of a patient with BPH. RESULTS: The analysis of the resulting dose-response curves showed that the entire S. repens extracts inhibited the 5α-RI showing no difference between the two kinds of extract or between the batches. The resulting IC50 values were the following: 8.809 (95% CI = 5.133-15.56) and 9.464 (95% CI = 5.094- 18.27) for ethanol extracts; 11.08 (95% CI = 6.389-19.98) and 12.72 (95% CI = 7.758-21.53) for n-hexane extracts. CONCLUSIONS: The potency of ethanol extracts of S. repens was comparable with the one of n-hexane extracts.

Plasma kinetics of essential amino acids following their ingestion as free formula or as dietary protein components.

This investigation compares the levels of plasma kinetics of plasma essential amino acids (EAAs) after ingestion as free-form EAAs (FEAAs) or EAAs as components of dietary protein (DPEAAs), in eighteen healthy individuals, nine elderly (85 ± 6.7 years; 4 male) and nine young (28.7 ± 7 years; 3 males). For two consecutive days, each subject ingested EAAs in the form of (FEAAs) or (DPEAAs) in a random alternate pattern. Five minutes before EAA ingestion (baseline) and 30, 60, 90, 150 and 270 min after, venous blood samples were taken to determine the concentrations of EAAS (micromol/L). In both groups, ingested FEAAs compared to DPEAAs led to faster increase in plasma EAA levels at 30-150 min (p < 0.0001). Moreover, the increased plasma EAAs disappeared faster after FEAA compared to DPEAA. These results may be important in those subjects who have high requirement both for EAAs substrates and anabolic efficiency.

[Pt(O,O'-acac)(γ-acac)(DMS)] versus cisplatin: apoptotic effects in B50 neuroblastoma cells.

Cisplatin is one of the most active chemotherapeutic agents used in the treatment of childhood and adult malignancies. Cisplatin induces cell death through different pathways. Despite its effectiveness, the continued clinical use of cisplatin is limited by onset of severe side effects (nephrotoxicity, ototoxicity and neurotoxicity) and drug resistance. Therefore, one of the main experimental oncology purpose is related to the search for new platinum-based drugs to create different types of adducts or more specific and effective subcellular targets. Thus, [Pt(O,O'-acac)(γ-acac)(DMS)], which reacts preferentially with protein thiols or thioether, was synthesized. In our research, different approaches were used to compare cisplatin and [Pt(O,O'-acac)(γ-acac)(DMS)] effects in B50 rat neuroblastoma cells. Our results, using immunocytochemical, cytometric and morphological techniques, showed that these compounds exert a cytostatic action and activate apoptosis with different pathways. Long-term effects demonstrated that [Pt(O,O'-acac)(γ-acac)(DMS)] exerts cytotoxic effects in neuronal B50 cell line not inducing drug resistance. Analysis was performed both to compare the ability of these platinum compounds to induce cell death and to investigate the intracellular mechanisms at the basis of their cytotoxicity.

Correlation of deglutition in subacute ischemic stroke patients with peripheral blood adaptive immunity: Essential amino acid improvement.

We aimed to document in stroke patients peripheral blood immune cell profiles, their relations with neuro-functional tests, and any possible influence of supplemented essential amino acids (EAAs) may have on both the immune system and the relationship of the latter with neuro-function.Forty-two dysphagic stroke patients (27 men; 71±9 years) underwent bio-humoral measurements, neuro-functional tests, including Functional Independence Measure (FIM) and Dysphagia Outcome and Severity Scale (DOSS), and were randomized to receive EAAs 8 g/d (EAA group) or isocaloric maltodextrin (placebo group).At discharge all measurements were repeated 38±1 days after randomization.At admission, total white cell (TWC), neutrophil (N), and lymphocyte (Lymph) counts were normal and the N/Lymph ratio was higher than normal values (<3.0). At discharge, both TWC and N decreased while Lymph increased significantly. As a result, the N/Lymph ratio significantly decreased (P <0.001) returning to normal levels. Absolute Lymph counts and Lymph % TWC correlated positively with DOSS (r = +0.235, P = 0.04 and r = +0.224, P = 0.05, respectively), negatively with C-reactive protein natural logarithm (ln CRP) (P = 0.02 and P = 0.0001, respectively), which is an inflammation marker. N correlated positively with ln CRP (P = 0.001) and had a slight negative association with FIM (P = 0.07). The N/Lymph ratio was inversely related to FIM (r = -0.262, P = 0.02) and DOSS (r = -0.279, P = 0.01). Finally, FIM correlated with DOSS (r = +0.35, P = 0.05).For the regression analysis, the overtime changes of Lymph % TWC correlated significantly with DOSS (P = 0.01). There was a positive correlation between Lymph % TWC and DOSS for the entire stroke population (P = 0.015). While this correlation was not important for the placebo group (P = 0.27), it was significant in the EAA subgroup (P = 0.018).In the sub-acute stroke stage, there may be slight alterations of peripheral blood immune cells. Lymph cells are associated with improved neuro-function tests with evidence that this association is enhanced by supplementing EAAs.

Is stroke rehabilitation a metabolic problem?

BACKGROUND: This study looks at the impact of inflammation during the rehabilitation stage of strokes and its effect on neuro-functional recovery. METHODS: This study investigated 94 patients suffering from strokes and admitted to rehabilitation. Anthropometric characteristics, serum proteins and inflammatory markers, plasma amino acids and neurofunction were all assessed. RESULTS: 55.3% patients had an inflammatory status (Interleukin-6 = 19.24 ± 23.01 pg ml⁻¹ vs. 4.1 ± 1.6 pg ml⁻¹ for non-inflamed subjects (p < 0.001). Inflammation was positively linked to positive proteins (alpha-1 globulin, p < 0.02) and negatively linked to negative proteins (albumin, p < 0.02; prealbumin, p < 0.01; transferrin, p < 0.05) of the acute-phase response. Inflammation was associated with low plasma concentrations of total amino acids. For the multiple logistic regression analysis, albumin (p < 0.001) and body weight maintenance (p < 0.001) were independent predictors of patient functional independence. Inflammation in dysphagic stroke (31.9%) patients was associated with more accentuated disability compared to non-inflamed dysphagics. The serum positive reactant alpha 1 globulin was the most powerful predictor of dysphagia severity (p < 0.001). At discharge, dysphagia improvement was associated with improved acute-phase negative proteins. CONCLUSIONS: An inflammatory status may persist for most patients with strokes during the rehabiliation stage of the disease, its prevalence being higher in dysphagic compared to non-dysphagic subjects. The improvement in circulating albumin and body weight maintenance are predictors of neuro-function, even in dysphagic subjects.

Plasma kinetic of ingested essential amino acids in healthy elderly people.

The purpose of this study was to investigate whether the documented difficulties of physiological amounts of essential amino acids (EAAs) (7 g) to induce protein synthesis could be reflected in a simple method adaptable to a clinical setting. Sixteen healthy individuals, nine elderly (75.3 ± 3.5 years), and seven young (28 ± 2.5 years) were enrolled in the study. Five minutes before EAA ingestion (baseline) and 20, 40, 60, 90, 120, 180 min after EAA ingestion, venous blood samples were taken from the ante-cubital vein to determine the concentrations of EAAs (µmol/L). The results show that plasma EAA increases were significantly higher in old than in young persons at the considered time points (from p < 0.004 to p < 0.001) (unpaired Student t test). However, the velocity rate of the increasing was slower in old subjects than in young group. The study shows that EAAs ingestion by old subject is associated with reduced muscle EAA uptake.

Nutrition for Podocyte Repair in Nephrotic Syndrome?

Nephrotic syndrome (NS) poses a number of nutritional and metabolic problems due to glomerulus injured podocytes, which are responsible for the loss of barrier function, causing proteinuria, altered fluid and electrolyte balances, and hypoalbuminemia [...].

Several dementia subtypes and mild cognitive impairment share brain reduction of neurotransmitter precursor amino acids, impaired energy metabolism, and lipid hyperoxidation.

Objective: Dementias and mild cognitive impairment (MCI) are associated with variously combined changes in the neurotransmitter system and signaling, from neurotransmitter synthesis to synaptic binding. The study tested the hypothesis that different dementia subtypes and MCI may share similar reductions of brain availability in amino acid precursors (AAPs) of neurotransmitter synthesis and concomitant similar impairment in energy production and increase of oxidative stress, i.e., two important metabolic alterations that impact neurotransmission. Materials and methods: Sixty-five demented patients (Alzheimer's disease, AD, n = 44; frontotemporal disease, FTD, n = 13; vascular disease, VaD, n = 8), 10 subjects with MCI and 15 control subjects (CTRL) were recruited for this study. Cerebrospinal fluid (CSF) and plasma levels of AAPs, energy substrates (lactate, pyruvate), and an oxidative stress marker (malondialdehyde, MDA) were measured in all participants. Results: Demented patients and subjects with MCI were similar for age, anthropometric parameters, biohumoral variables, insulin resistance (HOMA index model), and CSF neuropathology markers. Compared to age-matched CTRL, both demented patients and MCI subjects showed low CSF AAP tyrosine (precursor of dopamine and catecholamines), tryptophan (precursor of serotonin), methionine (precursor of acetylcholine) limited to AD and FTD, and phenylalanine (an essential amino acid largely used for protein synthesis) (p = 0.03 to <0.0001). No significant differences were found among dementia subtypes or between each dementia subtype and MCI subjects. In addition, demented patients and MCI subjects, compared to CTRL, had similar increases in CSF and plasma levels of pyruvate (CSF: p = 0.023 to <0.0001; plasma: p < 0.002 to <0.0001) and MDA (CSF: p < 0.035 to 0.002; plasma: p < 0.0001). Only in AD patients was the CSF level of lactate higher than in CTRL (p = 0.003). Lactate/pyruvate ratios were lower in all experimental groups than in CTRL. Conclusion: AD, FTD, and VaD dementia patients and MCI subjects may share similar deficits in AAPs, partly in energy substrates, and similar increases in oxidative stress. These metabolic alterations may be due to AAP overconsumption following high brain protein turnover (leading to phenylalanine reductions), altered mitochondrial structure and function, and an excess of free radical production. All these metabolic alterations may have a negative impact on synaptic plasticity and activity.

Bacterial-Assisted Extraction of Bioactive Compounds from Cauliflower.

The market for nutraceutical molecules is growing at an impressive pace in all Western countries. A convenient source of bioactive compounds is found in vegetable waste products, and their re-use for the recovery of healthy biomolecules would increase the sustainability of the food production system. However, safe, cheap, and sustainable technologies should be applied for the recovery of these beneficial molecules, avoiding the use of toxic organic solvents or expensive equipment. The soil bacterium Bacillus subtilis is naturally endowed with several enzymes targeting complex vegetable polymers. In this work, a raw bacterial culture supernatant was used to assist in the extraction of bioactives using isothermal pressurization cycles. Besides a wild-type Bacillus subtilis strain, a new strain showing increased secretion of cellulases and xylanases, pivotal enzymes for the digestion of the plant cell wall, was also used. Results indicate that the recovery of compounds correlates with the amount of cellulolytic enzymes applied, demonstrating that the pretreatment with non-purified culture broth effectively promotes the release of bioactives from the vegetable matrix. Therefore, this approach is a valid and sustainable procedure for the recovery of bioactive compounds from food waste.

Is the Brain Undernourished in Alzheimer's Disease?

Cerebrospinal fluid (CSF) amino acid (AA) levels and CSF/plasma AA ratios in Alzheimer Disease (AD) in relation to nutritional state are not known. Methods: In 30 fasting patients with AD (46% males, 74.4 ± 8.2 years; 3.4 ± 3.2 years from diagnosis) and nine control (CTRL) matched subjects, CSF and venous blood samples were drawn for AA measurements. Patients were stratified according to nutritional state (Mini Nutritional Assessment, MNA, scores). Results: Total CSF/plasma AA ratios were lower in the AD subpopulations than in NON-AD (p < 0.003 to 0.017. In combined malnourished (16.7%; MNA < 17) and at risk for malnutrition (36.6%, MNA 17−24) groups (CG), compared to CTRL, all essential amino acids (EAAs) and 30% of non-EAAs were lower (p < 0.018 to 0.0001), whereas in normo-nourished ADs (46.7%, MNA > 24) the CSF levels of 10% of EAAs and 25% of NON-EAAs were decreased (p < 0.05 to 0.00021). CG compared to normo-nourished ADs, had lower CSF aspartic acid, glutamic acid and Branched-Chain AA levels (all, p < 0.05 to 0.003). CSF/plasma AA ratios were <1 in NON-AD but even lower in the AD population. Conclusions: Compared to CTRL, ADs had decreased CSF AA Levels and CSF/plasma AA ratios, the degree of which depended on nutritional state.

Altered Amino Acid Metabolism in Patients with Cardiorenal Syndrome Type 2: Is It a Problem for Protein and Exercise Prescriptions?

The goal of this retrospective study was to document any alterations in plasma amino acids (AAs) in subjects with cardiorenal syndrome type 2 (CRS 2). We analyzed data from sixteen patients with CRS 2 and eight healthy subjects (control group, C), whose plasma arterial (A) and venous (V) AA concentrations had been measured. Compared to C, the group of CRS 2 patients showed significant reductions by more than 90% in A (p < 0.01) and V (p < 0.01) individual AAs, whereas negative A-V differences that indicated a net muscle AA release (muscle hypercatabolism) were found in 59% of CRS 2 patients (p < 0.03). No significant differences in plasma A and V AA concentrations nor in A-V differences were found between patients with mild kidney damage (N = 5; estimated glomerular filtration rate, eGFR ≥ 60 mL/min/1.73 m2) and patients with moderate-severe kidney damage (N = 11; eGFR < 60 mL/min/1.73 m2). Several plasma arterial AAs correlated with hemodynamic variables, but not with GFR. The study showed that patients with CRS 2 had very low concentrations of circulating AAs, independent of the degree of GFR damage.

Peripheral Blood Lymphocyte Percentage May Predict Chemotolerance and Survival in Patients with Advanced Pancreatic Cancer. Association between Adaptive Immunity and Nutritional State.

Pancreatic Carcinoma (PC) cells have the ability to induce patient immunosuppression and to escape immunosurveillance. Low circulating lymphocytes are associated with an advanced stage of PC and reduced survival. Blood lymphocytes expressed as a percentage of Total White Blood Cells (L% TWBC) could predict chemotolerance (n° of tolerated cycles), survival time and Body Weight (BW) more effectively than lymphocytes expressed as an absolute value (LAB > 1500 n°/mm3) or lymphocytes >22%, which is the lowest limit of normal values in our laboratory. Forty-one patients with advanced PC, treated with chemotherapy, were selected for this observational retrospective study. Patients were evaluated at baseline (pre-chemotherapy), and at 6, 12 and 18 months, respectively, after diagnosis of PC. The study found L ≥ 29.7% to be a better predictor of survival (COX model, using age, sex, BW, serum creatinine, bilirubin and lymphocytes as covariates), chemotolerance (r = +0.50, p = 0.001) and BW (r = +0.35, p = 0.027) than LAB > 1500 or L > 22%. BW did not significantly correlate with chemotolerance or survival. The preliminary results of this study suggest that L ≥ 29.7% is more effective than LAB > 1500 or L > 22% at predicting chemotolerance, survival time and nutritional status. A possible impact of nutritional status on chemotherapy and survival seems to be lymphocyte-mediated given the association between BW and L%. This study may serve as the basis for future research to explore whether nutritional interventions can improve lymphopenia, and if so, how this may be possible.

Essential amino acid supplementation is associated with reduced serum C-reactive protein levels and improved circulating lymphocytes in post-acute inflamed elderly patients.

BACKGROUND: Persistent systemic inflammation leads to multidistrectual body dysfunctions. Attenuation of inflammation may improve patients' functional and life prognoses. We hypothesized that essential amino acids (EAAs) given to elderly patients in rehabilitation after acute diseases may be associated with a reduced inflammatory state. Therefore, this retrospective study investigated whether the supplementation of EAAs - modulators of immune competence - was associated with a reduced inflammation rate in elderly patients. METHODS: The medical records of 282 patients admitted to the rehabilitation (rehab) institute after acute index events (surgery or medical diseases) (age: 81.18 ± 8.58 years; females: 67.9%) were analyzed. RESULTS: 46 patients (16.3% of the entire population) had received EAA supplements (S), whereas the remaining 236 patients had not (N-S). Systemic inflammation (I) (serum C-reactive protein (CRP) > 0.5 mg/dL) was present in 67.4% of the I-S group and 57.2% of the I-N-S group. During rehab, the I-S group (but not the I-N-S group) showed a reduction in CRP levels (p = 0.03) and an increase in circulating lymphocytes (p = 0.035), immune cells of the adaptive immune system. C-reactive protein levels remained virtually unchanged in non-inflamed patients who received supplements but increased in non-inflamed patients who did not receive supplements (p = 0.05). Stratified for developed infections, CRP levels reduced in S patients (p = 0.008) but did not in N-S patients. CONCLUSION: EAA supplementation was associated with reduced inflammation in both inflamed and infected patients. In addition, EAA supplementation was associated with increased circulating lymphocytes in inflamed patients.

The polyphenol/saponin-rich Rhus tripartita extract has an apoptotic effect on THP-1 cells through the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Hyperactivation of mechanistic target of rapamycin (mTOR) signaling pathway is involved in the regulation of cellular growth, proliferation, and more in general, is a common phenomenon in most types of cancers. Thus, natural substances targeting this pathway can be of great therapeutic potential in supporting the treatment of tumor patients. Rhus tripartita (Ucria) Grande is a plant growing in desertic areas which is traditionally used for the treatment of several diseases in Tunisia. In the present work, the biochemical profile of the main compounds present in the plant leaf extract was determined and the anti-leukemic potential of the plant extracts against acute monocytic leukaemia (AML) THP-1 cells was investigated. METHODS: After HPLC identification of some phenolic compounds present in the plant extract and the quantification of saponin content, the cytotoxic effect of Rhus tripartita extracts on THP-1 cell culture was evaluated using the colorimetric MTT assay for cell viability. THP-1 cells were incubated with medium containing the relative IC50 concentrations of total plant extract, saponin extract and some standard compounds (rutin (R); kaempferol (K); mixture of catechin, epicatechin, and epicatechin-gallate (CEEG); ellagic acid (EA). Finally, qRT-PCR and western blotting analysis were used to evaluate the effect of some flavonoids present in a crude extract of polyphenols and the total extract of saponins on cell survival and apoptosis. RESULTS: Analysis of expression level of some gene (PIK3CA, PTEN, AKT1, mTOR, EIF4E, RPS6KB1, and TSC1) involved in the mTOR pathway and the phosphorylation of S6 and AKT proteins allowed to observe that a total Rhus tripartita extract and some of the compounds found in the extract controls THP-1 cell proliferation and apoptosis via regulation of the PI3K-Akt-mTOR signaling pathway. CONCLUSION: Rhus tripartita-induced inhibition of cell cycle and induction of apoptosis may involve the mTOR pathway. Therefore, Rhus tripartita extract may be a useful candidate as a natural anti-cancer drug to support the treatment of AML.

Spontaneous neurocognitive retrieval of patients with sub-acute ischemic stroke is associated with dietary protein intake.

OBJECTIVE: To document the relationship between neurocognitive recovery and macronutrient intake of patients suffering from ischemic strokes. DESIGN: Thirty day prospective study of 17 patients suffering from sub-acute stroke (> 14 days from the index event; 10 males, 7 females; mean age 75 +/- 8 years) admitted to our rehabilitation unit. RESULTS: At admission (ADM), mean energy intake was inadequate (< 24 kcal/kg) for bodily needs, whereas protein (> 0.8 g/kg) and lipid (> 0.7 g/kg) intake was appropriate. Patients were moderately deficient for neurological (NIHSS 10.3 +/- 3.5) and cognitive tests (MMSE 22.5 +/- 3.3). NIHSS correlated negatively with proteins (r = -0.47, P = 0.05 at ADM; r = -0.52, P = 0.03 at 30 days) and positively with carbohydrate/protein ratio (CHO/protein; r = +0.45, P = 0.06 at ADM; r = +0.48, P = 0.05 at 30 days). However, MMSE correlated positively with proteins (r = +0.77, P = 0.0003 at ADM; r = +0.55, P = 0.02 at 30 days) and negatively with (CHO/Prot; r = -0.57, P = 0.02 at ADM; not significant at 30 days). The relationship remained significant even when the data at ADM and at 30 days where pooled. CONCLUSIONS: In sub-acute strokes, patient neurological and cognitive retrieval could positively be associated with protein intake.