Classifying subclinical depression using EEG spectral and connectivity measures.

Detecting depression on its early stages helps preventing the onset of severe depressive episodes. In this study, we propose an automatic classification pipeline to detect subclinical depression (i.e., dysphoria) through the electroencephalography (EEG) signal. To this aim, we recorded the EEG signals in resting condition from 26 female participants with dysphoria and 38 female controls. The EEG signals were processed to extract several spectral and functional connectivity features to feed a nonlinear Support Vector Machine (SVM) classifier embedded with a Recursive Feature Elimination (RFE) algorithm. Our recognition pipeline obtained a maximum classification accuracy of 83.91% in recognizing dysphoria patients with a combination of connectivity and spectral measures. Moreover, an accuracy of 76.11% was achieved with only the 4 most informative functional connections, suggesting a central role of cortical connectivity in the theta band for early depression recognition. The present study can facilitate the diagnosis of subclinical conditions of depression and may provide reliable indicators of depression for the clinical community.

A unique neuroendocrine cell model derived from the human foetal neural crest.

PURPOSE: Nowadays, no human neuroendocrine cell models derived from the neural crest are available. In this study, we present non-transformed long-term primary Neural Crest Cells (NCCs) isolated from the trunk region of the neural crest at VIII-XII gestational weeks of human foetuses obtained from voluntary legal abortion. METHODS AND RESULTS: In NCC, quantitative real-time RT PCR demonstrated the expression of neural crest specifier genes, such as Snail1, Snail2/SLUG, Sox10, FoxD3, c-Myc, and p75NTR. Moreover, these cell populations expressed stemness markers (such as Nanog and nestin), as well as markers of motility and invasion (TAGLN, MMP9, CXCR4, and CXCR7), and of neuronal/glial differentiation (MAP2, GFAP, SYP, and TAU). Functional analysis demonstrated that these cells not only possessed high migration properties, but most importantly, they expressed markers of sympatho-adrenal lineage, such as ASCL1 and tyrosine hydroxylase (TH). Moreover, the expression of TH increased after the induction with two different protocols of differentiation towards neuronal and sympatho-adrenal phenotypes. Finally, exposure to conditioned culture media from NCC induced a mature phenotype in a neuronal cell model (namely SH-SY5Y), suggesting that NCC may also act like Schwann precursors. CONCLUSION: This unique human cell model provides a solid tool for future studies addressing the bases of human neural crest-derived neuroendocrine tumours.

Neuronal distress induced by low extracellular sodium in vitro is partially reverted by the return to normal sodium.

BACKGROUND: Hyponatremia is associated with negative clinical outcomes even when chronic and mild. It is also known that hyponatremia treatment should be appropriately performed, to avoid dramatic consequences possibly leading to death. We have previously demonstrated that chronically low extracellular [Na(+)], independently of reduced osmolality, is associated with signs of neuronal cell distress, possibly involving oxidative stress. AIM: The aim of the present study was to assess whether the return to normal extracellular [Na(+)] is able to revert neuronal cell damage. METHODS: After exposing SH-SY5Y and SK-N-AS cells to low [Na(+)] and returning to normal [Na(+)], we analyzed cell viability by MTS assay, ROS accumulation by FASCan and expression of anti-apoptotic genes. RESULTS: We found that the viability of cells was restored upon return to normal [Na(+)]. However, when more subtle signs of cell distress were assessed, such as the expression level of the anti-apoptotic genes Bcl-2 and DHCR24 or of the heme oxygenase 1 gene, a complete return to basal values was not observed, in particular in SK-N-AS, even when [Na(+)] was gradually increased. We also demonstrated that the amount of ROS significantly increased in low [Na(+)], thus confirming that oxidative stress appears to contribute to the effects of low [Na(+)] on cell homeostasis. CONCLUSIONS: Overall, this study provided the first demonstration that the correction of chronically low extracellular [Na(+)] may not be able to revert all the cell alterations associated with reduced [Na(+)]. These results suggest that prompt hyponatremia treatment might prevent possible residual abnormalities.

Low extracellular sodium promotes adipogenic commitment of human mesenchymal stromal cells: a novel mechanism for chronic hyponatremia-induced bone loss.

Hyponatremia represents an independent risk factor for osteoporosis and fractures, affecting both bone density and quality. A direct stimulation of bone resorption in the presence of reduced extracellular sodium concentrations ([Na(+)]) has been shown, but the effects of low [Na(+)] on osteoblasts have not been elucidated. We investigated the effects of a chronic reduction of extracellular [Na(+)], independently of osmotic stress, on human mesenchymal stromal cells (hMSC) from bone marrow, the common progenitor for osteoblasts and adipocytes. hMSC adhesion and viability were significantly inhibited by reduced [Na(+)], but their surface antigen profile and immuno-modulatory properties were not altered. In low [Na(+)], hMSC were able to commit toward both the osteogenic and the adipogenic phenotypes, as demonstrated by differentiation markers analysis. However, the dose-dependent increase in the number of adipocytes as a function of reduced [Na(+)] suggested a preferential commitment toward the adipogenic phenotype at the expense of osteogenesis. The amplified inhibitory effect on the expression of osteoblastic markers exerted by adipocytes-derived conditioned media in low [Na(+)] further supported this observation. The analysis of cytoskeleton showed that low [Na(+)] were associated with disruption of tubulin organization in hMSC-derived osteoblasts, thus suggesting a negative effect on bone quality. Finally, hMSC-derived osteoblasts increased their expression of factors stimulating osteoclast recruitment and activity. These findings confirm that hyponatremia should be carefully taken into account because of its negative effects on bone, in addition to the known neurological effects, and indicate for the first time that impaired osteogenesis may be involved.

Preliminary evidence for reduced preoperative cerebral blood flow velocity as a risk factor for cognitive decline three months after cardiac surgery: an extension study.

This extension study investigated the association between preoperative cerebral blood flow (CBF) velocity and postoperative cognitive decline (POCD) at a three-month follow-up in patients who underwent cardiac surgery. Continuous transcranial Doppler ultrasound on both middle cerebral arteries (MCAs) was used preoperatively in 31 right-handed cardiac surgery patients at rest. Each patient performed a neuropsychological evaluation to assess cognitive performance before surgery, at discharge and at three-month follow-up. Patients with POCD at the three-month follow-up had a marginally significantly lower preoperative CBF velocity in the left MCA than patients without POCD. Moreover, the group with POCD had a significantly lower CBF velocity in the left than in the right MCA, whereas no difference between the left and right CBF velocity was found in the group without POCD. These preliminary findings suggest that reduced preoperative CBF velocity in the left MCA may represent an independent risk factor for cognitive decline in patients three months after surgery.

Relationship between the neuroprotective effects of insulin-like growth factor-1 and 17ß-oestradiol in human neuroblasts.

Insulin-like growth factor-1 (IGF-1) and oestrogens interact with each other as neuroprotective factors. We have previously demonstrated that 17ß-oestradiol protects against ß-amyloid and oxidative stress toxicity and increases the amount of cell cholesterol in human foetal neuroblasts (FNC). The present study aimed: (i) to assess the protective effects of IGF-1 in FNC cells; (ii) to investigate the relationship between IGF-1 and 17ß-oestradiol; and (iii) to determine whether cholesterol was a major mediator of the effects of IGF-1, similarly to 17ß-oestradiol. We found that IGF-1 effectively exerts neuroprotective effects in FNC cells. We also demonstrated that the IGF-1 receptor (IGF-1R) pathway is needed to maintain oestrogen-mediated neuroprotection. Finally, we found that, opposite to 17ß-oestradiol, IGF-1 did not cause a significant increase in cell cholesterol. These findings indicate that a cross-talk between IGF-1 and 17ß-oestradiol occurs in FNC cells. In particular, the activation of the IGF-1R cascade appears to be fundamental to warrant 17ß-oestradiol-mediated neuroprotection, even though cell cholesterol does not play a major role as an effector of this pathway.

Pain-related middle-latency somatosensory evoked potentials in the prognosis of post anoxic coma: a preliminary report.

BACKGROUND: Regarding hypoxic-ischemic encephalopathy, while the bilateral absence of N20/P25 somatosensory evoked potentials (SEPs) is considered to be the best indicator of adverse outcomes, the presence of middle latency evoked potentials (MLCEPs) is associated with a favourable neurological prognosis. The main aim of the present study was to investigate whether painful electrical stimulation might be considered a provocative test in producing MLCEPs and predictor of patient's outcomes after cardiac arrest. METHODS: Retrospective pilot study. SEPs with and without pain-related electrical stimulation in both median nerves were recorded in 17 patients with post anoxic coma after cardiac arrest. Glasgow Coma Scale, electroencephalograms, heart rate and blood pressure changes were also recorded at the same time. Three months after cardiac arrest the same measures with inclusion of Glasgow Outcome Scale Extended were also performed only in the remaining patients with severe neurological outcome. No one intervention was made. RESULTS: Patients who showed MLCEPs had a good outcome, while patients without N20/P25 SEPs but with increases in blood pressure remained in a vegetative state. Patients who did not show N20/P25 SEPs and increase in blood pressure died within one week. Only one patient who showed N20/P25 SEPs was minimally conscious. CONCLUSION: These preliminary data suggest that MLCEPs elicited by painful electrical stimulation seem to be a sensitive method to predict the neurological outcome of patients in the acute phase of coma. Blood pressure response might be a prognostic physiological measure of survival in the vegetative state in patients without N20/P25 SEPs.

The role of asymmetry and the nature of microembolization in cognitive decline after heart valve surgery: a pilot study.

Our objective was to determine the role of asymmetry and the nature of microembolization on postoperative cognitive decline in patients who had undergone heart valve surgery. Continuous transcranial Doppler ultrasound was intraoperatively used for both middle cerebral arteries in 13 right-handed heart valve surgery patients to detect microembolization. The Trail Making Test A and B, Memory with 10/30 s interference, the Digit Span Test and Phonemic Fluency were performed preoperatively, at discharge and three months after surgery. Our data suggest that early and late postoperative psychomotor and executive functions may be sensitive to microemboli in the left, but not in the right middle cerebral artery. Moreover, solid and gaseous microemboli are both similarly associated with early postoperative cognitive decline while, surprisingly, late postoperative cognitive decline is more likely to be associated with gaseous than solid microemboli.

Androgens and estrogens prevent rosiglitazone-induced adipogenesis in human mesenchymal stem cells.

Thiazolidinediones (TZD), a class of anti-diabetic drugs, determine bone loss and increase fractures particularly in post-menopausal women, thus suggesting a protective role of sex steroids. We have previously demonstrated that the TZD rosiglitazone (RGZ) negatively affects bone mass by inhibiting osteoblastogenesis, yet inducing adipogenesis, in bone marrow-derived human mesenchymal stem cells (hMSC). The aim of this study was to determine whether estrogens and androgens are able to revert the effects of RGZ on bone. hMSC express estrogen receptor α and ß and the androgen receptor. We found that 17ß-estradiol (10 nM), the phytoestrogen genistein (10 nM), testosterone (10 nM) and the non-aromatizable androgens dihydrotestosterone (10 nM) and methyltrienolone (10 nM) effectively counteracted the adipogenic effect of RGZ (1 µM) in hMSC induced to differentiate into adipocytes, as determined by evaluating the expression of the adipogenic marker peroxisome proliferator-activated receptor γ and the percentage of fat cells. Furthermore, when hMSC were induced to differentiate into osteoblasts, all the above-mentioned molecules and also quercetin, another phytoestrogen, significantly reverted the inhibitory effect of RGZ on the expression of the osteogenic marker osteocalcin and decreased the number of fat cells observed after RGZ exposure. Our study represents, to our knowledge, the first demonstration in hMSC that androgens, independently of their aromatization, and estrogens are able to counteract the negative effects of RGZ on bone. Our data, yet preliminary, suggest the possibility to try to prevent the negative effects of TZD on bone, using steroid receptor modulators, such as plant-derived phytoestrogens, which lack evident adverse effects.

Membrane cholesterol as a mediator of the neuroprotective effects of estrogens.

Alzheimer's disease (AD), the most common neurodegenerative disease associated with aging, is still an incurable condition. Although in vitro evidence strongly indicates that estrogens exert neurotrophic and neuroprotective effects, the role of this class of hormones in the treatment of AD is still a debated issue. In 2000 a new gene, named seladin-1 (for SELective Alzheimer's Disease INdicator-1), was identified and found to be down regulated in vulnerable brain regions in AD. Seladin-1 was considered a novel neuroprotective factor, because of its anti-apoptotic activity. Subsequently, it was demonstrated that seladin-1 has also enzymatic activity [3-ß-hydroxysterol delta-24-reductase, (DHCR24)], which catalyzes the synthesis of cholesterol from desmosterol. The amount of membrane cholesterol may play an important role both in protecting neuronal cells against toxic insults and in inhibiting the production of ß-amyloid. We demonstrated that seladin-1 overexpression increases the amount of membrane cholesterol and induces resistance against ß-amyloid aggregates in neuroblastoma cells, whereas a specific inhibitor of DHCR24 increased cell vulnerability. We also hypothesized that seladin-1 might be a mediator of the neuroprotective effects of estrogens. We first demonstrated that, in human fetal neuroepithelial cells (FNC), 17ß-estradiol, raloxifene, and tamoxifen exert protective effects against ß-amyloid toxicity and oxidative stress. In addition, these molecules significantly increased the expression of seladin-1 and the amount of cell cholesterol. Then, we showed that, upon seladin-1 silencing, the protective effects of estrogens were abolished, thus indicating this factor as a fundamental mediator of estrogen-mediated neuroprotection, at least in FNC cells. Furthermore, we detected the presence of functionally active half-palindromic estrogen responsive elements upstream the coding region of the seladin-1 gene. Overall, our results indicate that seladin-1 may be viewed as a multi-faceted protein, which conjugates both the neuroprotective properties of estrogens and the important functions of cholesterol in maintaining brain homeostasis. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Influence of wing loading on the trade-off between pursuit-diving and flight in common guillemots and razorbills.

Species of bird that use their wings for underwater propulsion are thought to face evolutionary trade-offs between flight and diving, leading to the prediction that species with different wing areas relative to body mass (i.e. different wing loadings) also differ in the relative importance of flight and diving activity during foraging trips. We tested this hypothesis for two similarly sized species of Alcidae (common guillemots and razorbills) by using bird-borne devices to examine three-dimensional foraging behaviour at a single colony. Guillemots have 30% higher wing loading than razorbills and, in keeping with this difference, razorbills spent twice as long in flight as a proportion of trip duration whereas guillemots spent twice as long in diving activity. Razorbills made a large number of short, relatively shallow dives and spent little time in the bottom phase of the dive whereas guillemots made fewer dives but frequently attained depths suggesting that they were near the seabed (ca. 35-70 m). The bottom phase of dives by guillemots was relatively long, indicating that they spent considerable time searching for and pursuing prey. Guillemots also spent a greater proportion of each dive bout underwater and had faster rates of descent, indicating that they were more adept at maximising time for pursuit and capture of prey. These differences in foraging behaviour may partly reflect guillemots feeding their chicks single large prey obtained near the bottom and razorbills feeding their chicks multiple prey from the water column. Nonetheless, our data support the notion that interspecific differences in wing loadings of auks reflect an evolutionary trade-off between aerial and underwater locomotion.

In vivo effects of rosiglitazone in a human neuroblastoma xenograft.

BACKGROUND: Neuroblastoma (NB) is the most common extra-cranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. There is in vitro evidence that the peroxisome proliferator-activated receptor gamma (PPARgamma) might be a target for pharmacological intervention in NB. We have previously demonstrated that the PPARgamma agonist rosiglitazone (RGZ) exerts strong anti-tumoural effects in the human NB cell line, SK-N-AS. The aim of this study was to evaluate whether RGZ maintains its anti-tumoural effects against SK-N-AS NB cells in vivo. METHODS AND RESULTS: For this purpose, tumour cells were subcutaneously implanted in nude mice, and RGZ (150 mg kg(-1)) was administered by gavage daily for 4 weeks. At the end of treatment, a significant tumour weight inhibition (70%) was observed in RGZ-treated mice compared with control mice. The inhibition of tumour growth was supported by a strong anti-angiogenic activity, as assessed by CD-31 immunostaining in tumour samples. The number of apoptotic cells, as determined by cleaved caspase-3 immunostaining, seemed lower in RGZ-treated animals at the end of the treatment period than in control mice, likely because of the large tumour size observed in the latter group. CONCLUSIONS: To our knowledge, this is the first demonstration that RGZ effectively inhibits tumour growth in a human NB xenograft and our results suggest that PPARgamma agonists may have a role in anti-tumoural strategies against NB.

Degree of concordance between double-balloon enteroscopy and capsule endoscopy in obscure gastrointestinal bleeding: a multicenter study.

BACKGROUND AND STUDY AIMS: Capsule endoscopy is considered the diagnostic procedure of choice in patients with obscure gastrointestinal bleeding (OGIB). Double-balloon endoscopy (DBE) offers both diagnostic and therapeutic potential, but is invasive, complex, and time-consuming. The aim was to evaluate diagnostic agreement between capsule endoscopy and DBE in patients with OGIB, and secondarily the diagnostic gain of DBE when capsule endoscopy detected only blood or clots in the small-bowel lumen. METHODS: Multicenter prospective study carried out at six institutions in Italy. RESULTS: 193 patients (119 men, mean age 61.6 +/- 16.2) first underwent capsule endoscopy and then DBE. The most frequent positive findings at capsule endoscopy were vascular lesions (74 patients, 38.3 %), blood or clot in the lumen (34, 17.6 %), and tumor mass (20, 10.4 %). The most frequent findings at DBE were vascular lesions (72 patients, 37.3 %), neoplasia (30, 15.5 %) and ulcers/inflammatory lesions (12, 6.2 %). Overall kappa coefficient was 0.46 (95 %CI 0.38 - 0.54), with maximum concordance for vascular (0.72 [95 %CI 0.59 - 0.84]) and inflammatory (0.78 [0.58 - 0.99]) lesions and minimum for polyps (0.46 [0.16 - 0.80]). Blood in the lumen was the only positive finding at capsule endoscopy in 34 cases; of these, 12 had negative DBE findings whereas 10 had vascular lesions, 6 neoplasia, 1 ulcer, and 5 diverticula. CONCLUSION: Capsule endoscopy and DBE have good agreement for vascular and inflammatory lesions but not for polyps or neoplasia. DBE provides valuable adjunctive information, particularly in patients with neoplasia or polyp at capsule endoscopy. DBE clarified the origin of bleeding in two-thirds of patients with capsule endoscopy showing only blood in the lumen.

Sphingosine 1-phosphate induces differentiation of adipose tissue-derived mesenchymal stem cells towards smooth muscle cells.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid which regulates multiple biological parameters in a number of cell types, including stem cells. Here we report, for the first time, that S1P dose-dependently stimulates differentiation of adipose tissue-derived mesenchymal stem cells (ASMC) towards smooth muscle cells. Indeed, S1P not only induced the expression of smooth muscle cell-specific proteins such as alpha-smooth muscle actin (alpha SMA) and transgelin, but also profoundly affected ASMC morphology by enhancing cytoskeletal F-actin assembly, which incorporated alpha SMA. More importantly, S1P challenge was responsible for the functional appearance of Ca(2+) currents, characteristic of differentiated excitable cells such as smooth muscle cells. By employing various agonists and antagonists to inhibit S1P receptor subtypes, S1P(2) turned out to be critical for the pro-differentiating effect of S1P, while S1P(3) appeared to play a secondary role. This study individuates an important role of S1P in AMSC which can be exploited to favour vascular regeneration.

Intermittent high glucose concentrations reduce neuronal precursor survival by altering the IGF system: the involvement of the neuroprotective factor DHCR24 (Seladin-1).

The exposure of neurons to high glucose concentrations is considered a determinant of diabetic neuropathy, whereas members of the IGF system are neurotropic factors. Here, we investigated the effects of constant and intermittent high glucose concentrations on IGF1 and IGF-binding proteins (IGFBPs) in human neuroblast long-term cell cultures fetal neuroepithelial cells (FNC). These cells express the IGF1 receptor, and express and release in the culture medium IGFBP2, IGFBP4, and IGF1. The release of IGF1 was significantly increased by 17beta-estradiol (10 nM). IGF1 (100 nM) treatment determined a significant increase of IGFBP2 and a decrease of IGFBP4 release. In addition, IGF1 (1-100 nM) stimulated FNC cell proliferation in a dose-dependent manner. We hypothesized that this effect may be, at least partially, due to IGF1-induced up-regulation of the expression of the Alzheimer's disease related gene SELADIN-1 (now known as DHCR24 ), which acts as a pro-survival factor for neuronal cells. Conversely, the exposure to intermittent (20/10 mM), but not stable (20 mM), high glucose concentrations decreased the release of IGF1 and IGFBP2 in the culture medium and inhibited FNC growth by inducing apoptosis. The latter was prevented by the addition of IGF1 to the culture medium. Furthermore, high glucose concentrations reduced the expression of DHCR24. In conclusion, our results indicate for the first time that intermittent high glucose concentrations, similar to those observed in poorly controlled diabetic patients, may contribute to the development of diabetic neuropathy by interfering with the tropic effects exerted by the IGF system, and suggest the involvement of the neuroprotective factor DHCR24.

Thyroid hormones promote cell differentiation and up-regulate the expression of the seladin-1 gene in in vitro models of human neuronal precursors.

Thyroid hormones (TH) play an important role in the development of human brain, by regulating the expression of specific genes. Selective Alzheimer's disease indicator-1 (seladin-1) is a recently discovered gene with neuroprotective properties, which has been found to be down-regulated in brain regions affected by Alzheimer's disease. Seladin-1 has anti-apoptotic properties mainly due to the inhibition of the activation of caspase 3. The aim of this study was to determine whether seladin-1 may be regarded as a new mediator of the effects of TH in the developing brain. In order to demonstrate this hypothesis, the effects of TH both on cell differentiation and on the expression of seladin-1 were assessed in two different cell models, i.e. fetal human neuroepithelial cells (FNC) and human mesenchymal stem cells (hMSC), which can be differentiated into neurons. 3,3',5-Triiodothyronine (T3) determined different biological responses (inhibition of cell adhesion, induction of migration, and increase in the expression of the neuronal marker neurofilament-M and Na+ and Ca2+ channel functionality) in both FNC and hMSC, which express TH receptors. Then, we showed that TH significantly increase the expression levels of seladin-1, and that T3 effectively prevents camptothecin-induced apoptosis. However, in hMSC-derived neurons the expression of seladin-1 was not affected by TH. Our results demonstrated for the first time that seladin-1 is a novel TH-regulated gene in neuronal precursors. In view of its anti-apoptotic activity, it might be hypothesized that one of the functions of the increased seladin-1 levels in the developing brain may be to protect neuronal precursor cells from death.

Cytotoxic activity of polyacetylenes and polyenes isolated from roots of Echinacea pallida.

BACKGROUND AND PURPOSE: The n-hexane extracts of the roots of three medicinally used Echinacea species exhibited cytotoxic activity on human cancer cell lines, with Echinacea pallida found to be the most cytotoxic. Acetylenes are present in E. pallida lipophilic extracts but essentially absent in extracts from the other two species. In the present study, the cytotoxic effects of five compounds, two polyacetylenes (namely, 8-hydroxy-pentadeca-(9E)-ene-11,13-diyn-2-one (1) and pentadeca-(9E)-ene-11,13-diyne-2,8-dione (3)) and three polyenes (namely, 8-hydroxy-pentadeca-(9E,13Z)-dien-11-yn-2-one (2), pentadeca-(9E,13Z)-dien-11-yne-2,8-dione (4) and pentadeca-(8Z,13Z)-dien-11-yn-2-one (5)), isolated from the n-hexane extract of E. pallida roots by bioassay-guided fractionation, were investigated and the potential bioavailability of these compounds in the extract was studied. EXPERIMENTAL APPROACH: Cytotoxic effects were assessed on human pancreatic MIA PaCa-2 and colonic COLO320 cancer cell lines. Cell viability was evaluated by the WST-1 assay and apoptotic cell death by the cytosolic internucleosomal DNA enrichment and the caspase 3/7 activity tests. Caco-2 cell monolayers were used to assess the potential bioavailability of the acetylenes. KEY RESULTS: The five compounds exhibited concentration-dependent cytotoxicity in both cell types, with a greater potency in the colonic cancer cells. Apoptotic cell death was found to be involved in the cytotoxic effect of the most active, compound 5. Compounds 2 and 5 were found to cross the Caco-2 monolayer with apparent permeabilities above 10 x 10(-6) cm s(-1). CONCLUSIONS AND IMPLICATIONS: Compounds isolated from n-hexane extracts of E. pallida roots have a direct cytotoxicity on cancer cells and good potential for absorption in humans when taken orally.

Rosiglitazone stimulates adipogenesis and decreases osteoblastogenesis in human mesenchymal stem cells.

Thiazolidinediones (TZD) are widely prescribed for the treatment of Type 2 diabetes. Increased loss of bone mass and a higher incidence of fractures have been associated with the use of this class of drugs in post-menopausal women. In vitro studies performed in rodent cell models indicated that rosiglitazone (RGZ), one of the TZD, inhibited osteoblastogenesis and induced adipogenesis in bone marrow progenitor cells. The objective of the present study was to determine for the first time the RGZ-dependent shift from osteoblastogenesis toward adipogenesis using a human cell model. To this purpose, bone marrow-derived mesenchymal stem cells were characterized and induced to differentiate along osteogenic and adipogenic lineages. We found that the exposure to RGZ potentiated adipogenic differentiation and shifted the differentiation toward an osteogenic phenotype into an adipogenic phenotype, as assessed by the appearance of lipid droplets. Accordingly, RGZ markedly increased the expression of the typical marker of adipogenesis fatty-acid binding protein 4, whereas it reduced the expression of Runx2, a marker of osteoblastogenesis. This is the first demonstration that RGZ counteracts osteoblastogenesis and induces a preferential differentiation into adipocytes in human mesenchymal stem cells.