Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro activity of compounds isolated from Piper crassinervium against Trypanosoma cruzi

This study describes the antichagasic potential of five compounds isolated from leaves of Piper crassinervium (Piperaceae). Two prenylated benzoic acid derivatives, one prenylated hydroquinone and two flavanones, were evaluated. The in vitro trypanocidal activity was determined against epimastigote forms of Trypanosoma cruzi (Y strain), the etiologic agent of Chagas disease. The most active compound was the prenylated hydroquinone [1,4-dihydroxy-2-(30,70-dimethyl-10-oxo-20-E,60-octadienyl)benzene] with an IC50 value of 6.10 µg mL−1, which was in the same order of activity if compared with the positive control benznidazole (IC50 = 1.60 µg mL−1). This is the first report of trypanocidal activity for prenylated hydroquinone and benzoic acid derivatives.
Membrane‐bound melatonin receptor MT1 down‐regulates estrogen responsive genes in breast cancer cells

Abstract: Melatonin possesses anti‐estrogenic effects on estrogen receptor expressing (ER+) breast cancer cells in culture by reducing cell cycle progression and cell proliferation. There is increasing agreement that on a cellular level the effects of melatonin are primarily induced by the membrane‐bound receptor MT1. The participation of a second, nuclear receptor of the group of ligand‐dependent transcription factors, called RZRα, is under debate. In this study we used a number of breast cancer cell lines differing in their expression of the estrogen receptor and the two known melatonin receptors. In MCF‐7 breast cancer cells transfected with a vector carrying the MT1 gene (MCF‐7Mel1a) binding of CREB‐protein to the cAMP‐responsive element of the breast cancer suppressing gene BRCA‐1 was more strongly reduced by treatment with melatonin than in the parental cells. Expression of estrogen responsive genes was determined in serum‐starved cells, cells stimulated for 16 hr with estradiol and cells subsequently treated with melatonin. Expression of BRCA‐1, p53, p21WAF and c‐myc were up‐regulated by estradiol. Treatment of the stimulated cells with melatonin counteracted the increase induced by estradiol almost completely. The more MT1 a cell line expressed, the stronger was the reduction of the expression of the estradiol‐induced genes. There was no correlation between the expression of the nuclear receptor RZRα and the effects of melatonin on these genes.
Association of Physical Activity with Lipodystrophy Syndrome in HIV- Infected Patients

Highly Active Antiretroviral Therapy (HAART) has increased life expectancy of HIV-infected patients, but may also increase triglyceride and cholesterol levels, triggering lipodystrophy syndrome. Physical activity may prevent or attenuate such adverse effects, but it has not been fully evaluated in HIV-infected patients. This cross-sectional study aimed to investigate the association between physical activity and lipodystrophy syndrome in HIV-infected individuals, 18 years or older. Physical activity was evaluated by the short version of the International Physical Activity Questionnaire. Lipodystrophy was verified by at least two reporting of changes in different parts of the body, or directly assessed, categorized as lipoatrophy or lipohypertrophy. Among 1,240 participants, 46% had lipohypertrophy, which was independently associated with insufficient physical activity in men, but not in women. The prevalence of lipoatrophy was 53.2%. Metabolic parameters were higher among individuals on HAART, in comparison to HAART-naive patients. In conclusion, HAART-naive physically active individuals had lower metabolic profile than among insufficiently active.
Dynamics in enzymatic protein complexes offer a novel principle for the regulation of melatonin synthesis in the human pineal gland

Abstract: Time of day is communicated to the body through rhythmic cues, including pineal gland melatonin synthesis, which is restricted to nighttime. Whereas in most rodents transcriptional regulation of the arylalkylamine N‐acetyltransferase (Aanat) gene is essential for rhythmic melatonin synthesis, investigations into nonrodent mammalian species have shown post‐transcriptional regulation to be of central importance, with molecular mechanisms still elusive. Therefore, human pineal tissues, taken from routine autopsies were allocated to four time‐of‐death groups (night/dawn/day/dusk) and analyzed for daytime‐dependent changes in phosphorylated AANAT (p31T‐AANAT) and in acetyl‐serotonin‐methyltransferase (ASMT) expression and activity. Protein content, intracellular localization, and colocalization of p31T‐AANAT and ASMT were assessed, using immunoblotting, immunofluorescence, and immunoprecipitation techniques. Fresh sheep pineal gland preparations were used for comparative purposes. The amount of p31T‐AANAT and ASMT proteins as well as their intracellular localization showed no diurnal variation in autoptic human and fresh sheep pineal glands. Moreover, in human and sheep pineal extracts, AANAT could not be dephosphorylated, which was at variance to data derived from rat pineal extracts. P31T‐AANAT and ASMT were often found to colocalize in cellular rod‐like structures that were also partly immunoreactive for the pinealocyte process‐specific marker S‐antigen (arrestin) in both, human and sheep pinealocytes. Protein–protein interaction studies with p31T‐AANAT, ASMT, and S‐antigen demonstrated a direct association and formation of robust complexes, involving also 14‐3‐3. This work provides evidence for a regulation principle for AANAT activity in the human pineal gland, which may not be based on a p31T‐AANAT phosphorylation/dephosphorylation switch, as described for other mammalian species.
Body Mass Index, Waist, Waist to Hip Ratio and Lipid Profile in Elderly Subjects Living in a Nursing Home

In the present study, lipid profile and indices of obesity in elderly residents living in the Riyadh-nursing home, Kingdom of Saudi Arabia was assessed. All elderly males (n = 48) living in the nursing home were included in the study. Body mass index, waist circumference and waist to hip ratio were measured. In addition, total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglyceride concentrations were measured in serum. The results show that 43.8% of the elderly were considered to be either overweight or obese. The results show that 29.2 and 33.3% of the subjects were having central obesity, as measured by waist circumference and waist to hip ratio, respectively. Twenty five percent and 20.8% of the subjects had high total cholesterol and high low-density lipoprotein-cholesterol, respectively. About 42% of the elderly classified as having low high-density lipoprotein-cholesterol and 10.4% classified as having high triglyceride. Waist circumference was strongly correlated with body mass index (r = 90), whereas waist-to-hip ratio was less correlated (r = 0.64). Body mass index, waist circumference and wait-to-hip ratio were positively associated with triglyceride, whereas waist circumference and waist-to-hip ratio were negatively associated with high density lipoprotein-cholesterol. To conclude, the prevalence of central obesity was appreciable. Early detection of obesity, upon admission to nursing homes, would lead to early nutritional intervention, thus, help in preventing obesity-related complications and reducing medical-treatment costs.
Oligodendroglial maldevelopment in the cerebellum after postnatal hyperoxia and its prevention by minocycline

According to recent research, brain injury after premature birth often includes impaired growth of the cerebellum. However, causes of cerebellar injury in this population are poorly understood. In this study, we analyzed whether postnatal hyperoxia perturbs white matter development of the cerebellum, and whether cerebellar glial damage can be prevented by minocycline. We used a hyperoxia model in neonatal rats providing 24 h exposure to fourfold increased oxygen concentration (80% O2) from P6 to P7, followed by recovery in room air until P9, P11, P15, P30. Injections with minocycline were performed at the beginning and 12 h into hyperoxia exposure. Hyperoxia induced oxidative stress in the cerebellum at P7 as evidenced by increased nitrotyrosine concentrations. Numbers of proliferating, NG2+Ki67+ oligodendroglial precursor cells were decreased at P7 after hyperoxia and at P11 following recovery in room air. Numbers of mature, CC1+ oligodendrocytes were diminished in recovering hyperoxia rats, and myelin basic protein expression was still decreased at P30. Electron microscopy analysis of myelinated fibers at P30 revealed thinner myelin sheath after hyperoxia. Long‐term injury of the cerebellum by neonatal hyperoxia was confirmed by reduced volumes in MRI measurements at P30. In response to 80% O2, expression of platelet‐derived growth factor (PDGF)‐A was largely reduced in cerebellar tissue and also in cultured cerebellar astrocytes. Treatment with minocycline during hyperoxia prevented oxidative stress, attenuated oligodendroglial injury, and improved astroglial PDGF‐A levels. In conclusion, early hyperoxia causes white matter damage in the cerebellum with astroglial dysfunction being involved, and both can be prevented by treatment with minocycline. Neonatal exposure to hyperoxia causes hypomyelination of the cerebellum. Reduced astroglial growth factor production but not microglial inflammation seems to contribute to oligodendroglial damage, and minocycline rescues oligodendroglia development in the cerebellum after hyperoxia. GLIA 2015;63:1825–1839
Kidney regeneration using developing xenoembryo

Purpose of reviewWe provide an overview of the recent progress in kidney regeneration with a particular focus on our previous study, which used developing xenoembryos for differentiating human mesenchymal stem cells (hMSCs). The principle of the methodology, recent advances, and limitations and challenges associated with kidney regeneration are outlined. Recent findingsOur primary study objective is to generate neokidney from dialysis patient-derived hMSCs. We previously showed that glial cell-derived neurotrophic factor-expressing hMSCs can differentiate into functional chimeric nephrons in developing mammalian embryos. Recently, we succeeded in eliminating xenotissues in transgenic oestrogen receptor-E2F transcription factor 1 (ER-E2F1) mice by introducing a suicide gene. We also showed MSCs derived from dialysis patients can be used for kidney regeneration. Blastocyst complementation strategy was used to generate chimeric nephrons by injecting mouse pluripotent stem cells into spalt-like transcription factor 1 (Sall1) knockout mouse blastocysts. SummaryKidney tissue can be generated from human mouse pluripotent stem cells or MSCs by several methods. The size and function of regenerated kidney tissue do not meet the transplantation requirements for clinical applications. Although many outstanding problems remain for kidney regeneration, including ethical issues and the formation of chimeric structures, the neokidney generation exclusively from dialysis patient-derived cells is expected to be a reality in the future.
A Phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma

Anastrozole is a new oral aromatase inhibitor with highly potent and selective activity for the aromatase enzyme. In a Phase III trial, the efficacy and tolerability of anastrozole, given in doses of 1 and 10 mg orally once daily, and megestrol acetate, given in doses of 40 mg orally 4 times daily, were compared in 386 postmenopausal women with advanced breast carcinoma who progressed after tamoxifen therapy.
Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin

Abstract: Insulin resistance, oxidative stress, and an abnormal production of adipokines and cytokines are implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently, we reported a significant improvement in plasma liver enzymes among patients with NASH treated with melatonin. In this study, we investigated the effect of melatonin, administered at a dose of 10 mg/day for 28 days to 16 patients with histologically proven NASH on insulin resistance (HOMA‐IR), on the plasma levels of adiponectin, leptin, ghrelin, and resistin. Additionally, plasma levels of aminotransferases and gamma glutamyltranspeptidase as well as plasma concentrations of melatonin were evaluated. Median baseline values of HOMA‐IR, leptin (ng/mL), and resistin (pg/mL) in patients with NASH were significantly higher in comparison with controls: 4.90 versus 1.60, 10.70 versus 4.30, and 152 versus 91, respectively. Median adiponectin level (μg/mL) was decreased in patients compared to controls: 6.40 versus 16.25; no significant difference in ghrelin levels between patients and controls was found. After melatonin treatment, the median value of HOMA‐IR was significantly reduced by 60% as compared to baseline values, whereas adiponectin, leptin, and ghrelin plasma levels rose significantly by 119%, 33%, and 20%, respectively; the difference between pre‐/posttreatment in plasma resistin levels was not significant. These findings make melatonin a suitable candidate for testing in patients with NASH in the large controlled clinical trials.
Lack of NG2 exacerbates neurological outcome and modulates glial responses after traumatic brain injury

Traumatic brain injury (TBI) is a major cause of death and disability. The underlying pathophysiology is characterized by secondary processes including neuronal death and gliosis. To elucidate the role of the NG2 proteoglycan we investigated the response of NG2‐knockout mice (NG2‐KO) to TBI. Seven days after TBI behavioral analysis, brain damage volumetry and assessment of blood brain barrier integrity demonstrated an exacerbated response of NG2‐KO compared to wild‐type (WT) mice. Reactive astrocytes and expression of the reactive astrocyte and neurotoxicity marker Lcn2 (Lipocalin‐2) were increased in the perilesional brain tissue of NG2‐KO mice. In addition, microglia/macrophages with activated morphology were increased in number and mRNA expression of the M2 marker Arg1 (Arginase 1) was enhanced in NG2‐KO mice. While TBI‐induced expression of pro‐inflammatory cytokine genes was unchanged between genotypes, PCR array screening revealed a marked TBI‐induced up‐regulation of the C‐X‐C motif chemokine 13 gene Cxcl13 in NG2‐KO mice. CXCL13, known to attract immune cells to the inflamed brain, was expressed by activated perilesional microglia/macrophages seven days after TBI. Thirty days after TBI, NG2‐KO mice still exhibited more pronounced neurological deficits than WT mice, up‐regulation of Cxcl13, enhanced CD45+ leukocyte infiltration and a relative increase of activated Iba‐1+/CD45+ microglia/macrophages. Our study demonstrates that lack of NG2 exacerbates the neurological outcome after TBI and associates with abnormal activation of astrocytes, microglia/macrophages and increased leukocyte recruitment to the injured brain. These findings suggest that NG2 may counteract neurological deficits and adverse glial responses in TBI. GLIA 2016;64:507–523
The dodo bird verdict and the elephant in the room: A service user-led investigation of crisis resolution and home treatment

Abstract Recent years have seen an international move towards home treatment of acute mental health difficulties. This has been based upon trial data which do little to develop understanding of how or why this approach is as effective as it seems to be. In order to explore this question the study interviewed patients who had recently used the services of a crisis resolution home treatment (CRHT) team in the English East Midlands. Triangulated parallel qualitative analyses of 33 semi-structured interviews conducted by service users trained in research techniques demonstrated that successful CRHT reflected practitioners’ ability to provide clients with a sense of feeling safe, accepted and understood. Unhelpful outcomes followed when participants did not experience such unconditionally supportive relationships. These findings further endorse the primacy of relational factors in mental health practice. They are discussed in relation to the Dodo Bird verdict upon psychological therapies and systemic difficulties acknowledging an inconvenient truth.
Isolation and structure determination of one new metabolite isolated from the red fermented rice of Monascus purpureus

The n-BuOH-soluble portion of the 95% EtOH extract of red fermented rice fermented with the yellow mutant of the fungus Monascus purpureus BCRC 38113 (Monascaceae) led to the isolation of one new pyran-2-one derivative, namely peroxymonascuspyrone (1), along with nine known compounds, monasfluore A (2), monasfluore B (3), 3-epi-betulinic acid (4), 3-epi-betulinic acid acetate (5), α-tocospiro A (6), friedelan-3-one (7), α-cadinol (8), anticopalol (9), and spathulenol (10). Interestingly, this is the first report of a naturally occurring pyran-2-one skeleton isolated from Monascus sp. Their structures and relative configurations were elucidated by spectroscopic methods, including 1D- and 2D-NMR (1H,1H-COSY, HMQC, HMBC and NOESY), as well as low- and high-resolution mass spectrometric analyses. In addition, cytotoxicities against MCF-7, NCI-H460 and SF-268 cancer cell lines were measured in vitro; the results revealed that these metabolites have no cytotoxicity against the selected tumour cells.
What makes coaches tick? The impact of coaches' intrinsic and extrinsic motives on their own satisfaction and that of their athletes

This study aims to investigate the influence of two types of motivational forces on coach and athlete satisfaction. The focus is on intrinsic and extrinsic motives that initiate coach‐related behavior. A questionnaire that measures both types of motivation and three facets of satisfaction (i.e., satisfaction with performance, with instruction, and with the coach–athlete relationship) was completed by 138 coaches. One athlete from each of the coaches who participated in the study was also asked to complete a questionnaire that measures their satisfaction with performance, instruction, and the coach–athlete relationship. Results from a series of regression analyses indicated that while intrinsic motivation was moderately and positively related to all facets of coach satisfaction, extrinsic motivation was only related to coach satisfaction with the coach–athlete relationship. Athletes' satisfaction with the coach–athlete relationship was only associated with the coach's intrinsic motivation. Interaction effects among the two types of motivation were significant suggesting that extrinsic motivation can potentially undermine intrinsic motivation when intrinsic motivation is low. The findings are discussed based on assumptions put forward by self‐determination theory.
Novel immunotherapeutic strategies to target alloantibody-producing B and plasma cells in transplantation

Purpose of reviewThere is an unmet need for immunotherapeutic agents that target humoral alloimmunity in solid organ transplantation. This includes sensitized patients with preformed donor-specific human leucocyte antigen antibodies and patients who develop de-novo donor-specific antibodies, both of which are associated with acute and chronic antibody-mediated rejection and allograft loss. Recent findingsIn this review, we discuss recent progress in the generation of B-cell and plasma cell-targeted therapeutics, with an emphasis on novel agents. To deplete or inhibit B cells, B-cell-specific mAbs have been developed, including CD20, CD22, CD19 and bi-specific antibodies that target two B-cell antigens. In addition, inhibition of B-cell-activating cytokines, such as B cell-activating factor, may also reduce allo-B-cell activation. Plasma cells remain a difficult therapeutic target, but inhibition of germinal centre responses via costimulatory blockade or IL21 neutralization, induction of plasma cell apoptosis using proteasome inhibitors or disruption of the plasma cell niche are potential avenues being explored. SummaryThe ultimate aim of these animal and human studies is to develop agents that efficiently target humoral effectors, whilst sparing B and plasma cells with a regulatory capacity to promote long-term allograft survival, but we remain some distance away from this goal.
Recent advances in allograft vasculopathy

Purpose of review Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy. This review discusses recently reported mechanistic insights of allograft vasculopathy pathogenesis as well as recent clinical evaluations of new therapeutic approaches. Recent findings Although adaptive immunity is the major driver of allograft vasculopathy, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA). However, natural killer cells may also dampen chronic inflammatory responses by killing donor-derived tissue-resident CD4+ T cells that provide help to host B cells, the source of DSA. DSA may directly contribute to vascular inflammation by inducing intracellular signaling cascades that upregulate leukocyte adhesion molecules, facilitating recruitment of neutrophils and monocytes. DSA-mediated complement activation additionally enhances endothelial alloimmunogenicity through activation of noncanonical NF-&kgr;B signaling. New clinical studies evaluating mammalian target of rapamycin and proteasome inhibitors to target these pathways have been reported. Summary Allograft vasculopathy is a disorder resulting from several innate and adaptive alloimmune responses. Mechanistic insights from preclinical studies have identified agents that are currently being investigated in clinical trials.
Calamenenes – aromatic bicyclic sesquiterpenes – from the Indian gorgonian Subergorgia reticulata (Ellis and Solander, 1786)

Three aromatic sesquiterpene derivatives, (+)-(7R, 10S)-2-methoxy calamenene (1), (+)-(7R, 10S)-2,5-dimethoxy calamenene (2) and (+)-(7R, 10S)-2-methoxy-5-acetoxy calamenene (3) were isolated from the methanol extract of the Indian gorgonian Subergorgia reticulata. Compound 2 has not been previously described in the literature. Compound 3 has not been isolated previously from a natural source. Compounds 1, 2 and 3 showed settlement inhibition activity against cyprids of Balanus amphitrite with EC50 values of 4.4, 7.8 and 0.03 µg mL−1, respectively. These compounds also exhibited considerable activity against Artemia nauplii at 50 µg mL−1, indicative of their potential use as cytotoxic agents.
Stress appraisals, emotions, and coping among international adolescent golfers

The aims of this study were to (a) explore the emotions generated during or as a consequence of stress appraisals, after coping, and after the event outcome, (b) explore whether multiple emotions were generated from the initial stress appraisal through to event outcome, and (c) to explore whether outcomes that were perceived as favorable resulted in positive emotions and outcomes that were perceived as unfavorable or neither favorable nor unfavorable resulted in negatively toned emotions. Participants were 10 male English international adolescent golfers (mean±SD; age 16.7±1.6 years), who were interviewed regarding their experiences of stress appraisals, emotions, and coping during competitive golf. Results revealed that emotions were generated within or as a consequence of stress appraisals, after coping, and after the event outcome. Additionally, multiple emotions were generated from the stressful appraisal to the event outcome. Positively toned emotions were cited more frequently than negatively toned emotions after favorable events, whereas negatively toned emotions were reported more frequently than positively toned emotions after unfavorable events. Coping appears important in generating positively toned emotions.