Purpose:To examine the effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness in children aged 7-8 years.Methods:Twenty schools in 5 different European coun...Purpose:To examine the effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness in children aged 7-8 years.Methods:Twenty schools in 5 different European countries(2 second-grade classrooms per school)participated in a cluster randomized controlled trial(Sport at School trial).Participants were assigned to either a control group,which continued with their habitual physical education lessons,or to an intervention group,which replaced these lessons with a 1-year karate intervention(Karate Mind and Movement program).A total of 721 children(344 girls and 377 boys,7.4±0.5 years old,mean±SD)completed the study,of which 333 and 388 were assigned to the control group and intervention group,respectively.Outcomes included academic performance(average grade),psychosocial functioning(Strengths and Difficulties Questionnaire for parents),and different markers of physical fitness(cardiorespiratory fitness,balance,and flexibility).Results:The intervention provided small but significant benefits compared to the control group for academic achievement(d=0.16;p=0.003),conduct problems(d=-0.28;p=0.003),cardiorespiratory fitness(d=0.36;p<0.001),and balance(d=0.24;p=0.015).There was a trend towards significant benefits for flexibility(d=0.24;p=0.056).No significant benefits were observed for other variables,including psychosocial difficulties,emotional symptoms,hyperactivity/inattention,peer problems,or prosocial behaviour(all p>0.05).Conclusion:A 1-year school-based karate intervention was effective in improving academic achievement,conduct problems,and physical fitness in primary school children.The results support the inclusion of karate during physical education lessons.展开更多
Currently, hepatitis B virus(HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan(HSPG) via an antigenic loop of HBV envelope S protein. Then, it is promptly tra...Currently, hepatitis B virus(HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan(HSPG) via an antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide(NTCP) via the myristoylated N-terminal sequence of pre-S1 region(from Gly-2 to Gly-48, HBV genotype D), and it finally enters the cell by endocytosis. However, it is not clear how HSPG passes HBV to NTCP and how NTCP contributes to the cellular entry of HBV. Owing to the poor availability and the difficulty of manipulations, including fluorophore encapsulation, it has been nearly impossible to perform biochemical and cytochemical analyses using a substantial amount of HBV. A bio-nanocapsule(BNC), which is a hollow nanoparticle consisting of HBV envelope L protein, was efficiently synthesized in Saccharomyces cerevisiae. Since BNC could encapsulate payloads(drugs, genes, proteins) and specifically enter human hepatic cells utilizing HBV-derived infection machinery, it could be used as a model of HBV infection to elucidate the early infection machinery. Recently, it was demonstrated that the N-terminal sequence of pre-S1 region(from Asn-9 to Gly-24) possesses low p H-dependent fusogenic activity, which might play a crucial role in the endosomal escape of BNC payloads and in the uncoating process of HBV. In this minireview, we describe a model in which each domain of the HBV L protein contributes to attachment onto human hepatic cells through HSPG, initiation of endocytosis, interaction with NTCP in endosomes, and consequent provocation of membrane fusion followed by endosomal escape.展开更多
To explore how the intrinsic apoptosis pathway is controlled in the spontaneous fog (forebrain overgrowth) mutant mice with an Apafl splicing deficiency, we examined spleen and bone marrow cells from Apafl+/+ (+...To explore how the intrinsic apoptosis pathway is controlled in the spontaneous fog (forebrain overgrowth) mutant mice with an Apafl splicing deficiency, we examined spleen and bone marrow cells from Apafl+/+ (+/+) and Apafl^fog/fog (fog/fog) mice for initiator caspase-9 activation by cellular stresses. When the mitochondrial inner membrane potential (△ψm) was disrupted by staurosporine, +/+ cells but not fog/fog cells activated caspase-9 to cause apoptosis, indicating the lack of apoptosome (apoptosis protease activating factor 1 (Apaf-l)/cytochrome c/(d)ATP/procaspase-9) function in fog/fog cells. However, when a marginal (-20%) decrease in △ψm was caused by hydrogen peroxide (0.1 mM), peroxynitrite donor 3-morpholinosydnonimine (0.1 mM) and UV-C irradiation (20 J/m^2), both +/+ and fog/fog cells triggered procaspase-9 auto-processing and its downstream cascade activation. Supporting our previous results, procaspase-9 pre-existing in the mitochondria induced its auto-processing before the cytosolic caspase activation regardless of the genotypes. Cellular ATP concentration significantly decreased under the hypoactive △ψm condition. Furthermore, we detected accumulation of citrate, a kosmotrope known to facilitate procaspase-9 dimerization, probably due to a feedback control of the Krebs cycle by the electron transfer system. Thus, mitochondrial in situ caspase-9 activation may be caused by the major metabolic reactions in response to physiological stresses, which may represent a mode of Apaf-l-independent apoptosis hypothesized from recent genetic studies.展开更多
All-trans retinoic acid (ATRA) triggers a wide range of effects on vertebrate development by regulating cell proliferation, differentiation, and apoptosis. ATRA activates retinoic acid receptors (RARs) which heterodim...All-trans retinoic acid (ATRA) triggers a wide range of effects on vertebrate development by regulating cell proliferation, differentiation, and apoptosis. ATRA activates retinoic acid receptors (RARs) which heterodimerize with retinoid X receptors (RXRs). RAR/RXR heterodimers function as ATRA-dependent transcriptional regulators by binding to retinoic acid response elements (RAREs). To identify RAR/RXR heterodimer-binding sites in the human genome, we performed a modified yeast one-hybrid assays and identified 193 RAR/RXR heterodimer-binding fragments in the human genome. The putative target genes included genes involved in development process and cell differentiation. Gel mobility shift assays indicated that 160 putative RAREs could directly interact with the RAR/RXR heterodimer. Moreover, 19 functional regulatory single nucleotide polymorphisms (rSNPs) on the RAR/RXR-binding sequences were identified by analyzing the difference in the DNA-binding affinities. These results provide insights into the molecular mechanisms underlying the physiological and pathological actions of RAR/RXR heterodimers.展开更多
Very long chain fatty acids (VLCFAs) are accumulated in cells and blood in patients with peroxisomal diseases, such as adrenoleukodystrophy (ALD) and Zellwger Syndrome (ZS). The purpose of this study is to investigate...Very long chain fatty acids (VLCFAs) are accumulated in cells and blood in patients with peroxisomal diseases, such as adrenoleukodystrophy (ALD) and Zellwger Syndrome (ZS). The purpose of this study is to investigate usefulness of Fourier transform infrared spectroscopy (FTIR) with attenuated total reflection (ATR) analysis method for clinical diagnosis of those diseases, thereby we measured the infrared spectra of the sera of patients and healthy controls. Correlation coefficients between 2nd derivative FTIR spectra of the serum samples and the VLCFA content ratio which is used as a clinical parameter to date were comprehensively calculated to investigate which wavenumber showed high correlation with the VLCFA ratio. Multiple regression analysis using the serum FTIR spectra showed that high correlations were observed with VLCFA ratios (C26:0/C22:0 ratio), and we could construct a suitable regression model (R2 = 0.97, p ﹣19). In addition, the model system using various VLCFAs in newborn bovine serum also showed that several FTIR peaks in 800 ~ 900 cm﹣1 region were found to have good correlation with VLCFA ratios. Our results support that FTIR analysis is useful for diagnosis of peroxisomal diseases.展开更多
Objective To identify the mRNA sequence, genetic construction, imprinting status, and expression profile of human MURR1 gene, the homologue of mouse imprinted Murr1 gene. Methods The MURR1 mRNA sequence was identified...Objective To identify the mRNA sequence, genetic construction, imprinting status, and expression profile of human MURR1 gene, the homologue of mouse imprinted Murr1 gene. Methods The MURR1 mRNA sequence was identified by colony hybridization screening of human cDNA library and the 5'-RACE analyses; Absence of U2AF1-RS1 gene within MURR1 was confirmed by Southern Blotting; Expression profile of MURR1 was examined by Northern Blotting; The imprinting status of MURR1 were revealed by SNP investigation and RT-PCR followed by sequencings and RFLP analyses. Results The full-length mRNA sequence of MURR1 spans 711 bp, transcribed from 3 exons, encodes predicted MURR1 protein of 190 amino acids. The gene was expressed in all the 12 kinds of human adult tissues and 6 kinds of fetal tissues. It showed biallelic expression in all 32 investigated samples including 6 kinds of human fetal tissues and 8 adult brains. Unlike mouse imprinted U2af1-rs1 gene existing in the intron of Murr1, the human U2AF1-RS1 gene was not located in the MURR1 locus. Conclusion Human MURR1 gene is not imprinted and the non-imprinting is possible due to the absence of human homologue of mouse U2af1-rs1 within MURR1 locus.展开更多
The constitutive androstane receptor (CAR) is a transcription factor that belongs to the nuclear receptor superfamily. CAR binds as a heterodimer with the retinoid X receptor α (RXRα) to CAR response elements (CAREs...The constitutive androstane receptor (CAR) is a transcription factor that belongs to the nuclear receptor superfamily. CAR binds as a heterodimer with the retinoid X receptor α (RXRα) to CAR response elements (CAREs) and regulates the expression of various drug metabolizing enzymes and transporters. To identify CAR/RXRα binding sites in the human genome, we performed a modified yeast one-hybrid assay that enables rapid and efficient identification of genomic targets for DNA-binding proteins. DNA fragments were recovered from positive yeast colonies by PCR and sequenced. A motif enrichment analysis revealed that the most frequent motif was a direct repeat (DR) of RGKTCA-like core sequence spaced by 4 bp. Next, we predicted 149 putative CAR/RXRα binding sites from 414 unique clones, by searching for DRs, everted repeats (ERs) and inverted repeats (IRs) of the RGKTCA-like core motif. Based on gel mobility shift assays, the CAR/RXRα heterodimer could directly interact with the 108 predicted sequences, which included not only classical CAREs but also a wide variety of arrangements. Furthermore, we identified 17 regulatory polymorphisms on the CAR/RXRα-binding sites that may influence individual variation in the expression of CAR-regulated genes. These results provide insights into the molecular mechanisms underlying the physiological and pathological actions of CAR/RXRα het-erodimers.展开更多
Aims: We focused on DNA methylation of the promoter regions of the Monoamine Oxidase (MAO) A and B genes from postmortem brains of subjects with schizophrenia. Methods: We determined levels of DNA methylation using ge...Aims: We focused on DNA methylation of the promoter regions of the Monoamine Oxidase (MAO) A and B genes from postmortem brains of subjects with schizophrenia. Methods: We determined levels of DNA methylation using genomic DNA samples purified from four brain areas: prefrontal cortex (PFC), hippocampus, occipital cortex and nucleus accumbens (NAc), by a bisulfite sequencing method from seven normal subjects and six subjects with schizophrenia. Results: Although very few methylated CpGs of the MAOA and MAOB genes were detected in male samples, various DNA methylation patterns were present in female samples, and some differences were found in such patterns between normal subjects and subjects with schizophrenia. In the PFC, the average level of methylation of both genes was significantly higher in subjects with schizophrenia than in normal subjects. The content of highly methylated alleles of the MAOA gene in the NAc was significantly associated with schizophrenia, with similar results obtained for the MAOB gene in both the NAc and PFC. Some CpG sites showed higher levels of methylation in schizophrenia than in normal subjects. Conclusions: Levels of methylation were quite high in NAc and PFC in female subjects with schizophrenia compared with those in female normal subjects.展开更多
The aim of this research was to analyze the PPM of Armenian Premier League using 25 GPS 10 Hz(K-Sport,Montelabbate,Italy),in order to compare data from literature from major European championship.In total 25 matches w...The aim of this research was to analyze the PPM of Armenian Premier League using 25 GPS 10 Hz(K-Sport,Montelabbate,Italy),in order to compare data from literature from major European championship.In total 25 matches were analyzed from one team militant in Armenian Premier League(10 wins,10 loses and 5 draws),33 different players(age 24.3±4.2,height 1.76±4.2 and weight 74±3.5)and in total 270 performances(10.8 for matches).Matches were divided in First Half(T1),Second Half(T2),Second Half Substitution(T2 Sub),Full Match,Full Match Substitution(Full Match Sub)and Total Match(Total)that include all the players detected during a games.Furthermore,all matches were divided even by quarters 0-15,15-30,30-45,45-60,60-75 and 75-90,only players that played all match were included in this analyses,in order to check the performance decreasing during the time.All data were added in an Excel Spreadsheet in order to build a database,to organize and better analyze data,cataloging events for data,results,and role of players.Average data from Armenian Premier League in comparison with literature data from European and Italian Championship show that in every parameter,the Armenian Premier League is under the average.This is obviously related to the non-high level of the Armenian football that is in fact placed at the 106°place of the FIFA ranking(update 7 June 2019).Physical data represent an indicator of performance but also of the qualitative level of the league and of individual players.For this reason,the use of the match analysis can be decisive to verify the PPM,in order to better evaluate the championships,teams,and players,in order to build an easier search and discovery of talents.展开更多
Ability to accelerate, decelerate, recover and sprint again, is a crucial ability for team sports, athletes are forced in repeatingthis actions several times during matches. The objective parameters that influence res...Ability to accelerate, decelerate, recover and sprint again, is a crucial ability for team sports, athletes are forced in repeatingthis actions several times during matches. The objective parameters that influence resistance to sprints are their duration and recovery.The aim of this study was to analyze performance of young under 18 football players on high intensity running thresholds with the useof GPS 20 Hz (K-Sport Universal, Montelabbate, Italy). We have analyzed three football matches of Marche Amateur under 18Championship (Italy) during 2017 season, using 10 GPS, one for each players except the goalkeeper. In order to better define a moreaccurate PPM (players performance model), the players that have been substituted were removed from analysis, using only data fromfull match to build database. Total of detection is 26, with an average of 8.6 players for match divided by role. Our result according withliterature shows that in total distance, the role that obtained higher value was external midfielder and forward traveled more distance insprint.展开更多
AIM:To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS:Rats were treated with an intraperitoneal injection of MK-801 [0.08(low-dose) and 0.16(highdose) mg/kg] or ...AIM:To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS:Rats were treated with an intraperitoneal injection of MK-801 [0.08(low-dose) and 0.16(highdose) mg/kg] or NaC l(vehicle control). In a first series of experiment,the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments,the whole brain of each animal was rapidly removed at 40 min post-injection,and different regions were separated:amygdala,cerebral cortex,hippocampus,hypothalamus,midbrain and ventral striatum on ice followed by DNA microarray(4 × 44 K whole rat genome chip) analysis.RESULTS:Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency(30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number(up- and down- regulations) of gene expressions in the cerebral cortex(378),midbrain(376),hippocampus(375),ventral striatum(353),amygdala(301),and hypothalamus(201) under low-dose(0.08 mg/kg) of MK-801. Under high-dose(0.16 mg/kg),ventral striatum(811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region.CONCLUSION:Acute MK-801 treatment increases synchrony of baseline gamma oscillations,and causes very early changes in gene expressions in six individual rat brain regions,a first report.展开更多
Background:Liqoseal (Polyganics,B.V.) is a dural sealant patch for preventing postoperative cerebrospinal fluid (CSF) leakage.It has been extensively tested preclinically and CE (Conformite Européenne) approved f...Background:Liqoseal (Polyganics,B.V.) is a dural sealant patch for preventing postoperative cerebrospinal fluid (CSF) leakage.It has been extensively tested preclinically and CE (Conformite Européenne) approved for human use after a first cranial in-human study.However,the safety of Liqoseal for spinal application is still unknown.The aim of this study was to assess the safety of spinal Liqoseal application compared with cranial application using histology and magnetic resonance imaging characteristics.Methods:Eight female Dutch Landrace pigs underwent laminectomy,durotomy with standard suturing and Liqoseal application.Three control animals underwent the same procedure without sealant application.The histological characteristics and imaging characteristics of animals with similar survival times were compared to data from a previous cranial porcine model.Results:Similar foreign body reactions were observed in spinal and cranial dura.The foreign body reaction consisted of neutrophils and reactive fibroblasts in the first3 days,changing to a chronic granulomatous inflammatory reaction with an increasing number of macrophages and lymphocytes and the formation of a fibroblast layer on the dura by day 7.Mean Liqoseal plus dura thickness reached a maximum of 1.2mm(range 0.7-2.0mm) at day 7.Conclusion:The spinal dural histological reaction to Liqoseal during the first 7days was similar to the cranial dural reaction.Liqoseal did not swell significantly in both application areas over time.Given the current lack of a safe and effective dural sealant for spinal application,we propose that an in-human safety study of Liqoseal is the logical next step.展开更多
A series of diarylureas and diarylamides possessing pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities were tested against a panel of 49 cell lines of eight diffe...A series of diarylureas and diarylamides possessing pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities were tested against a panel of 49 cell lines of eight different cancer types at the NCI and compared with Sorafenib as a reference compound. Most of the compounds showed strong and broad-spectrum antiproliferative activities with superior potencies to Sorafenib. Compounds 8a, 9d and 9f showed lethal effect with mean %inhibition more than 100% over the 49 tested cell lines. In addition, the mean %inhibition results of compounds 8d, 8e, 9e, 9g and 9h were more than 80%. And most of the IC50 values of the target compounds were in submicromolar scale. Compounds 8a, 9b and 9e demonstrated high selectivity towards cancer cell lines compared with NIH3T3 fibroblasts.展开更多
Objectives: Alliinase is a pyridoxal-5'-phosphate (PLP)-dependent enzyme responsible for the production of diallyl thiosulfinate (allicin), the biologically active component of garlic, from alliin. The use of al...Objectives: Alliinase is a pyridoxal-5'-phosphate (PLP)-dependent enzyme responsible for the production of diallyl thiosulfinate (allicin), the biologically active component of garlic, from alliin. The use of allicin for treatment of various diseases has been proposed but it is very unstable in the blood stream. This difficulty can be overcome by administration of alliin, together with a conjugate of alliinase directed towards the target cells. This, in turn requires a stable and active form of the enzyme. In this study we evaluate the stability of alliinase itself, in the presence mad absence of osmolytes, as well as that of its catalytically active complex with a mannose-specific lectin, ASAI (Allium sativum agglutinin I), also presents in garlic. Methods: Alliinase, mad ASAI were both purified from garlic cloves. Thermal stability of alliinase itself, mad of its complexes with PLP and ASAI, in the presence mad absence of osmolytes, was analyzed by monitoring enzymic activity, and using DSC (differential scanning calorimetry). Key findings: PLP exerts only a minor influence on alliinase structure and stablity. But both osmolytes and ASAI stabilize the enzyme considerably. Conclusions: The principle finding is that ASAI greatly stabilizes alliinase. Thus, the lectin-enzyme complex, which can be lyophilized and stored until used, provides an effective formulation of alliinase for generation of allicin from alliin in vivo.展开更多
Gastric cancer(GC),the third leading cause of cancer-related death globally,is complex and heterogeneous.This review explores multidisciplinary investigations of traditional Chinese medicine(TCM)combined with Western ...Gastric cancer(GC),the third leading cause of cancer-related death globally,is complex and heterogeneous.This review explores multidisciplinary investigations of traditional Chinese medicine(TCM)combined with Western medical practices,emphasizing the development of nutraceuticals for cancer prevention.Using advanced analytical chemistry and food chemistry techniques,this study investigated how TCM components may be optimized for nutraceutical development.Focusing on molecular interactions with GC pathways,particularly the NF-κB,PI3K/Akt,and Wnt/β-catenin pathways,we examined the effects of TCM polyherbal formulas,extracts,and isolated compounds.These agents modulate apoptosis and cellular proliferation,underscoring their potential in preventive strategies.The convergence of nutraceutical and medicine food homology studies highlights a significant shift towards integrating TCM-derived compounds in a preventive health framework.This approach aims not only to enhance efficacy and reduce side effects but also to champion a preventive paradigm using personalized medicine to advance proactive health maintenance and disease prevention.The combination of TCM and western medical practices offers promising avenues for future research and practical applications in GC prevention.展开更多
Background and Objectives: Ankle injuries are the most common type of injury in healthy active individuals. If not treated properly, recurrent sprains can lead to a condition of chronic ankle instability (CAI). The pr...Background and Objectives: Ankle injuries are the most common type of injury in healthy active individuals. If not treated properly, recurrent sprains can lead to a condition of chronic ankle instability (CAI). The present paper examines some subjects with a previous history of acute inversion ankle sprain who have developed a subsequent condition of instability, grouping them according to inclusion criteria and analyzing them through four field tests considered objective by the scientific literature: SEBT test, BEES test, TIBT test, SHT test. The data obtained were stored in order to compare them following a re-education protocol aimed at improving proprioception, balance, walking and strengthening the extrinsic and intrinsic muscles of the foot. per year. The subjects were then divided into two categories: subjects with CAI > 1 year and subjects with CAI ≤ 1 year. A protocol lasting 6 weeks was administered to both groups, trying to work on improving balance in single stance, improving static and dynamic stability, strengthening the gluteus medius and maximus (pelvis stabilizers) and strengthening of the intrinsic muscles of the foot. At the end of the protocol the subjects were all re-evaluated with the same field tests used previously and the data obtained were compared both with the pre-protocol data and with the data measured by the control subjects.展开更多
Cancer chemotherapy efficacy is frequently impaired by either intrinsic or acquired tumor resistance.A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growt...Cancer chemotherapy efficacy is frequently impaired by either intrinsic or acquired tumor resistance.A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells.In recent years,the cancer stem cell(CSC) theory has changed the classical view of tumor growth and therefore the therapeutic perspective.Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers.On the other hand,the identification of CSCs in vivo and in vitro relies on specific surface markers that should allow the sorting cancer cells into phenotypically distinct subpopulations.In the present review,recent papers published on CSCs in solid tumors(breast,prostate,brain and melanoma) are discussed,highlighting critical points such as the choice of markers to sort CSCs and mouse models to demonstrate that CSCs are able to replicate the original tumor.A discussion of the possible role of aldehyde dehydrogenase and CXCR6 biomarkers as signaling molecules in CSCs and normal stem cells is also discussed.The author believes that efforts have to be made to investigate the functional and biological properties of putative CSCs in cancer.Developing diagnostic/prognostic tools to follow cancer development is also a challenge.In this connection it would be useful to develop a multidisciplinary approach combining mathematics,physics and biology which merges experimental approaches and theory.Biological models alone are probably unable to resolve the problem completely.展开更多
Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs.Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to trans...Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs.Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various lineages.However,when transplanted,they lose part of their multipotency and immunomodulatory properties,and most of them die after injection into the damaged tissue.In this review,we discuss the potential utility of melatonin in preserving mesenchymal stem cells’survival and function after transplantation.Melatonin is a pleiotropic molecule regulating critical cell functions including apoptosis,endoplasmic reticulum stress,and autophagy.Melatonin is also synthesized in the mitochondria where it reduces oxidative stress,the opening of the mitochondrial permeability transition pore and the downstream caspase activation,activates uncoupling proteins,and curtails the proinflammatory response.In addition,recent findings showed that melatonin also promotes the formation of tunneling nanotubes and the transfer of mitochondria between cells through the connecting tubules.As mitochondrial dysfunction is a primary cause of mesenchymal stem cells death and senescence and a critical issue for survival after transplantation,we propose that melatonin by favoring mitochondria functionality and their transfer through tunneling nanotubes from healthy to suffering cells could improve mesenchymal stem cellbased therapy in a large number of diseases for which basic and clinical trials are underway.展开更多
Cancer is one of the leading causes of death in America, and there is an urgent need for new therapeutic approaches. The progesterone receptor membrane component 1 (PGRMC1) is a cytochrome b5 related protein that bind...Cancer is one of the leading causes of death in America, and there is an urgent need for new therapeutic approaches. The progesterone receptor membrane component 1 (PGRMC1) is a cytochrome b5 related protein that binds heme and is associated with signaling, apoptotic suppression and autophagy. PGRMC1 is essential for tumor formation, invasion and metastasis, and is upregulated in breast, colon, lung and thyroid tumors. In the present study, we have analyzed PGRMC1 levels in over 600 tumor sections, including a larger cohort of lung tumors than in previous studies, and report the first clinical analysis of PGRMC1 levels in human oral cavity and ovarian tumors compared to corresponding nonmalignant tissues. PGRMC1 was highly expressed in lung and ovarian cancers and correlated with patient survival. PGRMC1 has been previously associated with drug resistance, a characteristic of cancer stem cells. The stem cell theory proposes that a subset of cancerous stem cells contribute to drug resistance and tumor maintenance, and PGRMC1 was detected in lung-tumor derived stem cells. Drug treatment with a PGRMC1 inhibitor, AG-205, triggered stem cell death whereas treatment with erlotinib and the ERK inhibitor, PD98059, did not, suggesting a specific role for PGRMC1 in cancer stem cell viability. Together, our data demonstrate PGRMC1 as a potential tumor biomarker across a variety of tumors, as well as a therapeutic target for cancer stem cells.展开更多
The athletic component in football is nowadays one of the most important factor to determinate the performance. This consideration is part of our study, which aims to evaluate and quantify the difference between the w...The athletic component in football is nowadays one of the most important factor to determinate the performance. This consideration is part of our study, which aims to evaluate and quantify the difference between the workload of an amateur footballer and an elite one. All this is allowed by match analysis made by GPS evaluation method for amateur and video tracking for elite. The examined teams were playing in 7th Italian league, and we used 10 GPS to track 6 games, 5 for each team. For every team and every game were analysed a forward, a central midfielder, a wide midfielder, a central defender and a full back (Age 25.3 + 4.2, Weight 74.5 Kg a: 5.3, Height 1.76 cm + 5.2). In our study, we used a 20 Hz GPS (thanks to Advanced Research Group in Sport, School of Health and Sport Science with K-Sport Universal, Italy) to detect performance data, and then we compared the outcome with matches performance data from elite players gather from scientific literature. Data analysis shows that elite players reach higher values in almost all parameters taken into account. In particular, they obtained higher value in meters per minutes, High Speed Distance (〉 16 Km/h), High Metabolic Power Distance (〉 20 W/Kg) and in high and very high and acceleration (2 m/s, 3 m/s, 〉 3 m/s) and deceleration (-2 m/s, -3 m/s, 〉 -3 m/s). This study can be useful to select and catalogue player performance model, in order to better understand the real value of a player, and to help coaches and teams to identify talent, at least in physical values.展开更多
基金supported by the Erasmus+program of the European Union(567201-EPP-1-2015-2-IT-SPO-SCP)supported by the University of Alcala(FPI2016)。
文摘Purpose:To examine the effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness in children aged 7-8 years.Methods:Twenty schools in 5 different European countries(2 second-grade classrooms per school)participated in a cluster randomized controlled trial(Sport at School trial).Participants were assigned to either a control group,which continued with their habitual physical education lessons,or to an intervention group,which replaced these lessons with a 1-year karate intervention(Karate Mind and Movement program).A total of 721 children(344 girls and 377 boys,7.4±0.5 years old,mean±SD)completed the study,of which 333 and 388 were assigned to the control group and intervention group,respectively.Outcomes included academic performance(average grade),psychosocial functioning(Strengths and Difficulties Questionnaire for parents),and different markers of physical fitness(cardiorespiratory fitness,balance,and flexibility).Results:The intervention provided small but significant benefits compared to the control group for academic achievement(d=0.16;p=0.003),conduct problems(d=-0.28;p=0.003),cardiorespiratory fitness(d=0.36;p<0.001),and balance(d=0.24;p=0.015).There was a trend towards significant benefits for flexibility(d=0.24;p=0.056).No significant benefits were observed for other variables,including psychosocial difficulties,emotional symptoms,hyperactivity/inattention,peer problems,or prosocial behaviour(all p>0.05).Conclusion:A 1-year school-based karate intervention was effective in improving academic achievement,conduct problems,and physical fitness in primary school children.The results support the inclusion of karate during physical education lessons.
文摘Currently, hepatitis B virus(HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan(HSPG) via an antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide(NTCP) via the myristoylated N-terminal sequence of pre-S1 region(from Gly-2 to Gly-48, HBV genotype D), and it finally enters the cell by endocytosis. However, it is not clear how HSPG passes HBV to NTCP and how NTCP contributes to the cellular entry of HBV. Owing to the poor availability and the difficulty of manipulations, including fluorophore encapsulation, it has been nearly impossible to perform biochemical and cytochemical analyses using a substantial amount of HBV. A bio-nanocapsule(BNC), which is a hollow nanoparticle consisting of HBV envelope L protein, was efficiently synthesized in Saccharomyces cerevisiae. Since BNC could encapsulate payloads(drugs, genes, proteins) and specifically enter human hepatic cells utilizing HBV-derived infection machinery, it could be used as a model of HBV infection to elucidate the early infection machinery. Recently, it was demonstrated that the N-terminal sequence of pre-S1 region(from Asn-9 to Gly-24) possesses low p H-dependent fusogenic activity, which might play a crucial role in the endosomal escape of BNC payloads and in the uncoating process of HBV. In this minireview, we describe a model in which each domain of the HBV L protein contributes to attachment onto human hepatic cells through HSPG, initiation of endocytosis, interaction with NTCP in endosomes, and consequent provocation of membrane fusion followed by endosomal escape.
文摘To explore how the intrinsic apoptosis pathway is controlled in the spontaneous fog (forebrain overgrowth) mutant mice with an Apafl splicing deficiency, we examined spleen and bone marrow cells from Apafl+/+ (+/+) and Apafl^fog/fog (fog/fog) mice for initiator caspase-9 activation by cellular stresses. When the mitochondrial inner membrane potential (△ψm) was disrupted by staurosporine, +/+ cells but not fog/fog cells activated caspase-9 to cause apoptosis, indicating the lack of apoptosome (apoptosis protease activating factor 1 (Apaf-l)/cytochrome c/(d)ATP/procaspase-9) function in fog/fog cells. However, when a marginal (-20%) decrease in △ψm was caused by hydrogen peroxide (0.1 mM), peroxynitrite donor 3-morpholinosydnonimine (0.1 mM) and UV-C irradiation (20 J/m^2), both +/+ and fog/fog cells triggered procaspase-9 auto-processing and its downstream cascade activation. Supporting our previous results, procaspase-9 pre-existing in the mitochondria induced its auto-processing before the cytosolic caspase activation regardless of the genotypes. Cellular ATP concentration significantly decreased under the hypoactive △ψm condition. Furthermore, we detected accumulation of citrate, a kosmotrope known to facilitate procaspase-9 dimerization, probably due to a feedback control of the Krebs cycle by the electron transfer system. Thus, mitochondrial in situ caspase-9 activation may be caused by the major metabolic reactions in response to physiological stresses, which may represent a mode of Apaf-l-independent apoptosis hypothesized from recent genetic studies.
文摘All-trans retinoic acid (ATRA) triggers a wide range of effects on vertebrate development by regulating cell proliferation, differentiation, and apoptosis. ATRA activates retinoic acid receptors (RARs) which heterodimerize with retinoid X receptors (RXRs). RAR/RXR heterodimers function as ATRA-dependent transcriptional regulators by binding to retinoic acid response elements (RAREs). To identify RAR/RXR heterodimer-binding sites in the human genome, we performed a modified yeast one-hybrid assays and identified 193 RAR/RXR heterodimer-binding fragments in the human genome. The putative target genes included genes involved in development process and cell differentiation. Gel mobility shift assays indicated that 160 putative RAREs could directly interact with the RAR/RXR heterodimer. Moreover, 19 functional regulatory single nucleotide polymorphisms (rSNPs) on the RAR/RXR-binding sequences were identified by analyzing the difference in the DNA-binding affinities. These results provide insights into the molecular mechanisms underlying the physiological and pathological actions of RAR/RXR heterodimers.
文摘Very long chain fatty acids (VLCFAs) are accumulated in cells and blood in patients with peroxisomal diseases, such as adrenoleukodystrophy (ALD) and Zellwger Syndrome (ZS). The purpose of this study is to investigate usefulness of Fourier transform infrared spectroscopy (FTIR) with attenuated total reflection (ATR) analysis method for clinical diagnosis of those diseases, thereby we measured the infrared spectra of the sera of patients and healthy controls. Correlation coefficients between 2nd derivative FTIR spectra of the serum samples and the VLCFA content ratio which is used as a clinical parameter to date were comprehensively calculated to investigate which wavenumber showed high correlation with the VLCFA ratio. Multiple regression analysis using the serum FTIR spectra showed that high correlations were observed with VLCFA ratios (C26:0/C22:0 ratio), and we could construct a suitable regression model (R2 = 0.97, p ﹣19). In addition, the model system using various VLCFAs in newborn bovine serum also showed that several FTIR peaks in 800 ~ 900 cm﹣1 region were found to have good correlation with VLCFA ratios. Our results support that FTIR analysis is useful for diagnosis of peroxisomal diseases.
文摘Objective To identify the mRNA sequence, genetic construction, imprinting status, and expression profile of human MURR1 gene, the homologue of mouse imprinted Murr1 gene. Methods The MURR1 mRNA sequence was identified by colony hybridization screening of human cDNA library and the 5'-RACE analyses; Absence of U2AF1-RS1 gene within MURR1 was confirmed by Southern Blotting; Expression profile of MURR1 was examined by Northern Blotting; The imprinting status of MURR1 were revealed by SNP investigation and RT-PCR followed by sequencings and RFLP analyses. Results The full-length mRNA sequence of MURR1 spans 711 bp, transcribed from 3 exons, encodes predicted MURR1 protein of 190 amino acids. The gene was expressed in all the 12 kinds of human adult tissues and 6 kinds of fetal tissues. It showed biallelic expression in all 32 investigated samples including 6 kinds of human fetal tissues and 8 adult brains. Unlike mouse imprinted U2af1-rs1 gene existing in the intron of Murr1, the human U2AF1-RS1 gene was not located in the MURR1 locus. Conclusion Human MURR1 gene is not imprinted and the non-imprinting is possible due to the absence of human homologue of mouse U2af1-rs1 within MURR1 locus.
文摘The constitutive androstane receptor (CAR) is a transcription factor that belongs to the nuclear receptor superfamily. CAR binds as a heterodimer with the retinoid X receptor α (RXRα) to CAR response elements (CAREs) and regulates the expression of various drug metabolizing enzymes and transporters. To identify CAR/RXRα binding sites in the human genome, we performed a modified yeast one-hybrid assay that enables rapid and efficient identification of genomic targets for DNA-binding proteins. DNA fragments were recovered from positive yeast colonies by PCR and sequenced. A motif enrichment analysis revealed that the most frequent motif was a direct repeat (DR) of RGKTCA-like core sequence spaced by 4 bp. Next, we predicted 149 putative CAR/RXRα binding sites from 414 unique clones, by searching for DRs, everted repeats (ERs) and inverted repeats (IRs) of the RGKTCA-like core motif. Based on gel mobility shift assays, the CAR/RXRα heterodimer could directly interact with the 108 predicted sequences, which included not only classical CAREs but also a wide variety of arrangements. Furthermore, we identified 17 regulatory polymorphisms on the CAR/RXRα-binding sites that may influence individual variation in the expression of CAR-regulated genes. These results provide insights into the molecular mechanisms underlying the physiological and pathological actions of CAR/RXRα het-erodimers.
文摘Aims: We focused on DNA methylation of the promoter regions of the Monoamine Oxidase (MAO) A and B genes from postmortem brains of subjects with schizophrenia. Methods: We determined levels of DNA methylation using genomic DNA samples purified from four brain areas: prefrontal cortex (PFC), hippocampus, occipital cortex and nucleus accumbens (NAc), by a bisulfite sequencing method from seven normal subjects and six subjects with schizophrenia. Results: Although very few methylated CpGs of the MAOA and MAOB genes were detected in male samples, various DNA methylation patterns were present in female samples, and some differences were found in such patterns between normal subjects and subjects with schizophrenia. In the PFC, the average level of methylation of both genes was significantly higher in subjects with schizophrenia than in normal subjects. The content of highly methylated alleles of the MAOA gene in the NAc was significantly associated with schizophrenia, with similar results obtained for the MAOB gene in both the NAc and PFC. Some CpG sites showed higher levels of methylation in schizophrenia than in normal subjects. Conclusions: Levels of methylation were quite high in NAc and PFC in female subjects with schizophrenia compared with those in female normal subjects.
文摘The aim of this research was to analyze the PPM of Armenian Premier League using 25 GPS 10 Hz(K-Sport,Montelabbate,Italy),in order to compare data from literature from major European championship.In total 25 matches were analyzed from one team militant in Armenian Premier League(10 wins,10 loses and 5 draws),33 different players(age 24.3±4.2,height 1.76±4.2 and weight 74±3.5)and in total 270 performances(10.8 for matches).Matches were divided in First Half(T1),Second Half(T2),Second Half Substitution(T2 Sub),Full Match,Full Match Substitution(Full Match Sub)and Total Match(Total)that include all the players detected during a games.Furthermore,all matches were divided even by quarters 0-15,15-30,30-45,45-60,60-75 and 75-90,only players that played all match were included in this analyses,in order to check the performance decreasing during the time.All data were added in an Excel Spreadsheet in order to build a database,to organize and better analyze data,cataloging events for data,results,and role of players.Average data from Armenian Premier League in comparison with literature data from European and Italian Championship show that in every parameter,the Armenian Premier League is under the average.This is obviously related to the non-high level of the Armenian football that is in fact placed at the 106°place of the FIFA ranking(update 7 June 2019).Physical data represent an indicator of performance but also of the qualitative level of the league and of individual players.For this reason,the use of the match analysis can be decisive to verify the PPM,in order to better evaluate the championships,teams,and players,in order to build an easier search and discovery of talents.
文摘Ability to accelerate, decelerate, recover and sprint again, is a crucial ability for team sports, athletes are forced in repeatingthis actions several times during matches. The objective parameters that influence resistance to sprints are their duration and recovery.The aim of this study was to analyze performance of young under 18 football players on high intensity running thresholds with the useof GPS 20 Hz (K-Sport Universal, Montelabbate, Italy). We have analyzed three football matches of Marche Amateur under 18Championship (Italy) during 2017 season, using 10 GPS, one for each players except the goalkeeper. In order to better define a moreaccurate PPM (players performance model), the players that have been substituted were removed from analysis, using only data fromfull match to build database. Total of detection is 26, with an average of 8.6 players for match divided by role. Our result according withliterature shows that in total distance, the role that obtained higher value was external midfielder and forward traveled more distance insprint.
基金supported by The French Institute of health and Medical Research (Inserm),Université de Strasbourg and Neurex
文摘AIM:To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS:Rats were treated with an intraperitoneal injection of MK-801 [0.08(low-dose) and 0.16(highdose) mg/kg] or NaC l(vehicle control). In a first series of experiment,the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments,the whole brain of each animal was rapidly removed at 40 min post-injection,and different regions were separated:amygdala,cerebral cortex,hippocampus,hypothalamus,midbrain and ventral striatum on ice followed by DNA microarray(4 × 44 K whole rat genome chip) analysis.RESULTS:Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency(30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number(up- and down- regulations) of gene expressions in the cerebral cortex(378),midbrain(376),hippocampus(375),ventral striatum(353),amygdala(301),and hypothalamus(201) under low-dose(0.08 mg/kg) of MK-801. Under high-dose(0.16 mg/kg),ventral striatum(811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region.CONCLUSION:Acute MK-801 treatment increases synchrony of baseline gamma oscillations,and causes very early changes in gene expressions in six individual rat brain regions,a first report.
文摘Background:Liqoseal (Polyganics,B.V.) is a dural sealant patch for preventing postoperative cerebrospinal fluid (CSF) leakage.It has been extensively tested preclinically and CE (Conformite Européenne) approved for human use after a first cranial in-human study.However,the safety of Liqoseal for spinal application is still unknown.The aim of this study was to assess the safety of spinal Liqoseal application compared with cranial application using histology and magnetic resonance imaging characteristics.Methods:Eight female Dutch Landrace pigs underwent laminectomy,durotomy with standard suturing and Liqoseal application.Three control animals underwent the same procedure without sealant application.The histological characteristics and imaging characteristics of animals with similar survival times were compared to data from a previous cranial porcine model.Results:Similar foreign body reactions were observed in spinal and cranial dura.The foreign body reaction consisted of neutrophils and reactive fibroblasts in the first3 days,changing to a chronic granulomatous inflammatory reaction with an increasing number of macrophages and lymphocytes and the formation of a fibroblast layer on the dura by day 7.Mean Liqoseal plus dura thickness reached a maximum of 1.2mm(range 0.7-2.0mm) at day 7.Conclusion:The spinal dural histological reaction to Liqoseal during the first 7days was similar to the cranial dural reaction.Liqoseal did not swell significantly in both application areas over time.Given the current lack of a safe and effective dural sealant for spinal application,we propose that an in-human safety study of Liqoseal is the logical next step.
文摘A series of diarylureas and diarylamides possessing pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities were tested against a panel of 49 cell lines of eight different cancer types at the NCI and compared with Sorafenib as a reference compound. Most of the compounds showed strong and broad-spectrum antiproliferative activities with superior potencies to Sorafenib. Compounds 8a, 9d and 9f showed lethal effect with mean %inhibition more than 100% over the 49 tested cell lines. In addition, the mean %inhibition results of compounds 8d, 8e, 9e, 9g and 9h were more than 80%. And most of the IC50 values of the target compounds were in submicromolar scale. Compounds 8a, 9b and 9e demonstrated high selectivity towards cancer cell lines compared with NIH3T3 fibroblasts.
文摘Objectives: Alliinase is a pyridoxal-5'-phosphate (PLP)-dependent enzyme responsible for the production of diallyl thiosulfinate (allicin), the biologically active component of garlic, from alliin. The use of allicin for treatment of various diseases has been proposed but it is very unstable in the blood stream. This difficulty can be overcome by administration of alliin, together with a conjugate of alliinase directed towards the target cells. This, in turn requires a stable and active form of the enzyme. In this study we evaluate the stability of alliinase itself, in the presence mad absence of osmolytes, as well as that of its catalytically active complex with a mannose-specific lectin, ASAI (Allium sativum agglutinin I), also presents in garlic. Methods: Alliinase, mad ASAI were both purified from garlic cloves. Thermal stability of alliinase itself, mad of its complexes with PLP and ASAI, in the presence mad absence of osmolytes, was analyzed by monitoring enzymic activity, and using DSC (differential scanning calorimetry). Key findings: PLP exerts only a minor influence on alliinase structure and stablity. But both osmolytes and ASAI stabilize the enzyme considerably. Conclusions: The principle finding is that ASAI greatly stabilizes alliinase. Thus, the lectin-enzyme complex, which can be lyophilized and stored until used, provides an effective formulation of alliinase for generation of allicin from alliin in vivo.
文摘Gastric cancer(GC),the third leading cause of cancer-related death globally,is complex and heterogeneous.This review explores multidisciplinary investigations of traditional Chinese medicine(TCM)combined with Western medical practices,emphasizing the development of nutraceuticals for cancer prevention.Using advanced analytical chemistry and food chemistry techniques,this study investigated how TCM components may be optimized for nutraceutical development.Focusing on molecular interactions with GC pathways,particularly the NF-κB,PI3K/Akt,and Wnt/β-catenin pathways,we examined the effects of TCM polyherbal formulas,extracts,and isolated compounds.These agents modulate apoptosis and cellular proliferation,underscoring their potential in preventive strategies.The convergence of nutraceutical and medicine food homology studies highlights a significant shift towards integrating TCM-derived compounds in a preventive health framework.This approach aims not only to enhance efficacy and reduce side effects but also to champion a preventive paradigm using personalized medicine to advance proactive health maintenance and disease prevention.The combination of TCM and western medical practices offers promising avenues for future research and practical applications in GC prevention.
文摘Background and Objectives: Ankle injuries are the most common type of injury in healthy active individuals. If not treated properly, recurrent sprains can lead to a condition of chronic ankle instability (CAI). The present paper examines some subjects with a previous history of acute inversion ankle sprain who have developed a subsequent condition of instability, grouping them according to inclusion criteria and analyzing them through four field tests considered objective by the scientific literature: SEBT test, BEES test, TIBT test, SHT test. The data obtained were stored in order to compare them following a re-education protocol aimed at improving proprioception, balance, walking and strengthening the extrinsic and intrinsic muscles of the foot. per year. The subjects were then divided into two categories: subjects with CAI > 1 year and subjects with CAI ≤ 1 year. A protocol lasting 6 weeks was administered to both groups, trying to work on improving balance in single stance, improving static and dynamic stability, strengthening the gluteus medius and maximus (pelvis stabilizers) and strengthening of the intrinsic muscles of the foot. At the end of the protocol the subjects were all re-evaluated with the same field tests used previously and the data obtained were compared both with the pre-protocol data and with the data measured by the control subjects.
文摘Cancer chemotherapy efficacy is frequently impaired by either intrinsic or acquired tumor resistance.A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells.In recent years,the cancer stem cell(CSC) theory has changed the classical view of tumor growth and therefore the therapeutic perspective.Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers.On the other hand,the identification of CSCs in vivo and in vitro relies on specific surface markers that should allow the sorting cancer cells into phenotypically distinct subpopulations.In the present review,recent papers published on CSCs in solid tumors(breast,prostate,brain and melanoma) are discussed,highlighting critical points such as the choice of markers to sort CSCs and mouse models to demonstrate that CSCs are able to replicate the original tumor.A discussion of the possible role of aldehyde dehydrogenase and CXCR6 biomarkers as signaling molecules in CSCs and normal stem cells is also discussed.The author believes that efforts have to be made to investigate the functional and biological properties of putative CSCs in cancer.Developing diagnostic/prognostic tools to follow cancer development is also a challenge.In this connection it would be useful to develop a multidisciplinary approach combining mathematics,physics and biology which merges experimental approaches and theory.Biological models alone are probably unable to resolve the problem completely.
基金supported by the University of Urbino Carlo Bo(No.DR-473_2018)to WB。
文摘Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs.Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various lineages.However,when transplanted,they lose part of their multipotency and immunomodulatory properties,and most of them die after injection into the damaged tissue.In this review,we discuss the potential utility of melatonin in preserving mesenchymal stem cells’survival and function after transplantation.Melatonin is a pleiotropic molecule regulating critical cell functions including apoptosis,endoplasmic reticulum stress,and autophagy.Melatonin is also synthesized in the mitochondria where it reduces oxidative stress,the opening of the mitochondrial permeability transition pore and the downstream caspase activation,activates uncoupling proteins,and curtails the proinflammatory response.In addition,recent findings showed that melatonin also promotes the formation of tunneling nanotubes and the transfer of mitochondria between cells through the connecting tubules.As mitochondrial dysfunction is a primary cause of mesenchymal stem cells death and senescence and a critical issue for survival after transplantation,we propose that melatonin by favoring mitochondria functionality and their transfer through tunneling nanotubes from healthy to suffering cells could improve mesenchymal stem cellbased therapy in a large number of diseases for which basic and clinical trials are underway.
文摘Cancer is one of the leading causes of death in America, and there is an urgent need for new therapeutic approaches. The progesterone receptor membrane component 1 (PGRMC1) is a cytochrome b5 related protein that binds heme and is associated with signaling, apoptotic suppression and autophagy. PGRMC1 is essential for tumor formation, invasion and metastasis, and is upregulated in breast, colon, lung and thyroid tumors. In the present study, we have analyzed PGRMC1 levels in over 600 tumor sections, including a larger cohort of lung tumors than in previous studies, and report the first clinical analysis of PGRMC1 levels in human oral cavity and ovarian tumors compared to corresponding nonmalignant tissues. PGRMC1 was highly expressed in lung and ovarian cancers and correlated with patient survival. PGRMC1 has been previously associated with drug resistance, a characteristic of cancer stem cells. The stem cell theory proposes that a subset of cancerous stem cells contribute to drug resistance and tumor maintenance, and PGRMC1 was detected in lung-tumor derived stem cells. Drug treatment with a PGRMC1 inhibitor, AG-205, triggered stem cell death whereas treatment with erlotinib and the ERK inhibitor, PD98059, did not, suggesting a specific role for PGRMC1 in cancer stem cell viability. Together, our data demonstrate PGRMC1 as a potential tumor biomarker across a variety of tumors, as well as a therapeutic target for cancer stem cells.
文摘The athletic component in football is nowadays one of the most important factor to determinate the performance. This consideration is part of our study, which aims to evaluate and quantify the difference between the workload of an amateur footballer and an elite one. All this is allowed by match analysis made by GPS evaluation method for amateur and video tracking for elite. The examined teams were playing in 7th Italian league, and we used 10 GPS to track 6 games, 5 for each team. For every team and every game were analysed a forward, a central midfielder, a wide midfielder, a central defender and a full back (Age 25.3 + 4.2, Weight 74.5 Kg a: 5.3, Height 1.76 cm + 5.2). In our study, we used a 20 Hz GPS (thanks to Advanced Research Group in Sport, School of Health and Sport Science with K-Sport Universal, Italy) to detect performance data, and then we compared the outcome with matches performance data from elite players gather from scientific literature. Data analysis shows that elite players reach higher values in almost all parameters taken into account. In particular, they obtained higher value in meters per minutes, High Speed Distance (〉 16 Km/h), High Metabolic Power Distance (〉 20 W/Kg) and in high and very high and acceleration (2 m/s, 3 m/s, 〉 3 m/s) and deceleration (-2 m/s, -3 m/s, 〉 -3 m/s). This study can be useful to select and catalogue player performance model, in order to better understand the real value of a player, and to help coaches and teams to identify talent, at least in physical values.