Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essent...Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart function.MSCs can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental pulp.MSCs from various sources differ in their regenerative and therapeutic abilities for cardiovascular disorders.In this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.展开更多
Memory loss and dementia are major public health concerns with a substantial economic burden.Oxidative stress has been shown to play a crucial role in the pathophysiology of hippocampal damage-induced memory impairmen...Memory loss and dementia are major public health concerns with a substantial economic burden.Oxidative stress has been shown to play a crucial role in the pathophysiology of hippocampal damage-induced memory impairment.To investigate whether the antioxidant and anti-inflammatory compound vanillyla cetone(zingerone) can protect against hippocampal damage and memory loss induced by cadmium chloride(CdCl_(2)) administration in rats,we explo red the potential involvement of the nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway,which is known to modulate oxidative stress and inflammation.Sixty healt hy male Wistar rats were divided into five groups:vehicle-treated(control),vanillylacetone,CdCl_(2),vanillylacetone+ CdCl_(2),vanillylacetone+ CdCl_(2)+ brusatol(a selective pharmacological N rf2inhibitor) groups.Vanillylacetone effectively attenuated CdCl_(2)-induced damage in the dental gyrus of the hippocampus and improved the memory function assessed by the Morris Water Maze test.Additionally,vanillylacetone markedly decreased the hippocampal tissue levels of inflammatory biomarkers(interleukin-6,tumor necrosis factor-α,intracellular cell adhesive molecules) and apoptosis biomarkers(Bax and cleaved caspase-3).The control and CdCl_(2)-treated groups treated with va nillylacetone showed reduced generation of reactive oxygen species,decreased malondialdehyde levels,and increased superoxide dismutase and glutathione activities,along with significant elevation of nuclear Nrf2 mRNA and protein expression in hippocampal tissue.All the protective effects of vanillylacetone we re substantially blocked by the co-administration of brusatol(a selective N rf2 inhibitor).Va nillylacetone mitigated hippocampal damage and memory loss induced by CdCl_(2),at least in part, by activating the nuclear transcription factor Nrf2.Additionally,vanillylacetone exerted its potent antioxidant and antiinflammatory actions.展开更多
BACKGROUND Diabetes is known damage the liver and kidney,leading to hepatic dysfunction and kidney failure.Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic comp...BACKGROUND Diabetes is known damage the liver and kidney,leading to hepatic dysfunction and kidney failure.Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications.However,the effect of stingless bee honey(SBH)administration in relieving liver and kidney damage in diabetes has not been well-studied.AIM To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced(STZ;55 mg/kg)diabetic Sprague Dawley rats.METHODS The rats were grouped as follows(n=6 per group):non-diabetic(ND),untreated diabetic(UNT),metformin-treated(MET),and SBH+metformin-treated(SBME)groups.After successful diabetic induction,ND and UNT rats were given normal saline,whereas the treatment groups received SBH(2.0 g/kg and/or metformin(250 mg/kg)for 12 d.Serum biochemical parameters and histological changes using hematoxylin and eosin(H&E)and periodic acid–Schiff(PAS)staining were evaluated.RESULTS On H&E and PAS staining,the ND group showed normal architecture and cellularity of Bowman’s capsule and tubules,whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane.The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining,but the two were similar on PAS staining.Likewise,the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining,but it was comparable to the SBH and ND groups on PAS staining.UNT diabetic rats had tubular hydropic tubules,which were smaller than other groups.Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group.Conversely,the UNT group had high glucose levels,which subsequently increased MDA levels,ultimately leading to liver damage.SBH treatment reduced this damage,as evidenced by having the lowest fasting glucose,serum alanine transaminase,aspartate transaminase,and alkaline phosphatase levels compared to other groups,although the levels of liver enzymes were not statistically significant.CONCLUSION The cellularity of the Bowman’s capsule,as well as histological alteration of kidney tubules,glomerular membranes,and liver tissues in diabetic rats after oral SBH resembled those of ND rats.Therefore,SBH exhibited a protective hepatorenal effect in a diabetic rat model.展开更多
As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements...As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.展开更多
In a previous study from our laboratory, fucoxanthin purified from brown algae, Sargassum wightii Greville has found to exhibit antioxidant activity and inhibition of angiotensin-I-converting enzyme(ACE)in vitro. The ...In a previous study from our laboratory, fucoxanthin purified from brown algae, Sargassum wightii Greville has found to exhibit antioxidant activity and inhibition of angiotensin-I-converting enzyme(ACE)in vitro. The present study aims in understanding the protective effect of fucoxanthin purified from S. wightii against diabetes with hypertension in in vivo. Diabetes and hypertension were induced in rat by streptozotocin and sodium chloride treatment, respectively. In diabetes with hypertension rat, the blood pressure was increased along with hyperglycemia. Administration of fucoxanthin significantly reduced the blood pressure and ACE activity in diabetes with hypertension rat. Furthermore, administration of fucoxanthin significantly reduced the hyperglycemic state. The activity of various enzymes in the liver(hexokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase and fructose-1,6-phosphatase)and serum(creatine kinase)were normalized to that of control level. The level of glycogen, glycoprotein component and lipid profile were equivalent to control level by fucoxanthin administration in diabetes with hypertension rats. Fucoxanthin ameliorated the oxidative stress by preserving the endogenous antioxidant levels in diabetes with hypertension rats. Also, the pancreatic histological integrity was similar to that of control level in diabetes with hypertension rats by fucoxanthin treatment. Altogether, fucoxanthin showed dual antidiabetic and antihypertensive activity in vivo.展开更多
Objective:To investigate the role of vascular endothelial growth factor(VEGF)165a,VEGF165b,and VEGF receptor(VEGFR)in the development of bovine follicles.Methods:We cultured follicular cells that were collected from s...Objective:To investigate the role of vascular endothelial growth factor(VEGF)165a,VEGF165b,and VEGF receptor(VEGFR)in the development of bovine follicles.Methods:We cultured follicular cells that were collected from small,medium,and large sized bovine follicles with estrogen and measured the expression of VEGF,VEGFR2 and VEGF165b by Western blot analysis and immunofluorescence.Results:The expression of VEGF165 increased in all follicle sizes and the expression of VEGF165b was increased in the small and large follicles after culturing in an estrogen containing medium.The expression of VEGFR2 was increased in the medium and large follicles after culturing with estrogen for 96 h.VEGF165 was activated at 100 ng/mL estrogen in the large follicles for 96 h.In addition,VEGFR2 was upregulated in the medium and large follicles after treated with 100 ng/mL estrogen for 96 h.Conclusions:This evidence suggests that the expression of VEGF165 and VEGFR is associated with estrogen stimulation during the development of bovine follicles and in an autocrine or paracrine manner.This reveals an advantage during oocyte maturation in vitro.展开更多
BACKGROUND Progressive malnutrition coexists with liver diseases,particularly in patients with cirrhosis.Early diagnosis of malnutrition in patients with advanced stages of chronic liver disease and the implementation...BACKGROUND Progressive malnutrition coexists with liver diseases,particularly in patients with cirrhosis.Early diagnosis of malnutrition in patients with advanced stages of chronic liver disease and the implementation of appropriate nutritional treatment for malnourished patients should be an integral part of the therapeutic process.AIM To evaluate the nutritional status of patients with various severities of advanced liver fibrosis,using various nutritional status parameters.METHODS This study involved 118 patients with liver cirrhosis who were classified into three groups according to their Child-Pugh score.The nutritional status of the patients in each group was assessed using different methods.The average values obtained from the measurements were calculated for each research group.The influence of disease stage on the examined parameters of nutritional status was determined using one-way analysis of variance.To investigate the relationship between the parameters determining nutritional status and the stage of disease advancement,a correlation analysis was performed.RESULTS The Child-Pugh A group had the highest mean body weight(76.42 kg),highest mean body mass index(BMI)(26.72 kg/m²),and largest mean arm circumference(27.64 cm).In the Child-Pugh B group,the mean scores of all examined variables were lower than those of the Child-Pugh A group,whereas the mean body weight and BMI of the Child-Pugh C group were higher than those of the Child-Pugh B group.There was a very strong correlation between the Child-Pugh classification and subjective global assessment score;a very strong correlation between the Child-Pugh classification and arm circumference;a strong correlation between the Child-Pugh classification and body weight,albumin concentration,fat-free mass index,muscle mass index,phase angle,and BMI;and an average correlation between Child-Pugh classification and fat mass index.Notably,these indicators deteriorated with disease progression.CONCLUSION Advanced liver fibrosis leads to the deterioration of many nutritional status parameters.The extent of malnutrition increases with the progression of liver fibrosis.The Child-Pugh score reflects the nutritional status.展开更多
Eye state classification acts as a vital part of the biomedical sector,for instance,smart home device control,drowsy driving recognition,and so on.The modifications in the cognitive levels can be reflected via transformi...Eye state classification acts as a vital part of the biomedical sector,for instance,smart home device control,drowsy driving recognition,and so on.The modifications in the cognitive levels can be reflected via transforming the electro-encephalogram(EEG)signals.The deep learning(DL)models automated extract the features and often showcased improved outcomes over the conventional clas-sification model in the recognition processes.This paper presents an Ensemble Deep Learning with Chimp Optimization Algorithm for EEG Eye State Classifi-cation(EDLCOA-ESC).The proposed EDLCOA-ESC technique involves min-max normalization approach as a pre-processing step.Besides,wavelet packet decomposition(WPD)technique is employed for the extraction of useful features from the EEG signals.In addition,an ensemble of deep sparse autoencoder(DSAE)and kernel ridge regression(KRR)models are employed for EEG Eye State classification.Finally,hyperparameters tuning of the DSAE model takes place using COA and thereby boost the classification results to a maximum extent.An extensive range of simulation analysis on the benchmark dataset is car-ried out and the results reported the promising performance of the EDLCOA-ESC technique over the recent approaches with maximum accuracy of 98.50%.展开更多
Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an u...Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells occurs.MPNs are characterized by mutations in driver genes,the JAK2V617F point mutation being the most commonly detected genetic alteration in these hematological malignancies.Thus,JAK inhibition has emerged as a potential therapeutic strategy in MPNs,with ruxolitinib being the first JAK inhibitor developed,approved,and prescribed in the management of these blood cancers.However,the use of ruxolitinib has been associated with a potential risk of infection,including opportunistic infections and reactivation of hepatitis B.Here,we briefly describe the association between ruxolitinib treatment in MPNs and hepatitis B reactivation.展开更多
There have been numerous concerns about the disease and how it affects the human body since the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic began in December 2019.The impact of SARS-CoV-2 on th...There have been numerous concerns about the disease and how it affects the human body since the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic began in December 2019.The impact of SARS-CoV-2 on the liver is being carefully investigated due to an increase in individuals with hepatitis and other liver illnesses,such as alcoholic liver disease.Additionally,the liver is involved in the metabolism of numerous drugs used to treat comorbidities and coronavirus disease 2019(COVID-19).Determining how SARS-CoV-2 affects the liver and what factors place individuals with COVID-19 at a higher risk of developing liver problems are the two main objectives of this study.This evaluation of the literature included research from three major scientific databases.To provide an update on the current impact of COVID-19 on the liver,data was collected and relevant information was incorporated into the review.With more knowledge about the effect of the disease on the liver,better management and therapeutics can be developed,and education can ultimately save lives and reduce the long-term impact of the pandemic on our population.展开更多
BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based thera...BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile.This has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated.AIM To evaluate the effectiveness and safety of DAA in patients with various mental illnesses.METHODS This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment completion.The entire study population was included in the intent-to-treat(ITT)analysis.Per-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment.RESULTS Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychiatric disorders.The cure rate calculated PP was not significantly different in the two groups analyzed,with a SVR of 96.9% and 97.7%,respectively.Although patients with bipolar disorder achieved a significantly lower SVR,the multivariate analysis excluded it as an independent predictor of treatment non-response.Male sex,GT3 infection,cirrhosis,and failure of previous therapy were identified as independent negative predictors.The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders.In six patients,symptoms of mental illness(depression,schizophrenia)worsened,of which two discontinued treatments for this reason.New episodes of sleep disorders occurred significantly more often in patients with mental disorders.Patients with mental illness were more frequently lost to follow-up(4.2%vs 2.5%).CONCLUSION DAA treatment is safe and effective in HCV-infected patients with mental disorders.No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.展开更多
High cancer heterogeneity and aggressiveness are major factors contributing to the poor prognosis of patients with advanced cancer~(1-5).Early detection of cancer can significantly improve the prognosis of patients wi...High cancer heterogeneity and aggressiveness are major factors contributing to the poor prognosis of patients with advanced cancer~(1-5).Early detection of cancer can significantly improve the prognosis of patients with early-stage cancer after standard treatment.Although traditional cancer detection technologies,such as endoscopy for gastrointestinal cancer,mammography for breast cancer。展开更多
Alcohol use disorder(AUD)represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality.The gut microbiom...Alcohol use disorder(AUD)represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality.The gut microbiome plays a crucial role in maintaining overall health and has emerged as a significant contributor to the pathophysiology of various psychiatric disorders.Recent evidence suggests that the gut microbiome is intimately linked to the development and progression of AUD,with alcohol consumption directly impacting its composition and function.This review article aims to explore the intricate relationship between the gut microbiome and AUD,focusing on the implications for mental health outcomes and potential therapeutic strategies.We discuss the bidirectional communication between the gut microbiome and the brain,highlighting the role of microbiotaderived metabolites in neuroinflammation,neurotransmission,and mood regulation.Furthermore,we examine the influence of AUD-related factors,such as alcohol-induced gut dysbiosis and increased intestinal permeability,on mental health outcomes.Finally,we explore emerging therapeutic avenues targeting the gut microbiome in the management of AUD,including prebiotics,probiotics,and fecal microbiota transplantation.Understanding the complex interplay between the gut microbiome and AUD holds promise for developing novel interventions that could improve mental health outcomes in individuals with AUD.展开更多
Interstitial cells of Cajal (ICC) are important players in the symphony of gut motility. They have a very signif icant physiological role orchestrating the normal peristaltic activity of the digestive system. They are...Interstitial cells of Cajal (ICC) are important players in the symphony of gut motility. They have a very signif icant physiological role orchestrating the normal peristaltic activity of the digestive system. They are the pacemaker cells in gastrointestinal (GI) muscles. Absence, reduction in number or altered integrity of the ICC network may have a dramatic effect on GI system motility. More understanding of ICC physiology will foster advances in physiology of gut motility which will help in a future breakthrough in the pharmacological interventions to restore normal motor function of GI tract. This mini review describes what is known about the physiologic function and role of ICCs in GI system motility and in a variety of GI system motility disorders.展开更多
Functional gastrointestinal disorders(FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology...Functional gastrointestinal disorders(FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology remains obscure and, although it is expected to differ according to the specific FGID, disruptions in the brain-gut axis are now thought to be a common denominator in their pathogenesis. The hormone ghrelin is an important component of this axis,exerting a wide repertoire of physiological actions, including regulation of gastrointestinal motility and protection of mucosal tissue. Ghrelin's gene shows genetic polymorphism, while its protein product undergoes complex regulation and metabolism in the human body. Numerous studies have studied ghrelin's relation to the emergence of FGIDs, its potential value as an index of disease severity and as a predictive marker for symptom relief during attempted treatment. Despite the mixed results currently available in scientific literature, the plethora of statistically significant findings shows that disruptions in ghrelin genetics and expression are plausibly related to FGID pathogenesis. The aim of this paper is to review current literature studying these associations, in an effort to uncover certain patterns of alterations in both genetics and expression, which could delineate its true contribution to FGID emergence, either as a causative agent or as a pathogenetic intermediate.展开更多
Studies concerning the pathophysiological connection between obesity and osteoporosis are currently an intriguing area of research.Although the onset of these two diseases can occur in a different way,recent studies h...Studies concerning the pathophysiological connection between obesity and osteoporosis are currently an intriguing area of research.Although the onset of these two diseases can occur in a different way,recent studies have shown that obesity and osteoporosis share common genetic and environmental factors.Despite being a risk factor for health,obesity has traditionally been considered positive to bone because of beneficial effect of mechanical loading,exerted by high body mass,on bone formation.However,contrasting studies have not achieved a clear consensus,suggesting instead that excessive fat mass derived from obesity condition may not protect against osteoporosis or,even worse,could be rather detrimental to bone.On the other hand,it is hitherto better established that,since adipocytes and osteoblasts are derived from a common mesenchymal stem cell precursor,molecules that lead to osteoblastogenesis inhibit adipogenesis and vice versa.Here we will discuss the role of the key molecules regulating adipocytes and osteoblasts differentiation,which are peroxisome proliferators activated receptor-γand Wnts,respectively.In particular,wewill focus on the role of both canonical and non-canonical Wnt signalling,involved in mesenchymal cell fate regulation.Moreover,at present there are no experimental data that relate any influence of the Wnt inhibitor Sclerostin to adipogenesis,although it is well known its role on bone metabolism.In addition,the most common pathological condition in which there is a simultaneous increase of adiposity and decrease of bone mass is menopause.Given that postmenopausal women have high Sclerostin level inversely associated with circulating estradiol level and since the sex hormone replacement therapy has proved to be effective in attenuating bone loss and reversing menopause-related obesity,we hypothesize that Sclerostin contribution in adipogenesis could be an active focus of research in the coming years.展开更多
Irritable bowel syndrome(IBS)is a functional disorder characterized by abdominal pain,discomfort and bloating.The pathophysiology of IBS is poorly understood,but the presence of psychosocial basis is now known.There i...Irritable bowel syndrome(IBS)is a functional disorder characterized by abdominal pain,discomfort and bloating.The pathophysiology of IBS is poorly understood,but the presence of psychosocial basis is now known.There is an increasing number of publications supporting the role of genetics in IBS.Most of the variations are found in genes associated with the brain-gut axis,revealing the strong correlation of brain-gut axis and IBS.miRNAs,which play critical roles in physiological processes,are not well studied in IBS.However,so far there is found an involvement of alterations in miRNA expression or sequence,in IBS symptoms.IBS phenotype is affected by epigenetic alteration and environment.Changes in DNA and histone methylation are observed in patients who suffered childhood trauma or abuse,resulting in altered gene expression,such as the glucocorticoid receptor gene.Finally,diet is another factor associated with IBS,which may contribute to symptom onset.Certain foods may affect on bacterial metabolism and epigenetic modifications,predisposing to IBS.展开更多
Neurogenesis takes place in the adult mammalian brain in three areas:Subgranular zone of the dentate gyrus(DG);subventricular zone of the lateral ventricle;olfactory bulb.Different molecular markers can be used to cha...Neurogenesis takes place in the adult mammalian brain in three areas:Subgranular zone of the dentate gyrus(DG);subventricular zone of the lateral ventricle;olfactory bulb.Different molecular markers can be used to characterizethe cells involved in adult neurogenesis.It has been recently suggested that a population of bone marrow(BM)progenitor cells may migrate to the brain and differentiate into neuronal lineage.To explore this hypothesis,we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells.Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells,then after several months in mature neurons and microglial cells,and thus without central nervous system(CNS)lesion.Most of transgene-expressing cells expressed NeuN,a marker of mature neurons.Thus,BM-derived cells may function as progenitors of CNS cells in adult animals.The mechanism by which the cells from the BM come to be neurons remains to be determined.Although the observed gradual increase in transgene-expressing neurons over 16mo suggests that the pathway involved differentiation of BM-resident cells into neurons,cell fusion as the principal route cannot be totally ruled out.Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons.Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector.In addition to cells expressing markers of mature neurons,transgene-positive cells were also positive for nestin and doublecortin,molecules expressed by developing neuronal cells.These cells were actively proliferating,as shown by short term BrdU incorporation studies.Inducing seizures by using kainic acid increased the number of BM progenitor cells transduced by SV40vectors migrating to the hippocampus,and these cells were seen at earlier time points in the DG.We show that the cell membrane chemokine receptor,CCR5,and its ligands,enhance CNS inflammation and seizure activity in a model of neuronal excitotoxicity.SV40-based gene delivery of RNAi targeting CCR5 to the BM results in downregulating CCR5 in circulating cells,suggesting that CCR5 plays an important role in regulating traffic of BM-derived cells into the CNS,both in the basal state and in response to injury.Furthermore,reduction in CCR5 expression incirculating cells provides profound neuroprotection from excitotoxic neuronal injury,reduces neuroinflammation,and increases neuronal regeneration following this type of insult.These results suggest that BM-derived,transgeneexpressing,cells can migrate to the brain and that they become neurons,at least in part,by differentiating into neuron precursors and subsequently developing into mature neurons.展开更多
AIM:To investigate the prognostic and clinicopathological significance of glypican-3(GPC3)overexpression in hepatocellular carcinoma(HCC).METHODS:Publications were searched using PubMed,EMBASE,the Cochrane Library and...AIM:To investigate the prognostic and clinicopathological significance of glypican-3(GPC3)overexpression in hepatocellular carcinoma(HCC).METHODS:Publications were searched using PubMed,EMBASE,the Cochrane Library and the Chinese Biomedical Literature Database up to March 2013.Inclusion and exclusion criteria were established to screen eligible studies for meta-analysis.The hazard ratios(HRs)of the eligible studies were pooled using RevMan5.2 software to evaluate the impact of GPC3 overexpression on overall survival(OS)and disease-free survival(DFS)in HCC patients.The correlation between GPC3 expression and clinicopathological parameters of HCC was also analyzed.RESULTS:A total of five studies with 493 patients were included in the meta-analysis.The combined HRs indicated that GPC3 overexpression can predict poorOS(n=362 in 3 studies,HR=2.18,95%CI:1.47-3.24,Z=3.86,P=0.0001)and DFS(n=325 in 3 studies,HR=2.05,95%CI:1.43-2.93,Z=3.94,P<0.0001)in HCC patients without heterogeneity.Egger’s and Begg’s tests were applied to detect publication bias,and the results showed that there was no evidence of publication bias detected in the OS studies(the P value for Egger’s test was 0.216)or DFS studies(the P value for Egger’s test was 0.488).The combined odds ratios(ORs)suggested that GPC3 expression tends to be associated with tumor vascular invasion(OR=2.74,95%CI:1.15-6.52,P=0.02),hepatic cirrhosis(OR=2.10,95%CI:1.31-3.36,P=0.002),poor tumor differentiation(OR=0.22,95%CI:0.13-0.40,P<0.00001)and advanced TNM stage(OR=0.31,95%CI:0.18-0.51,P<0.00001).CONCLUSION:From this study,we conclude that GPC3 overexpression tends to be associated with a poor prognosis(poor OS or DFS)in HCC.展开更多
Colorectal cancer(CRC)is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States.Considering the risk factors of CRC,dietary therapy has ...Colorectal cancer(CRC)is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States.Considering the risk factors of CRC,dietary therapy has become one of the most effective approaches in reducing CRC morbidity and mortality.The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases.As the most common types of microbes used as probiotics,lactic acid bacteria(LAB)are comprised of an ecologically diverse group of microorganisms united by formation of lactic acid as the primary metabolite of sugar metabolism.LAB have been successfully used in managing diarrhea,food allergies,and inflammatory bowel disease.LAB also demonstrated a host of properties in preventing colorectal cancer development by inhibiting initiation or progression through multiple pathways.In this review,we discuss recent insights into cellular and molecular mechanisms of LAB in CRC prevention including apoptosis,antioxidant DNA damages,immune responses,and epigenetics.The emerging experimental findings from clinical trials as well as the proposed mechanisms of gut microbiota in carcinogenesis will also be briefly discussed.展开更多
文摘Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart function.MSCs can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental pulp.MSCs from various sources differ in their regenerative and therapeutic abilities for cardiovascular disorders.In this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.
基金funded by the Research Deanship of King Khalid University,No.GRP-215-43 (to FHA)Princess Nourah bint Abdulrohman University Researchers Supporting Project,No.PNURSP2023R110 (to AFD)。
文摘Memory loss and dementia are major public health concerns with a substantial economic burden.Oxidative stress has been shown to play a crucial role in the pathophysiology of hippocampal damage-induced memory impairment.To investigate whether the antioxidant and anti-inflammatory compound vanillyla cetone(zingerone) can protect against hippocampal damage and memory loss induced by cadmium chloride(CdCl_(2)) administration in rats,we explo red the potential involvement of the nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway,which is known to modulate oxidative stress and inflammation.Sixty healt hy male Wistar rats were divided into five groups:vehicle-treated(control),vanillylacetone,CdCl_(2),vanillylacetone+ CdCl_(2),vanillylacetone+ CdCl_(2)+ brusatol(a selective pharmacological N rf2inhibitor) groups.Vanillylacetone effectively attenuated CdCl_(2)-induced damage in the dental gyrus of the hippocampus and improved the memory function assessed by the Morris Water Maze test.Additionally,vanillylacetone markedly decreased the hippocampal tissue levels of inflammatory biomarkers(interleukin-6,tumor necrosis factor-α,intracellular cell adhesive molecules) and apoptosis biomarkers(Bax and cleaved caspase-3).The control and CdCl_(2)-treated groups treated with va nillylacetone showed reduced generation of reactive oxygen species,decreased malondialdehyde levels,and increased superoxide dismutase and glutathione activities,along with significant elevation of nuclear Nrf2 mRNA and protein expression in hippocampal tissue.All the protective effects of vanillylacetone we re substantially blocked by the co-administration of brusatol(a selective N rf2 inhibitor).Va nillylacetone mitigated hippocampal damage and memory loss induced by CdCl_(2),at least in part, by activating the nuclear transcription factor Nrf2.Additionally,vanillylacetone exerted its potent antioxidant and antiinflammatory actions.
基金Ministry of Higher Education,Malaysia for Fundamental Research Grant Scheme FRGS/1/2019/SKK06/USM/03/6,No.291983-329281.
文摘BACKGROUND Diabetes is known damage the liver and kidney,leading to hepatic dysfunction and kidney failure.Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications.However,the effect of stingless bee honey(SBH)administration in relieving liver and kidney damage in diabetes has not been well-studied.AIM To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced(STZ;55 mg/kg)diabetic Sprague Dawley rats.METHODS The rats were grouped as follows(n=6 per group):non-diabetic(ND),untreated diabetic(UNT),metformin-treated(MET),and SBH+metformin-treated(SBME)groups.After successful diabetic induction,ND and UNT rats were given normal saline,whereas the treatment groups received SBH(2.0 g/kg and/or metformin(250 mg/kg)for 12 d.Serum biochemical parameters and histological changes using hematoxylin and eosin(H&E)and periodic acid–Schiff(PAS)staining were evaluated.RESULTS On H&E and PAS staining,the ND group showed normal architecture and cellularity of Bowman’s capsule and tubules,whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane.The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining,but the two were similar on PAS staining.Likewise,the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining,but it was comparable to the SBH and ND groups on PAS staining.UNT diabetic rats had tubular hydropic tubules,which were smaller than other groups.Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group.Conversely,the UNT group had high glucose levels,which subsequently increased MDA levels,ultimately leading to liver damage.SBH treatment reduced this damage,as evidenced by having the lowest fasting glucose,serum alanine transaminase,aspartate transaminase,and alkaline phosphatase levels compared to other groups,although the levels of liver enzymes were not statistically significant.CONCLUSION The cellularity of the Bowman’s capsule,as well as histological alteration of kidney tubules,glomerular membranes,and liver tissues in diabetic rats after oral SBH resembled those of ND rats.Therefore,SBH exhibited a protective hepatorenal effect in a diabetic rat model.
基金Supported by the Scientific Research Project of the Sichuan Province Education Department,No. 16ZA0241the National Natural Science Foundation of China,No. 82060268the Guangxi Natural Science Foundation of China,No. 2020JJA140124。
文摘As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.
文摘In a previous study from our laboratory, fucoxanthin purified from brown algae, Sargassum wightii Greville has found to exhibit antioxidant activity and inhibition of angiotensin-I-converting enzyme(ACE)in vitro. The present study aims in understanding the protective effect of fucoxanthin purified from S. wightii against diabetes with hypertension in in vivo. Diabetes and hypertension were induced in rat by streptozotocin and sodium chloride treatment, respectively. In diabetes with hypertension rat, the blood pressure was increased along with hyperglycemia. Administration of fucoxanthin significantly reduced the blood pressure and ACE activity in diabetes with hypertension rat. Furthermore, administration of fucoxanthin significantly reduced the hyperglycemic state. The activity of various enzymes in the liver(hexokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase and fructose-1,6-phosphatase)and serum(creatine kinase)were normalized to that of control level. The level of glycogen, glycoprotein component and lipid profile were equivalent to control level by fucoxanthin administration in diabetes with hypertension rats. Fucoxanthin ameliorated the oxidative stress by preserving the endogenous antioxidant levels in diabetes with hypertension rats. Also, the pancreatic histological integrity was similar to that of control level in diabetes with hypertension rats by fucoxanthin treatment. Altogether, fucoxanthin showed dual antidiabetic and antihypertensive activity in vivo.
文摘Objective:To investigate the role of vascular endothelial growth factor(VEGF)165a,VEGF165b,and VEGF receptor(VEGFR)in the development of bovine follicles.Methods:We cultured follicular cells that were collected from small,medium,and large sized bovine follicles with estrogen and measured the expression of VEGF,VEGFR2 and VEGF165b by Western blot analysis and immunofluorescence.Results:The expression of VEGF165 increased in all follicle sizes and the expression of VEGF165b was increased in the small and large follicles after culturing in an estrogen containing medium.The expression of VEGFR2 was increased in the medium and large follicles after culturing with estrogen for 96 h.VEGF165 was activated at 100 ng/mL estrogen in the large follicles for 96 h.In addition,VEGFR2 was upregulated in the medium and large follicles after treated with 100 ng/mL estrogen for 96 h.Conclusions:This evidence suggests that the expression of VEGF165 and VEGFR is associated with estrogen stimulation during the development of bovine follicles and in an autocrine or paracrine manner.This reveals an advantage during oocyte maturation in vitro.
文摘BACKGROUND Progressive malnutrition coexists with liver diseases,particularly in patients with cirrhosis.Early diagnosis of malnutrition in patients with advanced stages of chronic liver disease and the implementation of appropriate nutritional treatment for malnourished patients should be an integral part of the therapeutic process.AIM To evaluate the nutritional status of patients with various severities of advanced liver fibrosis,using various nutritional status parameters.METHODS This study involved 118 patients with liver cirrhosis who were classified into three groups according to their Child-Pugh score.The nutritional status of the patients in each group was assessed using different methods.The average values obtained from the measurements were calculated for each research group.The influence of disease stage on the examined parameters of nutritional status was determined using one-way analysis of variance.To investigate the relationship between the parameters determining nutritional status and the stage of disease advancement,a correlation analysis was performed.RESULTS The Child-Pugh A group had the highest mean body weight(76.42 kg),highest mean body mass index(BMI)(26.72 kg/m²),and largest mean arm circumference(27.64 cm).In the Child-Pugh B group,the mean scores of all examined variables were lower than those of the Child-Pugh A group,whereas the mean body weight and BMI of the Child-Pugh C group were higher than those of the Child-Pugh B group.There was a very strong correlation between the Child-Pugh classification and subjective global assessment score;a very strong correlation between the Child-Pugh classification and arm circumference;a strong correlation between the Child-Pugh classification and body weight,albumin concentration,fat-free mass index,muscle mass index,phase angle,and BMI;and an average correlation between Child-Pugh classification and fat mass index.Notably,these indicators deteriorated with disease progression.CONCLUSION Advanced liver fibrosis leads to the deterioration of many nutritional status parameters.The extent of malnutrition increases with the progression of liver fibrosis.The Child-Pugh score reflects the nutritional status.
基金supported by the Researchers Supporting Program(TUMA-Project-2021–27)Almaarefa University,Riyadh,Saudi ArabiaTaif University Researchers Supporting Project Number(TURSP-2020/161),Taif University,Taif,Saudi Arabia.
文摘Eye state classification acts as a vital part of the biomedical sector,for instance,smart home device control,drowsy driving recognition,and so on.The modifications in the cognitive levels can be reflected via transforming the electro-encephalogram(EEG)signals.The deep learning(DL)models automated extract the features and often showcased improved outcomes over the conventional clas-sification model in the recognition processes.This paper presents an Ensemble Deep Learning with Chimp Optimization Algorithm for EEG Eye State Classifi-cation(EDLCOA-ESC).The proposed EDLCOA-ESC technique involves min-max normalization approach as a pre-processing step.Besides,wavelet packet decomposition(WPD)technique is employed for the extraction of useful features from the EEG signals.In addition,an ensemble of deep sparse autoencoder(DSAE)and kernel ridge regression(KRR)models are employed for EEG Eye State classification.Finally,hyperparameters tuning of the DSAE model takes place using COA and thereby boost the classification results to a maximum extent.An extensive range of simulation analysis on the benchmark dataset is car-ried out and the results reported the promising performance of the EDLCOA-ESC technique over the recent approaches with maximum accuracy of 98.50%.
文摘Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells occurs.MPNs are characterized by mutations in driver genes,the JAK2V617F point mutation being the most commonly detected genetic alteration in these hematological malignancies.Thus,JAK inhibition has emerged as a potential therapeutic strategy in MPNs,with ruxolitinib being the first JAK inhibitor developed,approved,and prescribed in the management of these blood cancers.However,the use of ruxolitinib has been associated with a potential risk of infection,including opportunistic infections and reactivation of hepatitis B.Here,we briefly describe the association between ruxolitinib treatment in MPNs and hepatitis B reactivation.
文摘There have been numerous concerns about the disease and how it affects the human body since the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic began in December 2019.The impact of SARS-CoV-2 on the liver is being carefully investigated due to an increase in individuals with hepatitis and other liver illnesses,such as alcoholic liver disease.Additionally,the liver is involved in the metabolism of numerous drugs used to treat comorbidities and coronavirus disease 2019(COVID-19).Determining how SARS-CoV-2 affects the liver and what factors place individuals with COVID-19 at a higher risk of developing liver problems are the two main objectives of this study.This evaluation of the literature included research from three major scientific databases.To provide an update on the current impact of COVID-19 on the liver,data was collected and relevant information was incorporated into the review.With more knowledge about the effect of the disease on the liver,better management and therapeutics can be developed,and education can ultimately save lives and reduce the long-term impact of the pandemic on our population.
文摘BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile.This has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated.AIM To evaluate the effectiveness and safety of DAA in patients with various mental illnesses.METHODS This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment completion.The entire study population was included in the intent-to-treat(ITT)analysis.Per-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment.RESULTS Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychiatric disorders.The cure rate calculated PP was not significantly different in the two groups analyzed,with a SVR of 96.9% and 97.7%,respectively.Although patients with bipolar disorder achieved a significantly lower SVR,the multivariate analysis excluded it as an independent predictor of treatment non-response.Male sex,GT3 infection,cirrhosis,and failure of previous therapy were identified as independent negative predictors.The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders.In six patients,symptoms of mental illness(depression,schizophrenia)worsened,of which two discontinued treatments for this reason.New episodes of sleep disorders occurred significantly more often in patients with mental disorders.Patients with mental illness were more frequently lost to follow-up(4.2%vs 2.5%).CONCLUSION DAA treatment is safe and effective in HCV-infected patients with mental disorders.No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.
基金partially supported by grants(Grant No.81972680 to X.L.)from the National Natural Science Foundation of Chinaa start-up fund from Tsinghua University-Peking University Joined Center for Life Science。
文摘High cancer heterogeneity and aggressiveness are major factors contributing to the poor prognosis of patients with advanced cancer~(1-5).Early detection of cancer can significantly improve the prognosis of patients with early-stage cancer after standard treatment.Although traditional cancer detection technologies,such as endoscopy for gastrointestinal cancer,mammography for breast cancer。
文摘Alcohol use disorder(AUD)represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality.The gut microbiome plays a crucial role in maintaining overall health and has emerged as a significant contributor to the pathophysiology of various psychiatric disorders.Recent evidence suggests that the gut microbiome is intimately linked to the development and progression of AUD,with alcohol consumption directly impacting its composition and function.This review article aims to explore the intricate relationship between the gut microbiome and AUD,focusing on the implications for mental health outcomes and potential therapeutic strategies.We discuss the bidirectional communication between the gut microbiome and the brain,highlighting the role of microbiotaderived metabolites in neuroinflammation,neurotransmission,and mood regulation.Furthermore,we examine the influence of AUD-related factors,such as alcohol-induced gut dysbiosis and increased intestinal permeability,on mental health outcomes.Finally,we explore emerging therapeutic avenues targeting the gut microbiome in the management of AUD,including prebiotics,probiotics,and fecal microbiota transplantation.Understanding the complex interplay between the gut microbiome and AUD holds promise for developing novel interventions that could improve mental health outcomes in individuals with AUD.
文摘Interstitial cells of Cajal (ICC) are important players in the symphony of gut motility. They have a very signif icant physiological role orchestrating the normal peristaltic activity of the digestive system. They are the pacemaker cells in gastrointestinal (GI) muscles. Absence, reduction in number or altered integrity of the ICC network may have a dramatic effect on GI system motility. More understanding of ICC physiology will foster advances in physiology of gut motility which will help in a future breakthrough in the pharmacological interventions to restore normal motor function of GI tract. This mini review describes what is known about the physiologic function and role of ICCs in GI system motility and in a variety of GI system motility disorders.
文摘Functional gastrointestinal disorders(FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology remains obscure and, although it is expected to differ according to the specific FGID, disruptions in the brain-gut axis are now thought to be a common denominator in their pathogenesis. The hormone ghrelin is an important component of this axis,exerting a wide repertoire of physiological actions, including regulation of gastrointestinal motility and protection of mucosal tissue. Ghrelin's gene shows genetic polymorphism, while its protein product undergoes complex regulation and metabolism in the human body. Numerous studies have studied ghrelin's relation to the emergence of FGIDs, its potential value as an index of disease severity and as a predictive marker for symptom relief during attempted treatment. Despite the mixed results currently available in scientific literature, the plethora of statistically significant findings shows that disruptions in ghrelin genetics and expression are plausibly related to FGID pathogenesis. The aim of this paper is to review current literature studying these associations, in an effort to uncover certain patterns of alterations in both genetics and expression, which could delineate its true contribution to FGID emergence, either as a causative agent or as a pathogenetic intermediate.
文摘Studies concerning the pathophysiological connection between obesity and osteoporosis are currently an intriguing area of research.Although the onset of these two diseases can occur in a different way,recent studies have shown that obesity and osteoporosis share common genetic and environmental factors.Despite being a risk factor for health,obesity has traditionally been considered positive to bone because of beneficial effect of mechanical loading,exerted by high body mass,on bone formation.However,contrasting studies have not achieved a clear consensus,suggesting instead that excessive fat mass derived from obesity condition may not protect against osteoporosis or,even worse,could be rather detrimental to bone.On the other hand,it is hitherto better established that,since adipocytes and osteoblasts are derived from a common mesenchymal stem cell precursor,molecules that lead to osteoblastogenesis inhibit adipogenesis and vice versa.Here we will discuss the role of the key molecules regulating adipocytes and osteoblasts differentiation,which are peroxisome proliferators activated receptor-γand Wnts,respectively.In particular,wewill focus on the role of both canonical and non-canonical Wnt signalling,involved in mesenchymal cell fate regulation.Moreover,at present there are no experimental data that relate any influence of the Wnt inhibitor Sclerostin to adipogenesis,although it is well known its role on bone metabolism.In addition,the most common pathological condition in which there is a simultaneous increase of adiposity and decrease of bone mass is menopause.Given that postmenopausal women have high Sclerostin level inversely associated with circulating estradiol level and since the sex hormone replacement therapy has proved to be effective in attenuating bone loss and reversing menopause-related obesity,we hypothesize that Sclerostin contribution in adipogenesis could be an active focus of research in the coming years.
文摘Irritable bowel syndrome(IBS)is a functional disorder characterized by abdominal pain,discomfort and bloating.The pathophysiology of IBS is poorly understood,but the presence of psychosocial basis is now known.There is an increasing number of publications supporting the role of genetics in IBS.Most of the variations are found in genes associated with the brain-gut axis,revealing the strong correlation of brain-gut axis and IBS.miRNAs,which play critical roles in physiological processes,are not well studied in IBS.However,so far there is found an involvement of alterations in miRNA expression or sequence,in IBS symptoms.IBS phenotype is affected by epigenetic alteration and environment.Changes in DNA and histone methylation are observed in patients who suffered childhood trauma or abuse,resulting in altered gene expression,such as the glucocorticoid receptor gene.Finally,diet is another factor associated with IBS,which may contribute to symptom onset.Certain foods may affect on bacterial metabolism and epigenetic modifications,predisposing to IBS.
文摘Neurogenesis takes place in the adult mammalian brain in three areas:Subgranular zone of the dentate gyrus(DG);subventricular zone of the lateral ventricle;olfactory bulb.Different molecular markers can be used to characterizethe cells involved in adult neurogenesis.It has been recently suggested that a population of bone marrow(BM)progenitor cells may migrate to the brain and differentiate into neuronal lineage.To explore this hypothesis,we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells.Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells,then after several months in mature neurons and microglial cells,and thus without central nervous system(CNS)lesion.Most of transgene-expressing cells expressed NeuN,a marker of mature neurons.Thus,BM-derived cells may function as progenitors of CNS cells in adult animals.The mechanism by which the cells from the BM come to be neurons remains to be determined.Although the observed gradual increase in transgene-expressing neurons over 16mo suggests that the pathway involved differentiation of BM-resident cells into neurons,cell fusion as the principal route cannot be totally ruled out.Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons.Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector.In addition to cells expressing markers of mature neurons,transgene-positive cells were also positive for nestin and doublecortin,molecules expressed by developing neuronal cells.These cells were actively proliferating,as shown by short term BrdU incorporation studies.Inducing seizures by using kainic acid increased the number of BM progenitor cells transduced by SV40vectors migrating to the hippocampus,and these cells were seen at earlier time points in the DG.We show that the cell membrane chemokine receptor,CCR5,and its ligands,enhance CNS inflammation and seizure activity in a model of neuronal excitotoxicity.SV40-based gene delivery of RNAi targeting CCR5 to the BM results in downregulating CCR5 in circulating cells,suggesting that CCR5 plays an important role in regulating traffic of BM-derived cells into the CNS,both in the basal state and in response to injury.Furthermore,reduction in CCR5 expression incirculating cells provides profound neuroprotection from excitotoxic neuronal injury,reduces neuroinflammation,and increases neuronal regeneration following this type of insult.These results suggest that BM-derived,transgeneexpressing,cells can migrate to the brain and that they become neurons,at least in part,by differentiating into neuron precursors and subsequently developing into mature neurons.
文摘AIM:To investigate the prognostic and clinicopathological significance of glypican-3(GPC3)overexpression in hepatocellular carcinoma(HCC).METHODS:Publications were searched using PubMed,EMBASE,the Cochrane Library and the Chinese Biomedical Literature Database up to March 2013.Inclusion and exclusion criteria were established to screen eligible studies for meta-analysis.The hazard ratios(HRs)of the eligible studies were pooled using RevMan5.2 software to evaluate the impact of GPC3 overexpression on overall survival(OS)and disease-free survival(DFS)in HCC patients.The correlation between GPC3 expression and clinicopathological parameters of HCC was also analyzed.RESULTS:A total of five studies with 493 patients were included in the meta-analysis.The combined HRs indicated that GPC3 overexpression can predict poorOS(n=362 in 3 studies,HR=2.18,95%CI:1.47-3.24,Z=3.86,P=0.0001)and DFS(n=325 in 3 studies,HR=2.05,95%CI:1.43-2.93,Z=3.94,P<0.0001)in HCC patients without heterogeneity.Egger’s and Begg’s tests were applied to detect publication bias,and the results showed that there was no evidence of publication bias detected in the OS studies(the P value for Egger’s test was 0.216)or DFS studies(the P value for Egger’s test was 0.488).The combined odds ratios(ORs)suggested that GPC3 expression tends to be associated with tumor vascular invasion(OR=2.74,95%CI:1.15-6.52,P=0.02),hepatic cirrhosis(OR=2.10,95%CI:1.31-3.36,P=0.002),poor tumor differentiation(OR=0.22,95%CI:0.13-0.40,P<0.00001)and advanced TNM stage(OR=0.31,95%CI:0.18-0.51,P<0.00001).CONCLUSION:From this study,we conclude that GPC3 overexpression tends to be associated with a poor prognosis(poor OS or DFS)in HCC.
基金Supported by Grant No.NSFC-81272444 to Zhong LNo.PN-II-ID-PCE-2012-4-0608 Nr.48/02.09.2013 to Covasa M
文摘Colorectal cancer(CRC)is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States.Considering the risk factors of CRC,dietary therapy has become one of the most effective approaches in reducing CRC morbidity and mortality.The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases.As the most common types of microbes used as probiotics,lactic acid bacteria(LAB)are comprised of an ecologically diverse group of microorganisms united by formation of lactic acid as the primary metabolite of sugar metabolism.LAB have been successfully used in managing diarrhea,food allergies,and inflammatory bowel disease.LAB also demonstrated a host of properties in preventing colorectal cancer development by inhibiting initiation or progression through multiple pathways.In this review,we discuss recent insights into cellular and molecular mechanisms of LAB in CRC prevention including apoptosis,antioxidant DNA damages,immune responses,and epigenetics.The emerging experimental findings from clinical trials as well as the proposed mechanisms of gut microbiota in carcinogenesis will also be briefly discussed.
