To the Editor:Pancreatic cancer is a malignancy characterized by a poor prog-nosis,with a 5-year survival rate of<10%[1].Furthermore,only a minority of patients(<20%)qualify for curative-intent resec-tion,and ev...To the Editor:Pancreatic cancer is a malignancy characterized by a poor prog-nosis,with a 5-year survival rate of<10%[1].Furthermore,only a minority of patients(<20%)qualify for curative-intent resec-tion,and even among those who undergo this procedure,the risk of recurrence within three years remains alarmingly high,reach-ing up to 70%[2].Due to the lack of specific clinical manifes-tations of pancreatic cancer,most cases have metastasized or in-vaded the major vessels around the pancreas at the time of initial diagnosis,resulting in a low surgical resection rate.Even patients who undergo surgical resection often face a poor prognosis[3].In recent years,neoadjuvant chemotherapy using agents such as gemcitabine,5-fluorouracil,albumin-bound paclitaxel,modified fluorouracil/leucovorin plus irinotecan,and oxaliplatin(mFOLFIRI-NOX),targeted therapies addressing molecular subtypes of pan-creatic cancer,and immunotherapies targeting PD-1 and PD-L1 have shown efficacy in improving the overall prognosis of patients with pancreatic cancer,although the impact remains modest[4,5].Therefore,novel therapeutic strategies and prognostic evaluation systems are urgently needed to enhance the survival of patients with pancreatic cancer.展开更多
Multiple sclerosis is a chronic, inflammatory and degenerative disease of the central nervous system of unknown aetiology although well-defined evidence supports an autoimmune pathogenesis. So far, the exact mechanism...Multiple sclerosis is a chronic, inflammatory and degenerative disease of the central nervous system of unknown aetiology although well-defined evidence supports an autoimmune pathogenesis. So far, the exact mechanisms leading to autoimmune diseases are still only partially understood. We know that genetic, epigenetic, molecular, and cellular factors resulting in pathogenic inflammatory responses are certainly involved. Long non-coding RNAs(lncRNAs) are non-protein coding transcripts longer than 200 nucleotides that play an important role in both innate and acquired immunity, so there is great interest in lncRNAs involved in autoimmune diseases. The research on multiple sclerosis has been enriched with many studies on the molecular role of lncRNAs in the pathogenesis of the disease and their potential application as diagnostic and prognostic biomarkers. In particular, many multiple sclerosis fields of research are based on the identification of lncRNAs as possible biomarkers able to predict the onset of the disease, its activity degree, its progression phase and the response to disease-modifying drugs. Last but not least, studies on lncRNAs can provide a new molecular target for new therapies, missing, so far, a cure for multiple sclerosis. While our knowledge on the role of lncRNA in multiple sclerosis has recently improved, further studies are required to better understand the specific role of lncRNAs in this neurological disease. In this review, we present the most recent studies on molecular characterization of lncRNAs in multiple sclerosis disorder discussing their clinical relevance as biomarkers for diagnosis and treatments.展开更多
Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced ra...Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced rat seizure model.A selected panel of long noncoding RNAs(lncRNAs),which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway,was also targeted.Methods:The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers,neurotrophic factors,and relevant lncRNA genes.Rat behavior was assessed using Y-maze test and open field test(OFT).Results:EPCs mitigated seizure associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits,as evidenced by improved performance in the Y-maze test and OFT.EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2,Pnky,Dlx1,APF,HOTAIR,and FLJ11812.EPCs also boosted vascular endothelial growth factor(VEGF)expression.The ameliorative effect achieved by EPCs was comparable to that produced by valproate.Conclusions:These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.展开更多
文摘To the Editor:Pancreatic cancer is a malignancy characterized by a poor prog-nosis,with a 5-year survival rate of<10%[1].Furthermore,only a minority of patients(<20%)qualify for curative-intent resec-tion,and even among those who undergo this procedure,the risk of recurrence within three years remains alarmingly high,reach-ing up to 70%[2].Due to the lack of specific clinical manifes-tations of pancreatic cancer,most cases have metastasized or in-vaded the major vessels around the pancreas at the time of initial diagnosis,resulting in a low surgical resection rate.Even patients who undergo surgical resection often face a poor prognosis[3].In recent years,neoadjuvant chemotherapy using agents such as gemcitabine,5-fluorouracil,albumin-bound paclitaxel,modified fluorouracil/leucovorin plus irinotecan,and oxaliplatin(mFOLFIRI-NOX),targeted therapies addressing molecular subtypes of pan-creatic cancer,and immunotherapies targeting PD-1 and PD-L1 have shown efficacy in improving the overall prognosis of patients with pancreatic cancer,although the impact remains modest[4,5].Therefore,novel therapeutic strategies and prognostic evaluation systems are urgently needed to enhance the survival of patients with pancreatic cancer.
文摘Multiple sclerosis is a chronic, inflammatory and degenerative disease of the central nervous system of unknown aetiology although well-defined evidence supports an autoimmune pathogenesis. So far, the exact mechanisms leading to autoimmune diseases are still only partially understood. We know that genetic, epigenetic, molecular, and cellular factors resulting in pathogenic inflammatory responses are certainly involved. Long non-coding RNAs(lncRNAs) are non-protein coding transcripts longer than 200 nucleotides that play an important role in both innate and acquired immunity, so there is great interest in lncRNAs involved in autoimmune diseases. The research on multiple sclerosis has been enriched with many studies on the molecular role of lncRNAs in the pathogenesis of the disease and their potential application as diagnostic and prognostic biomarkers. In particular, many multiple sclerosis fields of research are based on the identification of lncRNAs as possible biomarkers able to predict the onset of the disease, its activity degree, its progression phase and the response to disease-modifying drugs. Last but not least, studies on lncRNAs can provide a new molecular target for new therapies, missing, so far, a cure for multiple sclerosis. While our knowledge on the role of lncRNA in multiple sclerosis has recently improved, further studies are required to better understand the specific role of lncRNAs in this neurological disease. In this review, we present the most recent studies on molecular characterization of lncRNAs in multiple sclerosis disorder discussing their clinical relevance as biomarkers for diagnosis and treatments.
基金Open access funding provided by The Science,Technology&Innovation Funding Authority(STDF)in coop eration with The Egyptian Knowledge Bank(EKB).
文摘Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced rat seizure model.A selected panel of long noncoding RNAs(lncRNAs),which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway,was also targeted.Methods:The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers,neurotrophic factors,and relevant lncRNA genes.Rat behavior was assessed using Y-maze test and open field test(OFT).Results:EPCs mitigated seizure associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits,as evidenced by improved performance in the Y-maze test and OFT.EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2,Pnky,Dlx1,APF,HOTAIR,and FLJ11812.EPCs also boosted vascular endothelial growth factor(VEGF)expression.The ameliorative effect achieved by EPCs was comparable to that produced by valproate.Conclusions:These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.
