Background: Among patients treated for tuberculosis, 2% to 5% have a Central Nervous System (CNS) lesion, and its frequency rises to 10% in HIV-infected patients. Neuro-meningeal tuberculosis (NMT) is responsible for ...Background: Among patients treated for tuberculosis, 2% to 5% have a Central Nervous System (CNS) lesion, and its frequency rises to 10% in HIV-infected patients. Neuro-meningeal tuberculosis (NMT) is responsible for death and severe permanent neurological damage. This poor prognosis requires early diagnosis and rapid initiation of specific treatment. Unfortunately, the great clinical polymorphism and the lack of specificity of radiological and biological signs are frequently responsible for a delay in diagnosis and management. Senegal is one of the African countries where tuberculosis has remained a concern until now. And there are no studies carried out on this subject. Objective: The objective of this study was to describe the profile and outcome of Neuro-meningeal tuberculosis (NMT) cases diagnosed at the infectious diseases department (SMIT) of Fann University Hospital in Dakar, (referral service for management of tuberculosis). Methods: We carried out a retrospective, descriptive and analytical study, reviewing medical records of adults diagnosed with NMT at the SMIT of Fann Hospital from January 2015 to December 2020. Results: We collected 55 cases of NMT. The median age was 38 years [range 16 - 77 years]. The sex ratio (M/F) was 3.23. HIV patients represented 41.82% of cases. A history of tuberculosis was found in 25.5% of cases. The delay in consultation was greater than one month in 60% of patients. Headaches were the most constant reason for consultation (94.55%). Meningeal signs were present in 94.55% of patients, and consciousness disorders and intracranial hypertension were present in 63.64% and 56.36% respectively. Nerve palsy was found in 38.18%. CSF was clear in 81.64%. GeneXpert MTB/RIF in CSF was performed in 33 patients and was positive in 4 patients. Brain CT was abnormal in 72.09% of cases. Tuberculoma, hydrocephalus and meningeal contrast enhancement were the main lesions. The neuro-meningeal localization was associated with a pulmonary form in 32.7%. The lethality rate was 21.8%;higher in women (46.2% vs 14.3%;p = 0.01), in patients with a delay in consultation > 1 month (p = 0.03), and in patients who presented with consciousness disorders (p = 0.007). Conclusion: Despite the availability of the GeneXpert MTB/RIF, diagnosis of NMT remains difficult. Because of its variable clinical expression and the low sensitivity of the GeneXpert MTB/rif in the CSF, it exposes patients to serious complications. Among the factors associated with death, we found consciousness disorders, a long delay in diagnosis.展开更多
Objective:Glioblastoma(GBM)is the most prevalent and aggressive adult primary cancer in the central nervous system.Therapeutic approaches for GBM treatment are under intense investigation,including the use of emerging...Objective:Glioblastoma(GBM)is the most prevalent and aggressive adult primary cancer in the central nervous system.Therapeutic approaches for GBM treatment are under intense investigation,including the use of emerging immunotherapies.Here,we propose an alternative approach to treat GBM through reprogramming proliferative GBM cells into non-proliferative neurons.Methods:Retroviruses were used to target highly proliferative human GBM cells through overexpression of neural transcription factors.Immunostaining,electrophysiological recording,and bulk RNA-seq were performed to investigate the mechanisms underlying the neuronal conversion of human GBM cells.An in vivo intracranial xenograft mouse model was used to examine the neuronal conversion of human GBM cells.Results:We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1(Neuro D1),Neurogenin-2(Neurog2),or Achaete-scute homolog 1(Ascl1).Subtype characterization showed that the majority of Neurog2-and Neuro D1-converted neurons were glutamatergic,while Ascl1 favored GABAergic neuron generation.The GBM cell-converted neurons not only showed pan-neuronal markers but also exhibited neuron-specific electrophysiological activities.Transcriptome analyses revealed that neuronal genes were activated in glioma cells after overexpression of neural transcription factors,and different signaling pathways were activated by different neural transcription factors.Importantly,the neuronal conversion of GBM cells was accompanied by significant inhibition of GBM cell proliferation in both in vitro and in vivo models.Conclusions:These results suggest that GBM cells can be reprogrammed into different subtypes of neurons,leading to a potential alternative approach to treat brain tumors using in vivo cell conversion technology.展开更多
Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tra...Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell （RGC） death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases. In this review article, we will go through three current approaches to cure neu- rodegenerative eye diseases, including cell based therapy, neuro-regeneration and neuro-rejuvenation.展开更多
Large cell neuroendocrine carcinoma(LCNEC)in the biliary system is a poorly differentiated,high-grade neuroendocrine tumor.These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant...Large cell neuroendocrine carcinoma(LCNEC)in the biliary system is a poorly differentiated,high-grade neuroendocrine tumor.These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases.Herein,we report an unusual case of a pure primary LCNEC of the common bile duct(CBD).A 75-year-old female presented with nausea and jaundice.The patient underwent a CBD excision with lymph node dissection.Upon histological and immunohistochemical examination,the tumor exhibited pure large cell-type neuroendocrine features.Metastases were noted in two of the eight lymph nodes.The patient was administered adjuvant chemotherapy.The patient’s cancer recurred 7 mo after surgery,and the patient died from liver failure 5 mo after recurrence.The prognosis of LCNEC of CBD remains poor despitecurative resection and adjuvant chemotherapy.The role of additional therapies,such as multimodal treatment including radiation therapy,must be further studied to improve the prognoses of patients.展开更多
Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A ...Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A promotes neurite growth of dorsal root ganglia in embryonic chickens and inhibits nitric oxide secretion. The present study demonstrated for the first time that activin A could maintain cerebral cortex neuronal survival in vitro for a long period, and that activin A was shown to increase voltage-gated Na＋ current （/Na） in Neuro-2a cells, which was recorded by patch clamp technique. The present study revealed a novel mechanism for activin A, as well as the influence of activin A on neurons by regulating expressions of vasoactive intestine peptide and inducible nitric oxide synthase.展开更多
Retinoic acid can cause many types of cells,including mouse neuroblastoma Neuro-2 A cells,to differentiate into neurons.However,it is still unknown whether microRNAs(miRNAs)play a role in this neuronal differentiation...Retinoic acid can cause many types of cells,including mouse neuroblastoma Neuro-2 A cells,to differentiate into neurons.However,it is still unknown whether microRNAs(miRNAs)play a role in this neuronal differentiation.To address this issue,real-time polymerase chain reaction assays were used to detect the expression of several differentiation-related miRNAs during the differentiation of retinoic acid-treated Neuro-2 A cells.The results revealed that miR-124 and miR-9 were upregulated,while miR-125 b was downregulated in retinoic acid-treated Neuro-2 A cells.To identify the miRNA that may play a key role,miR-124 expression was regulated by transfection of miRNA mimics or inhibitors.Morphological analysis results showed that inhibition of miR-124 expression reversed the effects of retinoic acid on neurite outgrowth.Moreover,miR-124 overexpression alone caused Neuro-2 A cells to differentiate into neurons,and its inhibitor could block this effect.These results suggest that miR-124 plays an important role in retinoic acid-induced differentiation of Neuro-2 A cells.展开更多
Stroke is the third leading cause of death and the first cause of adult disability in industrial countries [1]. It is charicaterized by hemiplegia, hemianopsia, aphasia, mouth askew and sever sequelae. It is considere...Stroke is the third leading cause of death and the first cause of adult disability in industrial countries [1]. It is charicaterized by hemiplegia, hemianopsia, aphasia, mouth askew and sever sequelae. It is considered that an ischemic disease without any specific treatment method and few effective drugs such as tPA (human tissue-type plasminogen activator) and Edarovone with specific therapeutic window will cause a lot of disadvantages if being used inaccurate. Root of Panax notoginseng (PN) which is one of traditional Chinese medicines (TCMs), was first found in “Shennong’s Classic of Materia Medica” around 200 AD. Panax notogineng saponins(PNS) is a multi-components mixture containing ginseng and saponins as the most important bioactive components which are commonly used in clinical treatment. Also, ginseng and saponins form the main components of many herbal medicines in the market, e.g., Xueshuantong injection [2], Xuesaitong injection [3], Xuesaitong soft capsule [4] and so on. The main monomers of Panax notoginseng saponins (PNS) are Ginsenoside-Rb1, Gensenoside-Rg1, Gensenoside-Re, Gensenoside-Rd and Panax notoginseng saponins-R1 [5]. In this review, we found some important points as well as shortcomings that require special consideration. We therefore highlighted the advances in neuro-protection of PNS and its main monomers in the area of experimental research.展开更多
文摘Background: Among patients treated for tuberculosis, 2% to 5% have a Central Nervous System (CNS) lesion, and its frequency rises to 10% in HIV-infected patients. Neuro-meningeal tuberculosis (NMT) is responsible for death and severe permanent neurological damage. This poor prognosis requires early diagnosis and rapid initiation of specific treatment. Unfortunately, the great clinical polymorphism and the lack of specificity of radiological and biological signs are frequently responsible for a delay in diagnosis and management. Senegal is one of the African countries where tuberculosis has remained a concern until now. And there are no studies carried out on this subject. Objective: The objective of this study was to describe the profile and outcome of Neuro-meningeal tuberculosis (NMT) cases diagnosed at the infectious diseases department (SMIT) of Fann University Hospital in Dakar, (referral service for management of tuberculosis). Methods: We carried out a retrospective, descriptive and analytical study, reviewing medical records of adults diagnosed with NMT at the SMIT of Fann Hospital from January 2015 to December 2020. Results: We collected 55 cases of NMT. The median age was 38 years [range 16 - 77 years]. The sex ratio (M/F) was 3.23. HIV patients represented 41.82% of cases. A history of tuberculosis was found in 25.5% of cases. The delay in consultation was greater than one month in 60% of patients. Headaches were the most constant reason for consultation (94.55%). Meningeal signs were present in 94.55% of patients, and consciousness disorders and intracranial hypertension were present in 63.64% and 56.36% respectively. Nerve palsy was found in 38.18%. CSF was clear in 81.64%. GeneXpert MTB/RIF in CSF was performed in 33 patients and was positive in 4 patients. Brain CT was abnormal in 72.09% of cases. Tuberculoma, hydrocephalus and meningeal contrast enhancement were the main lesions. The neuro-meningeal localization was associated with a pulmonary form in 32.7%. The lethality rate was 21.8%;higher in women (46.2% vs 14.3%;p = 0.01), in patients with a delay in consultation > 1 month (p = 0.03), and in patients who presented with consciousness disorders (p = 0.007). Conclusion: Despite the availability of the GeneXpert MTB/RIF, diagnosis of NMT remains difficult. Because of its variable clinical expression and the low sensitivity of the GeneXpert MTB/rif in the CSF, it exposes patients to serious complications. Among the factors associated with death, we found consciousness disorders, a long delay in diagnosis.
基金supported by the Charles H.“Skip”Smith Endowment Fund and the Verne M.Willaman Endowment Fund from the Pennsylvania State University to G.C。
文摘Objective:Glioblastoma(GBM)is the most prevalent and aggressive adult primary cancer in the central nervous system.Therapeutic approaches for GBM treatment are under intense investigation,including the use of emerging immunotherapies.Here,we propose an alternative approach to treat GBM through reprogramming proliferative GBM cells into non-proliferative neurons.Methods:Retroviruses were used to target highly proliferative human GBM cells through overexpression of neural transcription factors.Immunostaining,electrophysiological recording,and bulk RNA-seq were performed to investigate the mechanisms underlying the neuronal conversion of human GBM cells.An in vivo intracranial xenograft mouse model was used to examine the neuronal conversion of human GBM cells.Results:We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1(Neuro D1),Neurogenin-2(Neurog2),or Achaete-scute homolog 1(Ascl1).Subtype characterization showed that the majority of Neurog2-and Neuro D1-converted neurons were glutamatergic,while Ascl1 favored GABAergic neuron generation.The GBM cell-converted neurons not only showed pan-neuronal markers but also exhibited neuron-specific electrophysiological activities.Transcriptome analyses revealed that neuronal genes were activated in glioma cells after overexpression of neural transcription factors,and different signaling pathways were activated by different neural transcription factors.Importantly,the neuronal conversion of GBM cells was accompanied by significant inhibition of GBM cell proliferation in both in vitro and in vivo models.Conclusions:These results suggest that GBM cells can be reprogrammed into different subtypes of neurons,leading to a potential alternative approach to treat brain tumors using in vivo cell conversion technology.
基金supported by the National Glaucoma Research Program of the Bright Focus Foundationsupported by an unrestricted research grant from Research to Prevent BlindnessNIH center grant EY014801
文摘Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell （RGC） death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases. In this review article, we will go through three current approaches to cure neu- rodegenerative eye diseases, including cell based therapy, neuro-regeneration and neuro-rejuvenation.
文摘Large cell neuroendocrine carcinoma(LCNEC)in the biliary system is a poorly differentiated,high-grade neuroendocrine tumor.These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases.Herein,we report an unusual case of a pure primary LCNEC of the common bile duct(CBD).A 75-year-old female presented with nausea and jaundice.The patient underwent a CBD excision with lymph node dissection.Upon histological and immunohistochemical examination,the tumor exhibited pure large cell-type neuroendocrine features.Metastases were noted in two of the eight lymph nodes.The patient was administered adjuvant chemotherapy.The patient’s cancer recurred 7 mo after surgery,and the patient died from liver failure 5 mo after recurrence.The prognosis of LCNEC of CBD remains poor despitecurative resection and adjuvant chemotherapy.The role of additional therapies,such as multimodal treatment including radiation therapy,must be further studied to improve the prognoses of patients.
基金the National Natural Science Foundation of China, No.30903123, 30901329the Project of Science and Technology of Jilin Province, No.20090741, 20090185
文摘Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A promotes neurite growth of dorsal root ganglia in embryonic chickens and inhibits nitric oxide secretion. The present study demonstrated for the first time that activin A could maintain cerebral cortex neuronal survival in vitro for a long period, and that activin A was shown to increase voltage-gated Na＋ current （/Na） in Neuro-2a cells, which was recorded by patch clamp technique. The present study revealed a novel mechanism for activin A, as well as the influence of activin A on neurons by regulating expressions of vasoactive intestine peptide and inducible nitric oxide synthase.
基金supported by the Natural Science Foundation of Shanghai of China,No.16ZR1410500(to SZD)
文摘Retinoic acid can cause many types of cells,including mouse neuroblastoma Neuro-2 A cells,to differentiate into neurons.However,it is still unknown whether microRNAs(miRNAs)play a role in this neuronal differentiation.To address this issue,real-time polymerase chain reaction assays were used to detect the expression of several differentiation-related miRNAs during the differentiation of retinoic acid-treated Neuro-2 A cells.The results revealed that miR-124 and miR-9 were upregulated,while miR-125 b was downregulated in retinoic acid-treated Neuro-2 A cells.To identify the miRNA that may play a key role,miR-124 expression was regulated by transfection of miRNA mimics or inhibitors.Morphological analysis results showed that inhibition of miR-124 expression reversed the effects of retinoic acid on neurite outgrowth.Moreover,miR-124 overexpression alone caused Neuro-2 A cells to differentiate into neurons,and its inhibitor could block this effect.These results suggest that miR-124 plays an important role in retinoic acid-induced differentiation of Neuro-2 A cells.
文摘Stroke is the third leading cause of death and the first cause of adult disability in industrial countries [1]. It is charicaterized by hemiplegia, hemianopsia, aphasia, mouth askew and sever sequelae. It is considered that an ischemic disease without any specific treatment method and few effective drugs such as tPA (human tissue-type plasminogen activator) and Edarovone with specific therapeutic window will cause a lot of disadvantages if being used inaccurate. Root of Panax notoginseng (PN) which is one of traditional Chinese medicines (TCMs), was first found in “Shennong’s Classic of Materia Medica” around 200 AD. Panax notogineng saponins(PNS) is a multi-components mixture containing ginseng and saponins as the most important bioactive components which are commonly used in clinical treatment. Also, ginseng and saponins form the main components of many herbal medicines in the market, e.g., Xueshuantong injection [2], Xuesaitong injection [3], Xuesaitong soft capsule [4] and so on. The main monomers of Panax notoginseng saponins (PNS) are Ginsenoside-Rb1, Gensenoside-Rg1, Gensenoside-Re, Gensenoside-Rd and Panax notoginseng saponins-R1 [5]. In this review, we found some important points as well as shortcomings that require special consideration. We therefore highlighted the advances in neuro-protection of PNS and its main monomers in the area of experimental research.
