Role of N6-methyladenosine RNA methylation in central nervous system: a review / 生物工程学报

There are a variety of post-transcriptional modifications in mRNA, which regulate the stability, splicing, translation, transport and other processes of mRNA, followed by affecting cell development, body immunity, learning and cognition and other important physiological functions. m6A modification is one of the most abundant post-transcriptional modifications widely existing in mRNA, regulating the metabolic activities of RNA and affecting gene expression. m6A modified homeostasis is critical for the development and maintenance of the nervous system. In recent years, m6A modification has been found in neurodegenerative diseases, mental diseases and brain tumors. This review summarizes the role of m6A methylation modification in the development, function and related diseases of the central nervous system in recent years, providing potential clinical therapeutic targets for neurological diseases.

Research Progress of Targeted Drug Delivery Nanocarriers Through Blood-brain Barrier / 中国实验方剂学杂志

The small size， moderate drug loading， and targeting properties of nano-preparations make them can be excellent delivery tools for drugs， genes or proteins crossing the cell or blood-brain barrier （BBB）. Currently， facilitating drug crossing BBB with innovative nano-drug delivery systems is considered as a strategic approach for the prevention， diagnosis and treatment of central nervous system （CNS） diseases. However， with the deepening of the research， the adverse reactions and toxicity of nanocarriers have gradually attracted the attention of researchers. Based on this， this paper summarized the situation of BBB-penetrating targeted nano-preparations at home and abroad in recent years from the perspective of classification of types and properties of nanocarriers， and analyzed the advantages and disadvantages of each carrier. The results showed that nano-preparations with active ingredients of traditional Chinese medicine （TCM） as carriers have become a promising way of cancer treatment， but the complexity and diversity of TCM components limited its application to a certain extent. Further studies should be strengthened to lay a foundation for the application and development of TCM nano-preparations in the field of CNS diseases.

Occurrence of The Pathogenic Amoeba Naegleria fowleri, Pathogenesis, Diagnosis, and Treatment Options

@#Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis (PAM) that infects the central nervous system (CNS). The amoeba is present ubiquitously. The infection is rare but has a high mortality rate. The pathogenic amoeba reaches the host through the nasal passage and migrates along the olfactory nerves to reach the human brain and cause severe destruction of the CNS. As Malaysia has a large population that practising ablutions in daily routine, the risk of infection increases. Two mechanisms associated with the infection include contact-dependent and contact-independent. Signs and symptoms vary from early stage to later stage of infection. CSF and brain biopsy are the common specimens collected used to diagnose the PAM infection and usually detect and identify by PCR method. As for treatment, the CDC of United States America has recommended the usage of miltefosine that provides promising in vitro therapy against N. fowleri. This review will discuss more on the occurrence of N. fowleri, pathogenicity, diagnostic tools, and pharmacotherapy approach against N. fowleri infection.

Development of a highly-specific

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified

Encefalomielitis diseminada aguda posinfecciosa en un paciente con sospecha de infección por virus dengue / Postinfectious acute disseminated encephalomyelitis in a patient with suspected dengue virus infection

Introducción: La infección por virus dengue es considerada una de las arbovirosis de mayor prevalencia en los países tropicales. La encefalomielitis diseminada aguda es un trastorno inflamatorio desmielinizante y multifocal que afecta al sistema nervioso central, de inicio agudo y curso clínico monofásico. El proceso inflamatorio se encuentra mediado por mecanismos inmunológicos y su relación con infecciones por el virus dengue aún no se establece con claridad. Objetivo: Describir un caso clínico con manifestaciones del sistema nervioso central después de una probable infección por el virus dengue. Presentación del caso: Paciente femenina de 50 años, con antecedentes de hipertensión arterial controlada. Quince días después de un cuadro de fiebre de 4 días de duración, que posiblemente fue por una infección por el virus dengue, comienza con síntomas y signos de afectación neurológica caracterizadas por ligera irritabilidad, dificultad para la concentración en una actividad específica de la vida cotidiana. Progresivamente se nota dificultad motora en el hemicuerpo izquierdo además de encontrarse agitada y distraída, motivo por el cual se decide su ingreso hospitalario. Se realiza el diagnóstico a través de los hallazgos en el examen físico, los estudios positivos de resonancia magnética nuclear y el resultado positivo de la IgM de dengue en sangre. Tanto la evolución clínica como la respuesta al tratamiento con esteroides fueron favorables. Conclusiones: El evento ocurrido en este caso sugiere que los facultativos deben tener presente el diagnóstico de encefalomielitis diseminada aguda en pacientes que han tenido infección previa o alta sospecha de esta por el virus dengue(AU)

Introduction: Dengue virus infection is one of the most prevalent arboviruses in tropical countries. Acute disseminated encephalomyelitis is an inflammatory demyelinating multifocal disorder affecting the central nervous system. Its onset is acute and its clinical course monophasic. The inflammatory process is mediated by immunological mechanisms, and its relationship to dengue virus infections is still not clear. Objective: Describe a clinical case of central nervous system manifestations after probable dengue virus infection. Case presentation: Female 50-year-old patient with a history of controlled hypertension. Fifteen days after a 4-day fever episode, possibly due to dengue virus infection, the patient starts presenting neurological signs and symptoms, such as slight irritability and difficulty to concentrate on a specific activity of daily living. The patient notices progressive motor difficulty in her left hemibody and she feels agitated and distracted. It is therefore decided for her to be hospitalized. A diagnosis is made based on physical examination findings, positive nuclear magnetic resonance studies, and the positive result of the dengue IgM blood test. Both the patient's clinical evolution and her response to treatment with steroids were favorable. Conclusions: The event herein described suggests that physicians should consider the diagnosis of acute disseminated encephalomyelitis in patients with previous infection or high suspicion of infection with dengue virus(AU)

Mechanobiological Response and Network Formation in Central Nervous Development / 医用生物力学

In the process of central nervous system (CNS) development and maturation, the biomechanical factors have not been highly valued for a long time. In recent years, a large number of studies have shown that mechanical environment strongly affects the migration, differentiation and maturation of nerve cells, as well as the cell-cell interactions. Mechanical factors play an important role in realization of the structure and function of the brain and spinal cord. This review briefly summarized the role of biomechanics in CNS perception, path-finding, regulation and network shaping during CNS development. The effects of static and dynamic mechanics on mechanobiological response of nerve cells were also introduced, hoping to provide some ideas for CNS reconstruction and repair in future.

Genetic Ablation of EWS RNA Binding Protein 1 (EWSR1) Leads to Neuroanatomical Changes and Motor Dysfunction in Mice

A recent study reveals that missense mutations of EWSR1 are associated with neurodegenerative disorders such as amyotrophic lateral sclerosis, but the function of wild-type (WT) EWSR1 in the central nervous system (CNS) is not known yet. Herein, we investigated the neuroanatomical and motor function changes in Ewsr1 knock out (KO) mice. First, we quantified neuronal nucleus size in the motor cortex, dorsal striatum and hippocampus of three different groups: WT, heterozygous Ewsr1 KO (+/−), and homozygous Ewsr1 KO (−/−) mice. The neuronal nucleus size was significantly smaller in the motor cortex and striatum of homozygous Ewsr1 KO (−/−) mice than that of WT. In addition, in the hippocampus, the neuronal nucleus size was significantly smaller in both heterozygous Ewsr1 KO (+/−) and homozygous Ewsr1 KO (−/−) mice. We then assessed motor function of Ewsr1 KO (−/−) and WT mice by a tail suspension test. Both forelimb and hindlimb movements were significantly increased in Ewsr1 KO (−/−) mice. Lastly, we performed immunohistochemistry to examine the expression of TH, DARPP-32, and phosphorylated (p)-DARPP-32 (Thr75) in the striatum and substantia nigra, which are associated with dopaminergic signaling. The immunoreactivity of TH and DARPP-32 was decreased in Ewsr1 KO (−/−) mice. Together, our results suggest that EWSR1 plays a significant role in neuronal morphology, dopaminergic signaling pathways, and motor function in the CNS of mice.

Patología secuelar asociada a tratamiento quirúrgico de tumores intracraneales intervenidos en el Hospital regional Teodoro Maldonado Carbo año 2014 / Sequelar pathology associated intracranial surgical treatment of tumors in the regional hospital surgery Teodoro Maldonado Carbo 2014

De la muestra de 222 pacientes operados de cirugías craneales, se identifican 49 pacientes que fueron sometidos a tratamiento quirúrgico por lesiones tumorales intracraneales cuyos resultados relevantes encontrados fueron los siguientes: los pacientes posquirúrgicos sin secuelas neurológicas representan el 47 %, el 61 % de los pacientes no necesitó tratamiento oncológico debido a presentar patología tumoral benigna, la edad promedio fue entre los 41 a 60 años; los tumores de mayor incidencia fueron los extra-axiales con un 43 %, aunque no hubo mayor diferencia predominó el sexo masculino. En cuanto a la evaluación del estado de los pacientes mediante la escala de Karnofsky entre 90 a 100, es decir pacientes que pudieron reintegrarse a su actividad laboral sin mayor inconveniente representó el 67 % de los pacientes tomados en cuenta en este estudio. De la muestra de 222 pacientes operados de cirugías craneales, se identifican 49 pacientes que fueron sometidos a tratamiento quirúrgico por lesiones tumorales intracraneales cuyos resultados relevantes encontrados fueron los siguientes: los pacientes posquirúrgicos sin secuelas neurológicas representan el 47 %, el 61 % de los pacientes no necesitó tratamiento oncológico debido a presentar patología tumoral benigna, la edad promedio fue entre los 41 a 60 años; los tumores de mayor incidencia fueron los extra-axiales con un 43 %, aunque no hubo mayor diferencia predominó el sexo masculino. En cuanto a la evaluación del estado de los pacientes mediante la escala de Karnofsky entre 90 a 100, es decir pacientes que pudieron reintegrarse a su actividad laboral sin mayor inconveniente representó el 67 % de los pacientes tomados en cuenta en este estudio. Objetivo general.- Determinar el porcentaje de pacientes con secuelas posquirúrgicas sometidos a extirpación de tumores intracraneales valorados mediante escala de Karnofsky. Objetivo específico.- Determinar porcentualmente las variables encontradas en el estudio con el fin de analizar nuestras fortalezas y amenazas ante este tipo de patologías.

Of the sample of 222 patients undergoing cranial surgery, we identified 49 patients who underwent surgical treatment for intracranial tumor lesions whose relevant results were: postoperative patients without neurological sequelae represent 47 %, 61 % of patients I did not need oncologic treatment due to enign tumor pathology, the average age was between 41 to 60 years, the tumors with the highest incidence were the extra-axial with 43 %, although there was no major difference the male gender, in terms of The evaluation of the patient's status using the Karnofsky scale between 90 and 100, that's meaning that patients who were able to return to their work without major inconvenience represented 67 % of the patients taken into account in this study. General objective.- To determine the percentage of patients with post-surgical sequelae submitted to excision of intracranial tumors evaluated by Karnofsky scale. Specific objective.- determine the variables found in the study in order to analyze our strengths and threats against this type of pathologies

A Case of Aspergillus Endophthalmitis as a Preceding Symptom of Central Nervous System Lymphoma

PURPOSE: To report a rare case of Aspergillus endophthalmitis as a preceding symptom of central nervous system (CNS) lymphoma. CASE SUMMARY: A 66-year-old female was admitted to our clinic with mental change for 3 days. Seven months earlier, she had been diagnosed with retinal vasculitis in an ophthalmology clinic because of blurred vision in both eyes and was administered steroid therapy. Three months earlier, because of progressive symptoms, vitreous fluid culture had been performed and showed Aspergillus endophthalmitis. She was treated with intravitreous voriconazole injection and oral voriconazole. Initial brain magnetic resonance imaging (MRI) and cerebrospinal fluid study was normal. Two months later, a second MRI showed multiple enhancing lesions, which were aggravated on the third MRI at admission to our clinic. Although brain biopsy was not performed due to the poor condition of the patient, CNS lymphoma was suspected based on the neuroimaging. After steroid pulse therapy and whole brain radiation, follow-up neurologic examination showed improved mental state, and follow-up MRI showed remarkable shrinkage of multiple lesions. CONCLUSIONS: As Aspergillus endophthalmitis is an opportunistic infection in those with an immune-compromised state and the orbit is near the central nervous system, the clinician should be alert to concomitant disorders in CNS. For a prompt and accurate diagnosis of CNS disorder, early evaluation of neurologic symptoms beyond symptoms of endophthalmitis and neuroimaging is essential.

Characteristics and resistance patterns of pathogens for nosocomial pneumonia in patients with central nervous system disease / 中国实用内科杂志

Objective To investigate the pathogenesis, distribution of the pathogens and resistance pattern of nosocomial pneumonia in patients with diseases of central nervous system(CNS).Methods Bacterial typing was conducted on the 59 strains separated from the sputum of 59 patients of nosocomial pneumonia with CNS diseases in our hospital in 2002.MIC drug sensitive test in vitro was conducted with the most common 15 antibiotics.Results The most common pathogens of nosocomial pneumonia in the diseases of CNS were:Staphylococcus aureus 23.7%,Pseudomonas aeruginosa 22.0%,Acinetobacter baumannii 18.6%,Klebsiella pneumoniae 8.5% Xanthomonas maltophilia 6.8%?According to the drug sensitive test,antimicrobial-resistant gram-negative bacilli were increasing.None of the vancomycin-resistant MRSA variant was seen.Conclusion The risk factors of nosocomial pneumonia in the diseases of CNS are long hospital stay,respiratory tract invasive operation and unreasonable antibiotic therapy.The most common pathogens were Staphylococcus aureus,Pseudomonas aeruginosa,Acinetobacter baumannii,Klebsiella pneumoniae and Xanthomonas maltophilia.Effective and infection-control procedures,surveillance systems and appropriate antimicrobial selection are key methods in limiting nosocomial pneumonia and antimicrobial-resistant pathogen occurrence.