47 results
Search Results
2. Nasal Drug Delivery and Nose-to-Brain Delivery Technology Development Status and Trend Analysis: Based on Questionnaire Survey and Patent Analysis.
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Ge, Yuanyuan, Xu, Xingying, Cao, Meng, Liu, Baijun, Wang, Ying, Liao, Ping, Wang, Jiajing, Chen, Yifei, Yuan, Hongmei, and Chen, Guiliang
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INTRANASAL administration , *PATENT applications , *CENTRAL nervous system , *TREND analysis , *RESEARCH personnel - Abstract
Nasal administration is a non-invasive method of drug delivery that offers several advantages, including rapid onset of action, ease of use, no first-pass effect, and fewer side effects. On this basis, nose-to-brain delivery technology offers a new method for drug delivery to the brain and central nervous system, which has attracted widespread attention. In this paper, the development status and trends of nasal drug delivery and nose-to-brain delivery technology are deeply analyzed through multiple dimensions: literature research, questionnaire surveys, and patent analysis. First, FDA-approved nasal formulations for nose-to-brain delivery were combed. Second, we collected a large amount of relevant information about nasal drug delivery through a questionnaire survey of 165 pharmaceutical industry practitioners in 28 provinces and 161 different organizations in China. Third, and most importantly, we conducted a patent analysis of approximately 700+ patents related to nose-to-brain delivery, both domestically and internationally. This analysis was conducted in terms of patent application trends, technology life cycle, technology composition, and technology evolution. The LDA topic model was employed to identify technological topics in each time window (1990–2023), and the five key major evolution paths were extracted. The research results in this paper will provide useful references for relevant researchers and enterprises in the pharmaceutical industry, promoting the further development and application of nasal drug delivery and nose-to-brain delivery technology. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Self-assembled dipeptide grafted nanohybrid material strips for reliable spectroscopic and electrochemical recognition of tryptamine.
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Divya, Saini, Sanjeev, Kalra, Sanchit, Kaur, Navneet, and Singh, Narinder
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TRYPTAMINE , *DIPEPTIDES , *FOODBORNE diseases , *BIOGENIC amines , *CENTRAL nervous system - Abstract
According to the World Health Organization (WHO), foods high in tryptamine may cause foodborne diseases and abnormal activity in the central nervous system (CNS). The real-time monitoring of tryptamine levels is an emphasized topic among scientific community. In the present work, we report a cost-effective fluorescent paper strips-based methodology impregnated with self-assembled dipeptide-modified (DM1) zinc oxide (ZnO) i.e. DM1@ZnO for the real-time monitoring of tryptamine levels. It is based on an organic-inorganic nanohybrid material of self-assembled N -functionalised dipeptide molecule coated over the surface of ZnO thus tailoring its properties for the detection of tryptamine employing spectroscopic and electrochemical methods. The designed material exhibited a noteworthy response towards tryptamine irrespective of the presence of other biogenic amines (BAs). It selectively displayed blue fluorescence under the 365 nm UV light. On top of that, the detection of tryptamine was also corroborated by its transition to 2-oxytryptamine, as deduced from its electrochemical route. Thus, the proposed paper strip-based methodology unbolts a realistic platform for the efficient recognition of varying levels of tryptamine thus tackling the prima facie reasons for foodborne diseases. [Display omitted] • Fabrication of self-assembled dipeptide-based nanohybrid material. • Spectroscopic and electrochemical recognition of tryptamine. • Interaction of DM1@ZnO with tryptamine and its electrochemical conversion to 2-oxytryptamine. • Fabrication of DM1@ZnO grafted fluorescent paper strips. • Realistic platform for the efficient recognition of tryptamine thus tackling the prima facie reasons for foodborne diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Is blood pTau a reliable indicator of the CSF status? A narrative review.
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Antonioni, Annibale, Raho, Emanuela Maria, and Di Lorenzo, Francesco
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ALZHEIMER'S disease , *LITERATURE reviews , *TAU proteins , *NEUROFIBRILLARY tangles , *CENTRAL nervous system - Abstract
Background: The identification of biomarkers for the early diagnosis of Alzheimer's disease (AD) is a crucial goal of the current research. Blood biomarkers are less invasive, easier to obtain and achievable by a cheaper means than those on cerebrospinal fluid (CSF) and significantly more economic than functional neuroimaging investigations; thus, a great interest is focused on blood isoforms of the phosphorylated Tau protein (pTau), indicators of ongoing tau pathology (i.e. neurofibrillary tangles, NFTs, an AD neuropathological hallmark) in the central nervous system (CNS). However, current data often highlight discordant results about the ability of blood pTau to predict CSF status. Objective: We aim to synthesise the studies that compared pTau levels on CSF and blood to assess their correlation in AD continuum. Methods: We performed a narrative literature review using, first, MEDLINE (via PubMed) by means of MeSH terms, and then, we expanded the reults by means of Scopus and Web of Sciences to be as inclusive as possible. Finally, we added work following an expert opinion. Only papers presenting original data on pTau values on both blood and CSF were included. Results: The 33 included studies show an extreme heterogeneity in terms of pTau isoform (pTau181, 217 and 231), laboratory methods, diagnostic criteria and choice of comparison groups. Most studies evaluated plasma pTau181, while data on other isoforms and serum are scarcer. Discussion: Most papers identify a correlation between CSF and blood measurements. Furthermore, even when not specified, it is often possible to show an increase in blood pTau values as AD-related damage progresses in the AD continuum and higher values in AD than in other neurodegenerative diseases. Notably, plasma pTau231 seems the first biomarker to look for in the earliest and pre-clinical stages, quickly followed by pTau217 and, finally, by pTau181. Conclusions: Our results encourage the use of blood pTau for the early identification of patients with AD continuum. [ABSTRACT FROM AUTHOR]
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- 2024
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5. A primer to vascular anatomy of the brain: an overview on anterior compartment.
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Morales-Roccuzzo, Diego, Sabahi, Mohammadmahdi, Obrzut, Michal, Najera, Edinson, Monterroso-Cohen, David, Bsat, Shadi, Adada, Badih, and Borghei-Razavi, Hamid
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BRAIN anatomy , *INTERNAL carotid artery , *ANTERIOR cerebral artery , *LITERATURE reviews , *VERTEBRAL artery , *CENTRAL nervous system - Abstract
Purpose: Knowledge of neurovascular anatomy is vital for neurosurgeons, neurologists, neuro-radiologists and anatomy students, amongst others, to fully comprehend the brain's anatomy with utmost depth. This paper aims to enhance the foundational knowledge of novice physicians in this area. Method: A comprehensive literature review was carried out by searching the PubMed and Google Scholar databases using primary keywords related to brain vasculature, without date restrictions. The identified literature was meticulously examined and scrutinized. In the process of screening pertinent papers, further articles and book chapters were obtained through analysis and additional assessing of the reference lists. Additionally, four formalin-fixed, color latex-injected cadaveric specimens preserved in 70% ethanol solution were dissected under surgical microscope (Leica Microsystems Inc, 1700 Leider Ln, Buffalo Grove, IL 60089 USA). Using microneurosurgical as well as standard instruments, and a high-speed surgical drill (Stryker Instruments 1941 Stryker Way Portage, MI 49002 USA). Ulterior anatomical dissection was documented in microscopic images. Results: Encephalic circulation functions as a complex network of intertwined vessels. The Internal Carotid Arteries (ICAs) and the Vertebral Arteries (VAs), form the anterior and posterior arterial circulations, respectively. This work provides a detailed exploration of the neurovascular anatomy of the anterior circulation and its key structures, such as the Anterior Cerebral Artery (ACA) and the Middle Cerebral Artery (MCA). Embryology is also briefly covered, offering insights into the early development of the vascular structures of the central nervous system. Cerebral venous system was detailed, highlighting the major veins and tributaries involved in the drainage of blood from the intracranial compartment, with a focus on the role of the Internal Jugular Veins (IJVs) as the primary, although not exclusive, deoxygenated blood outflow pathway. Conclusion: This work serves as initial guide, providing essential knowledge on neurovascular anatomy, hoping to reduce the initial impact when tackling the subject, albeit the intricate vasculature of the brain will necessitate further efforts to be conquered, that being crucial for neurosurgical and neurology related practice and clinical decision-making. [ABSTRACT FROM AUTHOR]
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- 2024
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6. The safety and efficacy of bevacizumab in treatment of recurrent low-grade glioma: a systematic review and meta-analysis.
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Habibi, Mohammad Amin, Rashidi, Farhang, Gharedaghi, Hossein, Arshadi, Mohammad Reza, and Kazemivand, Sana
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MEDICAL information storage & retrieval systems , *DRUG toxicity , *PATIENT safety , *GLIOMAS , *BEVACIZUMAB , *TREATMENT effectiveness , *META-analysis , *CENTRAL nervous system , *DESCRIPTIVE statistics , *SYSTEMATIC reviews , *MEDLINE , *DRUG efficacy , *DISEASE relapse , *ONLINE information services , *DATA analysis software , *CONFIDENCE intervals , *PROGRESSION-free survival , *DISEASE progression , *DRUG tolerance - Abstract
Background: Central nervous system (CNS) tumors are among the most common malignancies in various age ranges. Low-grade glioma (LGG) can account for nearly 30% of pediatric CNS malignancies. Progression or recurrence after the first-line treatments is common among these patients. Therefore, more treatments are required. Bevacizumab as an anti-VEGF antibody has come into the spotlight recently and is especially used in relapse or recurrence settings. This review aims to study the safety and efficacy of bevacizumab for patients with recurrent LGG. Methods: This study was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Scopus, Web of Science, and Embase were comprehensively searched using the relevant key terms until 24th August 2023 to retrieve the studies that investigated clinical outcomes of bevacizumab in patients with recurrent LGG. All statistical analysis was performed by STATA v.17. Results: A total of 1306 papers were gathered, out of which 13 were incorporated in the meta-analysis. The pooled incidence rate of treatment according to the RANO scale was 70% (95% CI = 43–98%) for objective response rate, 26% (95% CI = 58–96%) for partial response, 21% (95% CI = 15–28%) for minor response, 14% (95% CI = 3–24%) for complete response, 48% (95% CI = 37–59%) for stable disease, and 8% (95% CI = 4–11%) for progressive disease. Furthermore, according to progressive survival after treatment, it was 4% (95% CI = −1 to 9%) for 6-month PFS, 41% (95% CI = 32–50%) for 2-year PFS, and 29% (95% CI = 22–35%) for 3-year PFS. Conclusion: According to the RANO scale and PFS, clinicians should be aware that Bevacizumab could be a favorable alternative therapy for recurrent LGG. Furthermore, bevacizumab exhibits minimal toxicity and high tolerability in recurrent LGG. [ABSTRACT FROM AUTHOR]
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- 2024
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7. New and Evolving Treatments for Neurologic Dysphagia.
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Sasegbon, Ayodele, Cheng, Ivy, Labeit, Bendix, Lapa, Sriramya, Rommel, Nathalie, and Hamdy, Shaheen
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THERAPEUTICS , *SENSORIMOTOR integration , *CENTRAL nervous system , *DEEP brain stimulation , *TREATMENT effectiveness , *NEUROLOGICAL disorders , *TRANSCUTANEOUS electrical nerve stimulation , *PHARYNGEAL muscles , *QUALITY of life , *DEGLUTITION , *DRUGS , *TRANSCRANIAL direct current stimulation , *DEGLUTITION disorders , *TRANSCRANIAL magnetic stimulation - Abstract
Despite swallowing being a frequently performed daily function, it is highly complex. For a safe swallow to occur, muscles within the head, neck, and thorax need to contract in a concerted pattern, controlled by several swallowing centers at multiple levels of the central nervous system, including the midbrain, cerebral cortex, and cerebellum in addition to five cranial nerves. Dysphagia, or difficulty swallowing, is caused by a long list of pathologic processes and diseases, which can interfere with various stages along the swallowing sensorimotor pathway. When present, dysphagia leads to increased mortality, morbidity, hospital length of stay, and reduced quality of life. Current dysphagia management approaches, such as altering the texture and consistency of foods and fluids and teaching patients rehabilitative exercises, have been broadly unchanged for many years and, in the case of texture modification, are of uncertain effectiveness. However, evidence is emerging in support of new medication-based and neuromodulatory treatment approaches. Regarding medication-based therapies, most research has focused on capsaicinoids, which studies have shown are able to improve swallowing in patients with post-stroke dysphagia. Separately, albeit convergently, in the field of neuromodulation, there is a growing and positive evidential base behind three non-invasive brain stimulation techniques: repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (TDCS), and pharyngeal electrical stimulation (PES). Should some or all of these emerging therapies fulfill their promise, dysphagia-related patient outcomes may be improved. This paper describes the current state of our understanding regarding new medication and neuromodulation-based neurogenic oropharyngeal dysphagia treatments. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Research progress on the regulation of intestinal flora on glioma.
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XI Kexin, ZHAO Yuqi, XIE Xiaoting, LU Yuntao, FAN Hongying, and HE Xiaoyan
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GLIOMAS , *BOTANY , *INTESTINES , *CENTRAL nervous system , *GUT microbiome , *BRAIN tumors - Abstract
Glioma is the most common primary tumor of the brain, accounting for 81 % of central nervous system (CNS) malignant tumors. The degree of malignancy is high, and the current treatment methods are limited. In recent years, with the in-depth study of intestinal flora and brain-gut axis, it has been found that the diversity of gut microbiota plays an important role in the regulation of glioma. The mechanism is that the intestinal flora affects the development of glioma through the role of immune regulation and metabolites. In addition, it has been confirmed that there is a certain correlation between some probiotics and glioma, which provides a new application prospect for the treatment of glioma. This paper discusses the main intestinal bacteria that regulate gliomas as well as the role and regulatory mechanisms of intestinal flora in the development of gliomas, and provides ideas for the discovery of new targets for glioma treatment and further improvement of treatment options. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Inner Structure of the Lateral Geniculate Complex of Adult and Newborn Acomys cahirinus.
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Merkulyeva, Natalia, Mikhalkin, Aleksandr, and Veshchitskii, Aleksandr
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LATERAL geniculate body , *CALCIUM-binding proteins , *GLUTAMATE decarboxylase , *NEWBORN infants , *ADULTS , *CENTRAL nervous system - Abstract
Acomys cahirinus is a unique Rodentia species with several distinctive physiological traits, such as precocial development and remarkable regenerative abilities. These characteristics render A. cahirinus increasingly valuable for regenerative and developmental physiology studies. Despite this, the structure and postnatal development of the central nervous system in A. cahirinus have been inadequately explored, with only sporadic data available. This study is the first in a series of papers addressing these gaps. Our first objective was to characterize the structure of the main visual thalamic region, the lateral geniculate complex, using several neuronal markers (including Ca2+-binding proteins, glutamic acid decarboxylase enzyme, and non-phosphorylated domains of heavy-chain neurofilaments) to label populations of principal neurons and interneurons in adult and newborn A. cahirinus. As typically found in other rodents, we identified three subdivisions in the geniculate complex: the dorsal and ventral lateral geniculate nuclei (LGNd and LGNv) and the intergeniculate leaflet (IGL). Additionally, we characterized internal diversity in the LGN nuclei. The "shell" and "core" regions of the LGNd were identified using calretinin in adults and newborns. In adults, the inner and outer parts of the LGNv were identified using calbindin, calretinin, parvalbumin, GAD67, and SMI-32, whereas in newborns, calretinin and SMI-32 were employed for this purpose. Our findings revealed more pronounced developmental changes in LGNd compared to LGNv and IGL, suggesting that LGNd is less mature at birth and more influenced by visual experience. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Feed Intake Regulation in Fish: Implications for Aquaculture.
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Soengas, José L., Comesaña, Sara, Blanco, Ayelén M., and Conde-Sieira, Marta
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FISH farming , *CENTRAL nervous system , *FISHERY laws , *SEXUAL dimorphism , *AQUACULTURE - Abstract
AbstractUnderstanding how feed intake is regulated in fish is essential for feeding efficiency in aquaculture. For this regulation, the central nervous system in fish orchestrates behavioral and physiological responses involving homeostatic and hedonic regulatory systems. Knowledge about these mechanisms in fish is variable, and this paper reviews available information following a time frame of processes occurring before, during and after feeding. Furthermore, a comprehensive understanding of feed intake regulation in fish is essential for achieving responsible aquaculture practices since regulation of feed intake goes beyond nutritional considerations, impacting growth, health, and performance. Therefore, available information about the impact on feed intake regulation of inclusion of ingredients, stressors, environmental factors, sexual dimorphism, and ontogeny are also described. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Aided Diagnosis Model Based on Deep Learning for Glioblastoma, Solitary Brain Metastases, and Primary Central Nervous System Lymphoma with Multi-Modal MRI.
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Liu, Xiao and Liu, Jie
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DEEP learning , *CENTRAL nervous system , *CINGULATE cortex , *CANCER diagnosis , *DIAGNOSIS , *MAGNETIC resonance imaging ,CENTRAL nervous system tumors - Abstract
Simple Summary: Diagnosing glioblastoma multiforme (GBM), solitary brain metastases (SBM), and primary central nervous system lymphoma (PCNSL) in malignant tumors of the central nervous system using multi-modal magnetic resonance imaging (MRI) is significantly important in helping physicians develop treatment plans and enhance patient prognosis. In this paper, MFFC-Net is developed and validated using deep learning methods to predict these three tumor categories from multi-modal MRI without the manual region of interest (ROI). MFFC-Net first uses a multi-encoder with DenseBlocks to extract deep features from multi-modal MRI. Then, the feature fusion layer fuses the deep information between different modalities and tissues. Finally, the spatial-channel attention module suppresses redundant new information and activates tumor classification-related features. Compared with radiomics models, MFFC-Net demonstrated higher accuracy. In addition, the results in the different sequences provide important references for future clinical work on MRI image acquisition. We believe that MFFC-Net has the potential to assist in the diagnosis and treatment of brain tumors in the future. (1) Background: Diagnosis of glioblastoma (GBM), solitary brain metastases (SBM), and primary central nervous system lymphoma (PCNSL) plays a decisive role in the development of personalized treatment plans. Constructing a deep learning classification network to diagnose GBM, SBM, and PCNSL with multi-modal MRI is important and necessary. (2) Subjects: GBM, SBM, and PCNSL were confirmed by histopathology with the multi-modal MRI examination (study from 1225 subjects, average age 53 years, 671 males), 3.0 T T2 fluid-attenuated inversion recovery (T2-Flair), and Contrast-enhanced T1-weighted imaging (CE-T1WI). (3) Methods: This paper introduces MFFC-Net, a classification model based on the fusion of multi-modal MRIs, for the classification of GBM, SBM, and PCNSL. The network architecture consists of parallel encoders using DenseBlocks to extract features from different modalities of MRI images. Subsequently, an L 1 − n o r m feature fusion module is applied to enhance the interrelationships among tumor tissues. Then, a spatial-channel self-attention weighting operation is performed after the feature fusion. Finally, the classification results are obtained using the full convolutional layer (FC) and Soft-max. (4) Results: The ACC of MFFC-Net based on feature fusion was 0.920, better than the radiomics model (ACC of 0.829). There was no significant difference in the ACC compared to the expert radiologist (0.920 vs. 0.924, p = 0.774). (5) Conclusions: Our MFFC-Net model could distinguish GBM, SBM, and PCNSL preoperatively based on multi-modal MRI, with a higher performance than the radiomics model and was comparable to radiologists. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Central precocious puberty - etiology with particular consideration of neurological causes.
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Gracjasz-Palikij, Izabela, Paprocka, Justyna, and Gawlik, Aneta
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PRECOCIOUS puberty , *DISEASE risk factors , *CENTRAL nervous system , *ETIOLOGY of diseases , *HYPOTHALAMIC-pituitary-gonadal axis , *RARE diseases - Abstract
Central precocious puberty (CPP) is a rare disease of poorly understood etiology. The cause is mostly idiopathic. However, congenital and acquired structural changes in the central nervous system are also involved. Prevalent organic changes in the central nervous system, especially among boys, prompt imaging assessment in each case of CPP. In addition, genetic and environmental factors have been reported. Safe and effective treatment is available. The time of treatment implementation is crucial to the successful outcome. Proper diagnosis and treatment make it possible to avoid a number of complications of untreated CPP. There are only a few studies analyzing the prevalence and risk factors for the disease. The aim of this paper is to discuss the current causes of CPP with particular consideration of neurological aspects. [ABSTRACT FROM AUTHOR]
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- 2024
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13. The Emerging Role of Microglial Hv1 as a Target for Immunomodulation in Myelin Repair.
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Yingxin Tang, Xuan Wu, Jiarui Li, Yuanwei Li, Xiaoxiao Xu, Gaigai Li, Ping Zhang, Chuan Qin, Long-Jun Wu, Zhouping Tang, and Dai-Shi Tian
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MICROGLIA , *IMMUNOREGULATION , *CENTRAL nervous system - Abstract
In the central nervous system (CNS), the myelin sheath ensures efficient interconnection between neurons and contributes to the regulation of the proper function of neuronal networks. The maintenance of myelin and the well-organized subtle process of myelin plasticity requires cooperation among myelin-forming cells, glial cells, and neural networks. The process of cooperation is fragile, and the balance is highly susceptible to disruption by microenvironment influences. Reactive microglia play a critical and complicated role in the demyelination and remyelination process. Recent studies have shown that the voltage-gated proton channel Hv1 is selectively expressed in microglia in CNS, which regulates intracellular pH and is involved in the production of reactive oxygen species, underlying multifaceted roles in maintaining microglia function. This paper begins by examining the molecular mechanisms of demyelination and emphasizes the crucial role of the microenvironment in demyelination. It focuses specifically on the role of Hv1 in myelin repair and its therapeutic potential in CNS demyelinating diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Microbiome-Glia Crosstalk: Bridging the Communication Divide in the Central Nervous System.
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Tabatabaee, Mitra
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CENTRAL nervous system , *NEUROGLIA , *HUMAN microbiota , *NEUROPLASTICITY , *NEUROLOGICAL disorders - Abstract
The traditional neuron-centric view of the central nervous system (CNS) is shifting toward recognizing the importance of communication between the neurons and the network of glial cells. This shift is leading to a more comprehensive understanding of how glial cells contribute to CNS function. Alongside this shift, recent discoveries have illuminated the significant role of the human microbiome, comprising trillions of microorganisms, mirroring the number of human cells in an individual. This paper delves into the multifaceted functions of neuroglia, or glial cells, which extend far beyond their traditional roles of supporting and protecting neurons. Neuroglia modulate synaptic activity, insulate axons, support neurogenesis and synaptic plasticity, respond to injury and inflammation, and engage in phagocytosis. Meanwhile, the microbiome, long overlooked, emerges as a crucial player in brain functionality akin to glial cells. This review aims to underscore the importance of the interaction between glial cells and resident microorganisms in shaping the development and function of the human brain, a concept that has been less studied. Through a comprehensive examination of existing literature, we discuss the mechanisms by which glial cells interface with the microbiome, offering insights into the contribution of this relationship to neural homeostasis and health. Furthermore, we discuss the implications of dysbiosis within this interaction, highlighting its potential contribution to neurological disorders and paving the way for novel therapeutic interventions targeting both glial cells and the microbiome. [ABSTRACT FROM AUTHOR]
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- 2024
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15. New Heterostilbene and Triazole Oximes as Potential CNS-Active and Cholinesterase-Targeted Therapeutics.
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Mlakić, Milena, Čadež, Tena, Šinko, Goran, Škorić, Irena, and Kovarik, Zrinka
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OXIMES , *OXIME derivatives , *BLOOD-brain barrier , *PARKINSON'S disease , *TRIAZOLES , *ORGANOPHOSPHORUS compounds , *CENTRAL nervous system - Abstract
New furan, thiophene, and triazole oximes were synthesized through several-step reaction paths to investigate their potential for the development of central nervous systems (CNS)-active and cholinesterase-targeted therapeutics in organophosphorus compound (OP) poisonings. Treating patients with acute OP poisoning is still a challenge despite the development of a large number of oxime compounds that should have the capacity to reactivate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The activity of these two enzymes, crucial for neurotransmission, is blocked by OP, which has the consequence of disturbing normal cholinergic nerve signal transduction in the peripheral and CNS, leading to a cholinergic crisis. The oximes in use have one or two pyridinium rings and cross the brain–blood barrier poorly due to the quaternary nitrogen. Following our recent study on 2-thienostilbene oximes, in this paper, we described the synthesis of 63 heterostilbene derivatives, of which 26 oximes were tested as inhibitors and reactivators of AChE and BChE inhibited by OP nerve agents–sarin and cyclosarin. While the majority of oximes were potent inhibitors of both enzymes in the micromolar range, we identified several oximes as BChE or AChE selective inhibitors with the potential for drug development. Furthermore, the oximes were poor reactivators of AChE; four heterocyclic derivatives reactivated cyclosarin-inhibited BChE up to 70%, and cis,trans-5 [2-((Z)-2-(5-((E)-(hydroxyimino)methyl)thiophen-2-yl)vinyl)benzonitrile] had a reactivation efficacy comparable to the standard oxime HI-6. In silico analysis and molecular docking studies, including molecular dynamics simulation, connected kinetic data to the structural features of these oximes and confirmed their productive interactions with the active site of cyclosarin-inhibited BChE. Based on inhibition and reactivation and their ADMET properties regarding lipophilicity, CNS activity, and hepatotoxicity, these compounds could be considered for further development of CNS-active reactivators in OP poisoning as well as cholinesterase-targeted therapeutics in neurodegenerative diseases such as Alzheimer's and Parkinson's. [ABSTRACT FROM AUTHOR]
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- 2024
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16. The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models.
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Furst, Liam M., Roussel, Enola M., Leung, Ryan F., George, Ankita M., Best, Sarah A., Whittle, James R., Firestein, Ron, Faux, Maree C., and Eisenstat, David D.
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ANIMAL models in research , *CANCER cell culture , *GLIOMAS , *BRAIN tumors , *GENE expression profiling , *CENTRAL nervous system - Abstract
Simple Summary: Pediatric high-grade gliomas are aggressive and deadly brain tumors that arise in children and are notoriously difficult to cure. Researchers require accurate methods, or "model systems," to better understand these tumors. Model systems include culturing cancer cells in a dish, observing how cancer cells grow in an animal brain, and growing cells in self-organizing 3D cultures called organoids, which more accurately resemble the brain. In this paper, we describe the molecular changes that these cancers acquire that cause them to be so aggressive, the development of past and present model systems, highlight the newest model systems being developed, and offer suggestions regarding how these model systems can be used in the future to develop better therapies for patients. Further, we outline the benefits and limitations of each model system to better guide researchers in the design of their experiments. Developing a variety of model systems that adequately and faithfully represent how tumors exist, progress, recur, and respond to treatment in a patient is absolutely essential to the eventual development of effective therapeutics. Therefore, investing in the continued development of these model systems is paramount to improving patient outcomes. Pediatric high-grade gliomas (pHGG) are malignant and usually fatal central nervous system (CNS) WHO Grade 4 tumors. The majority of pHGG consist of diffuse midline gliomas (DMG), H3.3 or H3.1 K27 altered, or diffuse hemispheric gliomas (DHG) (H3.3 G34-mutant). Due to diffuse tumor infiltration of eloquent brain areas, especially for DMG, surgery has often been limited and chemotherapy has not been effective, leaving fractionated radiation to the involved field as the current standard of care. pHGG has only been classified as molecularly distinct from adult HGG since 2012 through Next-Generation sequencing approaches, which have shown pHGG to be epigenetically regulated and specific tumor sub-types to be representative of dysregulated differentiating cells. To translate discovery research into novel therapies, improved pre-clinical models that more adequately represent the tumor biology of pHGG are required. This review will summarize the molecular characteristics of different pHGG sub-types, with a specific focus on histone K27M mutations and the dysregulated gene expression profiles arising from these mutations. Current and emerging pre-clinical models for pHGG will be discussed, including commonly used patient-derived cell lines and in vivo modeling techniques, encompassing patient-derived xenograft murine models and genetically engineered mouse models (GEMMs). Lastly, emerging techniques to model CNS tumors within a human brain environment using brain organoids through co-culture will be explored. As models that more reliably represent pHGG continue to be developed, targetable biological and genetic vulnerabilities in the disease will be more rapidly identified, leading to better treatments and improved clinical outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Exosomes in the Diagnosis of Neuropsychiatric Diseases: A Review.
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Wu, Song, Shang, Xinmiao, Guo, Meng, Su, Lei, and Wang, Jun
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EXOSOMES , *DIAGNOSIS , *EXTRACELLULAR vesicles , *LINCRNA , *CENTRAL nervous system - Abstract
Simple Summary: The diagnostic value of exosomes has been well recognized by researchers. The use of exosomal biomarkers as an adjunct diagnosis method not only improves diagnostic accuracy but can also be used for early diagnosis and disease progression differentiation, thus supporting personalized clinical treatment strategies for patients with neuropsychiatric disorders. In this paper, we summarize potential exosomal biomarkers in the diagnosis of neuropsychiatric diseases. Exosomes are 30–150 nm small extracellular vesicles (sEVs) which are highly stable and encapsulated by a phospholipid bilayer. Exosomes contain proteins, lipids, RNAs (mRNAs, microRNAs/miRNAs, long non-coding RNAs/lncRNAs), and DNA of their parent cell. In pathological conditions, the composition of exosomes is altered, making exosomes a potential source of biomarkers for disease diagnosis. Exosomes can cross the blood–brain barrier (BBB), which is an advantage for using exosomes in the diagnosis of central nervous system (CNS) diseases. Neuropsychiatric diseases belong to the CNS diseases, and many potential diagnostic markers have been identified for neuropsychiatric diseases. Here, we review the potential diagnostic markers of exosomes in neuropsychiatric diseases and discuss the potential application of exosomal biomarkers in the early and accurate diagnosis of these diseases. Additionally, we outline the limitations and future directions of exosomes in the diagnosis of neuropsychiatric diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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18. The role of annexins in central nervous system development and disease.
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White II, Zachary B., Nair, Sindhu, and Bredel, Markus
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CENTRAL nervous system diseases , *ANNEXINS , *CENTRAL nervous system viral diseases , *ALZHEIMER'S disease , *CELL membranes , *CENTRAL nervous system ,CENTRAL nervous system tumors - Abstract
Annexins, a group of Ca2+-dependent phospholipid-binding proteins, exert diverse roles in neuronal development, normal central nervous system (CNS) functioning, neurological disorders, and CNS tumors. This paper reviews the roles of individual annexins (A1-A13) in these contexts. Annexins possess unique structural and functional features, such as Ca2+-dependent binding to phospholipids, participating in membrane organization, and modulating cell signaling. They are implicated in various CNS processes, including endocytosis, exocytosis, and stabilization of plasma membranes. Annexins exhibit dynamic roles in neuronal development, influencing differentiation, proliferation, and synaptic formation in CNS tissues. Notably, annexins such as ANXA1 and ANXA2 play roles in apoptosis and blood-brain barrier (BBB) integrity. Neurological disorders, including Alzheimer's disease, multiple sclerosis, and depression, involve annexin dysregulation, influencing neuroinflammation, blood-brain barrier integrity, and stress responses. Moreover, annexins contribute to the pathogenesis of CNS tumors, either promoting or suppressing tumor growth, angiogenesis, and invasion. Annexin expression patterns vary across different CNS tumor types, providing potential prognostic markers and therapeutic targets. This review underscores the multifaceted roles of annexins in the CNS, highlighting their importance in normal functioning, disease progression, and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Multifunctional roles of γ-enolase in the central nervous system: more than a neuronal marker.
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Horvat, Selena, Kos, Janko, and Pišlar, Anja
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CENTRAL nervous system , *ALZHEIMER'S disease , *SCAFFOLD proteins , *NEURONS , *NEUROLOGICAL disorders - Abstract
Enolase, a multifunctional protein with diverse isoforms, has generally been recognized for its primary roles in glycolysis and gluconeogenesis. The shift in isoform expression from α-enolase to neuron-specific γ-enolase extends beyond its enzymatic role. Enolase is essential for neuronal survival, differentiation, and the maturation of neurons and glial cells in the central nervous system. Neuron-specific γ-enolase is a critical biomarker for neurodegenerative pathologies and neurological conditions, not only indicating disease but also participating in nerve cell formation and neuroprotection and exhibiting neurotrophic-like properties. These properties are precisely regulated by cysteine peptidase cathepsin X and scaffold protein γ1-syntrophin. Our findings suggest that γ-enolase, specifically its C-terminal part, may offer neuroprotective benefits against neurotoxicity seen in Alzheimer's and Parkinson's disease. Furthermore, although the therapeutic potential of γ-enolase seems promising, the effectiveness of enolase inhibitors is under debate. This paper reviews the research on the roles of γ-enolase in the central nervous system, especially in pathophysiological events and the regulation of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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20. The Scope, Trends, and Challenges of Neurosurgical Research in Nigeria: A Bibliometric Review.
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Ukachukwu, Alvan-Emeka K., Ogundeji, Olaniyi D., Abu-Bonsrah, Nancy, Still, Megan E.H., Trillo-Ordonez, Yesel, Oboh, Ehita N., Nischal, Shiva A., Deng, Di D., Ugorji, Chiazam, Seas, Andreas, Badejo, Oluwakemi A., Malomo, Toluyemi A., Nwaribe, Evaristus E., Oyemolade, Toyin A., Okere, Oghenekevwe E., Oboh, Ena, Waguia-Kouam, Romaric, Rahman, Raphia, Asemota, Isaac, and Reddy, Ramya
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BIBLIOMETRICS , *BRAIN injuries , *CENTRAL nervous system , *EVIDENCE-based management , *MEDICAL research , *CENTRAL nervous system injuries , *GINGIVAL recession - Abstract
This study investigates the scope, trends, and challenges of neurosurgical research in Nigeria since inception of the specialty in 1962. A bibliometric review of the neurosurgical literature from Nigeria was performed. Variables extracted included year and journal of publication, article topic, article type, research type, study design, article focus area, and limitations. Descriptive and quantitative analyses were performed for all variables. Trends of research publications were described in three periods: pioneering (1962–1981), recession (1982–2001), and resurgent (2002–2021). Of the 1023 included articles, 10.0% were published in the pioneering period, 9.2% in the recession period, and 80.8% in the resurgent period. Papers were predominantly published in World Neurosurgery (4.5%) and Nigerian Journal of Clinical Practice (4.0%). A total of 79.9% of the 4618 authors were from Nigerian institutions; 86.3% of the articles covered clinical research and were mainly focused on service delivery and epidemiology (89.9%). The most prominent topics were traumatic brain injury (25.8%) and central nervous system malignancy (21.4%). Only 4.4% of the publications received funding, mostly from agencies in the United States (31.7%). Barriers to neurosurgical research included lack of clinical databases (18.0%), increasing burden of disease (12.5%), and diagnostic challenges (12.4%). Neurosurgical research in Nigeria continues to grow due to increased training, workforce, and infrastructural improvements. Addressing the major challenges through establishment of research databases, development of evidence-based management guidelines, and increasing research training, funding and opportunities can increase research capacity in Nigeria. [ABSTRACT FROM AUTHOR]
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- 2024
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21. HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology.
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Thompson, Landon John-Patrick, Genovese, Jessica, Hong, Zhenzi, Singh, Meera Vir, and Singh, Vir Bahadur
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NEUROBEHAVIORAL disorders , *CELLULAR pathology , *BLOOD-brain barrier , *TAT protein , *HIV-1 glycoprotein 120 , *MOLECULAR pathology , *CENTRAL nervous system - Abstract
Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood–brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND. [ABSTRACT FROM AUTHOR]
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- 2024
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22. The Canadian Breast Cancer Symposium 2023 Meeting Report.
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Cil, Tulin, Boileau, Jean-François, Chia, Stephen, DeCoteau, MJ, Jerzak, Katarzyna J., Koch, Anne, Nixon, Nancy, Quan, May Lynn, Roberts, Amanda, and Brezden-Masley, Christine
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BREAST cancer , *MEDICAL personnel , *CENTRAL nervous system , *ONCOLOGIC surgery , *DUCTAL carcinoma , *CARCINOMA in situ , *EXPERIMENTAL medicine , *ONCOLOGY nursing - Abstract
On 15–16 June 2023, healthcare professionals and breast cancer patients and advocates from across Canada met in Toronto, Ontario, for the 2023 Canadian Breast Cancer Symposium (CBSC.). The CBSC. is a national, multidisciplinary event that occurs every 2 years with the goal of developing a personalized approach to the management of breast cancer in Canada. Experts provided state-of-the-art information to help optimally manage breast cancer patients, including etiology, prevention, diagnosis, experimental biology, and therapy of breast cancer and premalignant breast disease. The symposium also had the objectives of increasing communication and collaboration among breast cancer healthcare providers nationwide and providing a comprehensive and real-life review of the many facets of breast cancer. The sessions covered the patient voice, the top breast cancer papers from different disciplines in 2022, artificial intelligence in breast cancer, systemic therapy updates, the management of central nervous system metastases, multidisciplinary management of ductal carcinoma in situ, special populations, optimization-based individual prognostic factors, toxicity management of novel therapeutics, survivorship, and updates in surgical oncology. The key takeaways of these sessions have been summarized in this conference report. [ABSTRACT FROM AUTHOR]
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- 2024
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23. The Development of a New Patient-Reported Outcome Measure in Recessive Ataxias: The Person-Reported Ataxia Impact Scale.
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Tremblay, Marjolaine, Brais, Bernard, Asselin, Véronique, Buffet, Martin, Girard, André, Girard, Denis, Berbiche, Djamal, and Gagnon, Cynthia
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ATAXIA , *PERIPHERAL nervous system , *TEST validity , *NEUROLOGICAL disorders , *CENTRAL nervous system - Abstract
Autosomal recessive cerebellar ataxias (ARCAs) are inherited neurological disorders that can affect both the central and peripheral nervous systems. To assess the effects of interventions according to the perception of people affected, patient-reported outcome measures (PROMs) must be available. This paper presents the development process of the Person-Reported Ataxia Impact Scale (PRAIS), a new PROM in recessive ataxias, and the documentation of its content validity, interpretability, and construct validity (structural and discriminant). The development followed the PROMIS framework and the Food and Drug Administration guidelines. A mixed-method study design was used to develop the PROM. A systematic review of the literature, semistructured interviews, and discussion groups was conducted to constitute an item pool. Experts' consultation helped formulate items, and the questionnaire was sent online to be completed by people affected. Statistical analyses were performed to assess the structural and discriminant validity. A total of 125 people affected by recessive ataxia completed the questionnaire. The factor analysis confirmed the three components: physical functions and activities, mental functions, and social functions. The statistical analysis showed that it can discriminate between stages of mobility and level of autonomy. It showed very good levels of internal consistency (0.79 to 0.89). The Person-Reported Ataxia Impact Scale (PRAIS) is a 38-item questionnaire that assesses the manifestations and impacts of the disease according to the perception of people affected by recessive ataxia. It can be used in clinical and research settings. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Procyanidins and sensory nutrition; do procyanidins modulate homeostasis via astringent taste receptors?
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Osakabe, Naomi, Fushimi, Taiki, Fujii, Yasuyuki, and Calabrese, Vittorio
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TASTE receptors , *PROCYANIDINS , *HOMEOSTASIS , *NEUROENDOCRINE system , *CENTRAL nervous system , *NUTRITION - Abstract
Long-term intake of procyanidins has been suggested to reduce the risk of cardiovascular disease, dementia, and sensory function decline associated with aging. However, most of the ingested procyanidins are not absorbed and are excreted in the feces, so the mechanism of their beneficial impact is unknown. Procyanidins are the components of astringency in plant foods and their stimulation appears to be directly transmitted to the central nervous system via sensory nerves. Recent attention has been focused on the taste receptors expressed in the extra-oral gastrointestinal tract may regulate homeostasis via the neuroendocrine system. In this paper, we have reviewed recent findings on the relationship between the astringency of procyanidins and their bioregulatory effects. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Amide proton transfer-weighted imaging of the abdomen: Current progress and future directions.
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Sheng, Liuji, Yuan, Enyu, Yuan, Fang, and Song, Bin
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PROTONS , *MAGNETIZATION transfer , *ALZHEIMER'S disease , *CENTRAL nervous system , *STROKE - Abstract
The chemical exchange saturation transfer technique serves as a valuable tool for generating in vivo image contrast based on the content of various proton groups, including amide protons, amine protons, and aliphatic protons. Among these, amide proton transfer-weighted (APTw) imaging has seen extensive development as a means to assess the biochemical status of lesions. The exchange from saturated amide protons to bulk water protons during and following the saturation ratio frequency pulse contributes to detectable APT signals. While APTw imaging has garnered significant attention in the central nervous system, demonstrating noteworthy findings in cerebral neoplasia, stroke, and Alzheimer's disease over the past decade, its application in the abdomen has been a relatively recent progression. Notably, studies have explored its utility in hepatocellular carcinoma, prostate cancer, and cervical carcinoma within the abdominal context. Despite these advancements, there is a paucity of reviews on APTw imaging in abdominal applications. This paper aims to fill this gap by providing a concise overview of the fundamental theories underpinning APTw imaging. Additionally, we systematically summarize its diverse clinical applications in the abdomen, with a particular focus on the digestive and urogenital systems. Finally, the manuscript concludes by discussing technical limitations and factors influencing APTw imaging in abdominal applications, along with prospects for future research. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Annual Research Review: Neuroimmune network model of depression: a developmental perspective.
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Nusslock, Robin, Alloy, Lauren B., Brody, Gene H., and Miller, Gregory E.
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PREVENTION of mental depression , *BRAIN anatomy , *EMOTION regulation , *CELL communication , *MONOCYTES , *NEURAL pathways , *NEUROPHYSIOLOGY , *BRAIN , *CELLULAR immunity , *CENTRAL nervous system , *ANHEDONIA , *NEUROLOGICAL disorders , *NEUROBIOLOGY , *AUTOIMMUNE diseases , *INFLAMMATION , *DRUGS , *CYTOKINES , *MENTAL depression , *IMMUNITY , *NEUROTRANSMITTERS , *ADVERSE childhood experiences , *ADOLESCENCE ,BRAIN metabolism - Abstract
Depression is a serious public health problem, and adolescence is an 'age of risk' for the onset of Major Depressive Disorder. Recently, we and others have proposed neuroimmune network models that highlight bidirectional communication between the brain and the immune system in both mental and physical health, including depression. These models draw on research indicating that the cellular actors (particularly monocytes) and signaling molecules (particularly cytokines) that orchestrate inflammation in the periphery can directly modulate the structure and function of the brain. In the brain, inflammatory activity heightens sensitivity to threats in the cortico‐amygdala circuit, lowers sensitivity to rewards in the cortico‐striatal circuit, and alters executive control and emotion regulation in the prefrontal cortex. When dysregulated, and particularly under conditions of chronic stress, inflammation can generate feelings of dysphoria, distress, and anhedonia. This is proposed to initiate unhealthy, self‐medicating behaviors (e.g. substance use, poor diet) to manage the dysphoria, which further heighten inflammation. Over time, dysregulation in these brain circuits and the inflammatory response may compound each other to form a positive feedback loop, whereby dysregulation in one organ system exacerbates the other. We and others suggest that this neuroimmune dysregulation is a dynamic joint vulnerability for depression, particularly during adolescence. We have three goals for the present paper. First, we extend neuroimmune network models of mental and physical health to generate a developmental framework of risk for the onset of depression during adolescence. Second, we examine how a neuroimmune network perspective can help explain the high rates of comorbidity between depression and other psychiatric disorders across development, and multimorbidity between depression and stress‐related medical illnesses. Finally, we consider how identifying neuroimmune pathways to depression can facilitate a 'next generation' of behavioral and biological interventions that target neuroimmune signaling to treat, and ideally prevent, depression in youth and adolescents. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Electroacupuncture stimulation enhances the permeability of the blood-brain barrier: A systematic review and meta-analysis of preclinical evidence and possible mechanisms.
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Xu, Nuo, Gong, Peng, Xu, Shiting, Chen, Yangyun, Dai, Mengyuan, Jia, Zhaoxing, and Lin, Xianming
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BLOOD-brain barrier , *GLIAL fibrillary acidic protein , *ELECTROACUPUNCTURE , *VASCULAR endothelial growth factors , *NERVE growth factor , *CENTRAL nervous system - Abstract
An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful substances from entering brain tissue through blood circulation while providing protection for the central nervous system. It should be noted, however, that the intact BBB can be a barrier to the transport of most drugs into the brain via the conventional route of administration, which can prevent them from reaching effective concentrations for the treatment of disorders affecting the central nervous system. Electroacupuncture stimulation has been shown to be effective at opening the BBB in a series of experimental studies. This study systematically analyzes the possibility and mechanism by which electroacupuncture opens the BBB. In PubMed, Web of Science, VIP Database, Wanfang Database, and the Chinese National Knowledge Infrastructure, papers have been published for nearly 22 years aimed at opening the BBB and its associated structures. A comparison of EB content between electroacupuncture and control was selected as the primary outcome. There were also results on vascular endothelial growth factor (VEGF), nerve growth factor (NGF), P-Glycoprotein (P-gp), Matrix Metalloproteinase 9 (MMP-9), and glial fibrillary acidic protein (GFAP). We utilized Review Manager software analysis to analyze correlations between studies with a view to exploring the mechanisms of similarity. Evans Blue infiltration forest plot: pooled effect size of 2.04, 95% CI: 1.21 to 2.87, P < 0.01. These results indicate that electroacupuncture significantly increases EB penetration across the BBB. Most studies have reported that GFAP, MMP-9, and VEGF were upregulated after treatment. P-gp expression decreased as well. Electroacupuncture can open the BBB, and the sparse-dense wave is currently the most effective electroacupuncture frequency for opening the BBB. VEGF plays an important role in opening the BBB. It is also important to regulate the expression of MMP-9 and GFAP and inhibit the expression of P-gp. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Synthesis and Characterization of ZIF-90 Nanoparticles as Potential Brain Cancer Therapy.
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Monarca, Lorenzo, Ragonese, Francesco, Sabbatini, Paola, Caglioti, Concetta, Stamegna, Matteo, Palazzetti, Federico, Sportoletti, Paolo, Costantino, Ferdinando, and Fioretti, Bernard
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BRAIN cancer , *CANCER treatment , *NANOPARTICLES , *CENTRAL nervous system , *DRUG therapy - Abstract
Human glioblastoma is probably the most malignant and aggressive among cerebral tumors, of which it represents approximately 80% of the reported cases, with an overall survival rate that is quite low. Current therapies include surgery, chemotherapy, and radiotherapy, with associated consistent side effects and low efficacy. The hardness in reaching the site of action, and overcoming the blood–brain barrier, is a major limitation of pharmacological treatments. In this paper, we report the synthesis and characterization of ZIF-90 (ZIF, Zeolitic Imidazolate Framework) nanoparticles as putative carriers of anticancer drugs to the brain. In particular, we successfully evaluated the biocompatibility of these nanoparticles, their stability in body fluids, and their ability to uptake in U251 human glioblastoma cell lines. Furthermore, we managed to synthesize ZIF-90 particles loaded with berberine, an alkaloid reported as a possible effective adjuvant in the treatment of glioblastoma. These findings could suggest ZIF-90 as a possible new strategy for brain cancer therapy and to study the physiological processes present in the central nervous system. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Navigating the Nose-to-Brain Route: A Systematic Review on Lipid-Based Nanocarriers for Central Nervous System Disorders.
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Agosti, Edoardo, Zeppieri, Marco, Antonietti, Sara, Battaglia, Luigi, Ius, Tamara, Gagliano, Caterina, Fontanella, Marco Maria, and Panciani, Pier Paolo
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CENTRAL nervous system , *INTRANASAL administration , *NANOCARRIERS , *BLOOD-brain barrier , *ALZHEIMER'S disease , *INTRANASAL medication , *LIPIDS - Abstract
Background: The blood–brain barrier (BBB) regulates brain substance entry, posing challenges for treating brain diseases. Traditional methods face limitations, leading to the exploration of non-invasive intranasal drug delivery. This approach exploits the direct nose-to-brain connection, overcoming BBB restrictions. Intranasal delivery enhances drug bioavailability, reduces dosage, and minimizes systemic side effects. Notably, lipid nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, offer advantages like improved stability and controlled release. Their nanoscale size facilitates efficient drug loading, enhancing solubility and bioavailability. Tailored lipid compositions enable optimal drug release, which is crucial for chronic brain diseases. This review assesses lipid nanoparticles in treating neuro-oncological and neurodegenerative conditions, providing insights for effective nose-to-brain drug delivery. Methods: A systematic search was conducted across major medical databases (PubMed, Ovid MEDLINE, and Scopus) up to 6 January 2024. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "lipid nanoparticles", "intranasal administration", "neuro-oncological diseases", and "neurodegenerative disorders". This review consists of studies in vitro, in vivo, or ex vivo on the intranasal administration of lipid-based nanocarriers for the treatment of brain diseases. Results: Out of the initial 891 papers identified, 26 articles met the eligibility criteria after a rigorous analysis. The exclusion of 360 articles was due to reasons such as irrelevance, non-reporting selected outcomes, the article being a systematic literature review or meta-analysis, and lack of method/results details. This systematic literature review, focusing on nose-to-brain drug delivery via lipid-based nanocarriers for neuro-oncological, neurodegenerative, and other brain diseases, encompassed 60 studies. A temporal distribution analysis indicated a peak in research interest between 2018 and 2020 (28.3%), with a steady increase over time. Regarding drug categories, Alzheimer's disease was prominent (26.7%), followed by antiblastic drugs (25.0%). Among the 65 drugs investigated, Rivastigmine, Doxorubicin, and Carmustine were the most studied (5.0%), showcasing a diverse approach to neurological disorders. Notably, solid lipid nanoparticles (SLNs) were predominant (65.0%), followed by nanostructured lipid carriers (NLCs) (28.3%), highlighting their efficacy in intranasal drug delivery. Various lipids were employed, with glyceryl monostearate being prominent (20.0%), indicating preferences in formulation. Performance assessment assays were balanced, with in vivo studies taking precedence (43.3%), emphasizing the translation of findings to complex biological systems for potential clinical applications. Conclusions: This systematic review reveals the transformative potential of intranasal lipid nanoparticles in treating brain diseases, overcoming the BBB. Positive outcomes highlight the effectiveness of SLNs and NLCs, which are promising new approaches for ailments from AD to stroke and gliomas. While celebrating progress, addressing challenges like nanoparticle toxicity is also crucial. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Application of artificial intelligence in HE risk prediction modelling and research advances.
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HUANG Liangji-ang, MAO Dewen, ZHENG Jinghui, WANG Minggang, and YAO Chun
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ARTIFICIAL intelligence , *HEPATIC encephalopathy , *PREDICTION models , *CENTRAL nervous system , *BRAIN diseases - Abstract
Hepatic encephalopathy is a clinical syndrome of central nervous system dysfunction caused by liver insufficiency. It severely affects the quality of life of patients and may lead to death. Accurate prediction of the risk of developing hepatic encephalopathy is crucial for early intervention and treatment. In order to identify the risk of hepatic encephalopathy in patients in advance, many studies have been devoted to efforts to develop tools and methods to identify the risk of hepatic encephalopathy as early as possible, so as to develop preventive and early management strategies. Most conventional hepatic encephalopathy risk prediction models currently assess the probability of a patient developing hepatic encephalopathy by analysing factors such as clinical data and biochemical indicators, however, their accuracy, sensitivity and positive predictive value are not high. The application of artificial intelligence to clinical predictive modelling is a very hot and promising area, which can use large amounts of data and complex algorithms to improve the accuracy and efficiency of diagnosis and prognosis. To date, there have been few studies using AI techniques to predict hepatic encephalopathy. Therefore, this paper reviews the research progress of hepatic encephalopathy risk prediction models, and also discusses the prospect of AI application in hepatic encephalopathy risk prediction models. It also points out the challenges and future research directions of AI in HE risk prediction model research in order to promote the development and clinical application of hepatic encephalopathy risk prediction models. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Photobiomodulation for Neurodegenerative Diseases: A Scoping Review.
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Shen, Qi, Guo, Haoyun, and Yan, Yihua
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NEURODEGENERATION , *PHOTOBIOMODULATION therapy , *ALZHEIMER'S disease , *PARKINSON'S disease , *CENTRAL nervous system - Abstract
Neurodegenerative diseases involve the progressive dysfunction and loss of neurons in the central nervous system and thus present a significant challenge due to the absence of effective therapies for halting or reversing their progression. Based on the characteristics of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), which have prolonged incubation periods and protracted courses, exploring non-invasive physical therapy methods is essential for alleviating such diseases and ensuring that patients have an improved quality of life. Photobiomodulation (PBM) uses red and infrared light for therapeutic benefits and functions by stimulating, healing, regenerating, and protecting organizations at risk of injury, degradation, or death. Over the last two decades, PBM has gained widespread recognition as a non-invasive physical therapy method, showing efficacy in pain relief, anti-inflammatory responses, and tissue regeneration. Its application has expanded into the fields of neurology and psychiatry, where extensive research has been conducted. This paper presents a review and evaluation of studies investigating PBM in neurodegenerative diseases, with a specific emphasis on recent applications in AD and PD treatment for both animal and human subjects. Molecular mechanisms related to neuron damage and cognitive impairment are scrutinized, offering valuable insights into PBM's potential as a non-invasive therapeutic strategy. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury.
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Czyżewski, Wojciech, Mazurek, Marek, Sakwa, Leon, Szymoniuk, Michał, Pham, Jennifer, Pasierb, Barbara, Litak, Jakub, Czyżewska, Ewa, Turek, Michał, Piotrowski, Bartłomiej, Torres, Kamil, and Rola, Radosław
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BRAIN injuries , *DRUG target , *CONNEXIN 43 , *MONOCLONAL antibodies , *CENTRAL nervous system , *NEURAL stem cells , *NERVE tissue - Abstract
Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents of the central nervous system (CNS), in both the pathophysiology and possible rehabilitation of TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) and neuroprotective (A2) phenotypes. This paper elucidates the interactions of astrocytes with neurons, their role in neuroinflammation, and the potential for their therapeutic exploitation. Emphasized strategies encompass the utilization of endocannabinoid and calcium signaling pathways, hormone-based treatments like 17β-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, and the innovative technique of astrocyte transplantation as a means to repair damaged neural tissues. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Central nervous system clear cell meningioma: a systematic literature review.
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Liang, Qi, Ge, Pengfei, Liu, Yanhua, Zhu, Xiaoxi, Lu, Shan, Pan, Chengliang, Ji, Zhilin, Wang, Qingxuan, and Wang, Yubo
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CENTRAL nervous system , *MENINGIOMA , *PROGNOSIS , *SKULL base , *SYMPTOMS - Abstract
Clear cell meningiomas are a rare histological subtype of World Health Organization (WHO) grade II meningioma. Despite its relatively low frequency, clear cell meningioma has attracted considerable attention because of its unique pathological characteristics, clinical behavior, and challenging management considerations. The purpose of our systematic review is to provide clinicians with a better understanding of this rare disease. PubMed was searched for articles in the English language published from 1988 to 2023 June. The keywords were as follows: "clear cell meningioma," "clear cell" and "meningioma." We analyzed clinical manifestations, radiological manifestations, pathological features, comprehensive treatment strategies, and prognosis to determine the factors influencing recurrence-free survival (RFS). Recurrence-free survival curves of related factors were calculated by the Kaplan‒Meier method. The log-rank test and Cox univariate analysis were adopted to assess the intergroup differences and seek significant factors influencing prognosis and recurrence. Fifty-seven papers met the eligibility criteria, including 207 cases of clear cell meningioma (CCM), which were confirmed by postoperative pathology. The fifty-seven articles involved 84 (40.6%) males and 123 (59.4%) females. The average age at diagnosis was 27.9 years (range, 14 months to 84 years). Among the symptoms observed, headache, neurologic deficit, and hearing loss were the most commonly reported clinical manifestations. Most tumors (47.8%) were located in the skull base region. Most tumors showed significant enhancement, and homogeneous enhancement was more common. A total of 152 (74.1%) patients underwent gross total resection (GTR), and 53 (25.9%) patients underwent subtotal resection (STR). During the follow-up, the tumor recurred in 80 (39.4%) patients. The log-rank test and the Cox univariate analysis revealed that tumor resection range (GTR vs. STR) and adjuvant treatment (YES vs. NO) were significant predictors of recurrence-free survival (RFS). Clear cell meningioma is a rare type of meningioma with challenging diagnosis and therapy. The prognosis of this disease is different from that of regular meningiomas. Recurrence remains a possibility even after total tumor resection. We found that the surgical resection range and adjuvant treatment affected the recurrence period. This finding provides significant guidance for the treatment of clear cell meningioma. [ABSTRACT FROM AUTHOR]
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- 2024
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34. The modulatory role of gut microbiota on host behavior: exploring the interaction between the brain-gut axis and the neuroendocrine system.
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Awe, Temitope, Fasawe, Ayoola, Sawe, Caleb, Ogunware, Adedayo, Jamiu, Abdullahi Temitope, and Allen, Michael
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GUT microbiome , *NEUROENDOCRINE system , *MICROBIAL communities , *CENTRAL nervous system , *GASTROINTESTINAL system - Abstract
The brain-gut axis refers to the communication between the central nervous system and the gastrointestinal tract, with the gut microbiome playing a crucial role. While our understanding of the interaction between the gut microbiome and the host's physiology is still in its nascent stage, evidence suggests that the gut microbiota can indeed modulate host behavior. Understanding the specific mechanisms by which the gut microbiota community modulates the host's behavior remains the focus of present and future neuro-gastroenterology studies. This paper reviews several pieces of evidence from the literature on the impact of gut microbiota on host behavior across animal taxa. We explore the different pathways through which this modulation occurs, with the aim of deepening our understanding of the fascinating relationship between the gut microbiome and the central nervous system. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Pyroptosis in glioma: Current management and future application.
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Guo, Zeshang, Su, Zhenjin, Wei, Ying, Zhang, Xingmei, and Hong, Xinyu
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PYROPTOSIS , *GLIOMAS , *APOPTOSIS , *CYTOKINE release syndrome , *BLEPHAROPTOSIS , *CENTRAL nervous system - Abstract
Summary: Glioma, the predominant form of central nervous system (CNS) malignancies, presents a significant challenge due to its high prevalence and low 5‐year survival rate. The efficacy of current treatment methods is limited by the presence of the blood–brain barrier, the immunosuppressive microenvironment, and other factors. Immunotherapy has emerged as a promising approach, as it can overcome the blood–brain barrier. A tumor's immune privilege, which is induced by an immunosuppressive environment, constricts immunotherapy's clinical impact in glioma. Pyroptosis, a programmed cell death mechanism facilitated by gasdermins, plays a significant role in the management of glioma. Its ability to initiate and regulate tumor occurrence, progression, and metastasis is well‐established. However, it is crucial to note that uncontrolled or excessive cell death can result in tissue damage, acute inflammation, and cytokine release syndrome, thereby potentially promoting tumor advancement or recurrence. This paper aims to elucidate the molecular pathways involved in pyroptosis and subsequently discuss its induction in cancer therapy. In addition, the current treatment methods of glioma and the use of pyroptosis in these treatments are introduced. It is hoped to provide more ideas for the treatment of glioma. [ABSTRACT FROM AUTHOR]
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- 2024
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36. From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC).
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Fabbri, Laura, Di Federico, Alessandro, Astore, Martina, Marchiori, Virginia, Rejtano, Agnese, Seminerio, Renata, Gelsomino, Francesco, and De Giglio, Andrea
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NON-small-cell lung carcinoma , *CRIZOTINIB , *CLINICAL trials , *ANAPLASTIC large-cell lymphoma , *BLOOD-brain barrier , *BRAIN diseases - Abstract
Following the results of the CROWN phase III trial, the third-generation macrocyclic ALK inhibitor lorlatinib has been introduced as a salvage option after the failure of a first-line TKI in ALK-rearranged NSCLC, while its precise role in the therapeutic algorithm of ROS1 positive disease is still to be completely defined. The ability to overcome acquired resistance to prior generation TKIs (alectinib, brigatinib, ceritinib, and crizotinib) and the high intracranial activity in brain metastatic disease thanks to increased blood–brain barrier penetration are the reasons for the growing popularity and interest in this molecule. Nevertheless, the major vulnerability of this drug resides in a peculiar profile of related collateral events, with neurological impairment being the most conflicting and debated clinical issue. The cognitive safety concern, the susceptibility to heterogeneous resistance pathways, and the absence of a valid alternative in the second line are strongly jeopardizing a potential paradigm shift in this oncogene-addicted disease. So, when prescribing lorlatinib, clinicians must face two diametrically opposed characteristics: a great therapeutic potential without the intrinsic limitations of its precursor TKIs, a cytotoxic activity threatened by suboptimal tolerability, and the unavoidable onset of resistance mechanisms we cannot properly manage yet. In this paper, we give a critical point of view on the stepwise introduction of this promising drug into clinical practice, starting from its innovative molecular and biochemical properties to intriguing future developments, without forgetting its weaknesses. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Exploring the Central Mechanisms of Botulinum Toxin in Parkinson's Disease: A Systematic Review from Animal Models to Human Evidence.
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Cutrona, Carolina, Marchet, Francesco, Costanzo, Matteo, De Bartolo, Maria Ilenia, Leodori, Giorgio, Ferrazzano, Gina, Conte, Antonella, Fabbrini, Giovanni, Berardelli, Alfredo, and Belvisi, Daniele
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BOTULINUM A toxins , *BOTULINUM toxin , *PARKINSON'S disease , *ANIMAL models in research , *CENTRAL nervous system , *SENSORIMOTOR integration - Abstract
Botulinum toxin (BoNT) is an effective and safe therapy for the symptomatic treatment of several neurological disturbances. An important line of research has provided numerous pieces of evidence about the mechanisms of action of BoNT in the central nervous system, especially in the context of dystonia and spasticity. However, only a few studies focused on the possible central effects of BoNT in Parkinson's disease (PD). We performed a systematic review to describe and discuss the evidence from studies focused on possible central effects of BoNT in PD animal models and PD patients. To this aim, a literature search in PubMed and SCOPUS was performed in May 2023. The records were screened according to title and abstract by two independent reviewers and relevant articles were selected for full-text review. Most of the papers highlighted by our review report that the intrastriatal administration of BoNT, through local anticholinergic action and the remodulation of striatal compensatory mechanisms secondary to dopaminergic denervation, induces an improvement in motor and non-motor symptoms in the absence of neuronal loss in animal models of PD. In human subjects, the data are scarce: a single neurophysiological study in tremulous PD patients found that the change in tremor severity after peripheral BoNT administration was associated with improved sensory–motor integration and intracortical inhibition measures. Further clinical, neurophysiological, and neuroimaging studies are necessary to clarify the possible central effects of BoNT in PD. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Leptin and energy balance: exploring Leptin's role in the regulation of energy intake and energy expenditure.
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Tucker, Jessica A.L., Bornath, Derek P.D., McCarthy, Seth F., and Hazell, Tom J.
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LEPTIN receptors , *BRAIN-derived neurotrophic factor , *LEPTIN , *GHRELIN receptors , *PEPTIDES , *AMYLIN , *CENTRAL nervous system , *GHRELIN - Abstract
Leptin is a tonic appetite-regulating hormone, which is integral for the long-term regulation of energy balance. The current evidence suggests that the typical orexigenic or anorexigenic response of many of these appetite-regulating hormones, most notably ghrelin and cholecystokinin (CCK), require leptin to function whereas glucagon-like peptide-1 (GLP-1) is required for leptin to function, and these responses are altered when leptin injection or gene therapy is administered in combination with these same hormones or respective agonists. The appetite-regulatory pathway is complex, thus peptide tyrosine tyrosine (PYY), brain-derived neurotrophic factor (BDNF), orexin-A (OXA), and amylin also maintain ties to leptin, however these are less well understood. While reviews to date have focused on the existing relationships between leptin and the various neuropeptide modulators of appetite within the central nervous system (CNS) or it's role in thermogenesis, no review paper has synthesised the information regarding the interactions between appetite-regulating hormones and how leptin as a chronic regulator of energy balance can influence the acute appetite-regulatory response. Current evidence suggests that potential relationships exist between leptin and the circulating peripheral appetite hormones ghrelin, GLP-1, CCK, OXA and amylin to exhibit either synergistic or opposing effects on appetite inhibition. Though more research is warranted, leptin appears to be integral in both energy intake and energy expenditure. More specifically, functional leptin receptors appear to play an essential role in these processes. [ABSTRACT FROM AUTHOR]
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- 2024
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39. Isolation, structure, biological activity and application progress of ginseng polysaccharides from the Araliaceae family.
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Liu, Silu, Geng, Jianan, Chen, Weijia, Zong, Ying, Zhao, Yan, Du, Rui, and He, Zhongmei
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AMERICAN ginseng , *CHINESE medicine , *BIOMACROMOLECULES , *CENTRAL nervous system , *GINSENG , *POLYSACCHARIDES - Abstract
Phytopolysaccharides are a class of natural macromolecules with a range of biological activities. Ginseng, red ginseng, American ginseng, and Panax notoginseng are all members of the Araliaceae family. They are known to contain a variety of medicinal properties and are typically rich in a wide range of medicinal values. Polysaccharides represent is one of the principal active ingredients in the aforementioned plants. However, there is a paucity of detailed reports on the separation methods, structural characteristics and comparison of various pharmacological effects of these polysaccharides. This paper presents a review of the latest research reports on ginseng, red ginseng, American ginseng and ginseng polysaccharides. The differences in extraction, separation, purification, structural characterization, and pharmacological activities of the four polysaccharides are compared and clarified. Upon examination of the current research literature, it becomes evident that the extraction and separation processes of the four polysaccharides are highly similar. Modern pharmacological studies have corroborated the multiple biological activities of these polysaccharides. These activities encompass a range of beneficial effects, including antioxidant stress injury, fatigue reduction, tumor inhibition, depression alleviation, regulation of intestinal flora, immunomodulation, diabetes management, central nervous system protection, anti-aging, and improvement of skin health. This paper presents a review of studies on the extraction, purification, characterization, and bioactivities of four natural plant ginseng polysaccharides. Furthermore, the review presents the most recent research findings on their pharmacological activities. The information provides a theoretical basis for the future application of natural plant polysaccharides and offers a new perspective for the in-depth development of the medicinal value of ginseng in the clinical practice of traditional Chinese medicine. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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40. Potential clinical applications of current and future oral forms of desmopressin (Review).
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Everaert, Karel, Holm-Larsen, Tove, Bou Kheir, George, Rottey, Sylvie, Weiss, Jeffrey P., Vande Walle, Johan, Kabarriti, Abdo E., Dossche, Lien, Hervé, François, Spinoit, Anne-Françoise, Nørgaard, Jens Peter, and Juul, Kristian Vinter
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DESMOPRESSIN , *RENAL colic , *CLINICAL medicine , *CENTRAL nervous system , *OVERACTIVE bladder - Abstract
Desmopressin is a synthetic analogue of vasopressin and a selective vasopressin receptor 2 agonist. It was first synthesised in 1967 and utilised for its antidiuretic properties. It is also used in bleeding disorders to enhance clotting. Other potential uses of the drug have been reported. The present review aims to provide a broad overview of the literature on potential further uses of oral forms of desmopressin. Key therapeutic areas of interest were identified based on known physiological activities/targets of desmopressin or reports of an effect of desmopressin in the literature. The feasibility of adequate dosing with oral forms of the drug was also considered. Systematic literature searches were carried out using the silvi.ai software for the identified areas, and summaries of available papers were included in tables and discussed. The results of the searches showed that desmopressin has been investigated for its efficacy in a number of areas, including bleeding control, renal colic, the central nervous system and oncology. Evidence suggests that oral desmopressin may have the potential to be of clinical benefit for renal colic and bleeding control in particular. However, further research is needed to clarify its effect in these areas, including randomised controlled studies and studies specifically of oral formulations (and doses). Further research may also yield findings for cancer, cognition and overactive bladder. [ABSTRACT FROM AUTHOR]
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- 2024
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41. CLDN5: From structure and regulation to roles in tumors and other diseases beyond CNS disorders.
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Ling, Yao, Kang, Xinxin, Yi, Ying, Feng, Shenao, Ma, Guanshen, and Qu, Huinan
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CENTRAL nervous system , *RESPIRATORY diseases , *INTESTINAL diseases , *TIGHT junctions , *HEART , *TUMORS , *BLOOD-brain barrier - Abstract
Claudin-5 (CLDN5) is an essential component of tight junctions (TJs) and is critical for the integrity of the blood-brain barrier (BBB), ensuring homeostasis and protection from damage to the central nervous system (CNS). Currently, many researchers have summarized the role and mechanisms of CLDN5 in CNS diseases. However, it is noteworthy that CLDN5 also plays a significant role in tumor growth and metastasis. In addition, abnormal CLDN5 expression is involved in the development of respiratory diseases, intestinal diseases, cardiac diseases, and diabetic ocular complications. This paper aims to review the structure, expression, and regulation of CLDN5, focusing on its role in tumors, including its expression and regulation, effects on malignant phenotypes, and clinical significance. Furthermore, this paper will provide an overview of the role and mechanisms of CLDN5 in respiratory diseases, intestinal diseases, cardiac diseases, and diabetic ocular complications. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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42. An entropy-based membership approach on type-II fuzzy set (EMT2FCM) for biomedical image segmentation.
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Bose, Ananya, Maulik, Ujjwal, and Sarkar, Anasua
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FUZZY sets , *MAGNETIC resonance imaging , *IMAGE segmentation , *MEMBERSHIP functions (Fuzzy logic) , *CENTRAL nervous system , *BRAIN imaging - Abstract
Medical image segmentation is a challenging task owing to its aliasing artifacts, existence of mixed pixels, interference of noise and blurring effect, etc. The brain and the spinal cord together constitute the Central Nervous System (CNS), with the brain being the most complex component. Brain segmentation is crucial for surgical planning, disease detection, and therapeutic interventions. A unique entropy based soft clustering approach (EMT2FCM) for the brain MRI imaging on both real and simulated datasets is proposed in this paper. This paper presents a refined version of the type-2 Fuzzy C-Means (FCM) technique (EMT2FCM) for isolating diverse tissues in Magnetic Resonance (MR) brain images, achieved through an enhanced entropy-based membership function. Difficulty in edge detection occurs due to the vagueness caused by mixed pixels. To overcome the problem with mixed pixels a new membership function proposal has been given. EMT2FCM, i.e., fuzzy membership function with Shannon's entropy-based variation, is able to handle uncertainty and vagueness in images offered by mixed pixels, by implementing new distance criteria modification for the calculation of optimum cluster. The approach has been validated using datasets from BRAINWEB (simulated) and IBSR (real-life). Following the deployment of our new algorithm, we assessed its performance using six observation criteria. The results demonstrated significant improvements in clustering performance, as evidenced by enhanced Mean Squared Error (MSE), Dice Index, and Jaccard Index, Accuracy, Sensitivity and Partition Indices validation measures. The evaluation of EMT2FCM in comparison to other state-of-the-art methods is established to reduce segmentation errors significantly. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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43. Saltiness perception mechanism and salt reduction strategies in food.
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Yang, Siqi, Zheng, Baodong, Huang, Luyao, Zhang, Yi, and Zeng, Hongliang
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TASTE perception , *SALT , *ODORS , *SALT crystals , *TASTE buds , *FOOD texture , *CENTRAL nervous system - Abstract
Globally, dietary risk factors cause far more deaths and disability-adjusted life years than any other risk, including smoking. Although salt, sugar and fat have been the main foci of dietary policy debates over the past two decades, the major contributing factor is high salt intake, which causes more than 2% global annual mortality, amounting to more than 160 million people. These shocking statistics highlight the necessity of reducing the salt content of food, which is a key challenge for the food industry. Here, the mechanisms by which taste cells, brain and organs perceive saltiness are reviewed. Then, we summarize the research progress of several salt reduction strategies and assessment methods for saltiness. NaCl is transmitted through amiloride-sensitive pathway and amiloride-insensitive pathway. The electrical signal generated by the salt receptors is transmitted to the central nervous system and saltiness perception can be enhanced by interaction with odor and taste substances. Strategies for reducing salt intake include salt substitutes, modifying food texture, changing the shape and size of salt crystals, modifying processing technology and multi-sensory synergism in perception, which enhance the perceived intensity of saltiness without otherwise affecting taste. To evaluate saltiness, most established animal models involve mice. In addition to taste bud cells in vivo , cell models in vitro are being explored. This review provides a scientific basis for the practice of salt reduction in the food industry and a theoretical basis for the evaluation of saltiness perception. • Salt reduction policies implemented in different countries and regions are summarized. • The mechanisms by which taste cells, brain and organs perceive saltiness are reviewed. • This paper reviews strategies for salt reduction in the food industry. • In vivo and in vitro models for evaluating saltiness are reviewed. [ABSTRACT FROM AUTHOR]
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- 2024
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44. The progress of small molecules against cannabinoid 2 receptor (CB2R).
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Zhang, Qinying, Zhao, Ying, Wu, Jianan, Zhong, Wanting, Huang, Wenhai, and Pan, Youlu
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SMALL molecules , *G protein coupled receptors , *CENTRAL nervous system , *CANNABINOID receptors , *NEURALGIA - Abstract
[Display omitted] The two subtypes of cannabinoid receptors (CBR), namely CB 1 R and CB 2 R, belong to the G protein-coupled receptor (GPCR) superfamily and are confirmed as potential therapeutic targets for a variety of diseases such as inflammation, neuropathic pain, and immune-related disorders. Since CB 1 R is mainly distributed in the central nervous system (CNS), it could produce severe psychiatric adverse reactions and addiction. In contrast, CB 2 R are predominantly distributed in the peripheral immune system with minimal CNS-related side effects. Therefore, more attention has been devoted to the discovery of CB 2 R ligands. In view of the favorable profile of CB 2 R, many high-binding affinity and selectivity CB 2 R ligands have been developed recently. This paper reviews recent research progress on CB 2 R ligands, including endogenous CB 2 R ligands, natural compounds, and novel small molecules, in order to provide a reference for subsequent CB 2 R ligand development. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Nanotechnology in the diagnostic and therapy for Alzheimer's disease.
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Panghal, Archna and Flora, S.J.S.
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ALZHEIMER'S disease , *NANOMEDICINE , *NANOTECHNOLOGY , *DRUG delivery systems , *CENTRAL nervous system , *TARGETED drug delivery - Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by β-amyloid plaque, intraneuronal tangles, significant neuronal loss and cognitive deficit. Treatment in the early stages of the disease is crucial for preventing or perhaps reversing the neurodegeneration in the AD cases. However, none of the current diagnostic procedures are capable of early diagnosis of AD. Further, the available treatments merely provide symptomatic alleviation in AD and do not address the underlying illness. Therefore, there is no permanent cure for AD currently. Better therapeutic outcomes need the optimum drug concentration in the central nervous system (CNS) by traversing blood-brain-barrier (BBB). Nanotechnology offers enormous promise to transform the treatment and diagnostics of neurodegenerative diseases. Nanotechnology based diagnostic tools, drug delivery systems and theragnostic are capable of highly sensitive molecular detection, effective drug targeting and their combination. Significant work has been done in this area over the last decade and prospective results have been obtained in AD therapy. This review explores the various applications of nanotechnology in addressing the varied facets of AD, ranging from early detection to therapeutic interventions. This review also looks at how nanotechnology can help with the development of disease-modifying medicines, such as the delivery of anti-amyloid, anti-tau, cholinesterase inhibitors, antioxidants and hormonal drugs. In conclusion, this paper discusses the role of nanotechnology in the early detection of AD, effective drug targeting to the CNS and theragnostic applications in the management of AD. • Nanotechnology as novel strategy for Alzheimer's disease • Significant delivery of anti-amyloid, anti-tau, cholinesterase inhib.itors, antioxidants and hormonal drugs. • Nanosensor, an effective tool in the early detection of AD. • Safety and ethical concern to be addressed. [ABSTRACT FROM AUTHOR]
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- 2024
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46. Study of low-frequency spectroscopic characteristics of γ-aminobutyric acid with THz and low-wavenumber Raman spectroscopy.
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Ge, Meilan, Wang, Yuye, Zhang, Feng, Wang, Zelong, Li, Haibin, Xu, Degang, and Yao, Jianquan
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RAMAN spectroscopy , *TERAHERTZ spectroscopy , *CENTRAL nervous system , *ABSORPTION coefficients , *REFRACTIVE index - Abstract
[Display omitted] • It proposed a detection method for the structural and quantitative analysis of GABA. • The limit of detection for GABA could reach up to 0.428% based on its THz spectrum. • The calculated results were in good agreement with their experimental results. • The vibrational motions of each THz and Raman peaks were quantitatively decomposed. γ-aminobutyric (GABA) is the most important inhibitory neurotransmitier in vertebrate central nervous systems. The content level of GABA is related to the different degree of malignancy gliomas. Thus, it can be considered a promising glioma biomarker. In this paper, the spectroscopic properties of GABA have been characterized by combining the THz spectroscopy with low-wavenumber Raman spectroscopy. The experimental results showed that, GABA exhibited three absorption peaks and three refractive index peaks in the range of 0.6–2.1 THz. The limit of detection can reach up to 0.428 % based on the absorption coefficient at the peak of 2.04 THz. Moreover, the low-wavenumber Raman spectrum of GABA showed seven characteristic peaks at 41.0, 50.8, 58.8, 77.2, 98.8, 115.6, 141.2 cm−1 in 0–150 cm−1 region. Moreover, the THz and low-wavenumber theoretical spectra of GABA were simulated with solid-state density function theory, respectively. The calculated results were in good agreement with the experimental observations. On the basis of calculated result, the vibrational motions of each THz and Raman characteristic modes were quantitatively decomposed by analytical mode-decoupling method, where the contribution percentages of external translation, external librations and intramolecular vibration of each vibration modes were analyzed Furthermore, the low-frequency characteristics of GABA was analyzed by combining the THz and low-wavenumber Raman spectroscopy. It is beneficial for the structural information analysis and quantitative identification of biomarker GABA in early stage diagnosis of glioma. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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47. Active ingredients of Chinese medicine with immunomodulatory properties: NF-κB pathway and Parkinson's disease.
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Song, Jingjing, Zhao, Yang, Shan, Xiaoqian, Luo, Yongyin, Hao, Nan, and Zhao, Lan
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PARKINSON'S disease , *CHINESE medicine , *DOPAMINE receptors , *APOMORPHINE , *CENTRAL nervous system , *DOPAMINERGIC neurons , *PHYTOCHEMICALS , *NEUROGLIA - Abstract
[Display omitted] • Neuroprotective and neurotoxic effects of glial cells. • Inhibition of NF-κB pathway activation may be the key to treating Parkinson's disease. • Active ingredients of Chinese medicine can inhibit neuroinflammation through the NF-κB pathway. • Active ingredients of Chinese medicine are safe and inexpensive and are expected to be beneficial treatments for Parkinson's disease. Parkinson's disease (PD) is a neurodegenerative disease with a complex pathogenesis and no cure. Persistent neuroinflammation plays an important role in the development of PD, and activation of microglia and astrocytes within the central nervous system leads to an inflammatory response and production of pro-inflammatory factors, and activation of NF-κB is key to neuroglial activation in chronic inflammation in PD and a hallmark of the onset of neuroinflammatory disease. Therefore, inhibiting NF-κB activation to prevent further loss of dopaminergic nerves is a more effective means of treating PD. It has been found that an increasing number of active ingredients in Chinese medicines, such as flavonoids, alkaloids, saponins, terpenoids, phenols and phenylpropanoids, have anti-inflammatory properties that can regulate neuroglia cell activation and ameliorate neuroinflammation through the NF-κB pathway, and increase dopamine release or protect dopaminergic neurons for neuroprotection to improve behavioural dysfunction in PD. The active ingredients of traditional Chinese medicine are expected to be good candidates for the treatment of PD, as they provide holistic regulation through multi-targeting and multi-level effects, and are safe, inexpensive and readily available. Therefore, this paper summarises that the active ingredients of some relevant Chinese medicines ameliorate the symptoms of PD and delay the development of PD by inhibiting glial cell-mediated neuroinflammation through the NF-κB pathway, which may provide new ideas for exploring the molecular mechanism of PD pathogenesis and developing new anti-PD drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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