keyword
https://read.qxmd.com/read/38649596/structural-insights-into-the-potential-binding-sites-of-cathepsin-d-using-molecular-modelling-techniques
#1
JOURNAL ARTICLE
Subodh A Kamble, Sagar S Barale, Ali Abdulmawjood Mohammed, Sneha B Paymal, Nitin M Naik, Kailas D Sonawane
Alzheimer's disease (AD) is the most prevalent type of dementia caused by the accumulation of amyloid beta (Aβ) peptides. The extracellular deposition of Aβ peptides in human AD brain causes neuronal death. Therefore, it has been found that Aβ peptide degradation is a possible therapeutic target for AD. CathD has been known to breakdown amyloid beta peptides. However, the structural role of CathD is not yet clear. Hence, for the purpose of gaining a deeper comprehension of the structure of CathD, the present computational investigation was performed using virtual screening technique to predict CathD's active site residues and substrate binding mode...
April 22, 2024: Amino Acids
https://read.qxmd.com/read/38648940/zinc-utilization-by-microglia-in-alzheimer-s-disease
#2
REVIEW
Daniel C Shippy, Sophia F Oliai, Tyler K Ulland
Alzheimer's disease (AD) is the most common form of dementia defined by two key pathological characteristics in the brain, amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Microglia, the primary innate immune cells of the central nervous system (CNS), provide neuroprotection through Aβ and tau clearance, but may also be neurotoxic by promoting neuroinflammation to exacerbate Aβ and tau pathogenesis in AD. Recent studies have demonstrated the importance of microglial utilization of nutrients and trace metals in controlling their activation and effector functions...
April 20, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38648870/aluminum-and-abc-transporter-activity
#3
JOURNAL ARTICLE
Goezde Oezen, Lisa Kraus, Eva-Maria Schentarra, Jan Stephan Bolten, Joerg Huwyler, Gert Fricker
Aluminum is the third most common element on Earth´s crust and despite its wide use in our workaday life it has been associated with several health risks after overexposure. In the present study the impact of aluminum salts upon ABC transporter activity was studied in the P-GP-expressing human blood-brain barrier cell line hCMEC/D3, in MDCKII cells overexpressing BCRP and MRP2, respectively, and in freshly isolated, functionally intact kidney tubules from Atlantic killifish (Fundulus heteroclitus), which express the analog ABC transporters, P-gp, Bcrp and Mrp2...
April 20, 2024: Environmental Toxicology and Pharmacology
https://read.qxmd.com/read/38643150/azgp1-in-pomc-neurons-modulates-energy-homeostasis-and-metabolism-through-leptin-mediated-stat3-phosphorylation
#4
JOURNAL ARTICLE
Sheng Qiu, Qinan Wu, Hao Wang, Dongfang Liu, Chen Chen, Zhiming Zhu, Hongting Zheng, Gangyi Yang, Ling Li, Mengliu Yang
Zinc-alpha2-glycoprotein (AZGP1) has been implicated in peripheral metabolism; however, its role in regulating energy metabolism in the brain, particularly in POMC neurons, remains unknown. Here, we show that AZGP1 in POMC neurons plays a crucial role in controlling whole-body metabolism. POMC neuron-specific overexpression of Azgp1 under high-fat diet conditions reduces energy intake, raises energy expenditure, elevates peripheral tissue leptin and insulin sensitivity, alleviates liver steatosis, and promotes adipose tissue browning...
April 20, 2024: Nature Communications
https://read.qxmd.com/read/38635860/vitamin-d3-and-zinc-supplements-augment-the-antimanic-efficacy-of-lithium-and-olanzapine-treatments-in-an-animal-model-of-mania
#5
JOURNAL ARTICLE
Aya A S Huzayyin, Michael K Ibrahim, Nahed M A Hassanein, Helmy M S Ahmed
Objective: Bipolar disorder (BD) is a challenging psychiatric disorder and a complex disease. The associated reduction in serum vitamin D3 (VitD3 ) levels in BD patients and the contribution of zinc (Zn) to the treatment, along with the severe side effects of lithium (Li) treatment, were encouraging to assess the efficacy of different correlated combinations of therapeutic/nutraceutical treatments such as olanzapine (Oln), VitD3, and Zn against Li. Methods: Mania was induced in C57BL/6 mice by administering methylphenidate (MPH) for 14 consecutive days...
April 18, 2024: Nutritional Neuroscience
https://read.qxmd.com/read/38631990/a-phosphodiesterase-4-pde4-inhibitor-amlexanox-reduces-neuroinflammation-and-neuronal-death-after-pilocarpine-induced-seizure
#6
JOURNAL ARTICLE
Hyun Wook Yang, A Ra Kho, Song Hee Lee, Beom Seok Kang, Min Kyu Park, Chang Jun Lee, Se Wan Park, Seo Young Woo, Dong Yeon Kim, Hyun Ho Jung, Bo Young Choi, Won Il Yang, Hong Ki Song, Hui Chul Choi, Jin Kyu Park, Sang Won Suh
Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses...
April 16, 2024: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://read.qxmd.com/read/38614160/the-emerging-role-of-fatty-acid-binding-protein-7-fabp7-in-cancers
#7
REVIEW
William George Warren, Myles Osborn, Andy Yates, Saoirse E O'Sullivan
Fatty acid binding protein 7 (FABP7) is an intracellular protein involved in the uptake, transportation, metabolism, and storage of fatty acids (FAs). FABP7 is upregulated up to 20-fold in multiple cancers, usually correlated with poor prognosis. FABP7 silencing or pharmacological inhibition suggest FABP7 promotes cell growth, migration, invasion, colony and spheroid formation/increased size, lipid uptake, and lipid droplet formation. Xenograft studies show that suppression of FABP7 inhibits tumour formation and tumour growth, and improves host survival...
April 11, 2024: Drug Discovery Today
https://read.qxmd.com/read/38613466/molecular-pathway-of-pancreatic-cancer-associated-neuropathic-pain
#8
REVIEW
Shweta Subhash Giri, Alok Shiomurti Tripathi, Pınar Erkekoğlu, Magdi E A Zaki
The pancreas is a heterocrine gland that has both exocrine and endocrine parts. Most pancreatic cancer begins in the cells that line the ducts of the pancreas and is called pancreatic ductal adenocarcinoma (PDAC). PDAC is the most encountered pancreatic cancer type. One of the most important characteristic features of PDAC is neuropathy which is primarily due to perineural invasion (PNI). PNI develops tumor microenvironment which includes overexpression of fibroblasts cells, macrophages, as well as angiogenesis which can be responsible for neuropathy pain...
April 2024: Journal of Biochemical and Molecular Toxicology
https://read.qxmd.com/read/38613125/biomarkers-of-brain-dysfunction-in-perinatal-iron-deficiency
#9
REVIEW
Raghavendra B Rao
Iron deficiency in the fetal and neonatal period (perinatal iron deficiency) bodes poorly for neurodevelopment. Given its common occurrence and the negative impact on brain development, a screening and treatment strategy that is focused on optimizing brain development in perinatal iron deficiency is necessary. Pediatric societies currently recommend a universal iron supplementation strategy for full-term and preterm infants that does not consider individual variation in body iron status and thus could lead to undertreatment or overtreatment...
April 8, 2024: Nutrients
https://read.qxmd.com/read/38609031/association-of-impulsive-behavior-and-cerebrospinal-fluid-plasma-oxidation-and-antioxidation-ratio-in-chinese-men
#10
JOURNAL ARTICLE
Xiaoning Jiang, Xiaoli Han, Tiantian Kong, Yan Wu, Ligang Shan, Zhuqing Yang, Yanlong Liu, Fan Wang
OBJECTIVES: Impulsive behavior is the precursor of many psychiatric and neurological conditions. High levels of impulsive behavior will increase health risk behavior and related injuries. Impulsive behavior is produced and regulated by central and peripheral biological factors, and oxidative stress (OS) can aggravate it. However, previous studies only showed that impulsive behavior was related to the level of the peripheral OS. Therefore, this study aims to clarify the relationship between OS and impulsive behavior in the brain and peripheral blood...
April 10, 2024: Brain Research
https://read.qxmd.com/read/38606777/apilimod-dimesylate-in-c9orf72-amyotrophic-lateral-sclerosis-a-randomized-phase-2a-clinical-trial
#11
JOURNAL ARTICLE
Suma Babu, Katharine A Nicholson, Jeffrey D Rothstein, Andrea Swenson, Paul J Sampognaro, Pravin Pant, Eric A Macklin, Susan Spruill, Sabrina Paganoni, Tania F Gendron, Mercedes Prudencio, Leonard Petrucelli, Darrell Nix, Sean Landrette, Esther Nkrumah, Keith Fandrick, Joan Edwards, Peter R Young
Apilimod dimesylate is a first-in-class phosphoinositide kinase, FYVE-type zinc finger containing (PIKfyve) inhibitor with favourable clinical safety profile and has demonstrated activity in preclinical C9orf72 and TDP-43 amyotrophic lateral sclerosis models. In this amyotrophic lateral sclerosis clinical trial, the safety, tolerability, CNS penetrance, and modulation of pharmacodynamic target engagement biomarkers were evaluated. This Phase 2a, randomized, double-blind, placebo-controlled, biomarker-endpoint clinical trial was conducted in four USA centres (ClinicalTrials...
April 12, 2024: Brain
https://read.qxmd.com/read/38605603/a-multi-omics-study-to-monitor-senescence-associated-secretory-phenotypes-of-alzheimer-s-disease
#12
JOURNAL ARTICLE
Jingzhi Yang, Yinge Zhou, Tianjiao Wang, Na Li, Yufan Chao, Songyan Gao, Qun Zhang, Shuo Wu, Liang Zhao, Xin Dong
OBJECTIVE: Alzheimer's disease (AD) is characterized by the progressive degeneration and damage of neurons in the brain. However, developing an accurate diagnostic assay using blood samples remains a challenge in clinic practice. The aim of this study was to explore senescence-associated secretory phenotypes (SASPs) in peripheral blood using mass spectrometry based multi-omics approach and to establish diagnostic assays for AD. METHODS: This retrospective study included 88 participants, consisting of 29 AD patients and 59 cognitively normal (CN) individuals...
April 11, 2024: Annals of Clinical and Translational Neurology
https://read.qxmd.com/read/38591780/zinc-finger-protein207-orchestrates-glioma-migration-through-regulation-of-epithelial-mesenchymal-transition
#13
JOURNAL ARTICLE
Chao Zhao, Yuduo Guo, Yujia Chen, Guanjie Shang, Dixiang Song, Jun Wang, Jingjing Yang, Hongwei Zhang
BACKGROUND: Glioma represents the predominant primary malignant brain tumor. For several years, molecular profiling has been instrumental in the management and therapeutic stratification of glioma, providing a deeper understanding of its biological complexity. Accumulating evidence unveils the putative involvement of zinc finger proteins (ZNFs) in cancer. This study aimed to elucidate the role and significance of ZNF207 in glioma. METHODS: Utilizing online data such as The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Genotype-Tissue Expression (GTEx) project, the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA) databases, in conjunction with bioinformatics methodologies including GO, KEGG, GSEA, CIBERSORT immune cell infiltration estimation, and protein-protein interaction (PPI) analysis, enabled a comprehensive exploration of ZNF207's involvement in gliomagenesis...
April 9, 2024: Environmental Toxicology
https://read.qxmd.com/read/38590838/sources-effects-and-present-perspectives-of-heavy-metals-contamination-soil-plants-and-human-food-chain
#14
REVIEW
Prodipto Bishnu Angon, Md Shafiul Islam, Shreejana Kc, Arpan Das, Nafisa Anjum, Amrit Poudel, Shaharia Akter Suchi
Heavy metal (HM) poisoning of agricultural soils poses a serious risk to plant life, human health, and global food supply. When HM levels in agricultural soils get to dangerous levels, it harms crop health and yield. Chromium (Cr), arsenic (As), nickel (Ni), cadmium (Cd), lead (Pb), mercury (Hg), zinc (Zn), and copper (Cu) are the main heavy metals. The environment contains these metals in varying degrees, such as in soil, food, water, and even the air. These substances damage plants and alter soil characteristics, which lowers crop yield...
April 15, 2024: Heliyon
https://read.qxmd.com/read/38583951/zinc-deficiency-decreases-neurite-extension-via-crmp2-signal-pathway
#15
JOURNAL ARTICLE
Hisaka Kurita, Misa Ueda, Miyu Kimura, Ayu Okuda, Kazuki Ohuchi, Isao Hozumi, Masatoshi Inden
Previous reports indicated that zinc deficiency could increase the risk of infectious diseases and developmental retardation in children. In experimental study, it has been reported that zinc deficiency during the embryonic period inhibited fetal growth, and disturbed neural differentiation and higher brain function later in adulthood. Although it has been suggested that zinc deficiency during development can have significant effects on neuronal differentiation and maturation, the molecular mechanisms of the effects of low zinc on neuronal differentiation during development have not been elucidated in detail...
2024: Biological & Pharmaceutical Bulletin
https://read.qxmd.com/read/38582529/artificial-q-grader-machine-learning-enabled-intelligent-olfactory-and-gustatory-sensing-system
#16
JOURNAL ARTICLE
Moonjeong Jang, Garam Bae, Yeong Min Kwon, Jae Hee Cho, Do Hyung Lee, Saewon Kang, Soonmin Yim, Sung Myung, Jongsun Lim, Sun Sook Lee, Wooseok Song, Ki-Seok An
Portable and personalized artificial intelligence (AI)-driven sensors mimicking human olfactory and gustatory systems have immense potential for the large-scale deployment and autonomous monitoring systems of Internet of Things (IoT) devices. In this study, an artificial Q-grader comprising surface-engineered zinc oxide (ZnO) thin films is developed as the artificial nose, tongue, and AI-based statistical data analysis as the artificial brain for identifying both aroma and flavor chemicals in coffee beans. A poly(vinylidene fluoride-co-hexafluoropropylene)/ZnO thin film transistor (TFT)-based liquid sensor is the artificial tongue, and an Au, Ag, or Pd nanoparticles/ZnO nanohybrid gas sensor is the artificial nose...
April 6, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38581598/systematic-analysis-of-the-relationship-between-elevated-zinc-and-epilepsy
#17
JOURNAL ARTICLE
Dadong Luo, Yaqing Liu, Junqiang Li, Xuhui Liu, Ruirui Zhang, Xuejuan Liu, Ningning Zhang, Wenzhao Zhang, Jiayi Liu, Lan Zhang, Tiancheng Wang
Previous studies have indicated a potential relationship between zinc and epilepsy. The aim of this study is to investigate the causal relationship between zinc, zinc-dependent carbonic anhydrase, and gray matter volume in brain regions enriched with zinc and epilepsy, as well as explore the possible mechanisms by which zinc contributes to epilepsy. First, this study assessed the risk causality between zinc, carbonic anhydrase, and gray matter volume alterations in zinc-enriched brain regions and various subtypes of epilepsy based on Two-sample Mendelian randomization analysis...
April 6, 2024: Journal of Molecular Neuroscience: MN
https://read.qxmd.com/read/38575033/assessing-the-water-quality-in-a-world-heritage-site-using-biomarkers-in-top-fish-predators
#18
JOURNAL ARTICLE
Hugo de Andrade Gonçalves Dos Santos, Rafael Shinji Akiyama Kitamura, Gésica da Costa Bernardo Soares, Mayara Padovan Dos Santos, Luis Phelipe de Souza Miranda, Maritana Mela, Jean Ricardo Simões Vitule, Marco Tadeu Grassi, Marta Margarete Cestari, Andre Andrian Padial, Helena Cristina Silva de Assis
The use of biomarkers in fish for biomonitoring is a valuable approach to reveal effects of human impacts on biota health. Top predator fish are effective models for monitoring human activities' impacts on aquatic ecosystems. The Guaraguaçu River is the largest river-system on coastal region of South Brazil and a World Heritage site. The river receives contaminants from disorderly urban growth, including discharges of domestic sewage and small fishery boats, particularly during the tourist season. Our study aimed to assess impact of anthropogenic activities on water quality in the Guaraguaçu River by analyzing environmental contamination biomarkers in the top fish predator Hoplias malabaricus...
April 2, 2024: Science of the Total Environment
https://read.qxmd.com/read/38574925/isolation-and-biochemical-characterization-of-novel-acid-phosphatase-and-zinc-dependent-acid-phosphatase-from-the-chicken-s-brain
#19
JOURNAL ARTICLE
Shazia Amin, Umber Zaman, Huda Salem AlSalem, Aliyah S Alhawiti, Amal N Alanazi, Imen Zghab, Mohammed Alissa, Suad A Alghamdi, Rubina Naz, Khalil Ur Rehman
The AcPase exhibits a specific activity of 31.32 U/mg of protein with a 728-fold purification, and the yield of the enzyme is raised to 3.15 %. The Zn2+ -dependent AcPase showed a purification factor of 1.34 specific activity of 14 U/mg of proteins and a total recovery of 5.14. The SDS-PAGE showed a single band corresponding to a molecular weight of 18 kDa of AcPase and 29 kDa of Zn2+ -dependent AcPase. The AcPase enzyme has shown a wide range of substrate specificity for p-NPP, phenyl phosphate and FMN, while in the case of ZnAcPase α and β-Naphthyl phosphate and p-NPP were proved to be superior substrates...
April 2, 2024: International Journal of Biological Macromolecules
https://read.qxmd.com/read/38573427/identification-of-potential-jnk3-inhibitors-through-virtual-screening-molecular-docking-and-molecular-dynamics-simulation-as-therapeutics-for-alzheimer-s-disease
#20
JOURNAL ARTICLE
Bharti Devi, Kailash Jangid, Naveen Kumar, Vinay Kumar, Vinod Kumar
Alzheimer's disease (AD) is a complex neurological disorder and no effective drug is available for its treatment. Numerous pathological conditions are believed to be responsible for the initiation and development of AD including c-Jun N-terminal kinases (JNKs). The JNKs are one of the enzymes from the mitogen-activated protein kinase (MAPK) family that controls the phosphorylation of various transcription factors on serine and threonine residues, and hold significant responsibilities in tasks like gene expression, cell proliferation, differentiation, and apoptosis...
April 4, 2024: Molecular Diversity
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