ABSTRACT
Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms. On the contrary, the support for utilizing quetiapine is not as substantial as other antipsychotics because research studies specifically investigating its application are still emerging and relatively recent. The broad mechanisms of action of AAPs, involving dopamine and serotonin receptors, provide improved outcomes and fewer side effects than typical antipsychotics. Conversely, other antipsychotics, including risperidone, olanzapine, aripiprazole, ziprasidone, and lurasidone, have been found to worsen motor symptoms and are generally not recommended for PDP. While AAPs offer favorable benefits, they are associated with specific adverse effects. Extrapyramidal symptoms, somnolence, hypotension, constipation, and cognitive impairment are commonly observed with AAP use. Clozapine, in particular, carries a risk of agranulocytosis, necessitating close monitoring of blood counts. Pimavanserin, a selective serotonin inverse agonist, avoids receptor-related side effects but has been linked to corrected QT (QTc) interval prolongation, while quetiapine has been reported to be associated with an increased risk of mortality. This review aims to analyze the benefits, risks, and mechanisms of action of antipsychotic medications to assist clinicians in making informed decisions and enhance patient care.
Subject(s)
Antipsychotic Agents , Clozapine , Hallucinations , Parkinson Disease , Piperidines , Quetiapine Fumarate , Humans , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Antipsychotic Agents/pharmacology , Clozapine/adverse effects , Clozapine/administration & dosage , Clozapine/pharmacology , Hallucinations/drug therapy , Hallucinations/etiology , Parkinson Disease/drug therapy , Parkinson Disease/complications , Piperidines/adverse effects , Piperidines/pharmacology , Piperidines/administration & dosage , Quetiapine Fumarate/adverse effects , Quetiapine Fumarate/pharmacology , Quetiapine Fumarate/administration & dosage , Urea/analogs & derivatives , Urea/pharmacology , Urea/adverse effectsABSTRACT
Brain cancer is an aggressive type of cancer with poor prognosis. While the immune system protects against cancer in the early stages, the tumor exploits the healing arm of inflammatory reactions to accelerate its growth and spread. Various immune cells penetrate the developing tumor region, establishing a pro-inflammatory tumor milieu. Additionally, tumor cells may release chemokines and cytokines to attract immune cells and promote cancer growth. Inflammation and its associated mechanisms in the progression of cancer have been extensively studied in the majority of solid tumors, especially brain tumors. However, treatment of the malignant brain cancer is hindered by several obstacles, such as the blood-brain barrier, transportation inside the brain interstitium, inflammatory mediators that promote tumor growth and invasiveness, complications in administering therapies to tumor cells specifically, the highly invasive nature of gliomas, and the resistance to drugs. To resolve these obstacles, nanomedicine could be a potential strategy that has facilitated advancements in diagnosing and treating brain cancer. Due to the numerous benefits provided by their small size and other features, nanoparticles have been a prominent focus of research in the drug-delivery field. The purpose of this article is to discuss the role of inflammatory mediators and signaling pathways in brain cancer as well as the recent advances in understanding the nano-carrier approaches for enhancing drug delivery to the brain in the treatment of brain cancer.
Subject(s)
Brain Neoplasms , Nanomedicine , Humans , Brain Neoplasms/metabolism , Drug Delivery Systems , Inflammation/drug therapy , Inflammation Mediators/therapeutic useABSTRACT
Considerable evidence supports that cytokines are important mediators of pathophysiologic processes within the central nervous system (CNS). Numerous studies have documented the increased production of various cytokines in the human CNS in various neurological and neuropsychiatric disorders. Deciphering cytokine actions in the intact CNS has important implications for our understanding of the pathogenesis and treatment of these disorders. The purpose of this study is to discuss the recent research on treating cytokine storm and amyloids, including stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's condition, Multi-sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). Neuroinflammation observed in neurological disorders has a pivotal role in exacerbating Aß burden and tau hyperphosphorylation, suggesting that stimulating cytokines in response to an undesirable external response could be a checkpoint for treating neurological disorders. Furthermore, the pro-inflammatory cytokines help our immune system through a neuroprotective mechanism in clearing viral infection by recruiting mononuclear cells. This study reveals that cytokine applications may play a vital role in providing novel regulation and methods for the therapeutic approach to neurological disorders and the causes of the deregulation, which is responsible for neuroinflammation and viral infection. However, it needs to be further investigated to clarify better the mechanisms of cytokine release in response to various stimuli, which could be the central point for treating neurological disorders.
Subject(s)
Alzheimer Disease , Nervous System Diseases , Virus Diseases , Cytokines/physiology , Humans , Nervous System Diseases/therapy , Neuroinflammatory DiseasesABSTRACT
Microglial cells serve as molecular sensors of the brain that play a role in physiological and pathological conditions. Under normal physiology, microglia are primarily responsible for regulating central nervous system homeostasis through the phagocytic clearance of redundant protein aggregates, apoptotic cells, damaged neurons, and synapses. Furthermore, microglial cells can promote and mitigate amyloid ß phagocytosis and tau phosphorylation. Dysregulation of the microglial programming alters cellular morphology, molecular signaling, and secretory inflammatory molecules that contribute to various neurodegenerative disorders especially Alzheimer's disease (AD). Furthermore, microglia are considered primary sources of inflammatory molecules and can induce or regulate a broad spectrum of cellular responses. Interestingly, in AD, microglia play a double-edged role in disease progression; for instance, the detrimental microglial effects increase in AD while microglial beneficiary mechanisms are jeopardized. Depending on the disease stages, microglial cells are expressed differently, which may open new avenues for AD therapy. However, the disease-related role of microglial cells and their receptors in the AD brain remain unclear. Therefore, this review represents the role of microglial cells and their involvement in AD pathogenesis.
Subject(s)
Alzheimer Disease , Microglia , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Brain/metabolism , Humans , Microglia/metabolism , PhagocytosisABSTRACT
Advancements in medicine have increased the longevity of humans, resulting in a higher incidence of chronic diseases. Due to the rise in the elderly population, age-dependent neurodegenerative disorders are becoming increasingly prevalent. The available treatment options only provide symptomatic relief and do not cure the underlying cause of the disease. Therefore, it has become imperative to discover new markers and therapies to modulate the course of disease progression and develop better treatment options for the affected individuals. Growing evidence indicates that neuroinflammation is a common factor and one of the main inducers of neuronal damage and degeneration. Galectins (Gals) are a class of ß-galactoside-binding proteins (lectins) ubiquitously expressed in almost all vital organs. Gals modulate various cellular responses and regulate significant biological functions, including immune response, proliferation, differentiation, migration, and cell growth, through their interaction with glycoproteins and glycolipids. In recent years, extensive research has been conducted on the Gal superfamily, with Gal-1, Gal-3, and Gal-9 in prime focus. Their roles have been described in modulating neuroinflammation and neurodegenerative processes. In this review, we discuss the role of Gals in the causation and progression of neurodegenerative disorders. We describe the role of Gals in microglia and astrocyte modulation, along with their pro- and anti-inflammatory functions. In addition, we discuss the potential use of Gals as a novel therapeutic target for neuroinflammation and restoring tissue damage in neurodegenerative diseases.
Subject(s)
Galectins , Neurodegenerative Diseases , Aged , Anti-Inflammatory Agents , Galectins/metabolism , Glycolipids , Humans , Microglia/metabolism , Neurodegenerative Diseases/drug therapyABSTRACT
Age-related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood-brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.
Subject(s)
Alzheimer Disease/complications , Cerebral Arterial Diseases/pathology , Cerebrovascular Circulation , Cognitive Aging , Cognitive Dysfunction/pathology , TOR Serine-Threonine Kinases/metabolism , Animals , Cerebral Arterial Diseases/etiology , Cerebral Arterial Diseases/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Disease Models, Animal , HumansABSTRACT
There are reports in scientific literature that the concentration of copper ions in Parkinsonian brain is at a level that could promote oxidative DNA damage. The possibility of copper chelation by antioxidants excited us to explore the generation of reactive oxygen species (ROS) and DNA damage by the interaction of L-DOPA with Cu(II) ions. In the present manuscript, L-DOPA was tested for its ability to bind with Cu(II) and reduce it to Cu(I). The generation of ROS, such as superoxide anion (O(2)(-)) and hydroxyl radical (OH(â¢)), was also ascertained. As a result of L-DOPA and Cu(II) interaction, the generation of O(2)(-) was found to be increased in a time-dependent manner. Moreover, the formation of OH(â¢) was also found to be enhanced with increasing concentrations of L-DOPA. Furthermore, Comet assay results clearly showed significantly higher cellular DNA breakage in lymphocytes treated with L-DOPA and Cu(II) as compared to those that were treated with L-DOPA alone. However, such DNA degradation was inhibited to a significant extent by scavengers of ROS and neocuproine, a membrane permeable Cu(I)-specific sequestering agent. These findings demonstrate that L-DOPA exhibits a pro-oxidant activity in the presence of copper ions.
Subject(s)
Copper/metabolism , DNA Breaks , Levodopa/metabolism , Reactive Oxygen Species/metabolism , Antiparkinson Agents/chemistry , Antiparkinson Agents/metabolism , Antiparkinson Agents/pharmacology , Chelating Agents/pharmacology , Comet Assay , Copper/chemistry , Copper/pharmacology , Humans , Hydroxyl Radical/chemistry , Hydroxyl Radical/metabolism , Levodopa/chemistry , Levodopa/pharmacology , Lymphocytes/drug effects , Lymphocytes/metabolism , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/pathology , Oxidation-Reduction/drug effects , Phenanthrolines/pharmacology , Reactive Oxygen Species/chemistry , Superoxides/chemistry , Superoxides/metabolismABSTRACT
Galectins are ß-galactoside binding mammalian proteins characterized by the presence of a conserved carbohydrate recognition domain, expressed in almost all taxa of living organisms and involved in broad range of significant biological and physiological functions. Previously, we reported the purification and extensive characterization of galectin-1 from goat (Capra hircus) heart. Interestingly, the purified protein was found to have significant level of glycosylation. This intrigued us to evaluate the involvement of glycosylation in relation to protein's structural and functional integrity in its purified form. In the present study, an extensive comparative physicochemical characterization has been performed between the glycosylated and deglycosylated form of the purified protein. Deglycosylation resulted in an enhanced fluorescence quenching and marked reduction in pH and thermal stability of the purified galectin. Exposure to various biologically active chemicals showed significant differences in the properties and stability profile, causing significant deviations from its regular secondary structure in the deglycosylated form. These results clearly indicated enhanced structural and functional stabilization in the glycosylated galectin. The data revealed herein adds a vital facet demonstrating the significance of galectin expression and glycosylation in causation, progression, and possible therapeutics of associated clinical disorders. Our approach also allowed us to define some key interactions between the purified galectin and carbohydrate ligands that could well serve as an important landmark for designing new drug protocols for various cardiovascular and neurological disorders.
Subject(s)
Galactosides/metabolism , Galectin 1/chemistry , Galectin 1/metabolism , Protein Structure, Secondary , Animals , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/therapy , Electrophoresis, Polyacrylamide Gel , Galectin 1/isolation & purification , Glycosylation , Goats , Humans , Hydrogen-Ion Concentration , Ligands , Myocardium/metabolism , Nervous System Diseases/diagnosis , Nervous System Diseases/metabolism , Nervous System Diseases/therapy , Protein Binding , Protein Stability , Spectrophotometry , TemperatureABSTRACT
The growing global demand for STEM professionals is not being met by the supply of new graduates, a supply that is characterised by a significant lag in the percentage of women pursuing STEM studies. Interestingly enough, the percentage of female applicants entering STEM majors has been increasing yet only a minority of them pursue, or complete, engineering programs. Several studies for the developed world have identified several environmental factors responsible for this phenomenon. The scarcity of engineering professionals is a handicapping factor for development, even for the most advanced countries of the Global South. The objective of this exploratory study is to examine whether the environmental factors identified in the international literature are sufficient to explain the asymmetry in selecting an engineering or a natural sciences career among female undergraduates in an exemplary Global South country, Kazakhstan. To this purpose, a multifaceted survey was conducted among the female students pursuing STEM majors in the premier Kazakhstani university in the academic year 2021-2022. This study utilized a Likert Scale questionnaire, ordinal logistic regression, and factor analysis to explore factors affecting female students. Data reliability was confirmed through Confirmatory Factor Analysis (CFA). The factor and regression analysis of the results obtained demonstrates that there is no discernible difference between the observations in the literature and the situation in Kazakhstan.
Subject(s)
Engineering , Students , Humans , Female , Reproducibility of Results , Universities , PerceptionABSTRACT
Bulk metallic glasses (BMGs) are growing in popularity prominently due to their potential in micro-electromechanical systems (MEMSs) and aerospace applications. BMGs have unique mechanical properties, i.e., high strength, hardness, modulus of elasticity, and wear resistance, due to their disordered atomic structure. Due to their unique mechanical properties and amorphous structures, machining of BMGs remains a challenge. This paper aims to carry out a detailed literature review on various aspects of the machining of bulk metallic glasses using both conventional and non-conventional processes, including experimental approaches, modeling, statistical findings, challenges, and guidelines for machining this difficult-to-machine material. Conventional machining processes were found to be challenging for machining bulk metallic glasses due to their high hardness, brittleness, and tendency to convert their amorphous structure into a crystalline structure, especially at the machined surface and sub-surface. Although their high electrical conductivity makes them suitable for machining by non-conventional processes, they impose new challenges such as heat-affected zones and crystallization. Therefore, the successful machining of BMGs requires more in-depth analysis of cutting forces, tool wear, burr formation, surface finish, recast layers or heat-affected zones, crystallization, and mechanical property changes among different varieties of BMGs. This review paper provides guidelines emerging from in-depth analysis of previous studies, as well as offering directions for future research in the machining of BMGs.
ABSTRACT
INTRODUCTION: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α-synuclein (p-syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring. METHODS: A literature search was conducted on PubMed, Scopus, and Google Scholar using specific keywords and MeSH terms without imposing a time limit. Inclusion criteria comprised various study designs including experimental studies, case-control studies, and cohort studies published only in English, while conference abstracts and unpublished sources were excluded. RESULTS: Increased levels of p-syn have been observed in various samples from MSA patients, such as red blood cells, cerebrospinal fluid, oral mucosal cells, skin, and colon biopsies, highlighting their diagnostic potential. The α-Syn RT-QuIC assay has shown sensitivity in diagnosing MSA and tracking its progression. Meta-analyses and multicenter investigations have confirmed the diagnostic value of p-syn in cerebrospinal fluid, demonstrating high specificity and sensitivity in distinguishing MSA from other neurodegenerative diseases. Moreover, combining p-syn with other biomarkers has further improved the diagnostic accuracy of MSA. CONCLUSION: The p-syn stands out as a promising biomarker for MSA. It is found in oligodendrocytes and shows a correlation with disease severity and progression. However, further research and validation studies are necessary to establish p-syn as a reliable biomarker for MSA. If proven, p-syn could significantly contribute to early diagnosis, disease monitoring, and assessing treatment response.
Subject(s)
Multiple System Atrophy , alpha-Synuclein , Humans , alpha-Synuclein/metabolism , Multiple System Atrophy/diagnosis , Brain/metabolism , Biomarkers/cerebrospinal fluid , Case-Control Studies , Multicenter Studies as TopicABSTRACT
Neurodegenerative diseases represent one of the utmost imperative well-being health issues and apprehensions due to their escalating incidence of mortality. Natural derivatives are more efficacious in various preclinical models of neurodegenerative illnesses. These natural compounds include phytoconstituents in herbs, vegetables, fruits, nuts, and marine and freshwater flora, with remarkable efficacy in mitigating neurodegeneration and enhancing cognitive abilities in preclinical models. According to the latest research, the therapeutic activity of natural substances can be increased by adding phytoconstituents in nanocarriers such as nanoparticles, nanogels, and nanostructured lipid carriers. They can enhance the stability and specificity of the bioactive compounds to a more considerable extent. Nanotechnology can also provide targeting, enhancing their specificity to the respective site of action. In light of these findings, this article discusses the biological and therapeutic potential of natural products and their bioactive derivatives to exert neuroprotective effects and some clinical studies assessing their translational potential to treat neurodegenerative disorders.
ABSTRACT
Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin-an integral component of traditional medicine in numerous cultures worldwide-has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti-inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo.
Subject(s)
Alzheimer Disease , Anti-Inflammatory Agents , Antioxidants , Curcumin , Epigenesis, Genetic , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Curcumin/pharmacology , Curcumin/therapeutic use , Humans , Epigenesis, Genetic/drug effects , Antioxidants/pharmacology , Antioxidants/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Animals , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Signal Transduction/drug effects , Oxidative Stress/drug effectsABSTRACT
Rapid investment casting is a casting process in which the sacrificial patterns are fabricated using additive manufacturing techniques, making the creation of advanced designs possible. One of the popular 3D printing methods applied in rapid investment casting is stereolithography because of its high dimensional precision and surface quality. Printing parameters of the used additive manufacturing method can influence the surface quality and accuracy of the rapid investment cast geometries. Hence, this study aims to investigate the effect of stereolithography printing parameters on the dimensional accuracy and surface roughness of printed patterns and investment cast parts. Castable wax material was used to print the sacrificial patterns for casting. A small-scale prosthetic biomedical implant for total hip replacement was selected to be the benchmark model due to its practical significance. The main results indicate that the most significant stereolithography printing parameter affecting surface roughness is build angle, followed by layer thickness. The optimum parameters that minimize the surface roughness are 0.025 mm layer thickness, 0° build angle, 1.0 support density index, and across the front base orientation. As for the dimensional accuracy, the optimum stereolithography parameters are 0.025 mm layer thickness, 30° build angle, 0.6 support density index, and diagonal to the front base orientation. The optimal printing parameters to obtain superior dimensional accuracy of the cast parts are 0.05 mm layer thickness, 45° build angle, 0.8 support density index, and diagonal to the front model base orientation. With respect to the surface roughness, lower values were obtained at 0.025 mm layer thickness, 0° build angle, 1.0 support density index, and parallel to the front base orientation.
ABSTRACT
This research work aims to proceed with the optimization of Fused Deposition Modeling (FDM) printing parameters for acrylonitrile butadiene styrene (ABS) and polyamide (Nylon) to improve fatigue resistance. For that purpose, the methodology of the paper involves two main approaches: experimental study and finite element analysis. The experimental part of the paper used the Taguchi method to find the effects of printing internal geometry, printing speed, and nozzle diameter on the fatigue life of ABS and Nylon plastic materials. ANCOVA multiple linear regression and sensitivity analysis was used to investigate the effects of printing parameters on the fatigue life of materials. The analysis of the results revealed: Nylon performed better than ABS, but had a higher slope; the 'tri-hexagon' structure resulted in the highest fatigue life, but the effect was statistically significant only for ABS material; the fatigue life of both materials increased with decreasing the nozzle diameter; the printing speed had no statistically significant influence neither on ABS nor Nylon. The experimental results then were validated by numerical simulations and the difference between the values was within ±14% depending on the experiment. Such differences might occur due to numerical and experimental errors.
ABSTRACT
This study aimed to identify the optimum printing parameters for the fused filament fabrication (FFF) of acrylonitrile butadiene styrene (ABS) and polyamide (nylon), to improve strength properties. For this purpose, the methodology of the paper involves an experimental study that used Taguchi's method to identify the effects of the infill pattern, infill density, and printing speed on the mechanical properties of the materials. ABS and nylon plastic parts were tested in tension to failure. Based on the results of the tensile tests, it was found that ABS material produced the highest ultimate tensile strength when printed using a tri-hexagonal infill pattern, 100% infill density, and a printing speed of 65 mm/s. On the other hand, nylon material exhibited a better performance when printed using an octet geometric structure, with identical other parameters.
ABSTRACT
Mitochondria are critical for homeostasis and metabolism in all cellular eukaryotes. Brain mitochondria are the primary source of fuel that supports many brain functions, including intracellular energy supply, cellular calcium regulation, regulation of limited cellular oxidative capacity, and control of cell death. Much evidence suggests that mitochondria play a central role in neurodegenerative disorders (NDDs) such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Ongoing studies of NDDs have revealed that mitochondrial pathology is mainly found in inherited or irregular NDDs and is thought to be associated with the pathophysiological cycle of these disorders. Typical mitochondrial disturbances in NDDs include increased free radical production, decreased ATP synthesis, alterations in mitochondrial permeability, and mitochondrial DNA damage. The main objective of this review is to highlight the basic mitochondrial problems that occur in NDDs and discuss the use mitochondrial drugs, especially mitochondrial antioxidants, mitochondrial permeability transition blockade, and mitochondrial gene therapy, for the treatment and control of NDDs.
Subject(s)
Mitochondrial Diseases , Neurodegenerative Diseases , Humans , Oxidative Stress/physiology , Mitochondrial Diseases/drug therapy , Mitochondrial Diseases/metabolism , Mitochondria/metabolism , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/genetics , DNA, Mitochondrial/metabolism , DNA, Mitochondrial/therapeutic useABSTRACT
Alzheimer's disease (AD) is a devastating neurodegenerative disease that mostly affects the elderly population. Mechanisms underlying AD pathogenesis are yet to be fully revealed, but there are several hypotheses regarding AD. Even though free radicals and inflammation are likely to be linked with AD pathogenesis, still amyloid-beta (Aß) cascade is the dominant hypothesis. According to the Aß hypothesis, a progressive buildup of extracellular and intracellular Aß aggregates has a significant contribution to the AD-linked neurodegeneration process. Since Aß plays an important role in the etiology of AD, therefore Aß-linked pathways are mainly targeted in order to develop potential AD therapies. Accumulation of Aß plaques in the brains of AD individuals is an important hallmark of AD. These plaques are mainly composed of Aß (a peptide of 39-42 amino acids) aggregates produced via the proteolytic cleavage of the amyloid precursor protein. Numerous studies have demonstrated that various polyphenols (PPHs), including cyanidins, anthocyanins, curcumin, catechins and their gallate esters were found to markedly suppress Aß aggregation and prevent the formation of Aß oligomers and toxicity, which is further suggesting that these PPHs might be regarded as effective therapeutic agents for the AD treatment. This review summarizes the roles of Aß in AD pathogenesis, the Aß aggregation pathway, types of PPHs, and distribution of PPHs in dietary sources. Furthermore, we have predominantly focused on the potential of food-derived PPHs as putative anti-amyloid drugs.
Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Aged , Humans , Alzheimer Disease/metabolism , Anthocyanins/therapeutic use , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Amyloid/metabolism , Plaque, Amyloid/metabolismABSTRACT
In the design of coat hanger extrusion dies, the main objective is to provide a uniform flow rate at the die exit. Previously, a multi-rheology isothermal method model for coat hanger extrusion dies was developed to reach this objective. Polymer melts in extrusion dies commonly experience high shear rates. Viscous dissipation rooted by high shear rate may lead to significant temperature differences across the die. Due to temperature-dependency of viscosity, temperature differences may lead to nonuniform flow rates, which may significantly affect the flow rate at the die exit. As a result, a new design method is proposed to take into account the effects of temperature and viscous dissipation in the design of coat hanger dies. Although more non-Newtonian fluid rheology models can be adapted in the proposed study, as demonstration, temperature-dependent power-law and Carreau-Yasuda models are adapted in this study. Performances are compared with our isothermal method published earlier. In addition, the novel nonisothermal method is comprehensively examined where the effect of viscous dissipation is studied through Brinkman number of extrusion die. It is demonstrated that, for a low Brinkman number, both isothermal and nonisothermal design give similar flow uniformity level. However, for higher Brinkman numbers, the proposed nonisothermal method produces a design with more desirable velocity uniformity level along with a maximum improvement of 5.24% over the isothermal method. In addition, dependency of flow field on temperature, due to temperature-dependent viscosity, is studied, and it is demonstrated that fully-developed velocity profile changes as temperature increases along the flow channel. Moreover, the effect of the temperature sensitivity parameter in temperature-dependent non-Newtonian models is considered. It is demonstrated that the temperature boundary condition with the Biot number of 1.0 gives adequate results for lower values of the temperature sensitivity parameter.
ABSTRACT
Introduction: The advent of COVID-19 has led to an exponential rise in related publications to provide a knowledge driven approach to tame the tide of infection and impact in all spheres. This study gives an insight into COVID-19 research publication pattern in Malaysia using bibliometric analysis. Method: COVID-19 publications on Scopus database between January 1, 2020, and August 26, 2022, were extracted using predetermined search strings. Inclusion and exclusion criteria were set, and data was extracted from the database. Descriptive statistics was used to summarize our findings. Results: A total of 3,553 COVID-19 related papers were retrieved out of global count of 392,613 and 16,466 for Southeast Asia (SEA). This implies that 0.9% and 21.6% is contributed globally and SEA respectively. Indonesia, Malaysia and Singapore are the three top countries with highest research outputs in the region. This may be correlated to high GDP per capita, research and development, and research and development expenditure. Most of the publications are article/original research (n = 2832, 67%). Ministry of Higher education is the top funding sponsor and Universiti Malaya is the highest contributor and the most cited (n = 466, 4920 citations). The majority of publications are from physical sciences (30.3%), but medicine subcategory produced the highest number of papers (1,586). The top journal was International Journal of Environmental and Public Health (n = 96 publications). Most active collaborating country was the United Kingdom and most active author was from Monash University. Conclusion: Malaysian institutions have made profound contributions to COVID-19 research globally and in SEA. However, there is a need for continuous efforts to improve research outputs on the topic.