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2.
Drug Metab Pers Ther ; 39(1): 5-20, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469723

RESUMO

INTRODUCTION: Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of "omic" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment. CONTENT: In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack. SUMMARY AND OUTLOOK: We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Estudos Prospectivos , Biomarcadores , Neoplasias/diagnóstico , Neoplasias/terapia , Biomarcadores Tumorais , Prognóstico
3.
Heliyon ; 9(11): e22052, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027733

RESUMO

Background: Ischemic preconditioning (IPC) is the utmost capable design to achieve protection over ischemia-reperfusion injury (I/R), but this phenomenon gets attenuated during various pathological conditions like diabetes. Chrysin exhibits cardioprotection in various experiments however, its therapeutic potential on IPC-mediated cardioprotection via PI3K-Akt-eNOS pathway in streptozotocin (STZ) triggered diabetes-challenged rat heart is yet to be assessed. For that reason, the experiment has been planned to investigate chrysin's effect on the cardioprotective action of IPC involving the PI3K-Akt-eNOS cascade in rat hearts challenged to diabetes. Methods: The project was accomplished through means of absorbance studies for biochemical parameters, infarct size measurement (TTC stain) and coronary flow. Results: The findings of the present study revealed that STZ drastically augmented the serum glucose level and the chrysin significantly reversed the IPC-stimulated increased coronary flow, nitrite release, and reduced LDH (lactate dehydrogenase), CK-MB (creatine kinase) activities as well as infarct size in diabetes-induced rat heart. Furthermore, chrysin also reversed the IPC-induced reduction in oxidative stress in an isolated Langendorff's perfused diabetic rat heart. Moreover, four episodes of preconditioning by either PI3K or eNOS inhibitor in chrysin-pretreated diabetic rat hearts significantly abolished the protective effect of chrysin. Conclusion: Consequently, these observations suggested that chrysin increases the therapeutic efficiency of IPC in mitigating I/R injury via PI3K-Akt-eNOS signalling in diabetes-challenged rat hearts. Hence, chrysin could be a potential alternative option to IPC in diabetic rat hearts.

4.
Neurotox Res ; 41(6): 698-707, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37847429

RESUMO

Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aß) and tau accumulation. Aß accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aß accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aß pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Proteínas tau/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
5.
Carbohydr Polym ; 308: 120448, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36813329

RESUMO

Numerous compounds, with extensive applications in biomedical and biotechnological fields, are present in the oceans, which serve as a prime renewable source of natural substances, further promoting the development of novel medical systems and devices. Polysaccharides are present in the marine ecosystem in abundance, promoting minimal extraction costs, in addition to their solubility in extraction media, and an aqueous solvent, along with their interactions with biological compounds. Certain algae-derived polysaccharides include fucoidan, alginate, and carrageenan, while animal-derived polysaccharides comprise hyaluronan, chitosan and many others. Furthermore, these compounds can be modified to facilitate their processing into multiple shapes and sizes, as well as exhibit response dependence to external conditions like temperature and pH. All these properties have promoted the use of these biomaterials as raw materials for the development of drug delivery carrier systems (hydrogels, particles, capsules). The present review enlightens marine polysaccharides providing its sources, structures, biological properties, and its biomedical applications. In addition to this, their role as nanomaterials is also portrayed by the authors, along with the methods employed to develop them and associated biological and physicochemical properties designed to develop suitable drug delivery systems.


Assuntos
Ecossistema , Polissacarídeos , Animais , Polissacarídeos/química , Sistemas de Liberação de Medicamentos , Carragenina/química , Materiais Biocompatíveis/química
6.
Ageing Res Rev ; 83: 101787, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36368649

RESUMO

The amyloid precursor protein (APP), presenilin 1 (PS1), amyloid beta (Aß), and GSK3 are the effectors, which are significantly associated with progression of Alzheimer's Disease (AD) and its symptoms. A significant protein, acetylcholinesterase (AChE) becomes dysfunctional as a result of cholinergic neuronal loss in AD pathology. However, certain associated peptides potentiate the release of primary neuropathological hallmarks, i.e., senile plaque and neurofibrillary tangles (NFTs), by modulating the alpha 7 acetylcholinesterase receptor (α7nAChR). The AChE variants, T30 and T14 have also been found to be elevated in AD patients and mimic the toxic actions of pathological events in patients. The manuscript discusses the significance of AChE inhibitors in AD therapeutics, by indicating the disastrous role of molecular alterations and elevation of AChE, accompanied with the downstream effects instigated by the peptide, supported by clinical evidence and investigations. The cyclized variant of AChE peptide, NBP14 has been identified as a novel candidate that reverses the harmful effects of T30, T14 and Aß, mainly calcium influx, cell viability and AChE release. The review aims to grab the attention of neuro-researchers towards the significance of triggering effectors in propagating AD and role of AChE in regulating them, which can potentially ace the development of reliable therapeutic candidates, similar to NBP14, to mitigate neurodegeneration.


Assuntos
Acetilcolinesterase , Doença de Alzheimer , Humanos , Acetilcolinesterase/metabolismo , Acetilcolinesterase/uso terapêutico , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Quinase 3 da Glicogênio Sintase/uso terapêutico , Emaranhados Neurofibrilares/patologia , Placa Amiloide/patologia , Precursor de Proteína beta-Amiloide/metabolismo
7.
Environ Sci Pollut Res Int ; 29(45): 67685-67703, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35933528

RESUMO

The 2019 outbreak of corona virus disease began from Wuhan (China), transforming into a leading pandemic, posing an immense threat to the global population. The WHO coined the term nCOVID-19 for the disease on 11th February, 2020 and the International Committee of Taxonomy of Viruses named it SARS-CoV-2, on account of its similarity with SARS-CoV-1 of 2003. The infection is associated with fever, cough, pneumonia, lung damage, and ARDS along with clinical implications of lung opacities. Brief understanding of the entry target of virus, i.e., ACE2 receptors has enabled numerous treatment options as discussed in this review. The manuscript provides a holistic picture of treatment options in COVID-19, such as non-specific anti-viral drugs, immunosuppressive agents, anti-inflammatory candidates, anti-HCV, nucleotide inhibitors, antibodies and anti-parasitic, RNA-dependent RNA polymerase inhibitors, anti-retroviral, vitamins and hormones, JAK inhibitors, and blood plasma therapy. The text targets to enlist the investigations conducted on all the above categories of drugs, with respect to the COVID-19 pandemic, to accelerate their significance in hindering the disease progression. The data collected primarily targets recently published articles and most recent records of clinical trials, focusing on the last 10-year database. The current review provides a comprehensive view on the critical need of finding a suitable treatment for the currently prevalent COVID-19 disease, and an opportunity for the researchers to investigate the varying possibilities to find and optimized treatment approach to mitigate and ameliorate the chaos created by the pandemic worldwide.


Assuntos
COVID-19 , Inibidores de Janus Quinases , Enzima de Conversão de Angiotensina 2 , Anti-Inflamatórios , Hormônios , Humanos , Nucleotídeos , Pandemias , RNA Polimerase Dependente de RNA , SARS-CoV-2 , Vitaminas
8.
Biomed Pharmacother ; 153: 113337, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35780617

RESUMO

The expeditious advancement of Alzheimer's Disease (AD) is a threat to the global healthcare system, that is further supplemented by therapeutic failure. The prevalence of this disorder has been expected to quadrupole by 2050, thereby exerting a tremendous economic pressure on medical sector, worldwide. Thus, there is a dire need of a change in conventional approaches and adopt a novel methodology of disease prevention, treatment and diagnosis. Precision medicine offers a personalized approach to disease management, It is dependent upon genetic, environmental and lifestyle factors associated with the individual, aiding to develop tailored therapeutics. Precision Medicine Initiatives are launched, worldwide, to facilitate the integration of personalized models and clinical medicine. The review aims to provide a comprehensive understanding of the neuroinflammatory processes causing AD, giving a brief overview of the disease interventions. This is further followed by the role of precision medicine in AD, constituting the genetic perspectives, operation of personalized form of medicine and optimization of clinical trials with the 3 R's, showcasing an in-depth understanding of this novel approach in varying aspects of the healthcare industry, to provide an opportunity to the global AD researchers to elucidate suitable therapeutic regimens in clinically and pathologically complex diseases, like AD.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Humanos , Estilo de Vida , Medicina de Precisão/métodos
9.
Stem Cell Rev Rep ; 18(8): 2757-2780, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35793037

RESUMO

Treatment of numerous ailments has been made accessible by the advent of genetic engineering, where the self-renewal property has unfolded the mysteries of regeneration, i.e., stem cells. This is narrowed down to pluripotency, the cell property of differentiating into other adult cells. The generation of induced pluripotent stem cells (iPSCs) was a major breakthrough in 2006, which was generated by a cocktail of 4 Yamanaka Factors, following which significant advancements have been reported in medical science and therapeutics. The iPSCs are reprogrammed from somatic cells, and the fascinating results focused on developing authentic techniques for their generation via molecular reprogramming mechanisms, with a plethora of molecules, like NANOG, miRNAs, and DNA modifying agents, etc. The iPSCs have exhibited reliable results in assessing the etiology and molecular mechanisms of diseases, followed by the development of possible treatments and the elimination of risks of immune rejection. The authors formulate a comprehensive review to develop a clear understanding of iPSC generation, their advantages and limitations, with potential challenges associated with their medical utility. In addition, a wide compendium of applications of iPSCs in regenerative medicine and disease modeling has been discussed, alongside bioengineering technologies for iPSC reprogramming, expansion, isolation, and differentiation. The manuscript aims to provide a holistic picture of the booming advancement of iPSC therapy, to attract the attention of global researchers, to investigate this versatile approach in treatment of multiple disorders, subsequently overcoming the challenges, in order to effectively expand its therapeutic window.


Assuntos
Células-Tronco Pluripotentes Induzidas , Mostardeira , Diferenciação Celular , Medicina Regenerativa , Atenção à Saúde
10.
Biomed Pharmacother ; 151: 113179, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35676784

RESUMO

Owing to the challenging ethos of global healthcare system, the Alzheimer's Disease (AD) researchers are consistently striving for a suitable target for disease amelioration. Besides the neurotransmitter release by neurons, the cells release tau proteins and amyloid peptides, within the extracellular vacancies, aggregating into tangles and plaques (AD pathological hallmarks). During neuro-stimulation, release of neuromodulator noradrenaline (NA), contained in the locus coeruleus (LC), exerts a significant impact on the neurons and microglia. The production of amyloid-ß (Aß) and hyperphosphorylation of tau proteins are affected by the α2A and ß adrenoreceptors, parallel to influencing their clearance. The manuscript entails a detailed understanding of the LC-NA system, as a possible avenue in AD management. The authors provide a comprehensive data on AD pathology and its link with LC neuroanatomical projections, followed by the pathogenic implications of LC-NA system in AD. The data also integrates numerous studies from online databases, evidently supporting the loss of the system integrity in AD patients, and the impact of the sympathetic system on specific AD hallmarks. Thus, the objective of this review is to compile a wide compendium of studies, for the convenience of the neuro-researchers, aiding in the establishment of a suitable therapeutic regimen for AD treatment.


Assuntos
Doença de Alzheimer , Locus Cerúleo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Humanos , Locus Cerúleo/fisiologia , Norepinefrina/metabolismo , Placa Amiloide/patologia , Proteínas tau/metabolismo
11.
Biomed Pharmacother ; 148: 112746, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35231697

RESUMO

Despite presence of substantial evidence suggesting the pivotal role of amyloid (Aß) in Alzheimer's disease (AD), very few therapeutic agents have been able to ameliorate the disease. This paved the way for the discovery of antibody-based immunotherapy to ace Aß clearance and curb neuronal toxicity, resulting in revival of aducanumab, which following its entry into the brain, interacts with the parenchymal amyloid and decreases Aß concentration, in a dose-dependent manner. However, the surprising approval from the FDA has created a controversy among healthcare professionals, due to Alzheimer's related imaging abnormality (ARIA) and hypersensitivity, serving as backlogs in its acceptance. Therefore, aducanumab is recognised as being "risen from the grave", accompanied with contrasting statements within the healthcare paradigm. The manuscript provides a collection of data, aiming to elucidate, both the commendable and critical faces, simultaneously intending to gain the attention of the global researchers towards the possibility of disease-modifying therapy in AD. The manuscript discusses the failure of anti-amyloid therapies in AD, that have accelerated the need to find a suitable therapeutic approach, followed by the discussion of timeline and impact of aducanumab in AD models, alongside the controversial judgement raising significant question. Besides, the authors throw some light on the onco-therapeutic implications of the drug approval, which is identified as a significant consequence of the event. The text provides a holistic picture of the drug action, and enlists the considerations for the future, that might be beneficial to both the acceptance of the drug, and the treatment of the disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas/metabolismo , Encéfalo/metabolismo , Aprovação de Drogas , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Estados Unidos , United States Food and Drug Administration
12.
Biomed Pharmacother ; 148: 112756, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35228064

RESUMO

The 2019 corona virus disease (COVID-19) has caused a global chaos, where a novel Omicron variant has challenged the healthcare system, followed by which it has been referred to as a variant of concern (VOC) by the World Health Organization (WHO), owing to its alarming transmission and infectivity rate. The large number of mutations in the receptor binding domain (RBD) of the spike protein is responsible for strengthening of the spike-angiotensin-converting enzyme 2 (ACE2) interaction, thereby explaining the elevated threat. This is supplemented by enhanced resistance of the variant towards pre-existing antibodies approved for the COVID-19 therapy. The manuscript brings into light failure of existing therapies to provide the desired effect, however simultaneously discussing the novel possibilities on the verge of establishing suitable treatment portfolio. The authors entail the risks associated with omicron resistance against antibodies and vaccine ineffectiveness on one side, and novel approaches and targets - kinase inhibitors, viral protease inhibitors, phytoconstituents, entry pathways - on the other. The manuscript aims to provide a holistic picture about the Omicron variant, by providing comprehensive discussions related to multiple aspects of the mutated spike variant, which might aid the global researchers and healthcare experts in finding an optimised solution to this pandemic.


Assuntos
COVID-19/fisiopatologia , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Catepsinas/metabolismo , Receptores ErbB/antagonistas & inibidores , Humanos , Esquemas de Imunização , Imunização Secundária , Fitoterapia/métodos , Plantas Medicinais , Ligação Proteica/fisiologia , Domínios e Motivos de Interação entre Proteínas/fisiologia , Elementos Estruturais de Proteínas/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Inibidores de Protease Viral/farmacologia , Inibidores de Protease Viral/uso terapêutico
13.
Chemosphere ; 288(Pt 2): 132533, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34655646

RESUMO

The unprecedented setbacks and environmental complications, faced by global agro-farming industry, have led to the advent of nanotechnology in agriculture, which has been recognized as a novel and innovative approach in development of sustainable farming practices. The agricultural regimen is the "head honcho" of the world, however presently certain approaches have been imposing grave danger to the environment and human civilization. The nano-farming paradigm has successfully elevated the growth and development of plants, parallel to the production, quality, germination/transpiration index, photosynthetic machinery, genetic progression, and so on. This has optimized the traditional farming into precision farming, utilising nano-based sensors and nanobionics, smart delivery tools, nanotech facets in plant disease management, nanofertilizers, enhancement of plant adaptive potential to external stress, role in bioenergy conservation and so on. These applications portray nanorevolution as "the big cheese" of global agriculture, mitigating the bottlenecks of conventional practices. Besides the applications of nanotechnology, the review identifies the limitations, like possible harmful impact on environment, mankind and plants, as the "Achilles heel" in agro-industry, aiming to establish its defined role in agriculture, while simultaneously considering the risks, in order to resolve them, thus abiding by "technology-yes, but safety-must". The authors aim to provide a significant opportunity to the nanotech researchers, Botanists and environmentalists, to promote judicial use of nanoparticles and establish a secure and safe environment.


Assuntos
Agricultura , Nanopartículas , Fazendas , Humanos , Nanopartículas/toxicidade , Nanotecnologia
14.
Sci Total Environ ; 808: 152072, 2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-34863742

RESUMO

The combat against the Corona virus disease of 2019 (COVID-19), has created a chaos among the healthcare institutions and researchers, in turn accelerating the dire need to curtail the infection spread. The already established entry mechanism, via ACE2 has not yet successfully aided in the development of a suitable and reliable therapy. Taking in account the constant progression and deterioration of the cases worldwide, a different perspective and mechanistic approach is required, which has thrown light onto the cluster of differentiation 147 (CD147) transmembrane protein, as a novel route for SARS-CoV-2 entry. Despite lesser affinity towards COVID-19 virus, as compared to ACE2, this receptor provides a suitable justification behind elevated blood glucose levels in infected patients, retarded COVID-19 risk in women, enhanced susceptibility in geriatrics, greater infection susceptibility of T cells, infection prevalence in non-susceptible human cardiac pericytes and so on. The manuscript invokes the title role and distribution of CD147 in COVID-19 as an entry receptor and mediator of endocytosis-promoted entry of the virus, along with the "catch and clump" hypothesis, thereby presenting its Fundamental significance as a therapeutic target for potential candidates, such as Azithromycin, melatonin, statins, beta adrenergic blockers, ivermectin, Meplazumab etc. Thus, the authors provide a comprehensive review of a different perspective in COVID-19 infection, aiming to aid the researchers and virologists in considering all aspects of viral entry, in order to develop a sustainable and potential cure for the 2019 COVID-19 disease.


Assuntos
Basigina , COVID-19 , Glicoproteína da Espícula de Coronavírus , Anticorpos Monoclonais Humanizados , Diferenciação Celular , Feminino , Humanos , SARS-CoV-2
15.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201152

RESUMO

With advanced technology and its development, bioinformatics is one of the avant-garde fields that has managed to make amazing progress in the pharmaceutical-medical field by modeling the infrastructural dimensions of healthcare and integrating computing tools in drug innovation, facilitating prevention, detection/more accurate diagnosis, and treatment of disorders, while saving time and money. By association, bioinformatics and pharmacovigilance promoted both sample analyzes and interpretation of drug side effects, also focusing on drug discovery and development (DDD), in which systems biology, a personalized approach, and drug repositioning were considered together with translational medicine. The role of bioinformatics has been highlighted in DDD, proteomics, genetics, modeling, miRNA discovery and assessment, and clinical genome sequencing. The authors have collated significant data from the most known online databases and publishers, also narrowing the diversified applications, in order to target four major areas (tetrad): DDD, anti-microbial research, genomic sequencing, and miRNA research and its significance in the management of current pandemic context. Our analysis aims to provide optimal data in the field by stratification of the information related to the published data in key sectors and to capture the attention of researchers interested in bioinformatics, a field that has succeeded in advancing the healthcare paradigm by introducing developing techniques and multiple database platforms, addressed in the manuscript.


Assuntos
Biologia Computacional , Desenvolvimento de Medicamentos , Descoberta de Drogas , MicroRNAs , Técnicas Microbiológicas/métodos , Sequenciamento Completo do Genoma , Animais , COVID-19 , Indústria Farmacêutica , Estudo de Associação Genômica Ampla , Humanos , Farmacovigilância , Saúde Pública , Pesquisa Translacional Biomédica
16.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201647

RESUMO

Progressive degeneration of neurons and aggravation of dopaminergic neurons in the substantia nigra pars compacta results in the loss of dopamine in the brain of Parkinson's disease (PD) patients. Numerous therapies, exhibiting transient efficacy have been developed; however, they are mostly accompanied by side effects and limited reliability, therefore instigating the need to develop novel optimistic treatment targets. Significant therapeutic targets have been identified, namely: chaperones, protein Abelson, glucocerebrosidase-1, calcium, neuromelanin, ubiquitin-proteasome system, neuroinflammation, mitochondrial dysfunction, and the kynurenine pathway (KP). The role of KP and its metabolites and enzymes in PD, namely quinolinic acid (QUIN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranillic acid (3-HAA), kunurenine-3-monooxygenase (KMO), etc. has been reported. The neurotoxic QUIN, N-methyl-D-aspartate (NMDA) receptor agonist, and neuroprotective KYNA-which antagonizes QUIN actions-primarily justify the Janus-faced role of KP in PD. Moreover, KP has been reported to play a biomarker role in PD detection. Therefore, the authors detail the neurotoxic, neuroprotective, and immunomodulatory neuroactive components, alongside the upstream and downstream metabolic pathways of KP, forming a basis for a therapeutic paradigm of the disease while recognizing KP as a potential biomarker in PD, thus facilitating the development of a suitable target in PD management.


Assuntos
Biomarcadores/análise , Cinurenina/metabolismo , Doença de Parkinson/metabolismo , Sistema Nervoso Central/metabolismo , Microbioma Gastrointestinal , Humanos , Cinurenina/análise , Redes e Vias Metabólicas , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Terapia de Alvo Molecular/métodos , Estresse Oxidativo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/microbiologia
17.
Environ Sci Pollut Res Int ; 28(32): 43102-43113, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34145545

RESUMO

Inflammasome activity plays a vital role in various non-microbial disease states correlated with prolonged inflammation. NLRP3 inflammasome function and IL-1ß formation are augmented in obesity and several obesity-linked metabolic disorders (i.e. diabetes mellitus, hypertension, hepatic steatosis, cancer, arthritis, and sleep apnea). Also, several factors are associated with the progression of diseases viz. increased plasma glucose, fatty acids, and ß-amyloid are augmented during obesity and activate NLRP3 inflammasome expression. Prolonged NLRP3 stimulation seems to play significant role in various disorders, though better knowledge of inflammasome regulation and action might result in improved therapeutic tactics. Numerous compounds that mitigate NLRP3 inflammasome expression and suppress its chief effector, IL-1ß are presently studied in clinical phases as therapeutics to manage or prevent these common disorders. A deep research on the literature available till date for inflammasome in obesity was conducted using various medical sites like PubMed, HINARI, MEDLINE from the internet, and data was collected simultaneously. The present review aims to examine the prospects of inflammasome as a major progenitor in the progression of obesity via directing their role in regulating appetite.


Assuntos
Inflamassomos , Resistência à Insulina , Proteína 3 que Contém Domínio de Pirina da Família NLR , Obesidade , Tecido Adiposo , Humanos , Inflamação
18.
Environ Sci Pollut Res Int ; 28(30): 40515-40532, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34036497

RESUMO

The world has never been prepared for global pandemics like the COVID-19, currently posing an immense threat to the public and consistent pressure on the global healthcare systems to navigate optimized tools, equipments, medicines, and techno-driven approaches to retard the infection spread. The synergized outcome of artificial intelligence paradigms and human-driven control measures elicit a significant impact on screening, analysis, prediction, and tracking the currently infected individuals, and likely the future patients, with precision and accuracy, generating regular international and national data on confirmed, recovered, and death cases, as the current status of 3,820,869 infected patients worldwide. Artificial intelligence is a frontline concept, with time-saving, cost-effective, and productive access to disease management, rendering positive results in physician assistance in high workload conditions, radiology imaging, computational tomography, and database formulations, to facilitate availability of information accessible to researchers all over the globe. The review tends to elaborate the role of industry 4.0 technology, fast diagnostic procedures, and convolutional neural networks, as artificial intelligence aspects, in potentiating the COVID-19 management criteria and differentiating infection in SARS-CoV-2 positive and negative groups. Therefore, the review successfully supplements the processes of vaccine development, disease management, diagnosis, patient records, transmission inhibition, social distancing, and future pandemic predictions, with artificial intelligence revolution and smart techno processes to ensure that the human race wins this battle with COVID-19 and many more combats in the future.


Assuntos
COVID-19 , Doenças Transmissíveis , Inteligência Artificial , Humanos , Pandemias , SARS-CoV-2
19.
Environ Sci Pollut Res Int ; 28(28): 37060-37081, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34053042

RESUMO

Mitochondria are unique cell organelles, which exhibit multifactorial roles in numerous cell physiological processes, significantly preserving the integrity of neural synaptic interconnections, mediating ATP production, and regulating apoptotic signaling pathways and calcium homeostasis. Multiple neurological disorders occur as a consequence of impaired mitochondrial functioning, with greater sensitivity of dopaminergic (DA) neurons to mitochondrial dysfunction, due to oxidative nature and low mitochondrial mass, thus supporting the contribution of mitochondrial impairment in Parkinson's disorder (neuronal damage due to curbed dopamine levels). The pathophysiology of the second most common disorder, PD, is potentiated by various mitochondrial homeostasis regulating genes, as discussed in the review. The PD symptoms are known to be aggravated by multiple mitochondria-linked alterations, like reactive oxygen species (ROS) production, Ca2+ buffering, imbalanced mitochondrial dynamics (fission, fusion, mitophagy), biogenetic dysfunctions, disrupted mitochondrial membrane potential (MMP), protein aggregation, neurotoxins, and genetic mutations, which manifest the central involvement of unhealthy mitochondria in neurodegeneration, resulting in retarded DA neurons in region of substantia nigra pars compacta (SNpc), causing PD. Furthermore, the review tends to target altered mitochondrial components, like oxidative stress, inflammation, biogenetic alterations, impaired dynamics, uncontrolled homeostasis, and genetic mutations, to provide a sustainable and reliable alternative in PD therapeutics and to overcome the pitfalls of conventional therapeutic agents. Therefore, the authors elaborate the relationship between PD pathogenesis and mitochondrial dysfunctions, followed by a suitable mitochondria-targeting therapeutic portfolio, as well as future considerations, aiding the researchers to investigate novel strategies to mitigate the severity of the disease.


Assuntos
Doença de Parkinson , Neurônios Dopaminérgicos/metabolismo , Humanos , Mitocôndrias , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença
20.
Int J Mol Sci ; 22(6)2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33804729

RESUMO

Obesity or overweight are not superficial problems, constituting a pressing issue. The obesity index has almost tripled since 1975, which is an alarming state. Most of the individuals are currently becoming overweight or have inappropriate body mass index (BMI) conditions. Obesity is characterized by increased fat accumulation and thus poses a higher health risk. There is increased size and volume of fat cells in the body, which usually accounts for obesity. Many investigations have been carried out in this area, such as behavioral improvements, dietary changes, chemical involvements, etc., but presently no such goals are established to manage these health concerns. Based on previous literature reports and our interpretation, the current review indicates the involvement of various transcriptional and transporter functions in modifying the above-mentioned health conditions. Various transcriptional factors such as Forkhead box O1 (FoxO1) impart a significant effect on the physiology and pathology of metabolic dysfunction such as obesity. FoxO1 plays a dual role whether in the progression or suppression of metabolic processes depending on its targets. Thus, in the current study, will be discussed the dual role of FoxO1 in metabolic conditions (such as obesity), also summarizing the role of various other transcriptional factors involved in obesity.


Assuntos
Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Predisposição Genética para Doença , Obesidade/etiologia , Obesidade/metabolismo , Adipogenia , Animais , Metabolismo Energético , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Insulina/metabolismo , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Obesidade/patologia , Especificidade de Órgãos , Estresse Oxidativo/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
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