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Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremor, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves at the potential of drug delivery systems based on chitosan (CS) to treat PD.
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Quercetin is a natural flavonoid with various pharmacological actions such as anti-inflammatory, antioxidant, antimicrobial, anticancer, antiviral, antidiabetic, cardioprotective, neuroprotective, and antiviral activities. Looking at these enormous potentials, researchers have explored how they can be used to manage numerous cancers. It's been studied for cancer management due to its anti-angiogenesis, anti-metastatic, and antiproliferative mechanisms. Despite having these proven pharmacological activities, the clinical use of quercetin is limited due to its first-- pass metabolism, poor solubility, and bioavailability. To address these shortcomings, researchers have fabricated various nanocarriers-based formulations to fight cancer. The present review overshadows the pharmacological potential, mechanisms, and application of nanoformulations against different cancers.
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Parkinsons disease (PD) is a chronic fast growing neurodegenerative disorder of Central Nervous System (CNS) characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and formation of Lewy bodies (LBs) which causes dopamine deficiency within basal ganglia leading to motor and non-motor manifestation. According to reports, many factors are responsible for pathogenesis of PD which includes environmental factors, genetic factors, and aging factors. Whereas death of dopaminergic neurons is also caused by oxidative stress, neuroinflammation, and autophagy disorder. Molecular chaperones/co-chaperones are proteins that binds to an unstable conformer of another protein and stabilizes it. Chaperones prevent incorrect interaction between non-native polypeptides which increases the yield but not the rate of reaction. The Bcl-2-associated athanogene (BAG) is a multifunctional group of proteins belonging to BAG family of co-chaperones. Recent studies demonstrates that chaperones interact with PD-related proteins. Co-chaperones like BAG family proteins regulate the function of chaperones. Molecular chaperones regulate the mitochondrial functions by interacting with the PD-related proteins associated with it. This review studies the contribution of chaperones and PD-related proteins in pathogenesis of PD aiming to provide an alternate molecular target for preventing the disease progression.
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Doença de Parkinson , Humanos , Doença de Parkinson/metabolismo , Animais , Chaperonas Moleculares/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neurônios Dopaminérgicos/metabolismoRESUMO
This manuscript proposes an innovative approach to mitigate the gastrointestinal adversities linked with nonsteroidal anti-inflammatory drugs (NSAIDs) by exploiting amylose as a novel drug delivery carrier. The intrinsic attributes of V-amylose, such as its structural uniqueness, biocompatibility and biodegradability, as well as its capacity to form inclusion complexes with diverse drug molecules, are meticulously explored. Through a comprehensive physicochemical analysis of V-amylose and ulcerogenic NSAIDs, the plausibility of amylose as a protective carrier for ulcerogenic NSAIDs to gastrointestinal regions is elucidated. This review further discusses the potential therapeutic advantages of amylose-based drug delivery systems in the management of gastric ulcers. By providing controlled release kinetics and enhanced bioavailability, these systems offer promising prospects for the development of more effective ulcer therapies.
[Box: see text].
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Amilose , Anti-Inflamatórios não Esteroides , Amilose/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Humanos , Portadores de Fármacos/química , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Sistemas de Liberação de Medicamentos , AnimaisRESUMO
Nucleic acid delivery by viral and non-viral methods has been a cornerstone for the contemporary gene therapy aimed at correcting the defective genes, replacing of the missing genes, or downregulating the expression of anomalous genes is highly desirable for the management of various diseases. Ostensibly, it becomes paramount for the delivery vectors to intersect the biological barriers for accessing their destined site within the cellular environment. However, the lipophilic nature of biological membranes and their potential to limit the entry of large sized, charged, hydrophilic molecules thus presenting a sizeable challenge for the cellular integration of negatively charged nucleic acids. Furthermore, the susceptibility of nucleic acids towards the degrading enzymes (nucleases) in the lysosomes present in cytoplasm is another matter of concern for their cellular and nuclear delivery. Hence, there is a pressing need for the identification and development of cationic delivery systems which encapsulate the cargo nucleic acids where the charge facilitates their cellular entry by evading the membrane barriers, and the encapsulation shields them from the enzymatic attack in cytoplasm. Cycloamylose bearing a closed loop conformation presents a robust candidature in this regard owing to its remarkable encapsulating tendency towards nucleic acids including siRNA, CpG DNA, and siRNA. The presence of numerous hydroxyl groups on the cycloamylose periphery provides sites for its chemical modification for the introduction of cationic groups, including spermine, (3-Chloro-2 hydroxypropyl) trimethylammonium chloride (Q188), and diethyl aminoethane (DEAE). The resulting cationic cycloamylose possesses a remarkable transfection efficiency and provides stability to cargo oligonucleotides against endonucleases, in addition to modulating the undesirable side effects such as unwanted immune stimulation. Cycloamylose is known to interact with the cell membranes where they release certain membrane components such as phospholipids and cholesterol thereby resulting in membrane destabilization and permeabilization. Furthermore, cycloamylose derivatives also serve as formulation excipients for improving the efficiency of other gene delivery systems. This review delves into the various vector and non-vector-based gene delivery systems, their advantages, and limitations, eventually leading to the identification of cycloamylose as an ideal candidate for nucleic acid delivery. The synthesis of cationic cycloamylose is briefly discussed in each section followed by its application for specific delivery/transfection of a particular nucleic acid.
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Cátions , Ácidos Nucleicos , Ácidos Nucleicos/química , Cátions/química , Humanos , Nanopartículas/química , Portadores de Fármacos/química , Técnicas de Transferência de Genes , AnimaisRESUMO
Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aß), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aß and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aß. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed.
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Lung cancer (LC) is the second leading cause of death across the globe after breast cancer. There are two types of LC viz. small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of all LC cases. NSCLC affects smokers and people who do not smoke and mainly arises in bronchi and peripheral lungs tissue. LC is often characterized by the alterations of key genes such as EGFR, Wnt/ß-catenin signaling, ALK, MET, K-Ras and p53 and downstream signaling pathways associated with tumor growth, differentiation, and survival. Numerous miRNAs have been discovered as a result of advances in biotechnology to treat LC. Various miRNAs those have been identified to treat LC include mir-Let7, mir-34a, mir-134, mir-16-1, mir-320a, mir-148a, mir-125a-5p, mir-497, mir-29, mir-133a, and mir-29a-3p. These miRNAs target various signaling pathways that are involved in pathogenesis of LC. However, due to rapid RNAse degradation, quick clearance, and heat instability, associated with necked miRNA leads to less effective therapeutic effect against LC. Therefore, to overcome these challenges nanocarrier loaded with miRNAs have been reported. They have been found promising because they have the capacity to target the tumor as well as they can penetrate the tumors deep due to nanometer size. Some of the clinical trials have been performed using miR-34a and let-7 for the treatment of LC. In the present manuscript we highlight the role miRNAs as well as their nanoparticle in tumor suppression.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , MicroRNAs/metabolismo , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Pulmão/patologia , Regulação Neoplásica da Expressão GênicaRESUMO
The eye is a most delicate organ protected by several complex biological barriers that are static and dynamic. The presence of these ocular barriers retards drug absorption from topically applied dosage forms at the conjunctival sac. The efficient topical delivery of the drug into the globe is more difficult to achieve and there is a need to develop a topical formulation that may reduce the use of injections and increase patient compliance with decreased frequency of administration. In the advancements of research in nanotechnology, nanoemulsions can be used as biocompatible carriers to deliver the drug to the ocular cavity. The lipophilic globules can increase the solubility of hydrophobic cargos which provides increased permeation ability and ocular bioavailability which can sustain drug release and corneal retention. Because of their small size, these formulations do not cause blurring of vision. Nanoemulsions (NEs) over the past decade have been used to treat several ocular diseases in the anterior eye segment. This review summarizes the economic burden, pathology of ocular diseases, formulation considerations for ocular formulations, and recent advances of these NEs as effective carriers for ocular drug delivery highlighting their performance in pre-clinical studies.
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Lung cancer (LC) is the leading cause of cancer-related mortality, and it is caused by many factors including cigarette smoking. Despite numerous treatment strategies for LC, its five-year survival is still poor (<20â¯%), attributable to treatment resistance and lack of early diagnosis and intervention. Importantly, LC incidence is higher in patients affected by chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disorder (COPD), and LC shares with other CRDs common pathophysiological features including chronic inflammation, oxidative stress, cellular senescence, and airway remodelling. Remodelling is a complex process resulting from the aberrant activation of tissue repair secondary to chronic inflammation, oxidative stress, and tissue damage observed in the airways of CRD patients, and it is characterized by irreversible airway structural and functional alterations, concomitantly with tissue fibrosis, epithelial-to-mesenchymal transition (EMT), excessive collagen deposition, and thickening of the basement membrane. Many processes involved in remodelling, particularly EMT, are also fundamental for LC pathogenesis, highlighting a potential connection between CRDs and LC. This provides rationale for the development of novel treatment strategies aimed at targeting components of the remodelling pathways. In this study, we tested the in vitro therapeutic activity of rat fecal microbiome extract (FME) on A549 human lung adenocarcinoma cells. We show that treatment with FME significantly downregulates the expression of six proteins whose function is at the forefront between airway remodelling and LC development: Snail, SPARC, MUC-1, Osteopontin, MMP-2, and HIF-1α. The results of this study, if confirmed by further investigations, provide proof-of-concept for a novel approach in the treatment of LC, focused on tackling the airway remodelling mechanisms underlying the increased susceptibility to develop LC observed in CRD patients.
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Remodelação das Vias Aéreas , Regulação para Baixo , Neoplasias Pulmonares , Remodelação das Vias Aéreas/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Animais , Ratos , Células A549 , Fezes/microbiologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacosRESUMO
The intricate molecular landscape of cancer pathogenesis continues to captivate researchers worldwide, with Circular RNAs (circRNAs) emerging as pivotal players in the dynamic regulation of biological functions. The study investigates the elusive link between circRNAs and the Transforming Growth Factor-ß (TGF-ß) signalling pathway, exploring their collective influence on cancer progression and metastasis. Our comprehensive investigation begins by profiling circRNA expression patterns in diverse cancer types, revealing a repertoire of circRNAs intricately linked to the TGF-ß pathway. Through integrated bioinformatics analyses and functional experiments, we elucidate the specific circRNA-mRNA interactions that modulate TGF-ß signalling, unveiling the regulatory controls governing this crucial pathway. Furthermore, we provide compelling evidence of the impact of circRNA-mediated TGF-ß modulation on key cellular processes, including epithelial-mesenchymal transition (EMT), migration, and cell proliferation. In addition to their mechanistic roles, circRNAs have shown promise as diagnostic and prognostic biomarkers, as well as potential molecular targets for cancer therapy. Their ability to modulate critical pathways, such as the TGF-ß signalling axis, underscores their significance in cancer biology and clinical applications. The intricate interplay between circRNAs and TGF-ß is dissected, uncovering novel regulatory circuits that contribute to the complexity of cancer biology. This review unravels a previously unexplored dimension of carcinogenesis, emphasizing the crucial role of circRNAs in shaping the TGF-ß signalling landscape.
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The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.
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The present work aimed to develop and evaluate AmB-loaded nano-emulsion (AmB-NE) which will augment the solubility of AmB and lead to enhanced anti-leishmanial activity. The composition of AmB-NE was optimized by systematic screening followed by DoE-extreme vertices mixture design. The optimized NE revealed mean droplet size and PDI of 44.19 ± 5.5 nm, 0.265 ± 0.0723, respectively. The NE could efficiently encapsulate AmB with drug content and efficiency 83.509 ± 0.369% and 81.659 ± 0.013%, respectively. The presence of cholesterol and stearyl amine retarded the release (P < 0.0001) of AmB significantly compared to AmB suspension. The AmB-NE and pure AmB suspension demonstrated the IC50 of 0.06309 µg/mL and 0.3309 µg/mL against L.donovani promastigotes after 48 h incubation. The formulation was robust at all exaggerated stability conditions such as freeze-thaw and centrifugation. These findings indicate that AmB-NE is an attractive approach to treat visceral leishmaniasis with improved activity.
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Antiprotozoários , Leishmania donovani , Leishmania , Leishmaniose Visceral , Animais , Anfotericina B/farmacologia , Antiprotozoários/farmacologia , Leishmaniose Visceral/tratamento farmacológico , Emulsões/farmacologiaRESUMO
Lung cancer (LCs) is still a serious health problem globally, with many incidences attributed to environmental triggers such as Volatile Organic Compounds (VOCs). VOCs are a broad class of compounds that can be released via various sources, including industrial operations, automobile emissions, and indoor air pollution. VOC exposure has been linked to an elevated risk of lung cancer via multiple routes. These chemicals can be chemically converted into hazardous intermediate molecules, resulting in DNA damage and genetic alterations. VOCs can also cause oxidative stress, inflammation, and a breakdown in the cellular protective antioxidant framework, all of which contribute to the growth of lung cancer. Moreover, VOCs have been reported to alter critical biological reactions such as cell growth, apoptosis, and angiogenesis, leading to tumor development and metastasis. Epidemiological investigations have found a link between certain VOCs and a higher probability of LCs. Benzene, formaldehyde, and polycyclic aromatic hydrocarbons (PAHs) are some of the most well-researched VOCs, with comprehensive data confirming their cancer-causing potential. Nevertheless, the possible health concerns linked with many more VOCs and their combined use remain unknown, necessitating further research. Identifying the toxicological consequences of VOCs in LCs is critical for establishing focused preventative tactics and therapeutic strategies. Better legislation and monitoring mechanisms can limit VOC contamination in occupational and environmental contexts, possibly reducing the prevalence of LCs. Developing VOC exposure indicators and analyzing their associations with genetic susceptibility characteristics may also aid in early identification and targeted therapies.
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Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Neoplasias Pulmonares , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/efeitos adversos , Compostos Orgânicos Voláteis/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análiseRESUMO
Sepsis, a potentially fatal illness caused by an improper host response to infection, remains a serious problem in the world of healthcare. In recent years, the role of ncRNA has emerged as a pivotal aspect in the intricate landscape of cellular regulation. The exploration of ncRNA-mediated regulatory networks reveals their profound influence on key molecular pathways orchestrating pyroptotic responses during septic conditions. Through a comprehensive analysis of current literature, we navigate the diverse classes of ncRNAs, including miRNAs, lncRNAs, and circRNAs, elucidating their roles as both facilitators and inhibitors in the modulation of pyroptotic processes. Furthermore, we highlight the potential diagnostic and therapeutic implications of targeting these ncRNAs in the context of sepsis, aiming to cover the method for novel and effective strategies to mitigate the devastating consequences of septic pathogenesis. As we unravel the complexities of this regulatory axis, a deeper understanding of the intricate crosstalk between ncRNAs and pyroptosis emerges, offering promising avenues for advancing our approach to sepsis intervention. The intricate pathophysiology of sepsis is examined in this review, which explores the dynamic interaction between ncRNAs and pyroptosis, a highly regulated kind of programmed cell death.
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MicroRNAs , RNA Longo não Codificante , Sepse , Humanos , Piroptose/fisiologia , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genéticaRESUMO
Circular RNAs (circRNAs) have been recognized as key components in the intricate regulatory network of the KRAS pathway across various cancers. The KRAS pathway, a central signalling cascade crucial in tumorigenesis, has gained substantial emphasis as a possible therapeutic target. CircRNAs, a subgroup of non-coding RNAs known for their closed circular arrangement, play diverse roles in gene regulation, contributing to the intricate landscape of cancer biology. This review consolidates existing knowledge on circRNAs within the framework of the KRAS pathway, emphasizing their multifaceted functions in cancer progression. Notable circRNAs, such as Circ_GLG1 and circITGA7, have been identified as pivotal regulators in colorectal cancer (CRC), influencing KRAS expression and the Ras signaling pathway. Aside from their significance in gene regulation, circRNAs contribute to immune evasion, apoptosis, and drug tolerance within KRAS-driven cancers, adding complexity to the intricate interplay. While our comprehension of circRNAs in the KRAS pathway is evolving, challenges such as the diverse landscape of KRAS mutant tumors and the necessity for synergistic combination therapies persist. Integrating cutting-edge technologies, including deep learning-based prediction methods, holds the potential for unveiling disease-associated circRNAs and identifying novel therapeutic targets. Sustained research efforts are crucial to comprehensively unravel the molecular mechanisms governing the intricate interplay between circRNAs and the KRAS pathway, offering insights that could potentially revolutionize cancer diagnostics and treatment strategies.
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Neoplasias , RNA Circular , Humanos , RNA Circular/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias/genética , Processos NeoplásicosRESUMO
Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway.
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Neoplasias Encefálicas , Glioblastoma , MicroRNAs , Humanos , Receptores ErbB/metabolismo , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Transdução de Sinais , MicroRNAs/metabolismo , RNA não Traduzido/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismoRESUMO
Long non-coding RNAs (lncRNAs) have been demonstrated to have a crucial function in the modulation of the activity of genes, impacting a variety of homeostatic processes involving growth, survival, movement, and genomic consistency. Certain lncRNAs' aberrant expression has been linked to carcinogenesis, tumor growth, and therapeutic resistance. They are beneficial for the management of malignancies since they can function as cancer-causing or cancer-suppressing genes and behave as screening or prognosis indicators. The modulation of the tumor microenvironment, metabolic modification, and spread have all been linked to lncRNAs in lung cancer. Recent research has indicated that lncRNAs may interact with various mTOR signalling systems to control expression in lung cancer. Furthermore, the route can affect how lncRNAs are expressed. Emphasizing the function of lncRNAs as crucial participants in the mTOR pathway, the current review intends to examine the interactions between the mTOR cascade and the advancement of lung cancer. The article will shed light on the roles and processes of a few lncRNAs associated with the development of lung cancer, as well as their therapeutic prospects.
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Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinogênese/genética , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Microambiente TumoralRESUMO
Tumour suppressor genes play a cardinal role in the development of a large array of human cancers, including lung cancer, which is one of the most frequently diagnosed cancers worldwide. Therefore, extensive studies have been committed to deciphering the underlying mechanisms of alterations of tumour suppressor genes in governing tumourigenesis, as well as resistance to cancer therapies. In spite of the encouraging clinical outcomes demonstrated by lung cancer patients on initial treatment, the subsequent unresponsiveness to first-line treatments manifested by virtually all the patients is inherently a contentious issue. In light of the aforementioned concerns, this review compiles the current knowledge on the molecular mechanisms of some of the tumour suppressor genes implicated in lung cancer that are either frequently mutated and/or are located on the chromosomal arms having high LOH rates (1p, 3p, 9p, 10q, 13q, and 17p). Our study identifies specific genomic loci prone to LOH, revealing a recurrent pattern in lung cancer cases. These loci, including 3p14.2 (FHIT), 9p21.3 (p16INK4a), 10q23 (PTEN), 17p13 (TP53), exhibit a higher susceptibility to LOH due to environmental factors such as exposure to DNA-damaging agents (carcinogens in cigarette smoke) and genetic factors such as chromosomal instability, genetic mutations, DNA replication errors, and genetic predisposition. Furthermore, this review summarizes the current treatment landscape and advancements for lung cancers, including the challenges and endeavours to overcome it. This review envisages inspired researchers to embark on a journey of discovery to add to the list of what was known in hopes of prompting the development of effective therapeutic strategies for lung cancer.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Perda de Heterozigosidade , Genes Supressores de Tumor , Mutação/genética , Transformação Celular Neoplásica/genéticaRESUMO
Over the last decade, nanoparticles have found great interest among scientists and researchers working in various fields within the realm of biomedicine including drug delivery, gene delivery, diagnostics, targeted therapy and biomarker mapping. While their physical and chemical properties are impressive, there is growing concern about the toxicological potential of nanoparticles and possible adverse health effects as enhanced exposure of biological systems to nanoparticles may result in toxic effects leading to serious contraindications. Toxicity associated with nanoparticles (nanotoxicity) may include the undesired response of several physiological mechanisms including the distressing of cells by external and internal interaction with nanoparticles. However, comprehensive knowledge of nanotoxicity mechanisms and mitigation strategies may be useful to overcome the hazardous situation while treating diseases with therapeutic nanoparticles. With the same objectives, this review discusses various mechanisms of nanotoxicity and provides an overview of the current state of knowledge on the impact of nanotoxicity on biological control systems and organs including liver, brain, kidneys and lungs. An attempt also been made to present various approaches of scientific research and strategies that could be useful to overcome the effect of nanotoxicity during the development of nanoparticle-based systems including coating, doping, grafting, ligation and addition of antioxidants.
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Nanopartículas , Humanos , Nanopartículas/toxicidade , Animais , Sistemas de Liberação de MedicamentosRESUMO
Lung cancer stands as the primary contributor to cancer-related fatalities worldwide, affecting both genders. Two primary types exist where non-small cell lung cancer (NSCLC), accounts for 80-85% and SCLC accounts for 10-15% of cases. NSCLC subtypes include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Smoking, second-hand smoke, radon gas, asbestos, and other pollutants, genetic predisposition, and COPD are lung cancer risk factors. On the other hand, stresses such as DNA damage, telomere shortening, and oncogene activation cause a prolonged cell cycle halt, known as senescence. Despite its initial role as a tumor-suppressing mechanism that slows cell growth, excessive or improper control of this process can cause age-related diseases, including cancer. Cellular senescence has two purposes in lung cancer. Researchers report that senescence slows tumor growth by constraining multiplication of impaired cells. However, senescent cells also demonstrate the pro-inflammatory senescence-associated secretory phenotype (SASP), which is widely reported to promote cancer. This review will look at the role of cellular senescence in lung cancer, describe its diagnostic markers, ask about current treatments to control it, look at case studies and clinical trials that show how senescence-targeting therapies can be used in lung cancer, and talk about problems currently being faced, and possible solutions for the same in the future.