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1.
Int J Nanomedicine ; 19: 2889-2915, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525012

RESUMO

Since the beginning of the coronavirus pandemic in late 2019, viral infections have become one of the top three causes of mortality worldwide. Immunization and the use of immunomodulatory drugs are effective ways to prevent and treat viral infections. However, the primary therapy for managing viral infections remains antiviral and antiretroviral medication. Unfortunately, these drugs are often limited by physicochemical constraints such as low target selectivity and poor aqueous solubility. Although several modifications have been made to enhance the physicochemical characteristics and efficacy of these drugs, there are few published studies that summarize and compare these modifications. Our review systematically synthesized and discussed antiviral drug modification reports from publications indexed in Scopus, PubMed, and Google Scholar databases. We examined various approaches that were investigated to address physicochemical issues and increase activity, including liposomes, cocrystals, solid dispersions, salt modifications, and nanoparticle drug delivery systems. We were impressed by how well each strategy addressed physicochemical issues and improved antiviral activity. In conclusion, these modifications represent a promising way to improve the physicochemical characteristics, functionality, and effectiveness of antivirals in clinical therapy.


Assuntos
Infecções por Coronavirus , Viroses , Humanos , Antivirais/uso terapêutico , Preparações Farmacêuticas/química , Viroses/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Sistemas de Liberação de Medicamentos
2.
Heliyon ; 10(1): e23624, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38187251

RESUMO

Halal is a crucial concept for Muslim consumers regarding consumed products, including pharmaceutical ingredients, which are essential in modern medicine. To address the issue of using porcine-sourced ingredients in pharmaceuticals, it is essential to search for halal alternatives derived from poultry, animal by-products from meat processing, marine sources, and plants. However, the complexity of this problem is further compounded by the rapid advances in innovation and technology, which can lead to adulteration of ingredients derived from pigs. Other challenges include the sustainability of alternative materials, management of waste or by-products practice, halal awareness, certification, government policies, religious adherence of consumers, food suppliers, marketers, and purchasing of products. The importance of halal and non-halal problems, specifically in the context of pharmaceutical materials, is still rarely discussed, including alternatives derived from poultry, animal by-products, marine sources, and plants. Due to the increasing global population, there is a growing need to increase awareness and concern among Muslim consumers for halal products, including pharmaceuticals. Therefore, this research aimed to investigate the importance of halal and non-halal issues in pharmaceutical ingredients, the potential impact on the Muslim community, as well as opportunities and challenges in the search for alternative ingredients.

3.
Molecules ; 28(22)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38005306

RESUMO

α-mangostin (AM) is a promising natural anticancer agent that can be used in cancer research. However, its effectiveness can be limited by poor solubility and bioavailability. To address this issue, chitosan-based nanoparticles (CSNPs) have been investigated as a potential delivery system to enhance the cytotoxicity to cancer cells and improve selectivity against normal cells. In this study, we developed folate-conjugated chitosan nanoparticles (F-CS-NPs) using a carbodiimide-based conjugation method to attach folate to chitosan (CS), which have different molecular weights. The NPs were crosslinked using tripolyphosphate (TPP) via ionic gelation. To characterize the F-CS-NPs, we utilized various analytical techniques, including transmission electron microscopy (TEM) to evaluate the particle size and morphology, Fourier-transform infrared spectroscopy (FTIR) to confirm the presence of functional groups, and ultraviolet-visible spectroscopy (UV-Vis) to measure the absorption spectrum and confirm the presence of folate. The particle size of AM-F-CS-NPs ranged from 180 nm to 250 nm, with many having favorable charges ranging from +40.33 ± 3.4 to 10.69 ± 1.3 mV. All NPs exhibited the same spherical morphology. The use of F-CS-NPs increased drug release, followed by a sustained release pattern. We evaluated the cytotoxicity of AM, AM-F-CS-HMW, and AM-F-CS-LMW NPs against MCF-7 cells and found IC50 values of 8.47 ± 0.49, 5.3 ± 0.01, and 4.70 ± 0.11 µg/mL, respectively. These results confirm the improved cytotoxicity of AM in MCF-7 cells when delivered via F-CS-NPs. Overall, our in vitro study demonstrated that the properties of F-CS-NPs greatly influence the cytotoxicity of AM in MCF-7 breast cancer cells (significantly different (p < 0.05)). The use of F-CS-NPs as a drug-delivery system for AM may have the potential to develop novel therapies for breast cancer.


Assuntos
Neoplasias da Mama , Quitosana , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Quitosana/química , Células MCF-7 , Ácido Fólico , Nanopartículas/química , Tamanho da Partícula , Portadores de Fármacos/química
4.
Behav Brain Res ; 452: 114568, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37414223

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative condition in civilizations worldwide. The distinctive occurrence of amyloid-beta (Aß) accumulation into insoluble fibrils is part of the disease pathophysiology with Aß42 being the most toxic and aggressive Aß species. The polyphenol, p-Coumaric acid (pCA), has been known to boost a number of therapeutic benefits. Here, pCA's potential to counteract the negative effects of Aß42 was investigated. First, pCA was confirmed to reduce Aß42 fibrillation using an in vitro activity assay. The compound was next examined on Aß42-exposed PC12 neuronal cells and was found to significantly decrease Aß42-induced cell mortality. pCA was then examined using an AD Drosophila melanogaster model. Feeding of pCA partially reversed the rough eye phenotype, significantly lengthened AD Drosophila's lifespan, and significantly enhanced the majority of the AD Drosophila's mobility in a sex-dependent manner. The findings of this study suggest that pCA may have therapeutic benefits for AD.


Assuntos
Doença de Alzheimer , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Drosophila , Drosophila melanogaster , Peptídeos beta-Amiloides , Fragmentos de Peptídeos
5.
Polymers (Basel) ; 15(13)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37447598

RESUMO

Breast cancer is a major cause of death globally, accounting for around 13% of all deaths. Chemotherapy, the common treatment for cancer, can have side effects that lead to the production of reactive oxygen species (ROS) and an increase in oxidative stress in the body. Antioxidants are important for maintaining the health of cells and helping the immune system function properly. They play a crucial role in balancing the body's internal environment. Using natural antioxidants is an alternative to mitigate the harmful effects of oxidative stress. However, around 80% of natural antioxidants have limited effectiveness when taken orally because they do not dissolve well in water or other solvents. This poor solubility affects their ability to be absorbed by the body and limits their bioavailability. One strategy that has been considered is to increase their water solubility to increase their oral bioavailability. Chitosan-based nanoparticle (CSNP) systems have been extensively explored due to their reliability and simpler synthesis routes. This review focuses on the various methods of chitosan-based nanoformulation for developing effective oral dosage forms for natural antioxidants based on the pharmacokinetics and pharmacodynamics properties. Chitosan (CS) could be a model, because of its wide use in polymeric NPs research, thus providing a better understanding of the role of vehicles that carry natural antioxidants in maintaining the stability and enhancing the performance of cancer drugs.

6.
J Gerontol A Biol Sci Med Sci ; 78(11): 1944-1952, 2023 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-37453137

RESUMO

Alzheimer's disease (AD) is the most prevalent type of dementia globally. The accumulation of amyloid-beta (Aß) extracellular senile plaques in the brain is one of the hallmark mechanisms found in AD. Aß42 is the most damaging and aggressively aggregating Aß isomer produced in the brain. Although Aß42 has been extensively researched as a crucial peptide connected to the development of the characteristic amyloid fibrils in AD, the specifics of its pathophysiology are still unknown. Therefore, the main objective was to identify novel compounds that could potentially mitigate the negative effects of Aß42. 3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-carbonyl]amino]propanoic acid (THICAPA) was identified as a ligand for Aß42 and for reducing fibrillary Aß42 aggregation. THICAPA also improved cell viability when administered to PC12 neuronal cells that were exposed to Aß42. Additionally, this compound diminished Aß42 toxicity in the current AD Drosophila model by rescuing the rough eye phenotype, prolonging the life span, and enhancing motor functions. Through next-generation RNA-sequencing, immune response pathways were downregulated in response to THICAPA treatment. Thus, this study suggests THICAPA as a possible disease-modifying treatment for AD.


Assuntos
Doença de Alzheimer , Tetra-Hidroisoquinolinas , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Drosophila/metabolismo , Propionatos/farmacologia , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos , Tetra-Hidroisoquinolinas/farmacologia
7.
Mol Neurobiol ; 60(8): 4716-4730, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37145377

RESUMO

Alzheimer's disease (AD) is the most common neurological ailment worldwide. Its process comprises the unique aggregation of extracellular senile plaques composed of amyloid-beta (Aß) in the brain. Aß42 is the most neurotoxic and aggressive of the Aß42 isomers released in the brain. Despite much research on AD, the complete pathophysiology of this disease remains unknown. Technical and ethical constraints place limits on experiments utilizing human subjects. Thus, animal models were used to replicate human diseases. The Drosophila melanogaster is an excellent model for studying both physiological and behavioural aspects of human neurodegenerative illnesses. Here, the negative effects of Aß42-expression on a Drosophila AD model were investigated through three behavioural assays followed by RNA-seq. The RNA-seq data was verified using qPCR. AD Drosophila expressing human Aß42 exhibited degenerated eye structures, shortened lifespan, and declined mobility function compared to the wild-type Control. RNA-seq revealed 1496 genes that were differentially expressed from the Aß42-expressing samples against the control. Among the pathways that were identified from the differentially expressed genes include carbon metabolism, oxidative phosphorylation, antimicrobial peptides, and longevity-regulating pathways. While AD is a complicated neurological condition whose aetiology is influenced by a number of factors, it is hoped that the current data will be sufficient to give a general picture of how Aß42 influences the disease pathology. The discovery of molecular connections from the current Drosophila AD model offers fresh perspectives on the usage of this Drosophila which could aid in the discovery of new anti-AD medications.


Assuntos
Doença de Alzheimer , Humanos , Animais , Doença de Alzheimer/patologia , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , RNA-Seq , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/metabolismo , Modelos Animais de Doenças
8.
Malays J Med Sci ; 30(1): 92-106, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36875187

RESUMO

Background: The present study aimed to understand the characterisation of human hippocampal astrocyte following hypoxia exposure. Based on the preliminary screening, 15 min was chosen as the time point and the cells were exposed to different oxygen percentages. Methods: The Trypan blue viability assay used to examine cell death. Immunofluorescence assay, glial fibrillary acidic protein (GFAP) was used to portray the morphology of astrocytes. The hypoxia-inducible factor 1 (HIF-1) staining was performed to confirm hypoxia induced cell death and there was a dramatic expression of HIF-1α displayed in exposed astrocyte cells compared to the control. In molecular level, genes were chosen, such as glyceraldehyde 3-phosphate dehydrogenase (GAPDH), GFAP, HIF-1α and B-cell lymphoma 2 (Bcl-2) and ran the reverse transcription-polymerase chain reaction (RT-PCR). Results: Microscope revealed a filamentous and clear nucleus appearance in a control whereas the rupture nuclei with no rigid structure of the cell were found in the 3% oxygen. The control and hypoxia cells were also stained with the annexin V-fluorescein isothiocyanate (annexin V-FITC). Fluorescence microscope reveals astrocyte cells after hypoxia showed higher expression of nuclei but not in control. Merging PI and FITC showed the differences of nuclei expression between the control and hypoxia. In the molecular analysis, there were significant changes of GFAP, HIF-1α and Bcl-2 in hypoxia exposed cells when compared to the control group. Conclusion: Cells that were exposed to hypoxia (3% oxygen for 15 min) clearly showed damage. General view of human hippocampal astrocyte genomic response to hypoxia was obtained.

9.
Pharmaceutics ; 15(3)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36986740

RESUMO

Despite recent advances, cancer remains the primary killer on a global scale. Numerous forms of research have been conducted to discover novel and efficient anticancer medications. The complexity of breast cancer is a major challenge which is coupled with patient-to-patient variations and heterogeneity between cells within the tumor. Revolutionary drug delivery is expected to provide a solution to that challenge. Chitosan nanoparticles (CSNPs) have prospects as a revolutionary delivery system capable of enhancing anticancer drug activity and reducing negative impacts on normal cells. The use of smart drug delivery systems (SDDs) as delivering materials to improve the bioactivity of NPs and to understand the intricacies of breast cancer has garnered significant interest. There are many reviews about CSNPs that present various points of view, but they have not yet described a series in cancer therapy from cell uptake to cell death. With this description, we will provide a more complete picture for designing preparations for SDDs. This review describes CSNPs as SDDSs, enhancing cancer therapy targeting and stimulus response using their anticancer mechanism. Multimodal chitosan SDDs as targeting and stimulus response medication delivery will improve therapeutic results.

10.
Polymers (Basel) ; 14(15)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35956654

RESUMO

The application of α-mangostin (AMG) in breast cancer research has wide intentions. Chitosan-based nanoparticles (CSNPs) have attractive prospects for developing anticancer drugs, especially in their high flexibility for modification to enhance their anticancer action. This research aimed to study the impact of depolymerized chitosan (CS) on the cytotoxicity enhancement of AMG in MCF-7 breast cancer cells. CSNPs effectivity depends on size, shape, crystallinity degree, and charge surface. Modifying CS molecular weight (MW) is expected to influence CSNPs' characteristics, impacting size, shape, crystallinity degree, and charge surface. CSNPs are developed using the method of ionic gelation with sodium tripolyphosphate (TPP) as a crosslinker and spray pyrolysis procedure. Nanoparticles' (NPs) sizes vary from 205.3 ± 81 nm to 450.9 ± 235 nm, ZP charges range from +10.56 mV to +51.56 mV, and entrapment efficiency from 85.35% to 90.45%. The morphology of NPs are all the same spherical forms. In vitro release studies confirmed that AMG-Chitosan-High Molecular Weight (AMG-CS-HMW) and AMG-Chitosan-Low Molecular Weight (AMG-CS-LMW) had a sustained-release system profile. MW has a great influence on surface, drug release, and cytotoxicity enhancement of AMG in CSNPs to MCF-7 cancer cells. The preparations AMG-CS-HMW and AMG-CS-LMW NPs considerably enhanced the cytotoxicity of MCF-7 cells with IC50 values of 5.90 ± 0.08 µg/mL and 4.90 ± 0.16 µg/mL, respectively, as compared with the non-nano particle formulation with an IC50 of 8.47 ± 0.29 µg/mL. These findings suggest that CSNPs can enhance the physicochemical characteristics and cytotoxicity of AMG in breast cancer treatment.

11.
J Genet Eng Biotechnol ; 20(1): 98, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35792966

RESUMO

BACKGROUND: The baculovirus expression vector system has been developed for expressing a wide range of proteins, including enzymes, glycoproteins, recombinant viruses, and vaccines. The availability of the SARS-CoV-2 genome sequence has enabled the synthesis of SARS-CoV2 proteins in a baculovirus-insect cell platform for various applications. The most cloned SARS-CoV-2 protein is the spike protein, which plays a critical role in SARS-CoV-2 infection. It is available in its whole length or as subunits like S1 or the receptor-binding domain (RBD). Non-structural proteins (Nsps), another recombinant SARS-CoV-2 protein generated by the baculovirus expression vector system (BEV), are used in the identification of new medications or the repurposing of existing therapies for the treatment of COVID-19. Non-SARS-CoV-2 proteins generated by BEV for SARS-CoV-2 diagnosis or treatment include moloney murine leukemia virus reverse transcriptase (MMLVRT), angiotensin converting enzyme 2 (ACE2), therapeutic proteins, and recombinant antibodies. The recombinant proteins were modified to boost the yield or to stabilize the protein. CONCLUSION: This review covers the wide application of the recombinant protein produced using the baculovirus expression technology for COVID-19 research. A lot of improvements have been made to produce functional proteins with high yields. However, there is still room for improvement and there are parts of this field of research that have not been investigated yet.

12.
Front Pediatr ; 10: 901605, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783328

RESUMO

Thalassemias are monogenic hematologic diseases that are classified as α- or ß-thalassemia according to its quantitative abnormalities of adult α- or ß-globin chains. ß-thalassemia has widely spread throughout the world especially in Mediterranean countries, the Middle East, Central Asia, India, Southern China, and the Far East as well as countries along the north coast of Africa and in South America. The one and the only cure for ß-thalassemia is allogenic hematopoietic stem cell transplantations (HSCT). Nevertheless, the difficulty to find matched donors has hindered the availability of this therapeutic option. Therefore, this present review explored the alternatives for ß-thalassemia treatment such as RNA manipulation therapy, splice-switching, genome editing and generation of corrected induced pluripotent stem cells (iPSCs). Manipulation of ß-globin RNA is mediated by antisense oligonucleotides (ASOs) or splice-switching oligonucleotides (SSOs), which redirect pre-mRNA splicing to significantly restore correct ß-globin pre-mRNA splicing and gene product in cultured erythropoietic cells. Zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) are designer proteins that can alter the genome precisely by creating specific DNA double-strand breaks. The treatment of ß-thalassemia patient-derived iPSCs with TALENs have been found to correct the ß-globin gene mutations, implying that TALENs could be used as a therapy option for ß-thalassemia. Additionally, CRISPR technologies using Cas9 have been used to fix mutations in the ß-globin gene in cultured cells as well as induction of hereditary persistence of fetal hemoglobin (HPFH), and α-globin gene deletions have proposed a possible therapeutic option for ß-thalassemia. Overall, the accumulated research evidence demonstrated the potential of ASOs-mediated aberrant splicing correction of ß-thalassemia mutations and the advancements of genome therapy approaches using ZFNs, TALENs, and CRISPR/Cas9 that provided insights in finding the permanent cure of ß-thalassemia.

13.
Heliyon ; 8(1): e08674, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35028457

RESUMO

Recently, multifunctional drug delivery systems (DDSs) have been designed to provide a comprehensive approach with multiple functionalities, including diagnostic imaging, targeted drug delivery, and controlled drug release. Chitosan-based drug nanoparticles (CSNPs) systems are employed as diagnostic imaging and delivering the drug to particular targeted sites in a regulated manner. Drug release is an important factor in ensuring high reproducibility, stability, quality control of CSNPs, and scientific-based for developing CSNPs. Several factors influence drug release from CSNPs, including composition, composition ratio, ingredient interactions, and preparation methods. Early, CSNPs were used for improving drug solubility, stability, pharmacokinetics, and pharmacotherapeutics properties. Chitosan has been developed toward a multifunctional drug delivery system by exploring positively charged properties and modifiable functional groups. Various modifications to the polymer backbone, charge, or functional groups will undoubtedly affect the drug release from CSNPs. The drug release from CSNPs has a significant influence on its therapeutic actions. Our review's objective was to summarize and discuss the relationship between the modification in CSNPs as multifunctional delivery systems and drug release properties and kinetics of the drug release model. Kinetic models help describe the release rate, leading to increased efficiency, accuracy, the safety of the dose, optimizing the drug delivery device's design, evaluating the drug release rate, and improvement of patient compatibility. In conclusion, almost all CSNPs showed bi-phasic release, initial burst release drug in a particular time followed controlled manner release in achieving the expected release, stimuli external can be applied. CSNPs are a promising technique for multifunctional drug delivery systems.

14.
Data Brief ; 38: 107413, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34632013

RESUMO

Ageing is defined as gradual decline of physiological, cellular and molecular state of an organism with time. The age-associated cell dysfunctions usually cause chronic diseases such as diabetes, cancers and other age-related diseases. Many of the genes and pathways involved in ageing are conserved in different species. These genes and pathways have been categorised into nine cellular and molecular hallmarks, namely, genomic instability, telomere attrition, loss of proteostasis, mitochondrial dysfunction, epigenetic alterations, deregulated nutrient sensing, stem cell exhaustion, cellular senescence and altered intercellular communication. Despite countless studies on ageing, the molecular mechanism of ageing is poorly understood. Here, we performed genome wide transcriptome mapping of ageing process in D. melanogaster. In which, transcriptomic analysis conducted on the 1 day and 60 days flies. Illumina Hiseq platform were used to generate raw data. Afterwards, further analysis including differential expression analysis, GO classification and KEGG pathway enrichment analysis were performed. The raw data were uploaded to SRA database and the BioProject ID is PRJNA718442. These data provide the basis for future research in order to discover the genes and pathways involved in ageing.

15.
Molecules ; 26(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34500560

RESUMO

α-Mangostin (AMG) is a potent anticancer xanthone that was discovered in mangosteen (Garcinia mangostana Linn.). AMG possesses the highest opportunity for chemopreventive and chemotherapeutic therapy. AMG inhibits every step in the process of carcinogenesis. AMG suppressed multiple breast cancer (BC) cell proliferation and apoptosis by decreasing the creation of cancerous compounds. Accumulating BC abnormalities and their associated molecular signaling pathways promotes novel treatment strategies. Chemotherapy is a commonly used treatment; due to the possibility of unpleasant side effects and multidrug resistance, there has been substantial progress in searching for alternative solutions, including the use of plant-derived natural chemicals. Due to the limitations of conventional cancer therapy, nanotechnology provides hope for effective and efficient cancer diagnosis and treatment. Nanotechnology enables the delivery of nanoparticles and increased solubility of drugs and drug targeting, resulting in increased cytotoxicity and cell death during BC treatment. This review summarizes the progress and development of AMG's cytotoxicity and the mechanism of death BC cells. The combination of natural medicine and nanotechnology into a synergistic capital will provide various benefits. This information will aid in the development of AMG nanoparticle preparations and may open up new avenues for discovering an effective BC treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Nanopartículas/química , Xantonas/farmacologia , Animais , Carcinogênese/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Transdução de Sinais/efeitos dos fármacos
16.
Genes (Basel) ; 12(6)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205960

RESUMO

Choline kinase (CK) is the enzyme catalyzing the first reaction in CDP-choline pathway for the biosynthesis of phosphatidylcholine. Higher expression of the α isozyme of CK has been implicated in carcinogenesis, and inhibition or downregulation of CKα (CHKA) is a promising anticancer approach. This study aimed to investigate the regulation of CKα expression by DNA methylation of the CpG islands found on the promoter of this gene in MCF-7 cells. Four CpG islands have been predicted in the 2000 bp promoter region of ckα (chka) gene. Six CpG island deletion mutants were constructed using PCR site-directed mutagenesis method and cloned into pGL4.10 vectors for promoter activity assays. Deletion of CpG4C region located between -225 and -56 significantly increased the promoter activity by 4-fold, indicating the presence of important repressive transcription factor binding site. The promoter activity of methylated full-length promoter was significantly lower than the methylated CpG4C deletion mutant by 16-fold. The results show that DNA methylation of CpG4C promotes the binding of the transcription factor that suppresses the promoter activity. Electrophoretic mobility shift assay analysis showed that cytosine methylation at MZF1 binding site in CpG4C increased the binding of putative MZF1 in nuclear extract. In conclusion, the results suggest that DNA methylation decreased the promoter activity by promoting the binding of putative MZF1 transcription factor at CpG4C region of the ckα gene promoter.


Assuntos
Colina Quinase/genética , Metilação de DNA , Ilhas de CpG , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Mutação , Regiões Promotoras Genéticas
17.
Biomolecules ; 11(5)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070036

RESUMO

Thalassemia, an inherited quantitative globin disorder, consists of two types, α- and ß-thalassemia. ß-thalassemia is a heterogeneous disease that can be asymptomatic, mild, or even severe. Considerable research has focused on investigating its underlying etiology. These studies found that DNA hypomethylation in the ß-globin gene cluster is significantly related to fetal hemoglobin (HbF) elevation. Histone modification reactivates γ-globin gene expression in adults and increases ß-globin expression. Down-regulation of γ-globin suppressor genes, i.e., BCL11A, KLF1, HBG-XMN1, HBS1L-MYB, and SOX6, elevates the HbF level. ß-thalassemia severity is predictable through FLT1, ARG2, NOS2A, and MAP3K5 gene expression. NOS2A and MAP3K5 may predict the ß-thalassemia patient's response to hydroxyurea, a HbF-inducing drug. The transcription factors NRF2 and BACH1 work with antioxidant enzymes, i.e., PRDX1, PRDX2, TRX1, and SOD1, to protect erythrocytes from oxidative damage, thus increasing their lifespan. A single ß-thalassemia-causing mutation can result in different phenotypes, and these are predictable by IGSF4 and LARP2 methylation as well as long non-coding RNA expression levels. Finally, the coinheritance of ß-thalassemia with α-thalassemia ameliorates the ß-thalassemia clinical presentation. In conclusion, the management of ß-thalassemia is currently limited to genetic and epigenetic approaches, and numerous factors should be further explored in the future.


Assuntos
Epigênese Genética , Globinas beta/genética , Talassemia beta/genética , Autoantígenos/genética , Molécula 1 de Adesão Celular/genética , Metilação de DNA/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Código das Histonas/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular , Mutação , RNA não Traduzido/genética , Ribonucleoproteínas/genética , Talassemia beta/tratamento farmacológico , Antígeno SS-B
18.
Polymers (Basel) ; 13(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34074020

RESUMO

Breast cancer remains one of the world's most dangerous diseases because of the difficulty of finding cost-effective and specific targets for effective and efficient treatment methods. The biodegradability and biocompatibility properties of chitosan-based nanoparticles (ChNPs) have good prospects for targeted drug delivery systems. ChNPs can transfer various antitumor drugs to targeted sites via passive and active targeting pathways. The modification of ChNPs has attracted the researcher to the loading of drugs to targeted cancer cells. The objective of our review was to summarize and discuss the modification in ChNPs in delivering anticancer drugs against breast cancer cells from published papers recorded in Scopus, PubMed, and Google Scholar. In order to improve cellular uptake, drug accumulation, cytotoxicity, and selectivity, we examined different kinds of modification of ChNPs. Notably, these forms of ChNPs use the characteristics of the enhanced permeability and retention (EPR) effect as a proper parameter and different biological ligands, such as proteins, peptides, monoclonal antibodies, and small particles. In addition, as a targeted delivery system, ChNPs provided and significantly improved the delivery of drugs into specific breast cancer cells (MDA-MB-231, 4T1 cells, SK-BR-3, MCF-7, T47D). In conclusion, a promising technique is presented for increasing the efficacy, selectivity, and effectiveness of candidate drug carriers in the treatment of breast cancer.

19.
Eur J Cell Biol ; 99(6): 151108, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32800277

RESUMO

Cellular theory of aging states that human aging is the result of cellular aging, in which an increasing proportion of cells reach senescence. Senescence, from the Latin word senex, means "growing old," is an irreversible growth arrest which occurs in response to damaging stimuli, such as DNA damage, telomere shortening, telomere dysfunction and oncogenic stress leading to suppression of potentially dysfunctional, transformed, or aged cells. Cellular senescence is characterized by irreversible cell cycle arrest, flattened and enlarged morphology, resistance to apoptosis, alteration in gene expression and chromatin structure, expression of senescence associated- ß-galactosidase (SA-ß-gal) and acquisition of senescence associated secretory phenotype (SASP). In this review paper, different types of cellular senescence including replicative senescence (RS) which occurs due to telomere shortening and stress induced premature senescence (SIPS) which occurs in response to different types of stress in cells, are discussed. Biomarkers of cellular senescence and senescent assays including BrdU incorporation assay, senescence associated- ß-galactosidase (SA-ß-gal) and senescence-associated heterochromatin foci assays to detect senescent cells are also addressed.


Assuntos
Senescência Celular/fisiologia , Envelhecimento , Humanos
20.
Malays J Med Sci ; 27(3): 7-19, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32684802

RESUMO

Ageing is a phenomenon where the accumulation of all the stresses that alter the functions of living organisms, halter them from maintaining their physiological balance and eventually lead to death. The emergence of epigenetic tremendously contributed to the knowledge of ageing. Epigenetic changes in cells or tissues like deoxyribonucleic acid (DNA) methylation, modification of histone proteins, transcriptional modification and also the involvement of non-coding DNA has been documented to be associated with ageing. In order to study ageing, scientists have taken advantage of several potential organisms to aid them in their study. Drosophila melanogaster has been an essential model in establishing current understanding of the mechanism of ageing as they possess several advantages over other competitors like having homologues to more than 75% of human disease genes, having 50% of Drosophila genes are homologues to human genes and most importantly they are genetically amenable. Here, we would like to summarise the extant knowledge about ageing and epigenetic process and the role of Drosophila as an ideal model to study epigenetics in association with ageing process.

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