Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 41
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Food Chem Toxicol ; 184: 114420, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38151072

RESUMO

In the present study, we have evaluated the effects of copper (Cu) nanoparticles (NPs) on the primary B-and T-lymphocytes proliferation, cytokine levels, and bio-distribution through in vitro, in vivo and ex-vivo studies to allow the possible exploitations of CuNPs in biomedical applications. CuNPs were characterized by UV-Visible spectroscopy, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). The proliferative response of lymphocytes was studied by 3H-thymidine incorporation assay and lymphocyte viability through trypan blue assay. The bio-distribution of CuNPs into lymphoid organs was examined by using ex-vivo imaging system. Cytokine levels in plasma of control and CuNPs treated animal groups were determined by enzyme-linked immunosorbent assay (ELISA) method along with other biochemical analysis. CuNPs significantly suppressed the proliferation of primary splenic and thymic lymphocytes in a dose dependent manner. Ex-vivo imaging exhibited the distribution of CuNPs in spleen and thymus. Oral administration of CuNPs (2 mg and 10 mg/kg body weight) significantly inhibited the proliferation of splenic and thymic lymphocytes along with lowered cytokines levels (TNF-alpha and IL-2) on comparison with controls. The results indicated the significant inhibition of lymphocytes proliferative response and secretion of cytokines, thus unveiling the immunomodulatory effects of CuNPs.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Ratos , Animais , Cobre/farmacologia , Cobre/química , Mitógenos , Baço , Nanopartículas Metálicas/química , Nanopartículas/química , Linfócitos , Citocinas
2.
Life Sci ; 332: 122104, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37730109

RESUMO

Gynecologic malignancies (GMs) are relatively less focused cancers by oncologists and researchers. The five-year survival rate of patients with GMs remained almost the same during the last decade. The development of drug resistance GMs makes it even more challenging to tackle due to tumor heterogeneity, genomic instability, viral/non-viral antigens, and etiological tumor origin. A precision medicine approach, including gene therapies, is under testing to restore tumor responsiveness to therapeutics and immunotherapy. With more data being uncovered, immunotherapy is emerging as a viable alternative for achieving promising results. This review highlights the drug resistance mechanisms and immunotherapeutic approaches to managing GMs better. The approval of immune therapeutic drugs in recent years shifted this notion. It provided hope for researchers, clinicians, and patients with GMs to experience the anti-cancer benefits of these therapies.

3.
J Biophotonics ; 16(9): e202300110, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37261437

RESUMO

Therapeutic potential and toxic effects of in vivo administered gold nanoparticles (GNPs) and silver nanoparticles (SNP) depend on distribution in tissues. Rhodamine (Rho) labeled bovine serum albumin (BSA) and chitosan (Chi) were prepared by covalent conjugation and were characterized by fluorescence spectral analysis. GNP and SNP were coated with the labeled conjugates of BSA and chitosan by adsorption. The soluble Rho-BSA or Rho-Chi conjugates, uncoated, and conjugate-coated GNP, and SNP were orally administered into 8-week-old rats. After 24 h, rats were euthanized and the liver, kidney, spleen, and thymus were dissected. The tissues were examined ex vivo using a small animal in vivo imaging system. The liver, kidney, and thymus displayed higher fluorescence due to increased accumulation of Rho-BSA or Rho-Chi conjugate-coated nanoparticles (NPs) in the tissues as compared to the spleen where lower fluorescence was noticed. Tissues obtained from rats that were administered Rho-BSA or Rho-Chi conjugate-coated GNP and SNP showed tenfold higher fluorescence intensity as compared to tissues from rats that were given soluble conjugates or NP alone. The results strongly suggest significant tissue distribution of NP following oral administration.


Assuntos
Quitosana , Nanopartículas Metálicas , Nanopartículas , Ratos , Animais , Ouro , Soroalbumina Bovina , Prata , Rodaminas , Imagem Óptica , Tamanho da Partícula
4.
J Biomol Struct Dyn ; 41(20): 11148-11165, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37098803

RESUMO

In view of Multi-Target Directed Ligand (MTDL) approach in treating Alzheimer's Disease (AD), a series of novel quinazolinone and vanillin cyanoacetamide based acrylamide derivatives (9a-z) were designed, synthesized, and assessed for their activity against a panel of selected AD targets including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), amyloid ß protein (Aß), and also 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and neuroprotective activities. Five of the target analogs 9e, 9h, 9 l, 9t and 9z showed elevated AChE inhibitory activity with IC50 values of 1.058 ± 0.06, 1.362 ± 0.09, 1.434 ± 0.10, 1.015 ± 0.10, 1.035 ± 0.02 µM respectively, high inhibition selectivity against AChE over BChE and good DPPH radical scavenging activity. Enzyme kinetic studies of the potent hybrids in the series disclosed their mixed inhibition approach. Active analogs were found to be non-toxic on SK-N-SH cell lines and have excellent neuroprotective effects against H2O2-induced cell death. Strong modulating affinities on Aß aggregation process were observed for most active compounds since; they irretrievably interrupted the morphology of Aß42 fibrils, increased the aggregates and declined the Aß-induced toxicity in neurons. From the fluorescence emission studies, the binding constants (K) were determined as 2.5 ± 0.021x103, 2.7 ± 0.015x103, 3.7 ± 0.020x103, 2.4 ± 0.013x104, and 5.0 ± 0.033x103 M-1 and binding free energies as -5.82 ± 0.033, -6.07 ± 0.042, -6.26 ± 0.015, -7.71 ± 0.024, and -6.29 ± 0.026 kcal M-1 for complexes of AChE-9e, 9h, 9 l, 9t and 9z, respectively. Moreover, the CD analysis inferred the limited modifications in the AChE secondary structure when it binds to 9e, 9h, 9 l, 9t and 9z. On the basis of docking studies against AChE, the most active congeners were well oriented in the enzyme's active site by interacting with both catalytic active site (CAS) and peripheral anionic site (PAS). In summary, these quinazolinone and vanillin acrylamide hybrid analogs can be used as promising molecular template to further explore their in vivo efficiency in the development of lead compound to treat AD.Communicated by Ramaswamy H. Sarma.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Acetilcolinesterase/química , Butirilcolinesterase/metabolismo , Peptídeos beta-Amiloides/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Acrilamida , Ligantes , Peróxido de Hidrogênio , Cinética , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular
5.
Front Genet ; 14: 1091575, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36777719

RESUMO

To date, numerous nucleotide, amino acid, and codon substitution models have been developed to estimate the evolutionary history of any sequence/organism in a more comprehensive way. Out of these three, the codon substitution model is the most powerful. These models have been utilized extensively to detect selective pressure on a protein, codon usage bias, ancestral reconstruction and phylogenetic reconstruction. However, due to more computational demanding, in comparison to nucleotide and amino acid substitution models, only a few studies have employed the codon substitution model to understand the heterogeneity of the evolutionary process in a genome-scale analysis. Hence, there is always a question of how to develop more robust but less computationally demanding codon substitution models to get more accurate results. In this review article, the authors attempted to understand the basis of the development of different types of codon-substitution models and how this information can be utilized to develop more robust but less computationally demanding codon substitution models. The codon substitution model enables to detect selection regime under which any gene or gene region is evolving, codon usage bias in any organism or tissue-specific region and phylogenetic relationship between different lineages more accurately than nucleotide and amino acid substitution models. Thus, in the near future, these codon models can be utilized in the field of conservation, breeding and medicine.

6.
Pharmaceutics ; 14(10)2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36297590

RESUMO

The synthesis of nanometer-sized metallic nanoparticles utilizing bio-sources is one of the most cost-effective and ecologically friendly approaches. Nano-zinc oxide particles (N-ZnO Ps) were made using a simple green synthesis method using an aqueous zinc nitrate salt and Perilla frutescens crude protein as a protecting and reducing agent in the current work. UV-visible (UV-vis) spectrophotometry, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), (energy dispersive x-ray spectroscopy) EDX and high-resolution transmission electron microscopy (HR-TEM) were used to characterize the synthesized N-ZnO Ps. A distinctive UV-vis absorption peak was observed at 370 nm due to N-ZnO Ps. The SEM and HR-TEM pictures revealed N-ZnO Ps with a triangular form. The XRD pattern indicated the wurtzite structure of N-ZnO Ps. Nanoparticles exhibited a zeta potential of -11.3 mV. The antibacterial activity of N-ZnO Ps was tested against Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumonia) microorganisms. The N-ZnO Ps were non-toxic to HMC-3 human normal brain microglia cells; however, they exhibited a potential cytotoxic effect on the LN-18 human brain glioblastoma cell line. These results indicate that N-ZnOPs can act as promising antibacterial and anticancer treatments in the prevention of Glioblastoma.

7.
World J Clin Oncol ; 12(5): 309-322, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34131563

RESUMO

Even though the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is related to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), identifying effective and safe therapeutic strategies remains challenging. In search of finding effective treatments to eradicate the virus and improve disease symptoms, scientists are exploring possible therapies such as anti-viral, anti-malaria, immune therapy, and hormone treatments. However, the efficacy of these treatments was not validated on either SARS-CoV or MERS-CoV. In this study, we have reviewed synthetic evidence achieved through systematic and meta-analysis of therapeutics specific for SARS-CoV-2 and observed that the use of the above-mentioned therapies had no clinical benefits in coronavirus disease 2019 patients and, conversely, displayed side effects.

8.
Crit Rev Oncog ; 26(1): 11-20, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33641281

RESUMO

Hepatocellular carcinoma (HCC) stands third among cancer-related deaths globally. Owing to its high incidence and linked mortality, early diagnosis is alarming for patient survival and the management of patients with developing HCC requires immediate attention. Advances in the knowledge of cancer biology and recognizing unique molecular candidates, including genomic and proteomic profiles, substantiate our understanding about several biological signatures connected with HCC. Precise identification and differential diagnosis of early HCC can remarkably improve patient survival. Currently, detection of HCC in clinical practice is performed by diagnostic imaging and noninvasive methods such as evaluation of serum biomarkers, growth factors, and the like. In this review, we discuss recent developments in targeting biomarkers for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Proteômica
10.
J Biomol Struct Dyn ; 39(4): 1447-1460, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32089084

RESUMO

Type 2 diabetes (T2D) is clinically characterized via hyperglycemia. Polymorphism rs5219 in the KCNJ11 gene is a risk factor for developing T2D in humans. KCNJ11 encodes the 'inward-rectifier potassium ion channel (Kir6.2)'. However, because of the absence of the complete crystal/NMR structures of Kir6.2 proteins, insight into its structure and function and its interaction with diverse ligands remain elusive to date. Therefore, a computational approach was employed for predicting the best plausible 'three-dimensional' structure of Kir6.2 as well as for studying the influence of mutation (p. GLU23LYS) on both architectures as well as the function of Kir6.2 employing simulation studies. Results obtained revealed that though, with increased time, 'Gibbs free energy' becomes positive, residues in wild type Kir6.2 experiences less random movement as compared to mutant Kir6.2. The less random movement of residues in wild type Kir6.2 represents the standard coupling between open and closing of 'KATP channel' and thus the normal secretion of insulin. The more dispersed motion of mutant Kir6.2 residues represents 'overactivity' of the 'KATP channel' and thus insulin 'under-secretion'. Further, molecular docking and simulation studies identified two phytochemicals/drugs, namely, A-348441 and chushizisin I, which retains the wild type property of Kir6.2 after binding with mutant protein. Unlike A-348441, this is for the first time, the present study is reporting about the plausible anti-diabetic property of chushizisin I. As these two phytochemicals/drugs, namely, A-348441 and chushizisin I, have passed ADMET test, in the near future, they may be utilized as anti-diabetic drugs after further investigation.Communicated by Ramaswamy H. Sarma.


Assuntos
Diabetes Mellitus Tipo 2 , Trifosfato de Adenosina , Biologia , Humanos , Simulação de Acoplamento Molecular , Mutação , Relação Estrutura-Atividade
11.
J Biomol Struct Dyn ; 39(7): 2617-2627, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32238078

RESUMO

Recent outbreak of Coronavirus disease (COVID-19) pandemic around the world is associated with 'severe acute respiratory syndrome' (SARS-CoV2) in humans. SARS-CoV2 is an enveloped virus and E proteins present in them are reported to form ion channels, which is mainly associated with pathogenesis. Thus, there is always a quest to inhibit these ion channels, which in turn may help in controlling diseases caused by SARS-CoV2 in humans. Considering this, in the present study, authors employed computational approaches for studying the structure as well as function of the human 'SARS-CoV2 E' protein as well as its interaction with various phytochemicals. Result obtained revealed that α-helix and loops present in this protein experience random movement under optimal condition, which in turn modulate ion channel activity; thereby aiding the pathogenesis caused via SARS-CoV2 in human and other vertebrates. However, after binding with Belachinal, Macaflavanone E, and Vibsanol B, the random motion of the human 'SARS-CoV2 E' protein gets reduced, this, in turn, inhibits the function of the 'SARS-CoV2 E' protein. It is pertinent to note that two amino acids, namely VAL25 and PHE26, play a key role while interacting with these three phytochemicals. As these three phytochemicals, namely, Belachinal, Macaflavanone E & Vibsanol B, have passed the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) property as well as 'Lipinski's Rule of 5s', they may be utilized as drugs in controlling disease caused via SARS-COV2, after further investigation.Communicated by Ramaswamy H. Sarma.


Assuntos
COVID-19 , Proteínas do Envelope de Coronavírus , Animais , Humanos , Canais Iônicos , RNA Viral , SARS-CoV-2
12.
Semin Cancer Biol ; 69: 376-390, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31301361

RESUMO

Female-specific cancers are the most common cancers in women worldwide. Early detection methods remain unavailable for most of these cancers, signifying that most of them are diagnosed at later stages. Furthermore, current treatment options for most female-specific cancers are surgery, radiation and chemotherapy. Although important milestones in molecularly targeted approaches have been achieved lately, current therapeutic strategies for female-specific cancers remain limited, ineffective and plagued by the emergence of chemoresistance, which aggravates prognosis. Recently, the application of nanotechnology to the medical field has allowed the development of novel nano-based approaches for the management and treatment of cancers, including female-specific cancers. These approaches promise to improve patient survival rates by reducing side effects, enabling selective delivery of drugs to tumor tissues and enhancing the uptake of therapeutic compounds, thus increasing anti-tumor activity. In this review, we focus on the application of nano-based technologies to the design of novel and innovative diagnostic and therapeutic strategies in the context of female-specific cancers, highlighting their potential uses and limitations.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Nanomedicina , Nanopartículas/administração & dosagem , Animais , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Nanopartículas/química
13.
CNS Neurol Disord Drug Targets ; 20(7): 625-643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33138765

RESUMO

Neuroblastoma (NBM) is the second leading pediatric cancer that develops from the precursors of the sympathetic nervous system. To date, surgery, chemotherapy, and radiation serve as the first-line treatment against NBM in high-risk patients. However, few of these approaches have severe side effects. Recently, numerous studies have also reported that high chemotherapy doses, along with stem cell rescue, improvise event-free survival in patients. In this review, the authors attempted to discuss the pathogenesis associated with NBM and how stem cell therapy can be employed for the treatment of NBM. Stem cells are a group of multipotent, undifferentiated cells that are capable of producing all cells in a particular tissue, organ, or organism. They have an endogenous self-renewal property. This property is tightly modulated for the normal homeostasis within the body. However, the failure of this process leads to carcinogenesis, including NBM. As these properties are modulated via various intrinsic as well as extrinsic pathways, the arrest of these pathways via various drugs may help in controlling various carcinomas, including NBM. Recently, stem cells were utilized for the diagnosis and treatment of NBM. Nevertheless, most of the studies conducted to date are mainly designed on bulk-cell analysis, which in turn provides little information about the population of cells. Thus, the authors believe that, by employing single-cell RNA sequencing technologies and computational approaches, we can unmask the tumor heterogeneity in NBM in a more comprehensive way. In the near future, this information will be highly useful for the identification of biomarkers and treatment associated with NBM in humans.


Assuntos
Neuroblastoma/terapia , Transplante de Células-Tronco/métodos , Criança , Humanos , Neuroblastoma/patologia
14.
Curr Pharm Des ; 26(41): 5278-5285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881659

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing, rapidly spreading pandemic caused by Severe Acute Respiratory Syndrome Coronavirus2 (SARS-CoV2). Among all the infected countries around the globe as of now (June 15, 2020), the total confirmed positive cases reported are 7,805,148, with the death of 431,192. At present, no specialized treatments evolved to cure COVID-19. Its treatment is symptomatic. Though huge efforts are being made to produce potential therapies to scuffle COVID-19, no drug has been discovered so far. OBJECTIVE: Natural products have been playing a significant role in disease control since ancient days. These products serve as templates for designing new anti-microbial agents with a different mechanism of action and also open a door for investigation of effective anti-viral drugs to combat COVID-19. By focusing on this, the authors have narrated the basic structure, infection, and pathogenesis of SARS-CoV2 virus in humans and also reported various natural products or plant-based extracts/bioactive compounds tested against coronaviruses like SARS and MERS, as these viruses are structurally similar to SARS-CoV2 and can be used in designing novel drug against this virus. CONCLUSION: The natural products having the potential to combat SARS, MERS, and other viruses reviewed in this review article might have anti-viral activities against the SARS-CoV2 virus and can be used directly for further preclinical studies. Therefore, all efforts should be focused on overcoming this serious problem to save many people's lives all over the world.


Assuntos
Antivirais , Produtos Biológicos , Tratamento Farmacológico da COVID-19 , Antivirais/farmacologia , Antivirais/uso terapêutico , Produtos Biológicos/farmacologia , Humanos , Pandemias , SARS-CoV-2
15.
Genetica ; 148(5-6): 269-282, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32804315

RESUMO

The recently developed phylogenomic approach provides a unique way to identify disease risk or protective allele in any organism. While risk alleles evolve mostly under purifying selection, protective alleles are evolving either under balancing or positive selection. Owing to insufficient information, authors employed the phylogenomic approach to detect the nature of selection acting on type 2 diabetes (T2D) genes in Drosophila genus using various models of CODEML utility of PAML. The obtained result revealed that T2D gene sequences are evolving under purifying selection. However, only a few sites in membrane proteins encoded via CG8051, ZnT35C, and kar, are significantly evolving under positive selection under specific scenarios, which might be because of positive or adaptive evolution in response to changing niche, diet or other factors. In the near future, this information will be highly useful in the field of evolutionary medicine and the drug discovery process.


Assuntos
Diabetes Mellitus Tipo 2/genética , Proteínas de Drosophila/genética , Evolução Molecular , Seleção Genética , Animais , Drosophila , Filogenia , Polimorfismo Genético
16.
Physiol Mol Biol Plants ; 26(5): 885-898, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32377039

RESUMO

Continuous rise in the human population has resulted in an upsurge in food demand, which in turn demand grain yield enhancement of cereal crops, including rice. Rice yield is estimated via the number of tillers, grain number per panicles, and the number of spikes present per panicle. Marker-assisted selection (MAS) serve as one of the best ways to introduce QTLs/gene associated with yield in the rice plant. MAS has also been employed effectively in dissecting several other complex agricultural traits, for instance, drought, cold tolerance, salinity, etc. in rice plants. Thus, in this review, authors attempted to collect information about various genes/QTLs associated with high yield, including grain number, in rice and how different scheme of MAS can be employed to introduce them in rice (Oryza sativa L.) plant, which in turn will enhance rice yield. Information obtained to date suggest that, numerous QTLs, e.g., Gn1a, Dep1, associated with grain number and yield-related traits, have been identified either via mapping or cloning approaches. These QTLs have been successfully introduced into rice plants using various schemes of MAS for grain yield enhancement in rice. However, sometimes, MAS does not perform well in breeding, which might be due to lack of resources, skilled labors, reliable markers, and high costs associated with MAS. Thus, by overcoming these problems, we can enhance the application of MAS in plant breeding, which, in turn, may help us in increasing yield, which subsequently may help in bridging the gap between demand and supply of food for the continuously growing population.

17.
Phytochemistry ; 175: 112365, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32247721

RESUMO

Mutation (p.LEU112PRO) in "carotenoid cleavage dioxygenase 8" (CCD8) protein increases tiller formation in rice plants by cross-talking with auxin and cytokinins. However, owing to the nonexistence of a "three-dimension" structure of CCD8, detail information about its structure and function remain elusive until date. Hence, in the present study, computational approaches were adopted to predict "three-dimensional" (3D) structure of CCD8 protein through comparative modeling techniques and to study the effect of mutation (p.LEU112PRO) on its function as well as architecture through "molecular dynamics" simulation studies. The obtained result reveals that wild-type CCD8 protein is made up of 10 α-helix and 25 ß-strands while mutant CCD8 is made up of 11 α-helix and 24 ß-strands. Further, molecular docking studies reveals that the wild-type has a better binding affinity with auxin and cytokinin in comparison to mutant. Subsequent molecular dynamics simulation of these four complexes, separately, reveals that the movement of both wild-type as well as mutant CCD8 get reduced after binding with auxin, which in turn prevent auxin transport out of the bud and increases tiller number. However, when cytokinin binds with wild-type and mutant CCD8, it inhibits and enhance CCD8 activity, respectively. As cytokinin positively regulates tiller number formation, enhance activity of mutant CCD8 after binding with cytokinin might be the main reason for more tiller number in mutant than wild-type plant. In the near future, mutant CCD8 along with auxin and cytokinin may be utilized for increasing grain yield in rice plants.


Assuntos
Dioxigenases , Oryza , Carotenoides , Citocininas , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos , Simulação de Acoplamento Molecular , Mutação , Proteínas de Plantas
18.
J Biomol Struct Dyn ; 38(4): 1158-1167, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30896372

RESUMO

Cytokinin oxidase/dehydrogenase (CKX) is the only known enzyme associated with irreversible degradation of cytokinins in plants. CKX2 contains flavin adenine dinucleotide (FAD) domain. Earlier studies utilising antisense & hpRNAi suppression techniques in mutant/transgenic rice plants revealed that when CKX2 binds with FAD, CKX2 expression reduces, which in turn causes cytokinin aggregation in inflorescence meristem that subsequently enhances both branches and grain number resulting in increased grain yield. Owing to the non-existence of complete three-dimensional structure of CKX2, insight into the structure and function of CKX2 and its relationship with its cofactor FAD is still a topic of debate. In the present study, computational approach was employed to estimate the three-dimensional structure of CKX2 through comparative modelling approach. Later, CKX2 and FAD interaction study was performed to understand the underlying mechanism involved with reduced expression of CKX2. Molecular dynamic simulation studies of both CKX2 and CKX-FAD complex revealed that after binding with FAD, CKX2 experienced increased pressure and reduced RMSD, potential energy and free energy landscape energy, which in turn lessen anti-correlation between almost all α and ß strands and random motion of C-α, subsequently reducing CKX2 expression. In near future, these information can be utilised for increasing rice yield under irrigated field condition by introgression of Gn1a gene through marker assisted back-crossing breeding. AbbreviationsGROMACSGROningen MAchine for Chemical SimulationsNPTConstant Number of Particles, Volume and TemperatureRMSDRoot Mean Square DeviationRMSFRoot Mean Square FluctuationsQTLquantitative trait lociFADflavin adenine dinucleotideNVTConstant Number of Particles, Pressure and TemperatureLINCSLinear Constraint SolverCKX2Cytokinin oxidase/dehydrogenase 2MM/PBSAMolecular Mechanics/Poisson-Boltzmann surface areaSDFStructure Data FileCommunicated by Ramaswamy H. Sarma.


Assuntos
Produção Agrícola , Modelos Moleculares , Conformação Molecular , Oryza/enzimologia , Oxirredutases/química , Fenômenos Químicos , Sequência Conservada , Flavina-Adenina Dinucleotídeo/química , Ligantes , Oxirredutases/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Relação Estrutura-Atividade
19.
J Biomol Struct Dyn ; 38(1): 137-151, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30633652

RESUMO

Polymorphism rs13266634 in SLC30A8 causes abnormal synthesis, maturation and secretion of insulin, resulting in decrease in efficiency of glucose metabolism and diabetes. SLC30A8 encodes Zinc transporter 8 protein (ZnT8). Due to lack of NMR/crystal structures of complete ZnT8 transporter, insights into the structure, function and its interaction with different drugs is still not known. Therefore, in-silico methods were adopted in the present studies for predicting three-dimensional structure of ZnT8 transporter via comparative modelling approach and studying the impact of mutation (p.ARG325TRP) on architecture and function via simulation studies. Wild-type protein comprises 15 α-helix and 3 ß-strands, while mutant consists of 12 α-helix and 2 ß-strands, respectively. Interaction studies of mutant ZnT8 transporter with phytochemicals/drugs screened the best phytochemicals, which can retain the wild-type property. Molecular docking studies reveal that mutant proteins have better binding energy with ligands of LY-2608204, Roseoside, and Luzonoid B. Further molecular dynamic simulation analysis exhibited a strong binding of these ligands with mutant protein and displaying similar behaviour as that of wild type. ALA79, ILE80, and ARG215 are the common interacting amino acids with ligand in all three complexes. As the ligands passed ADMET tests, these may be utilized as anti-diabetic drugs in near future. Although earlier studies have reported anti-diabetic property of LY-2608204 and Roseoside, for the first time, this study reporting Luzonoid B may have anti-diabetic property besides elucidating the structure and functions of ZnT8 transporter.


Assuntos
Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas Mutantes , Transportador 8 de Zinco/química , Algoritmos , Fenômenos Químicos , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Ligantes , Modelos Moleculares , Relação Estrutura-Atividade , Transportador 8 de Zinco/genética , Transportador 8 de Zinco/metabolismo
20.
Crit Rev Oncog ; 25(2): 111-128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33389861

RESUMO

Colorectal cancer (CRC) ranks second for incidence in females (third in males). Currently, a broad spectrum of treatment options exists for the treatment of colorectal tumors. However, existing therapeutic options often lead to trauma, side effects, and high cost. Hence, there is an ongoing quest to detect novel approaches for the treatment of colon cancer. Recently, multiple studies have reported that consuming functional foods that are loaded with natural compounds can prevent the risk of CRC. In this review, the authors have attempted to collect information about the best possible foods and their active ingredients that may be used in treatment. Information retrieved through research reveals that all functional foods have aroma, taste, and nutritive value along with active ingredients that are beneficial for human health. For instance, the consumption of red meat increases CRC risk; on the other hand, the consumption of fresh vegetables diminishes such risk. Additionally, plant-based diets comprise fibers, bioactive compounds, and micronutrients, which are reported to have antioxidant as well as anticancer properties. Bioactively rich functional foods have been reported to provide protection against CRC. However, few active components like curcumin work in a dose-dependent manner. Thus, the involvement of medical practitioners during a clinical trial is highly recommended. In general, these active dietary components may aid in improving the health and well-being of patients as well as in managing the risk associated with cancer in a more comprehensive way.


Assuntos
Neoplasias Colorretais/prevenção & controle , Alimento Funcional , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/terapia , Curcumina/administração & dosagem , Ácido Fólico/administração & dosagem , Alho , Humanos , Transdução de Sinais/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...