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1.
Oncology ; 102(4): 299-309, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37857267

RESUMEN

INTRODUCTION: Colorectal cancer (CRC) heritability is determined by the composite relations between inherited variants and environmental factors. In developing countries like India, the incidence rates of CRC are especially increasing. In this study, we have focused on the distribution of the FOXO3 gene polymorphisms among the patients with CRC in North India. METHODS: A case-control study was conducted on 487 CRC patients and 487 age-matched controls. We genotyped single-nucleotide polymorphisms rs2253310 and rs4946936 through polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and PCR-single-stranded conformation polymorphism procedure followed by sequence detection. RESULTS: A significantly increased risk of CRC was observed for the CC genotype of the rs4946936 polymorphism compared to the TT genotype (p = 0.02; odd ratio [OR] = 1.40, confidence interval [CI] = 1.05-1.87). GT haplotype appeared to be a "risk" haplotype (OR = 1.71, 95% CI = 0.82-2.19), while as other haplotypes CC (OR = 0.83, 95% CI = 0.32-1.54), CT (OR = 0.75, 95% CI = 0.25-1.01), and GC (OR = 0.98, 95% CI = 0.88-1.14) were found to be "protective" for developing CRC. CONCLUSION: This study suggests an association of increased risk of CRC with the rs4946936 polymorphism but not with the rs2253310 polymorphism.


Asunto(s)
Neoplasias Colorrectales , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Perfil Genético , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/epidemiología , Genotipo , Proteína Forkhead Box O3/genética
2.
Macromol Rapid Commun ; : e2400258, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39018482

RESUMEN

This study explores the synthesis and characterization of superabsorbent hydrogels derived from chemically modified gum Arabic, designed for controlled folic acid release. The synthesis involves a two-step process: carboxymethylation followed by grafting with 2-hydroxyethyl methacrylate via gamma irradiation. The resulting hydrogels exhibit enhanced mechanical strength and controlled diffusivity, essential for nutrient delivery systems. Key factors such as copolymer composition and irradiation dose are investigated, affecting the synthesis process. Systematic studies of swelling behaviors reveal that the hydrogel achieves a maximum swelling of 888.1% at 40 °C. The hydrogels are loaded with folic acid, and in vitro, sustained release profiles are examined under various pH conditions. The maximum release of 83.3% is observed after 24 h at pH 7.0, following a Korsmeyer-Peppas release mechanism. Different characterization techniques, confirm the successful synthesis and unique properties of the superabsorbent hydrogels. Rheological behavior analysis, scanning electron microscopy, and biocompatibility assessments provide a comprehensive understanding of the hydrogel structures. Gamma irradiation ensures a homogeneous network structure, crucial for optimal swelling behavior and mechanical properties. This research highlights the potential of eco-friendly biopolymer hydrogels in precise drug delivery applications, leveraging the safety and process control benefits of gamma irradiation.

3.
Int J Mol Sci ; 23(19)2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36232319

RESUMEN

The creation of novel anticancer treatments for a variety of human illnesses, including different malignancies and dangerous microbes, also potentially depends on nanoparticles including silver. Recently, it has been successful to biologically synthesize metal nanoparticles using plant extracts. The natural flavonoid 3,3', 4', 5,5', and 7 hexahydroxyflavon (myricetin) has anticancer properties. There is not much known about the regulatory effects of myricetin on the possible cell fate-determination mechanisms (such as apoptosis/proliferation) in colorectal cancer. Because the majority of investigations related to the anticancer activity of myricetin have dominantly focused on the enhancement of tumor cell uncontrolled growth (i.e., apoptosis). Thus, we have decided to explore the potential myricetin interactors and the associated biological functions by using an in-silico approach. Then, we focused on the main goal of the work which involved the synthesis of silver nanoparticles and the labeling of myricetin with it. The synthesized silver nanoparticles were examined using UV-visible spectroscopy, dynamic light scattering spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. In this study, we have investigated the effects of myricetin on colorectal cancer where numerous techniques were used to show myricetin's effect on colon cancer cells. Transmission Electron Microscopy was employed to monitor morphological changes. Furthermore, we have combined the results of the colorectal cancer gene expression dataset with those of the myricetin interactors and pathways. Based on the results, we conclude that myricetin is able to efficiently kill human colorectal cancer cell lines. Since, it shares important biological roles and possible route components and this myricetin may be a promising herbal treatment for colorectal cancer as per an in-silico analysis of the TCGA dataset.


Asunto(s)
Antineoplásicos , Nanopartículas del Metal , Neoplasias , Antibacterianos/farmacología , Antineoplásicos/química , Flavonoides/farmacología , Humanos , Nanopartículas del Metal/química , Extractos Vegetales/farmacología , Plata/química , Espectroscopía Infrarroja por Transformada de Fourier
4.
Biomacromolecules ; 22(9): 3731-3745, 2021 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-34436877

RESUMEN

Local delivery of anticancer agents via injectable hydrogels could be a promising method for achieving spatiotemporal control on drug release as well as minimizing the disadvantages related to the systemic mode of drug delivery. Keeping this in mind, we report the development of N,O-carboxymethyl chitosan (N,O-CMCS)-guar gum-based injectable hydrogels for the sustained delivery of anticancer drugs. The hydrogels were synthesized by chemical crosslinking of multialdehyde guar gum (MAGG) and N,O-CMCS through dynamic Schiff base linkages, without requiring any external crosslinker. Fabrication of injectable hydrogels, involving N,O-CMCS and MAGG via Schiff base crosslinking, is being reported for the first time. The hydrogels exhibited pH-responsive swelling behavior and good mechanical properties with a storage modulus of about 1625 Pa. Due to the reversible nature of Schiff base linkages, hydrogels displayed excellent self-healing and thixotropic properties. Doxorubicin (Dox), an anticancer agent, was loaded onto these hydrogels and its release studies were conducted at pH 7.4 (physiological) and pH 5.5 (tumoral). A sustained release of about 67.06% Dox was observed from the hydrogel after 5 days at pH 5.5 and about 32.13% at pH 7.4. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on the human embryonic kidney cell line (HEK-293) and the hemolytic assay demonstrated the biocompatible nature of the hydrogels. The Dox-loaded hydrogel exhibited a significant killing effect against breast cancer cells (MCF-7) with a cytotoxicity of about 72.13%. All the data presented support the efficiency of the synthesized N,O-CMCS/MAGG hydrogel as a biomaterial that may find promising applications in anticancer drug delivery.


Asunto(s)
Antineoplásicos , Quitosano , Antineoplásicos/farmacología , Liberación de Fármacos , Galactanos , Células HEK293 , Humanos , Hidrogeles , Concentración de Iones de Hidrógeno , Mananos , Gomas de Plantas
5.
Bioorg Chem ; 98: 103754, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32200329

RESUMEN

A diverse series of 1,2,4-oxadiazoles based substituted compounds were designed, synthesized and evaluated as anticancer agents targeting carbonic anhydrase IX (CAIX). Initial structure-activity analysis suggested that the thiazole/thiophene-sulfonamide conjugates of 1,2,4-oxadiazoles exhibited potent anticancer activities with low µM potencies. Compound OX12 exhibited antiproliferative activity (IC50 = 11.1 µM) along with appreciable inhibition potential for tumor-associated CAIX (IC50 = 4.23 µM) isoform. Therefore, OX12 was structurally optimized and its SAR oriented derivatives (OX17-27) were synthesized and evaluated. This iteration resulted in compound OX27 with an almost two-fold increase in antiproliferative effect (IC50 = 6.0 µM) comparable to the clinical drug doxorubicin and significantly higher potency against CAIX (IC50 = 0.74 µM). Additionally, OX27 treatment decreases the expression of CAIX, induces apoptosis and ROS production, inhibited colony formation and migration of colon cancer cells. Our studies provide preclinical rational for the further optimization of identified OX27 as a suitable lead for the possible treatment of CRC.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Oxadiazoles/farmacología , Sulfonamidas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Oxadiazoles/química , Relación Estructura-Actividad , Sulfonamidas/química , Células Tumorales Cultivadas
6.
Appl Microbiol Biotechnol ; 104(24): 10465-10479, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33175246

RESUMEN

In pharmaceutical industry, the prodrug approaches and drug-drug conjugates are being now vastly used to optimize the efficacy of the drugs for multipurpose. The combination or conjugation of antimicrobials agents with natural antimicrobials may lead to better synergistic antimicrobial activity. Currently, many publications show the potential of ionic liquids (ILs) as novel antimicrobials and even as active pharmaceutical ingredients. The current study showed the synthesis of novel pyrrolidinium-based ILs (Cx, x = 4, 6, 8, 10, 12) and their antibacterial activity alone and in combination with antimicrobial peptide, melittin (MEL), against clinically relevant microorganism, E. coli and S. aureus. The cytotoxicity of synthesized ILs was administered on HEK 293 cell line using MTT assay. The obtained results showed the dependency of antibacterial activity of ILs on alkyl chain length (C4 < C6 < C8 < C10 < C12). The remarkable improvement in the antibacterial efficiency of MEL was seen with ILs; however, antibacterial effect is more pronounced with IL having large alkyl chain length (C8, C10, and C12) at their minimal concentration with MEL to disrupt the cell membrane. In addition, the binding study and haemocompatibility results showed favourable biocompatibility and stability which could potentially improve its utility for the biomedical field. KEY POINTS: • The combination of melittin and pyrrolidinium-based ILs showed improved antibacterial activity against E. coli and S. aureus which may be used for developing new antibacterial agents. • Moreover, the cytotoxicity and haemocompatibility results showed excellent biocompatibility of the combinations on human cell line and human serum albumin, respectively, which could potentially improve its utility for the biomedical field.


Asunto(s)
Antiinfecciosos , Líquidos Iónicos , Antibacterianos/farmacología , Escherichia coli , Bacterias Gramnegativas , Bacterias Grampositivas , Células HEK293 , Humanos , Meliteno/farmacología , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus
7.
Tumour Biol ; 39(6): 1010428317703635, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28631565

RESUMEN

The recent investigation on PARK-2, a putative tumor suppressor gene, has found that it has been altered in multiple human malignancies. However, the clinical impact of PARK-2 alteration in uterine cervix carcinoma has not yet been studied. Therefore, we aimed to examine mutations, promoter hypermethylation, and protein expression of PARK-2 among the North Indian patients and their association with clinical parameters to evaluate the implication of PARK-2 in the genesis of cervical cancer. A total of 168 patient samples were processed for mutational analysis by single-strand conformation polymorphism, sequencing, and further in silico analysis of the identified mutations. Promoter hypermethylation by methylation-specific polymerase chain reaction and expression of PARK-2 were performed using immunohistochemistry. Statistical correlation between molecular findings and the clinicopathological parameters was taken to figure out the meaningful outcome. As per our findings, 3.5% (6/168) tumors showed novel missense mutations in exon 11 of PARK-2. In silico analysis showed high structural deviations manifested by mutations, A398D and Y391N, in both mutant proteins as compared to wild type. Promoter hypermethylation was observed in total of 29% of (48/168) tumor samples. Furthermore, 46.43% tumors (78/168) exhibited loss of PARK-2 expression in cervical carcinoma. The loss of expression of PARK-2 when correlated with clinical parameters resulted in significant association with tumor stage (p = 0.002) and with histological grade (p = 0.025). However, only clinical stage remained significant after Bonferroni correction (p < 0.007). A trend was observed between PARK-2 promoter hypermethylation and its protein expression. Our study provided sufficient information and insight for investigation of PARK-2 and highlighted its role as a tumor suppressor gene in cervical cancer in North Indian population.


Asunto(s)
Biomarcadores de Tumor/genética , Metilación de ADN/genética , Ubiquitina-Proteína Ligasas/genética , Neoplasias del Cuello Uterino/genética , Adulto , Anciano , Epigénesis Genética/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , India , Persona de Mediana Edad , Polimorfismo Conformacional Retorcido-Simple , Regiones Promotoras Genéticas , Conformación Proteica , Relación Estructura-Actividad , Proteínas Supresoras de Tumor/genética , Ubiquitina-Proteína Ligasas/química , Neoplasias del Cuello Uterino/patología
8.
Tumour Biol ; 39(11): 1010428317740296, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29182103

RESUMEN

Globally, colorectal cancer is the third most common type of cancer. Genetic instability leading to cancer development is one of the major causes for development of cancer. Alterations in mitochondrial genome, that is, mutations, single-nucleotide polymorphisms, and copy number variations are known to contribute in cancer development. The aim of our study was to investigate association of mitochondrial T16189C polymorphism and copy number variation with colorectal cancer in North Indian population. DNA isolated from peripheral blood of 126 colorectal cancer patients and 114 healthy North Indian subjects was analyzed for T16189C polymorphism and half of them for mitochondrial copy number variation. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism, and copy number variation was estimated using real-time polymerase chain reaction, numbers of mitochondrial copies and found to be significantly higher in colorectal cancer patients than healthy controls (88 (58-154), p = 0.001). In the regression analysis, increased mitochondrial copy number variation was associated with risk of colorectal cancer (odds ratio = 2.885, 95% confidence interval = 1.3-6.358). However, T16189C polymorphism was found to be significantly associated with the risk of rectal cancer (odds ratio = 5.213, p = 0.001) and non-significantly with colon cancer (odds ratio = 0.867, p = 0.791). Also, false-positive report probability analysis was done to validate the significant findings. Our results here indicate that mitochondrial copy number variation may be playing an important role in the development of colorectal cancer, and detection of mitochondrial copy number variation can be used as a biomarker for predicting the risk of colorectal cancer in North Indian subjects.


Asunto(s)
Neoplasias Colorrectales/genética , Variaciones en el Número de Copia de ADN , ADN Mitocondrial/genética , Predisposición Genética a la Enfermedad/genética , Adulto , Anciano , Pueblo Asiatico/genética , Femenino , Genotipo , Humanos , India , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple
9.
Biomarkers ; 21(8): 716-720, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27098297

RESUMEN

We evaluated the loss of heterozygosity (LOH) at 10q23.3 locus of microsatellite markers; D10S198, D10S192, and D10S541 of PTEN gene in 223 North Indian colorectal cancer (CRC) specimens. DNA was isolated and microsatellite-specific markers polymerase chain reaction was performed. Out of total 223 cases 102 showed LOH for at least one of the locus. In addition, thereto a significant association was found with the clinicopathologic features like grade of differentiation, clinical stage, invasion, lymph node invasion, and the clinical outcome (p < 0.05). These data argue that the given markers to check the possible LOH of PTEN gene at locus 10q23.3 could be considered as one of the diagnostic markers in CRC.

10.
Toxicol Appl Pharmacol ; 289(2): 251-61, 2015 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-26415834

RESUMEN

Ferulic acid (FA) is a plant polyphenol showing diverse therapeutic effects against cancer, diabetes, cardiovascular and neurodegenerative diseases. FA is a known antioxidant at lower concentrations, however at higher concentrations or in the presence of metal ions such as copper, it may act as a pro-oxidant. It has been reported that copper levels are significantly raised in different malignancies. Cancer cells are under increased oxidative stress as compared to normal cells. Certain therapeutic substances like polyphenols can further increase this oxidative stress and kill cancer cells without affecting the proliferation of normal cells. Through various in vitro experiments we have shown that the pro-oxidant properties of FA are enhanced in the presence of copper. Comet assay demonstrated the ability of FA to cause oxidative DNA breakage in human peripheral lymphocytes which was ameliorated by specific copper-chelating agent such as neocuproine and scavengers of ROS. This suggested the mobilization of endogenous copper in ROS generation and consequent DNA damage. These results were further validated through cytotoxicity experiments involving different cell lines. Thus, we conclude that such a pro-oxidant mechanism involving endogenous copper better explains the anticancer activities of FA. This would be an alternate non-enzymatic, and copper-mediated pathway for the cytotoxic activities of FA where it can selectively target cancer cells with elevated levels of copper and ROS.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Cobre/metabolismo , Ácidos Cumáricos/farmacología , Daño del ADN , Neoplasias/tratamiento farmacológico , Oxidantes/farmacología , Animales , Antineoplásicos Fitogénicos/química , Células CHO , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quelantes/farmacología , Ensayo Cometa , Cobre/química , Ácidos Cumáricos/química , Cricetulus , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/farmacología , Células HEK293 , Células Hep G2 , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Linfocitos/patología , Neoplasias/metabolismo , Neoplasias/patología , Oxidantes/química , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Carbonilación Proteica/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
11.
J Biomol Struct Dyn ; 41(15): 7339-7353, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36129011

RESUMEN

Fisetin, a natural flavonoid molecule, has been shown to have anticancer properties against various malignancies. In this investigation, we discovered that Fisetin decreased cell viability of both the treated skin cancer cell lines A375 and A431 in a dose and time-dependent manner. The IC50 values ranging from 57.60 µM ± 6.59 to 41.70 µM ± 1.25 in A375 and 48.70 µM ± 5.49 to 33.67 µM ± 1.03 for A431 at the observed time ranging between 24 h to 72 h of treatment remained quite enthusiastic when compared with the normal HEK 293 cells. Fisetin significantly decreased colony formation and migratory ability of the cancer cells. Flow cytometry analysis revealed that Fisetin significantly restricted the progression of skin cancer cells in the G0/G1 phase of the cell cycle and induced cells to undergo apoptosis by increasing reactive oxygen species, decreasing mitochondrial membrane potential, and elevating the count of early and late apoptotic cells. Our in silico studies of molecular docking followed by molecular dynamics simulation found that the interactions and stability of MTH1 protein with Fisetin further showed a considerable binding affinity for MTH1 (-11.4 kcal/mol) and developed stable complexes maintained throughout 100 ns trajectories. Our western blot analysis endorsed this. We found that Fisetin downregulated the expression levels of MTH1 also in addition, it played a crucial role in regulation of apoptotic events in cancer cells. We therefore, conclude that Fisetin anticancer properties against skin cancer cells are mediated through MTH1 inhibition followed by ATM and P53 upregulation.Communicated by Ramaswamy H. Sarma.

12.
Life Sci ; 321: 121535, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-36906255

RESUMEN

MicroRNAs are critical regulators of the plethora of genes, including FOXO "forkhead" dependent transcription factors, which are bonafide tumour suppressors. The FOXO family members modulate a hub of cellular processes like apoptosis, cell cycle arrest, differentiation, ROS detoxification, and longevity. Aberrant expression of FOXOs in human cancers has been observed due to their down-regulation by diverse microRNAs, which are predominantly involved in tumour initiation, chemo-resistance and tumour progression. Chemo-resistance is a major obstacle in cancer treatment. Over 90% of casualties in cancer patients are reportedly associated with chemo-resistance. Here, we have primarily discussed the structure, functions of FOXO and also their post-translational modifications which influence the activities of these FOXO family members. Further, we have addressed the role of microRNAs in carcinogenesis by regulating the FOXOs at post-transcriptional level. Therefore, microRNAs-FOXO axis can be exploited as a novel cancer therapy. The administration of microRNA-based cancer therapy is likely to be beneficial to curb chemo-resistance in cancers.


Asunto(s)
MicroARNs , Neoplasias , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Procesamiento Proteico-Postraduccional , Diferenciación Celular
13.
Tumour Biol ; 33(1): 17-22, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21931994

RESUMEN

Definite progress in understanding the etiology of cervical cancer has been achieved, and some types of human papillomavirus have been established as the central cause of cervical cancer worldwide. This study investigates the human papillomavirus infection and its correlation with apoptosis and clinicopathologic characteristics in squamous cell carcinoma of uterine cervix. Human papillomavirus typing was done by type-specific primers for high-risk human papillomavirus using standard polymerase chain reaction method. Programmed cell death (apoptosis) was determined by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay. Human papillomavirus infection in tissue biopsy of cervical carcinoma was detected in 131 of 135 (97%) cases. Among the positive cases of human papillomavirus, 123 (94%) cases were human papillomavirus type 16, and five (4%) cases were human papillomavirus type 18. Out of 135 cervical carcinoma cases, 81 (60%) cases showed presence of apoptosis. The phenomenon of apoptosis was seen slightly higher in squamous cell carcinoma than in adenocarcinoma (40% in squamous cell carcinoma and 33% in adenocarcinoma). The human papillomavirus infection in cervical cancer might not play any role in the occurrence of apoptosis.


Asunto(s)
Carcinoma/patología , Papillomavirus Humano 16/clasificación , Papillomavirus Humano 18/clasificación , Infecciones por Papillomavirus/patología , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Carcinoma/virología , Femenino , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Humanos , India , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Virología/métodos
14.
Life Sci ; 308: 120922, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36058262

RESUMEN

Renal cell carcinoma (RCC) is one of the most common kidney cancers, responsible for nearly 90 % of all renal malignancies. Despite the availability of many treatment strategies, RCC still remains to be an incurable disease due to its resistivity towards conventional therapies. Nanotechnology is an emerging field of science that offers newer possibilities in therapeutics including cancer medicine, specifically by targeted delivery of anticancer drugs. Several phytochemicals are known for their anti-cancer properties and have been regarded as chemopreventive agents. However, the hydrophobic nature of many phytochemicals decreases its bioavailability and distribution, thus showing limited therapeutic effect. Application of nanotechnology to enhance chemoprevention is an effective strategy to increase the bioavailability of phytochemicals and thereby its therapeutic efficacy. The present review focuses on the utility of nanotechnology in RCC treatment and chemopreventive agents of RCC. We have also visualized the future prospects of nanomolecules in the prevention and cure of RCC.


Asunto(s)
Anticarcinógenos , Carcinoma de Células Renales , Neoplasias Renales , Anticarcinógenos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/prevención & control , Quimioprevención , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/prevención & control , Fitoquímicos/uso terapéutico
15.
J Biomol Struct Dyn ; 40(23): 13075-13082, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34551668

RESUMEN

A new pyrazole-tethered thiazolidine-2,4-dione derivative (8) has been synthesized by the Knoevenagel condensation of 3-(4-nitrophenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (4) and 3-(2,4-dioxothiazolidin-3-yl)propanenitrile (7). The structure of the final compound was confirmed by standard spectroscopic techniques including IR spectroscopy, 1H-NMR spectroscopy, and ESI-MS mass spectrometry. Molecular features including frontier molecular orbital (HOMO-LUMO) energies, reactivity descriptors and molecular electrostatic potential (ESP) of the title molecule were determined using density functional theory (DFT) calculation. The in vitro cytotoxicity of both the intermediate (4) and final (8) compounds were investigated against cancerous (SW-480 and MCF-7) and normal (HEK-293) cell lines by MTT assay. Compound (8) displayed higher activity than (4) with higher sensitivity against breast cancer cell line and lesser toxicity. The experimental data were further complemented by docking and absorption, distribution, metabolism, and excretion (ADME) studies.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Pirazoles , Humanos , Simulación del Acoplamiento Molecular , Células HEK293 , Pirazoles/química , Fenómenos Químicos
16.
J Gastrointest Cancer ; 53(3): 674-682, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34467515

RESUMEN

PURPOSE: PARK2 is a potential tumour suppressor gene and its genetic alterations (regionic loss) are common across many human cancers. The association of PARK2 germline variations (SNPs) with Parkinson's has been shown, but their association in development and progression of cancer remains elusive. The aim of this study was to identify association of PARK2 polymorphisms (rs1801474, rs1801334) with colorectal cancer in a case control study design. METHODS: This case control study included a total of 650 genetically unrelated subjects comprising 300 colorectal cancer cases and 350 healthy controls belonging to North Indian. Both SNPs were analyzed using the PCR-RFLP assay. Statistical analysis for describing risk and association was performed using SPSS-17 software. Structural deviations due to non- synonymous substitutions (S167N and D394N) were analyzed using MD simulations. RESULTS: The genotype distributions of both the SNPs were in Hardy-Weinberg equilibrium. For both the polymorphisms, the allelic model showed statistically significant risk with OR ~ 1.3. Many of the associations remained significant even after Bonferroni correction (P < 0.00125). The result suggested that both S167N and D394N were deviated from wild type and structures and were stable after 5 ns. The average value of RMSD for backbone atoms was calculated from 5 to 10 ns molecular dynamics simulation data. CONCLUSION: In conclusion, our study revealed a significant association of PARK2 SNPs with colorectal cancer as well as their relations with other clinical parameters highlighting their contribution towards colorectal cancer susceptibility in North Indian population.


Asunto(s)
Neoplasias Colorrectales , Predisposición Genética a la Enfermedad , Pueblo Asiatico , Estudios de Casos y Controles , Neoplasias Colorrectales/genética , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Ubiquitina-Proteína Ligasas
17.
Int J Biol Macromol ; 221: 435-445, 2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36067850

RESUMEN

This study aims to develop chitosan-coated PLGA nanoparticles intended for nose-to-brain delivery of carmustine. Formulations were prepared by the double emulsion solvent evaporation method and optimized by using Box-Behnken Design. The optimized nanoparticles were obtained to satisfactory levels in terms of particle size, PDI, entrapment efficiency, and drug loading. In vitro drug release and ex-vivo permeation showed sustained release and enhanced permeability (approx. 2 fold) of carmustine compared to drug suspension. The AUC0-t of brain obtained with carmustine-loaded nanoparticles via nasal administration in Albino Wistar rats was 2.8 and 14.7 times that of intranasal carmustine suspension and intravenous carmustine, respectively. The MTT assay on U87 MG cell line showed a significant decrease (P < 0.05) in the IC50 value of the formulation (71.23 µg ml-1) as compared to drug suspension (90.02 µg ml-1).These findings suggest chitosan coated nanoparticles could be used to deliver carmustine via intranasal administration to treat Glioblastoma multiforme.


Asunto(s)
Quitosano , Glioblastoma , Nanopartículas , Animales , Ratas , Administración Intranasal , Quitosano/metabolismo , Carmustina/metabolismo , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Portadores de Fármacos/metabolismo , Encéfalo/metabolismo , Tamaño de la Partícula , Ratas Wistar , Sistemas de Liberación de Medicamentos/métodos
18.
ACS Omega ; 5(12): 6376-6388, 2020 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-32258872

RESUMEN

Growing antibiotic resistance has become a major health problem and has encouraged many researchers to find an alternative class of antibiotics. Combination therapy (covalent/noncovalent) is supposed to increase antibacterial activity leading to a decrease in administration dosage, thus lowering the risk of adverse side effects. The covalent coupling sometimes leads to instability and loss in the structure of AMPs. Therefore, herein, we have reported innovative research involving the noncovalent coupling of melittin (MEL), an antimicrobial peptide with a series of synthesized less toxic pyrrolidinium-based ionic liquids (ILs) for which MTT assay was performed. The antibacterial results of conjugates showed remarkable improvement in the MIC value as compared to MEL and ILs alone against Escherichia coli and Staphylococcus aureus . In addition, hemocompatibility results suggested good selectivity of the noncovalent conjugate as a potential antibiotic agent. Further, the docking study was employed to acquire the most favorable conformation of MEL in the presence of ILs. The best possible complex was further studied using various spectroscopic techniques, which showed appreciable binding and stability of the complex.

19.
ACS Omega ; 4(14): 16026-16036, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31592147

RESUMEN

The chemically oxidized gum arabic was prepared and used as a naturally derived nontoxic and pH-responsive cross-linker to develop smart polyvinyl alcohol (PVA)-based hydrogels for the first time. The formulated hydrogels exhibited high mechanical properties, good porosity, and pH sensitivity, which facilitated their application as promising biomaterials for sustained delivery of folic acid. Further, the synthesized cross-linked PVA hydrogels displayed no cytotoxicity toward the human embryonic kidney cell line and exhibited higher blood compatibility. The hydrolytic degradation study confirmed their biodegradable nature. While the sustained delivery along with photoprotective properties of these hydrogels confirmed their multifunctional characteristics, these results suggest that these hydrogels may act as an efficient photoprotective material and find their application in the field of drug delivery.

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