Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
1.
J Biomol Struct Dyn ; : 1-13, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715440

RESUMO

Various serum proteins, like Human Serum Albumin (HSA) and others, are susceptible to glycation and the formation of Advanced Glycation End Products (AGEs). Diabetes and other diseases are associated with AGE development. Recently, isoflavones have been studied for their therapeutic benefits. In the present study, we glycated HSA with Methylglyoxal (MGO) with and without the test compound, i.e., Biochanin A (BCA), to test its antiglycating capacity. We studied the biochemical and biophysical effects of glycation on HSA with and without BCA and also took the help of the in silico technique. Analytical methods included intrinsic and extrinsic fluorescence, polyacrylamide gel electrophoresis (PAGE), UV spectroscopy, far UV circular dichroism, and others. For structural comprehension, TEM and SEM were used. Molecular docking and simulation were employed to observe BCA-HSA's site-specific interaction. Since HSA is a therapeutically relevant protein involved in many disorders, this study's findings are important.Communicated by Ramaswamy H. Sarma.

3.
J Biomol Struct Dyn ; 42(2): 935-947, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37098813

RESUMO

Hyperglycaemia accelerates the aging process significantly. Diabetes problems can be mitigated by inhibiting glycation. To learn more about glycation and antiglycation mediated by methyl glyoxal and baicalein, we studied human serum albumin as a model protein. A Methylglyoxal (MGO) incubation period of seven days at 37 degrees Celsius induced glycation of Human Serum Albumin.s Hyperchromicity, decreased tryptophan and intrinsic fluorescence, increased AGE-specific fluorescence, and reduced mobility were all seen in glycated human serum albumin (MGO-HSA) in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Fourier transform infrared spectroscopy (FT-IR) and then far ultraviolet dichroism were used to detect secondary and tertiary structural perturbations (CD). The Congo red assay (CR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) all verified the presence of amyloid-like clumps. Structure (carbonyl groups on ketoamine moieties) (CO), physiological problems including diabetes mellitus, and cardiovascular disease, etc. are linked to the structural and functional changes in glycated HSA, as proven by these studies.Communicated by Ramaswamy H. Sarma.


Assuntos
Flavanonas , Produtos Finais de Glicação Avançada , Reação de Maillard , Humanos , Produtos Finais de Glicação Avançada/química , Espectroscopia de Infravermelho com Transformada de Fourier , Óxido de Magnésio , Albumina Sérica/química , Albumina Sérica Humana/química
4.
ACS Omega ; 8(49): 46715-46727, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38107932

RESUMO

Recently, biosynthesized nanoparticles (NPs) have played a vital role as an alternative to physical and chemical methods. Here, a distinctive bioinspired synthesis of zinc oxide nanoparticles (ZnO NPs) has been introduced using leaf extracts of Withania coagulans as the reducing agent by using distilled water and methanol. The synthesized catalysts were analyzed through ultraviolet-visible spectroscopy, dynamic light scattering, scanning electron microscopy, Fourier transform infrared, energy-dispersive X-ray analysis, and X-ray diffraction for NP synthesis, morphology, functional group, elemental composition, and peak crystallinity analysis. The phytochemical analysis of 2,2-diphenyl-1-picrylhydrazyl (DPPH), total flavonoid content, total alkaloid content, and total phenolic content of the crude methanolic extract of the plant was also performed, suggesting the greatest potential as the supporting material for ZnO NPs. The NPs were investigated for their catalytic efficiency in the degradation of dyes (rhodamine B dye) and against important human food-borne pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli). ZnO NPs exhibited a strong catalytic activity in the degradation of dyes and against bacteria. The results also showed an enhanced activity of ZnO NPs of methanolic extract (ZnO-M) composites compared to zinc oxide of distilled water (ZnO-D). The % age degradation of the dye, Kapp, and linear relationship were obtained from pseudo-first-order kinetics. The highest reduction rate in 30 and 60 min was observed under sunlight by ZnO-M and ZnO-D, respectively. The rate constant Kapp for the reduction of the dye was 13.6 × 10-1 min-1 and 6.8 × 10-1 min-1, respectively (numerical values). For ZnO-M, ln(Kapp) ≈ 0.309. For ZnO-D, ln(Kapp) ≈ -0.385. These rate constants represent the degradation of the dye in the presence of ZnO-M and ZnO-D catalysts. In addition, NPs were found to be most active against S. aureus (18 mm in the case of ZnO-M and 15 mm in the case of ZnO-D) than P. aeruginosa and E. coli. The results suggested that the prepared ZnO NPs could be used in pharmaceutical industries as well as photocatalysts. ZnO-M had greater control over particle size and morphology, potentially resulting in smaller, more uniform NPs. ZnO-D achieved fine size control but not potentially better than that compared to organic solvents.

6.
Exp Biol Med (Maywood) ; 248(17): 1507-1517, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37688505

RESUMO

Breast cancer (BC) continues to be the most common cancer in the women worldwide. Since estrogen receptor (ER)-positive BC accounts for the majority of newly diagnosed cases, endocrine therapy is advised to utilize either tamoxifen (Tam) or aromatase inhibitors. The use of Tam as a monotherapy or in conjunction with an aromatase inhibitor following two or three years of endocrine therapy has long been recommended. When used adjuvantly, Tam medication reduces BC mortality and relapses, while it extends survival times in metastatic BC when used in conjunction with other treatments. Unfortunately, the efficiency of Tam varies considerably. This study was conducted to explore the influence of genetic polymorphisms in CYP2C19 gene on Tam's pharmacogenetics and pharmacokinetics in estrogen-positive BC patients. Data from healthy, unrelated individuals (n = 410; control group) and ER-positive BC patients (n = 430) receiving 20 mg of Tam per day were recruited. Steady-state plasma concentrations of Tam and its three metabolites were quantified using the high-performance liquid chromatography in the patients. The CYP2C19 polymorphisms were genotyped using an Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) approach. More than 65% of healthy individuals were extensive metabolizers (*1/*1) for CYP2C19, whereas more than 70% of ER-positive BC patients were rapid and ultrarapid metabolizers (*1/17*, *17/17*). The polymorphism CYP2C19*17 is significantly associated with higher 4-hydroxytamoxifen (4-OH-Tam). Patients with the *17/*17 genotype exhibited 1- to 1.5-fold higher 4-OH-Tam, which was also high in patients with the *1/*2 and *2/*2 genotypes.


Assuntos
Neoplasias da Mama , Citocromo P-450 CYP2C19 , Tamoxifeno , Feminino , Humanos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Estrogênios , Paquistão , Tamoxifeno/uso terapêutico
7.
Arch Microbiol ; 205(9): 321, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37642791

RESUMO

Omega-3 fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and α-linolenic acid (ALA), are essential polyunsaturated fatty acids with diverse health benefits. The limited conversion of dietary DHA necessitates its consumption as food supplements. Omega-3 fatty acids possess anti-arrhythmic and anti-inflammatory capabilities, contributing to cardiovascular health. Additionally, DHA consumption is linked to improved vision, brain, and memory development. Furthermore, omega-3 fatty acids offer protection against various health conditions, such as celiac disease, Alzheimer's, hypertension, thrombosis, heart diseases, depression, diabetes, and certain cancers. Fish oil from pelagic cold-water fish remains the primary source of omega-3 fatty acids, but the global population burden creates a demand-supply gap. Thus, researchers have explored alternative sources, including microbial systems, for omega-3 production. Microbial sources, particularly oleaginous actinomycetes, microalgae like Nannochloropsis and among microbial systems, Thraustochytrids stand out as they can store up to 50% of their dry weight in lipids. The microbial production of omega-3 fatty acids is a potential solution to meet the global demand, as these microorganisms can utilize various carbon sources, including organic waste. The biosynthesis of omega-3 fatty acids involves both aerobic and anaerobic pathways, with bacterial polyketide and PKS-like PUFA synthase as essential enzymatic complexes. Optimization of physicochemical parameters, such as carbon and nitrogen sources, pH, temperature, and salinity, plays a crucial role in maximizing DHA production in microbial systems. Overall, microbial sources hold significant promise in meeting the global demand for omega-3 fatty acids, offering an efficient and sustainable solution for enhancing human health.


Assuntos
Actinobacteria , Ácidos Graxos Ômega-3 , Humanos , Ácidos Docosa-Hexaenoicos , Vias Biossintéticas , Carbono
8.
Int J Biol Macromol ; 245: 125497, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37369258

RESUMO

Advanced glycation end products (AGEs) are formed through non-enzymatic glycation, that have been linked to various diseases, including polycystic ovarian syndrome (PCOS) playing a critical role leading to secondary comorbidities such as diabetes-related problems, cardiovascular complications, infertility, etc. As a result, there has been a lot of research into AGE-inhibiting phytochemicals for the remediation and obstruct progression of glycation-related illnesses. The current study is based on in-vitro protein model, in which human serum albumin have been used to investigate the cumulative effect of chlorogenic acid (CGA) and cholecalciferol (vitamin D) on glycation and evaluate their inhibitory impact on AGEs production in the presence of methylglyoxal. Through the application of several biochemical and biophysical techniques, we were able to examine the synergistic impact of both the compounds on albumin structure and its biochemical properties during different stages of glycation. According to Nitro-blue tetrazolium assay results indicate that CGA and vitamin D inhibited fructosamine (early glycation product) production. Moreover, free thiol and lysine residues were significantly increased whereas protein carbonyl levels were significantly decreased. Additive effect of CGA and vitamin D were associated with reduced AGEs fluorescence and increased tryptophan and tyrosine fluorescence. Amadori-albumin after treatment showed some evidence of regaining its alpha-helicity as measured by far-UV CD spectrum. Furthermore, secondary structural alterations were confirmed by Fourier transform infrared spectroscopy (FTIR). ANS (1-anilinonaphthalene-8-sulfonic acid) fluorescence spectra also displayed less revelation of hydrophobic patches. Bilirubin binding capacity was also restored which showed functional recovery of HSA. The electrophoretic mobility was also restored which is portrayed by SDS-PAGE. Additionally, to predict the anti-aggregation potential of CGA and vitamin D, congo red assay and ThT fluorescence was performed which reveal low aggregate formation after treatment. These results corroborated with scanning electron microscopy and confocal microscopy. Docking and simulation results also reveal spontaneous binding of CGA and vitamin D on subdomain IIA of HSA favoring their binding thermodynamically. All the findings suggest that chlorogenic acid and cholecalciferol given in combination might help in prevention of PCOS progression and its related complications.

9.
J Coll Physicians Surg Pak ; 32(11): 1430-1434, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36377010

RESUMO

OBJECTIVE: To study the correlation of cytogenetic and molecular abnormalities on induction chemotherapy in childhood acute lymphoblastic leukaemia (ALL). STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Department of Haematology, Armed Forces Institute of Pathology (AFIP), from March 2021 to August 2021. METHODOLOGY: Patients aged 1-18 years with newly diagnosed acute lymphoblastic leukaemia were inducted. Patients aged less than 1 year and more than 18 years were excluded from the study. The diagnosis was based on morphology, cytochemistry, flow cytometry, and cytogenetic/molecular analysis. Risk stratification was done on the basis of age, TLC, and cytogenetic/molecular defects. The UKALL 2011 protocol was used for treatment with regimen-A for standard risk and regimen-B for high-risk patients. Bone marrow was repeated on day 29 of induction therapy and blast percentage was assessed to establish post-induction remission. Association between cytogenetic / molecular abnormalities and post-induction remission status was analysed using chi-square test. RESULTS: There were total 142 patients with mean age of 6.4 + 3.6 years and a male- to-female ratio of 2.7:1. Immunophenotyping revealed 85.9% cases as B-cell ALL and 14.1% as T-cell ALL. The most frequent cytogenetic and molecular abnormalities were hyperdiploidy (19%), t(9;22)/BCR-ABL1(p190) (10.6%), complex karyotype (5.6%), E2A-PBX1 (8.5%), and TEL-AML1 (4.9%). A total of 127/142 (89.4%) achieved haematological remission after induction therapy with two deaths during induction therapy (1.4%). Post-induction remission rate in patients with favorable cytogenetic/molecular defects was 100% and in children with bad prognostic changes, the rate of remission was 69.2%. Chi-square test showed a significant association between cytogenetic/molecular abnormalities and post-induction remission (p-value <0.001). CONCLUSION: Cytogenetic and molecular abnormalities have a significant association with post-induction remission in children with acute lymphoblastic leukaemia. KEY WORDS: Acute lymphoblastic leukaemia, Cytogenetics, Chemotherapy, Induction, Remission.


Assuntos
Quimioterapia de Indução , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Masculino , Feminino , Pré-Escolar , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Citogenética , Aberrações Cromossômicas , Análise Citogenética , Prognóstico , Indução de Remissão
10.
Arch Microbiol ; 204(11): 672, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36251102

RESUMO

The growing population increases the need to develop advanced biological methods for utilizing renewable and sustainable resources to produce environmentally friendly biofuels. Currently, energy resources are limited for global demand and are constantly depleting and creating environmental problems. Some higher chain alcohols, like butanol and ethanol, processing similar properties to gasoline, can be alternate sources of biofuel. However, the industrial production of these alcohols remains challenging because they cannot be efficiently produced by microbes naturally. Therefore, butanol is the most interesting biofuel candidate with a higher octane number produced naturally by microbes through Acetone-Butanol-Ethanol fermentation. Feedstock selection as the substrate is the most crucial step in biobutanol production. Lignocellulosic biomass has been widely used to produce cellulosic biobutanol using agricultural wastes and residue. Specific necessary pretreatments, fermentation strategies, bioreactor designing and kinetics, and modeling can also enhance the efficient production of biobutanol. The recent genetic engineering approaches of gene knock in, knock out, and overexpression to manipulate pathways can increase the production of biobutanol in a user friendly host organism. So far various genetic manipulation techniques like antisense RNA, TargeTron Technology and CRISPR have been used to target Clostridium acetobutylicum for biobutanol production. This review summarizes the recent research and development for the efficient production of biobutanol in various aspects.


Assuntos
Clostridium acetobutylicum , 1-Butanol/metabolismo , Acetona/metabolismo , Anaerobiose , Biocombustíveis , Biomassa , Butanóis/metabolismo , Clostridium acetobutylicum/genética , Clostridium acetobutylicum/metabolismo , Etanol/metabolismo , Fermentação , Gasolina , Octanos/metabolismo , RNA Antissenso/metabolismo
11.
J Coll Physicians Surg Pak ; 32(10): 1367-1369, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36205291

RESUMO

This study aimed to analyse the diagnostic accuracy of different laboratory parameters that can predict bone marrow metastasis. A cross-sectional analytical study was conducted at the Armed Forces Institute of Pathology (AFIP), Rawalpindi from March 2021 to August 2021. Bone marrow aspirates and biopsy procedures were done on 60 newly diagnosed cases of non-haematological malignancies as part of staging. Laboratory parameters noted for the study included peripheral blood smear findings, serum lactate dehydrogenase (LDH), radiological findings, and bone marrow aspirate/trephine biopsy results. Bone marrow metastasis was seen in 21/60 patients. The most common malignancies with bone marrow involvement were retinoblastoma and neuroblastoma. Laboratory findings showed no significant statistical difference in mean haemoglobin and total leukocyte count between cases and controls. Positive cases had a mean platelet count of 261.7 x 109/L and mean LDH of 750.1 U/L (p <0.05) for both parameters. ROC analysis showed the area under the curve (AUC) for LDH to be 0.969 (highly significant) showing a strong predictive value of LDH. Positive radiological findings were detected in only one case with bone marrow metastasis. The elevated level of serum LDH is not only cost-effective but also has high diagnostic accuracy to predict bone marrow metastasis. Key Words: Bone marrow, Biochemical, Lactate dehydrogenase, Metastasis, Non-haematological malignancies.


Assuntos
Neoplasias da Medula Óssea , Neoplasias Ósseas , Neuroblastoma , Neoplasias da Retina , Estudos Transversais , Humanos , Lactato Desidrogenases
12.
Front Plant Sci ; 13: 950120, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092395

RESUMO

Soil contamination with toxic heavy metals [such as lead (Pb)] is becoming a serious global problem due to the rapid development of the social economy. However, accumulation of Pb in plant parts is very toxic for plant growth and decreases crop yield and productivity. In the present study, we have investigated the different concentrations of Pb in the soil i.e., [0 (no Pb), 50, and 100 mg kg-1] to study plant growth and biomass, photosynthetic pigments and gas exchange characteristics, oxidative stress indicators and the response of various antioxidants (enzymatic and non-enzymatic), nutritional status of the plant, organic acid exudation pattern and also Pb accumulation in the roots and shoots of the plants of two varieties of tomato (Solanum lycopersicum L.) i.e., Roma and Cchuas, grown under different levels of synergic acid [no spray (NS), water spray (WS), 0.3-0.5°µM]. Results from the present study showed that the increasing levels of Pb in the soil decreased non-significantly (P < 0.05) shoot length, root length, shoot fresh weight, root fresh weight, shoot dry weight, root dry weight, chlorophyll-a, chlorophyll-b, total chlorophyll, carotenoid content, net photosynthesis, stomatal conductance, transpiration rate, soluble sugar, reducing sugar, non-reducing sugar contents, calcium (Ca2+), magnesium (Mg2+), iron (Fe2+), and phosphorus (P) contents in the roots and shoots of the plants. However, Pb toxicity also induced oxidative stress in the roots and shoots of the plants by increasing malondialdehyde (MDA), hydrogen peroxide (H2O2), and electrolyte leakage (EL) which also induced increased the compounds of various enzymatic and non-enzymatic antioxidants and also organic acids exudation pattern in the roots such as fumaric acid, acetic acid, citric acid, formic acid, malic acid, oxalic acid contents and increased the concentration of Pb in different parts of the plants. Results also show that the Cchuas showed better growth and development compared to Roma, under the same levels of Pb in the soil. The alleviation of Pb toxicity was induced by the application of synergic acid, and results showed that the application of synergic acid increased plant growth and biomass and also increased the gas exchange characteristics and antioxidant capacity in the roots and shoots of the plants. Research findings, therefore, suggested that synergic acid application can ameliorate Pb toxicity in S. lycopersicum varieties and result in improved plant growth and composition under metal stress as depicted by balanced exudation of organic acids.

13.
Saudi J Biol Sci ; 29(4): 2421-2431, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35531249

RESUMO

In this study bioassay-guided screening of Tecomella undulate was performed for its cytotoxic, antimutagenic and anticancer potential. The ariel parts were extracted on a polarity basis (methanol, dichloromethane and hexane). The in vivo toxicity was assessed on Caenorhabditis elegans, and its locomotion was affected by Tecomella undulata hexane (TUAH) the most. Ames test for antimutagenicity showed Tecomella undulata methanol (TUAM) exhibited against mutagen 2AA showed inhibition of 71.03% and 26.32% 2AA in TA98 while in in vitro MTT assay on carcinoma cell lines TUAM showed 68.1% cytotoxicity. Moreover, In resazurin assay on fibroblast cells African green monkey kidney VERO and on the panel of carcinoma cell lines, the most effective extract was TUAM on liver HepG-2 with CC50 value 117.37 ± 4.73 µg/ml followed by on lungs A549 with 142.01 ± 5.3. Furthermore, for the bioassay-guided screening, the selectivity index was calculated for TUAM CC50 ratio on HepG-2 and VERO which showed a decent 2.77 score. After column chromatography, the fraction TU-63 should remarkable cytotoxic effect in dose-response manner assay as (Hep-G2) CC50 value 11. 67 ± 1.37 µg/ml followed by (A549) CC50 value 17.23 ± 0.58 µg/ml. For qualitative analysis of anticancer potential LC-ESI-MS/MS the potential phytochemicals were identified. In silico molecular modelling against selected carcinogenic proteins. The results suggest Tecomella undulate the substantial anticancer potential which supports potential natural anticancer therapeutic drug candidate development for combating cancer.

14.
Exp Gerontol ; 162: 111763, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35248667

RESUMO

Aging is a collection of changes that contribute to decline in maximum function and ultimately death of an organism. This process is controlled and initiated by several mechanisms including telomere shortening, oxidative stress, AMP-activated protein kinase and sirt-1. Several therapies have been reported to relieve the process of aging. Among these, diet therapy seems to be the most appropriate approach. Fruits are an important part of regular diet. They contain several compounds which have potential to handle the problem of aging and its related disorders. The present paper provides a comprehensive review on different factors present in various fruits related to the process of aging together with their antiaging mechanisms.


Assuntos
Envelhecimento , Frutas , Encurtamento do Telômero , Proteínas Quinases Ativadas por AMP/metabolismo , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Estresse Oxidativo/fisiologia , Sirtuína 1/metabolismo , Telômero , Encurtamento do Telômero/fisiologia
15.
Arch Microbiol ; 204(1): 69, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34951685

RESUMO

Hepatitis C virus is still a global challenge affecting millions of carriers worldwide with the more devastating situation in developing countries. Present-day clinical manifestations are insufficient to tackle the increasing disease burden unaffordable cost, viral resistance and adverse effects of treatment. In this research, indigenous medicinal plants from Pakistan tested in bioassay guided manner on Huh-7 cell lines for their antiviral effect, synergism of purified fraction with interferon FDA approved drug regime, as the receptor for developing transfection model. The methanol extract of Syzgium cumine was observed against HCV through serum titter reduction in Quantitative Real Time PCR assay and the gene expression system, NS3protease inhibition was 76% and 51% against genotype 1a and 3a, respectively. More precisely the most active fraction SC14 was assessed in dose response assay and synergistic potential resulted in 50% reduction (EC50 Value) in HCV titer of genotype 1a and 3a at a concentration of 71.96 ± 8.67 µg and 31.75 ± 3.28 µg, respectively, at a concentration of 100 µg. As per our research work, the S. cumine extract has shown a promising effect on HCV genotypes 1a and 3a. Moreover the purified fraction S. cumine SC14 has a potential synergistic effect and ability to suppress the gene effect of NS3 during transfection in Huh-7 cells and GC/MS analysis reports the presence of Di-n-octyl phthalate (C24H38O4) which can be future direct-acting antiviral therapy against Hepatitis C virus.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/farmacologia , Antivirais/uso terapêutico , Bioensaio , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatócitos , Humanos , Proteínas não Estruturais Virais/genética
16.
Pak J Pharm Sci ; 34(3): 883-889, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602410

RESUMO

The in silico molecular dynamics and structure-based site-specific drug design of indigenous plant biomolecules and selected proteins have remarkable potential for cancer therapy. A set of five proteins included for this research were epidermal growth factor protein (PDB ID; 1M17), crystal structure of mutated EGFR kinase (PDB ID; 2EB3), crystal structure of Bcl-xl (PDB ID; 2YXJ), apoptosis regulator protein MCL-1 BH3 (PDB ID; 3MK8) and apoptosis proteins (PDB ID; 5C3H). The present study on in silico investigation of fifteen indigenous medicinal plants were selected there one hundred thirty four ligands available literature were docked against five proteins involved in carcinogenesis. The highest scoring in silico plant, Fagonia indica was subjected to in vitro cytotoxic effects on HCT116, HepG-2 and HeLa human carcinoma cell lines. Molecular dynamics showed best ligand-protein inhibition interaction between Coumarin-2xyj and Kaempferol-2eb3 with promising binding affinities. Whereas, on HeLa human cervical cancer cell line IC50 was 28.3±0.102/ml. Fagonia indica could be potential source from natural products that have cytotoxic properties against cervical cancer cells by blocking mutant epidermal growth factor tyrosine or peroxisome proliferators activated receptor proteins.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Zygophyllaceae/química , Antineoplásicos Fitogênicos/química , Simulação por Computador , Cumarínicos/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Células HCT116 , Células HeLa , Células Hep G2 , Humanos , Técnicas In Vitro , Concentração Inibidora 50 , Quempferóis/metabolismo , Simulação de Acoplamento Molecular , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/metabolismo , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Proteína bcl-X/metabolismo
17.
Heart Fail Rev ; 26(3): 531-543, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33169339

RESUMO

Atrial fibrillation (AF) is a common arrhythmia in patients with mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVR). In this systematic review, we aimed to investigate the outcomes of TMVR using MitraClip in AF patients. We performed a systematic search using PubMed, SCOPUS, EMBASE, and Google Scholar, from inception to May 10, 2020, for studies that reported outcomes following MitraClip, in patients with AF versus without AF. Seven studies with a total of 7678 patients met the inclusion criteria. The risk of 1-year all-cause mortality following TMVR was higher in AF patients (RR 1.40, 95% CI 1.27-1.54, p ≤ 0.001). Similarly, the risk of heart failure hospitalization was higher in patients with AF (RR 1.17, 95% CI 1.06-1.30, p = 0.002) and the risk of bleeding was elevated in AF patients (RR 1.29, 95% CI 1.15-1.45, p ≤ 0.001). The risk of procedural failure, in-hospital mortality, cardiovascular mortality, and stroke was not significantly different between the two groups. The higher risk of all-cause mortality, HF hospitalization, and risk of bleeding in AF patients undergoing MitraClip warrants attention.


Assuntos
Fibrilação Atrial , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Fibrilação Atrial/complicações , Cateterismo Cardíaco , Humanos , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/cirurgia , Resultado do Tratamento
18.
Pak J Pharm Sci ; 34(6(Supplementary)): 2325-2331, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35039270

RESUMO

Cancer is one of the most diagnosed and life threatening disease throughout the world. Nevertheless present day clinical management for cancers are surgery, radiations which are insufficient to contain the disease burden. In the past two decades, more than half of chemotherapeutic drugs developed are either directly or indirectly dependent on medicinal base phytocompounds or their derivative. The present study aims to provide the base for chemotherapeutic phytochemicals. Fagonia indica showed significant antimutagenic potential with reference to control IC50 values were calculated as 146.33±5.2µg/ml, TA100 (AZS) 105.33±4.0µg/ml, TA98 (2AA) 113.6±5.2µg/ml followed and TA98 (AZS) 112.6±4.4 in Ames test. For this reason, the antiproliferation effect of extracts on cancer cell lines was studied through resazurin fluorescence. On HepG-2 cell lines 50% cytotoxic concentration (CC50) of (FIWM) was recorded as 128.3±,2.43µg/ml. On the homo sapiens epithelial cell of lung tissue (A549), the high throughput instrumental analysis of Fagonia indica depicts maximum cytotoxic effect in 30hr. The electrical impedance displays the real-time evidence about qualitative apoptosis expressed. The impedance results were supported as palmitic acid from Fagonia indica virtually that inhibits Cyclin Dependent Kinase 2 (CDKs 2) in silico molecular docking studies. Fagonia indica extract possesses substantial antimutagenic, cytotoxic and anticancer activity which supports the potential of its phytochemicals for drug development.


Assuntos
Antimutagênicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Ácido Palmítico/farmacologia , Compostos Fitoquímicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Zygophyllaceae , Células A549 , Antimutagênicos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Quinase 2 Dependente de Ciclina/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Simulação de Acoplamento Molecular , Ácido Palmítico/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Inibidores de Proteínas Quinases/isolamento & purificação , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Zygophyllaceae/química
19.
Case Rep Cardiol ; 2020: 8813930, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343943

RESUMO

Marijuana has become the most widely used illicit drug in the United States. Approximately 43.5 million Americans aged 12 or above have reported the use of marijuana in the last year. The use of cannabinoids and its relationship with cardiac effects are not well known. Many types of arrhythmias have been noted with the use of cannabis products with atrial fibrillation being the most common arrhythmia associated with the use of cannabis. We present a case of a 36-year-old male who presented with pounding chest pain, dyspnea, and diaphoresis following marijuana use. He was found to be in ventricular tachycardia which responded to amiodarone. Workup done was negative for any structural disease, and cardiac catheterization was negative for coronary artery disease. He was ultimately discharged on metoprolol. In this report, we focus on how marijuana can be associated with many arrhythmias including ventricular tachycardia with focus on mechanisms by which it can occur. We believe a detailed social history with screening for cannabis use can identify more cases of arrhythmias that can be potentially associated with marijuana use.

20.
Cureus ; 12(8): e9911, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32968574

RESUMO

Neurotoxicity is a rare side effect of Cefepime use. Cefepime can cross the blood-brain barrier and can be neurotoxic by competitive albeit weak antagonism of the gamma-aminobutyric acid complex. It is cleared by the kidneys which puts individuals with renal impairment at risk of side effects. We describe a case of Cefepime neurotoxicity in the context of nephrotoxicity secondary to the use of other drugs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...