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1.
Phys Chem Chem Phys ; 21(30): 16726-16736, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31322149

RESUMO

Dry reforming of methane was carried out over La2-2xRu2xO3 (x = 0.005, 0.01). Substitution of just 0.5 atom% of Ru in La2O3 enhanced the activity by 20 times in terms of conversion when compared to the activity exhibited by La2O3. The oxygen storage capacity of the Ru doped sample was considerably higher than undoped La2O3, which resulted in higher conversions of CH4 and CO2. The measured conversion of CH4 and CO2 was 72 and 80%, respectively, at 850 °C. The same was merely 4% with La2O3 under the same experimental conditions. DRIFTS studies demonstrated the role of a specific type of carbonates in promoting the activity of the catalyst. DFT calculations provided the rationale behind the selection of the Ru-in-La2O3 methane dry reforming catalyst. The surface structures of the pure and Ru-substituted compounds were determined, corroborating the experimental observation of enhanced oxygen storage capacity on Ru substitution. Different active surface oxygen species were identified and their roles in improving reducibilities and improving reactivities were established. The experimentally observed surface carbonate species were also identified using calculations. The combined experiment + calculation approach proved ionic Ru in La2-2xRu2xO3 to be a novel and efficient dry reforming catalyst.

2.
Phys Chem Chem Phys ; 19(21): 14148-14159, 2017 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-28524921

RESUMO

The synthesis of novel and efficient catalysts for acetylene hydrogenation exhibiting high selectivity towards ethylene is important due to the presence of selective acetylene hydrogenation reaction in petrochemical processing. Since adsorption of C2 gases constitutes the primary step in catalytic hydrogenation and governs the selectivity of the catalysts, we have explored the C2-adsorption potential of reducible CeO2-based systems. The adsorption of C2-gases over CeO2-based materials was assessed using experimental in situ spectroscopic techniques and in silico theoretical studies based on density functional theory. The effect of Pd2+ substitution on adsorption was studied. The addition of Pd2+-ions was found to enhance the adsorption of the gases. Theoretical calculations provided insights into the modes of adsorption, adsorption energetics and reactant-catalyst interactions. The role of the presence of cationic substitution and anionic vacancies in strengthening the adsorption of gases was established. Pd-substituted reduced CeO2 showed activity for the adsorption of all C2 gases. On the basis of the aforementioned experimental and theoretical observations, the catalysts were tested for acetylene hydrogenation, and Pd-substituted CeO2 was found to be a good catalyst for the reaction with complete acetylene conversion observed below 100 °C.

3.
BMC Genomics ; 15 Suppl 1: S3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24564493

RESUMO

BACKGROUND: Tuberculosis has become a major health problem being the second leading cause of death worldwide. Mycobacterium tuberculosis secretes a virulence factor, protein tyrosine phosphatase B (mPTPB) in the cytoplasm of host macrophage which suppresses its natural innate immune response and helps the pathogen survive and proliferate in the phagosome. The present study aims at indentifying potent inhibitors of mPTPB by using computational approaches of ligand based molecular modeling and docking studies. RESULTS: A 3D QSAR model was developed using a set of benzofuran salicylic acid based mPTPB inhibitors with experimentally known IC50 values. The model was generated using the statistical method of principle component regression analysis in combination with step wise forward variable selection algorithm. It was observed that steric and hydrophobic descriptors positively contribute towards the inhibitory activity of the ligands. The developed model had a robust internal as well as external predictive power as indicated by the q(2) value of 0.8920 and predicted r(2) value of 0.8006 respectively. Hence, the generated model was used to screen a large set of naturally occurring chemical compounds and predict their biological activity to identify more potent natural compounds targeting mPTPB. The two top potential hits (with pIC50 value of 1.459 and 1.677 respectively) had a similar interaction pattern as that of the most potent compound (pIC50 = 1.42) of the congeneric series. CONCLUSION: The contour plot provided a better understanding of the relationship between structural features of substituted benzofuran salicylic acid derivatives and their activities which would facilitate design of novel mPTPB inhibitors. The QSAR modeling was used to obtain an equation, correlating the important steric and hydrophobic descriptors with the pIC50 value. Thus, we report two natural compounds of inhibitory nature active against mPTPB enzyme of Mycobacterium tuberculosis. These inhibitors have the potential to evolve as lead molecules in the development of drugs for the treatment of tuberculosis.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Benzofuranos/química , Inibidores Enzimáticos/farmacologia , Mycobacterium tuberculosis/enzimologia , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Antituberculosos/farmacologia , Benzofuranos/farmacologia , Inibidores Enzimáticos/química , Modelos Moleculares , Simulação de Acoplamento Molecular , Análise de Regressão
4.
Biochem Biophys Res Commun ; 443(3): 1054-9, 2014 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-24365147

RESUMO

Alzheimer's is a neurodegenerative disorder resulting in memory loss and decline in cognitive abilities. Accumulation of extracellular beta amyloidal plaques is one of the major pathology associated with this disease. ß-Secretase or BACE-1 performs the initial and rate limiting step of amyloidic pathway in which 37-43 amino acid long peptides are generated which aggregate to form plaques. Inhibition of this enzyme offers a viable prospect to check the growth of these plaques. Numerous efforts have been made in recent years for the generation of BACE-1 inhibitors but many of them failed during the preclinical or clinical trials due to drug related or drug induced toxicity. In the present work, we have used computational methods to screen a large dataset of natural compounds to search for small molecules having BACE-1 inhibitory activity with low toxicity to normal cells. Molecular dynamics simulations were performed to analyze molecular interactions between the screened compounds and the active residues of the enzyme. Herein, we report two natural compounds of inhibitory nature active against ß-secretase enzyme of amyloidic pathway and are potent lead molecules against Alzheimer's disease.


Assuntos
Doença de Alzheimer/enzimologia , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Produtos Biológicos/farmacologia , Inibidores Enzimáticos/farmacologia , Placa Amiloide/enzimologia , Placa Amiloide/patologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Sítios de Ligação , Biocatálise/efeitos dos fármacos , Produtos Biológicos/química , Bases de Dados de Compostos Químicos , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Humanos , Ligação de Hidrogênio/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Ligantes , Simulação de Dinâmica Molecular , Reprodutibilidade dos Testes , Interface Usuário-Computador
5.
BMC Cancer ; 14: 775, 2014 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-25336399

RESUMO

BACKGROUND: Embelin, a quinone derivative, is found in the fruits of Embelia ribes Burm (Myrsinaceae). It has been shown to have a variety of therapeutic potentials including anthelmintic, anti-tumor, anti-diabetic, anti-bacterial and anti-inflammation. Inflammation is an immunological response to external harmful stimuli and is regulated by an endogenous pyrogen and pleiotropic pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α). TNF-α production has been implicated in a variety of other human pathologies including neurodegeneration and cancer. Several studies have shown that the anti-inflammatory activity of embelin is mediated by reduction in TNF-α. The latter is synthesized as a membrane anchored protein (pro-TNF-α); the soluble component of pro-TNF-α is then released into the extracellular space by the action of a protease called TNF-α converting enzyme (TACE). TACE, hence, has been proposed as a therapeutic target for inflammation and cancer. METHODS: We used molecular docking and experimental approaches to investigate the docking potential and molecular effects of embelin to TACE and human cancer cell characteristics, respectively. RESULTS: We demonstrate that embelin is a potential inhibitor of TACE. Furthermore, in vitro studies revealed that it inhibits malignant properties of cancer cells through inactivation of metastatic signaling molecules including MMPs, VEGF and hnRNP-K in breast cancer cells. CONCLUSION: Based on the molecular dynamics and experimental data, embelin is proposed as a natural anti-inflammatory and anticancer drug.


Assuntos
Proteínas ADAM/antagonistas & inibidores , Benzoquinonas/farmacologia , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas ADAM/química , Proteína ADAM17 , Benzoquinonas/química , Domínio Catalítico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Ligantes , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Metástase Neoplásica , Neoplasias/tratamento farmacológico , Ligação Proteica , Ensaio Tumoral de Célula-Tronco
6.
Biochem Biophys Res Commun ; 433(4): 552-7, 2013 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-23510997

RESUMO

Tuberculosis (TB) is the second highest cause of mortality after HIV/AIDS and is one of the leading public health problems worldwide. The growing resistance to anti-TB drugs and the recalcitrant nature of tenacious infections present arduous challenges for the treatment of TB. Thus, the need to develop therapeutics against novel drug targets to help overcome multi-drug resistant TB is inevitable. Leader peptidase B (LepB), the sole signal peptidase of Mycobacterium tuberculosis (MTb), is one such potential drug target. The present work aims at identifying potential inhibitors of LepB, so as to repress the formation of the functional proteins essential for the growth and pathogenesis of MTb. In this study, we screened a large dataset of natural compounds against LepB using a high throughput approach. The screening was directed toward a binding pocket consisting of residues, some of which are critical for the catalytic activity of the enzyme, while others are part of the conserved domains of the signal peptidases. We also carried out molecular dynamics simulations of the two top-scoring compounds in order to study their molecular interactions with the active site functional residues of LepB and also to assess their dynamic behavior. We report herein two prospective non-covalent type inhibitory drugs of natural origin which are active against tuberculosis. These lead molecules possess improved binding properties, have low toxicity and are specific against MTb.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana Múltipla , Proteínas de Membrana/antagonistas & inibidores , Mycobacterium tuberculosis/efeitos dos fármacos , Sequência de Aminoácidos , Antituberculosos/química , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Produtos Biológicos/química , Ácidos Cafeicos/farmacologia , Domínio Catalítico , Cromonas/farmacologia , Bases de Dados de Produtos Farmacêuticos , Dissacarídeos/farmacologia , Ativação Enzimática , Ensaios de Triagem em Larga Escala , Ligantes , Proteínas de Membrana/química , Simulação de Dinâmica Molecular , Mycobacterium tuberculosis/química , Mycobacterium tuberculosis/enzimologia , Conformação Proteica , Mapeamento de Interação de Proteínas , Estabilidade Proteica , Estrutura Terciária de Proteína , Serina Endopeptidases/química
7.
Dermatol Surg ; 39(9): 1376-84, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23898910

RESUMO

BACKGROUND: Because of limitations of medical treatment in vitiligo, various surgical techniques have been devised. There is a scarcity of comparative studies of surgical techniques in vitiligo. OBJECTIVE: To compare the effectiveness and side-effect profile of flip-top transplantation (FTT) and punch grafting (PG) in patients with stable vitiligo. MATERIALS AND METHODS: Twenty patients with stable vitiligo were treated using PG and FTT on 26 lesions; 156 grafts were taken (78 PG, 78 flip-top grafts). They were graded for response in the form of repigmentation as excellent (91-100%), very good (76-90%), good (51-75%), fair (31-50%), poor (<30%). Onset and maximum pigment spread were observed. RESULTS: Sixty-five percent of our patients showed excellent repigmentation with FTT, versus 50% with PG (p = .44). Thirty percent of patients with FTT and 40% with PG had side effects. The differences in onset of repigmentation, completion, and pigment spread between the two techniques were statistically significant (p < .001). CONCLUSIONS: Flip-top transplantation was equally effective as PG for treating vitiligo, although graft uptake rate was higher with FTT, with more pigment spread, and cost less.


Assuntos
Pigmentação da Pele , Transplante de Pele/métodos , Vitiligo/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Transplante de Pele/efeitos adversos , Resultado do Tratamento , Adulto Jovem
8.
ACS Omega ; 8(5): 5072-5087, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36777618

RESUMO

Glioblastomas (GBMs) represent the most aggressive form of brain tumor arising from the malignant transformation of astrocytes. Despite various advancements, treatment options remain limited to chemotherapy and radiotherapy followed by surgery giving an overall survival of 14-15 months. These therapies are somewhere restricted in giving a better survival and cure. There is a need for new therapeutics that could potentially target GBM based on molecular pathways and pathology. Here, ubiquitin E3 ligases can be used as targets as they bind a wide array of substrates and therefore can be attractive targets for new inhibitors. Through this study, we have tried to sort various ubiquitin E3 ligases based on their expression, pathways to which these ligases are associated, and mutational frequencies, and then we tried to screen potent inhibitors against the most favorable E3 ligase as very few studies are available concerning inhibition of E3 ligase in GBM. Our study found MDM2 to be the most ideal E3 ligase and further we tried to target MDM2 against various compounds under the alkaloid class. Molecular Docking and MD simulations combined with ADMET properties and BBB scores revealed that only evodiamine and sanguinarine were effective in inhibiting MDM2. We also tried to give a proposed mechanism of how these inhibitors mediate the p53 signaling in GBM. Therefore, the new scaffolds predicted by the computational approach could help in designing promising therapeutic agents targeting MDM2 in glioblastoma.

9.
Neuropeptides ; 102: 102383, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37729687

RESUMO

Heat shock proteins (HSPs) are the evolutionary family of proteins that are highly conserved and present widely in various organisms and play an array of important roles and cellular functions. Currently, very few or no studies are based on the systematic analysis of the HSPs in Glioblastoma (GBMs) and ependymomas. We performed an integrated omics analysis to predict the mutual regulatory differential HSP signatures that were associated with both glioblastoma and ependymomas. Further, we explored the various common dysregulated biological processes operating in both the tumors, and were analyzed using functional enrichment, gene ontology along with the pathway analysis of the predicted HSPs. We established an interactome network of protein-protein interaction (PPIN) to identify the hub HSPs that were commonly associated with GBMs and ependymoma. To understand the mutual molecular mechanism of the HSPs in both malignancies, transcription factors, and miRNAs overlapping with both diseases were explored. Moreover, a transcription factor-miRNAs-HSPs coregulatory network was constructed along with the prediction of potential candidate drugs that were based on perturbation-induced gene expression analysis. Based on the RNA-sequencing data, HSP90AB1 was identified as the most promising target among other predicted HSPs. Finally, the ranking of the drugs was arranged based on various drug scores. In conclusion, this study gave a spotlight on the mutual targetable HSPs, biological pathways, and regulatory signatures associated with GBMs and ependymoma with an improved understanding of crosstalk involved. Additionally, the role of therapeutics was also explored against HSP90AB1. These findings could potentially be able to explain the interplay of HSP90AB1 and other HSPs within these two malignancies.


Assuntos
Ependimoma , Glioblastoma , MicroRNAs , Humanos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Regulação da Expressão Gênica , Ependimoma/tratamento farmacológico , Ependimoma/genética , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo
10.
J Biomol Struct Dyn ; : 1-14, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904335

RESUMO

In this paper, we report the binding interaction of milk protein, beta-lactoglobulin (BLG), with an antibiotic against tuberculosis, rifampicin (RIF). BLG intrinsic fluorescence from tryptophan (Trp) amino acids was monitored to understand protein-drug interactions. Binding parameters and stoichiometry were estimated with the help of fluorescence spectral changes. Synchronous fluorescence spectroscopy was employed to exclusively monitor the Trp and Tyrosine (Tyr) environment in the presence of RIF. With the help of steady state fluorescence at different temperatures supported by time-resolved fluorescence, we confirmed that the protein forms a static complex with RIF. Thermodynamic parameters, ΔH and ΔS values, showed the involvement of hydrophobic forces between the RIF and BLG. Competitive displacement assay with ANS confirmed the BLG calyx as the binding site for RIF. Energy transfer mechanism from Trp to RIF was attributed to the fluorescence changes in protein upon complexation. The Förster resonance energy transfer (FRET) was used to find distance, energy transfer efficiency and rate of energy transfer between donor (BLG) and acceptor (RIF). Fourier-transform infrared (FTIR) spectroscopy was utilized for estimating changes in the secondary structure of BLG induced by RIF. Molecular docking was used to visualise the binding location of RIF on BLG. Molecular dynamics (MD) simulation studies showed a consistent binding interactions between BLG and RIF during the 100 ns simulation period and this well supported the increased beta sheet content in FTIR. Overall our results establish the potential of intrinsic fluorescence of BLG in combination with biophysical tools to rationalize drug-protein interactions.Communicated by Ramaswamy H. Sarma.

11.
ACS Appl Bio Mater ; 6(1): 117-125, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36503255

RESUMO

With the continuous growth in world population and economy, the global energy demand is increasing rapidly. Given that non-renewable energy sources will eventually deplete, there is increasing need for clean, alternative renewable energy sources, which will be inexpensive and involve minimum risk of environmental pollution. In this paper, harnessing the activity of cupric reductase NDH-2 enzyme present in Escherichia coli bacterial cells, we demonstrate a simple and efficient energy harvesting strategy within an electrochemical chamber without the requirement of any external fuels or force fields. The transduction of energy has been demonstrated with various strains of E. coli, indicating that this strategy could, in principle, be applicable for other microbial catalytic systems. We offer a simple mechanism of the energy transduction process considering the bacterial enzyme-mediated redox reaction occurring over the working electrode of the electrochemical cell. Also, the amount of energy generated has been found to be depending on the motility of bacteria within the experimental chamber, suggesting possible opportunities for developing microbial motility-controlled small scale power generators. Finally, we show that the Faradaic electrochemical energy harvested is large enough to power a commercial light emitting diode connected to an amplifier circuit. We expect the present study to generate sufficient interest within soft condensed matter and biophysics communities, and offer useful platforms for controlled energy generation at the small scales.


Assuntos
Bactérias , Escherichia coli , Oxirredução
12.
Infect Disord Drug Targets ; 23(6): e280423216334, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37132314

RESUMO

BACKGROUND: Dermatophytosis has gained significant importance in recent years owing to increased incidence, more atypical lesions, changing mycological profile and growing antifungal resistance. Therefore, this study was planned to know the clinicomycological profile of dermatophytic infections in patients attending our tertiary care centre. MATERIALS AND METHODS: A total of 700 patients with superficial fungal infections belonging to all age groups and both sexes were taken up for this cross-sectional study. Sociodemographic and clinical details were noted on a prestructured proforma. Superficial lesions were clinically examined and the sample was collected by appropriate collection methods. Direct microscopy by potassium hydroxide wet mount was done to see hyphae. For culture Sabouraud's dextrose agar (SDA) with chloramphenicol and cyclohexamide was used. RESULTS: Dermatophytic infections were detected in 75.8% (531/700) patients. Young people belonging to age group of 21-30 years were commonly affected. Tinea corporis was the commonest clinical picture seen in 20% of the cases. Oral antifungals were taken by 33.1% and topical creams were used by 74.2% of the patients. Direct microscopy was positive in 91.3% and culture was positive for dermatophytes in 61% of the study subjects. T. mentagrophytes was the commonest dermatophyte isolated. CONCLUSION: Irrational use of topical steroids needs to be controlled. KOH microscopy can be useful as a point of care test for rapid screening of dermatophytic infections. Culture is necessary to differentiate various dermatophytes and to guide the antifungal treatment.


Assuntos
Antifúngicos , Tinha , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Antifúngicos/uso terapêutico , Estudos Transversais , Centros de Atenção Terciária , Tinha/tratamento farmacológico , Tinha/epidemiologia , Tinha/diagnóstico , Índia/epidemiologia , Fatores de Risco
13.
iScience ; 26(4): 106510, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37123242

RESUMO

Developing materials for controlled hydrogen production through water splitting is one of the most promising ways to meet current energy demand. Here, we demonstrate spontaneous and green production of hydrogen at high evolution rate using gadolinium telluride (GdTe) under ambient conditions. The spent materials can be reused after melting, which regain the original activity of the pristine sample. The phase formation and reusability are supported by the thermodynamics calculations. The theoretical calculation reveals ultralow activation energy for hydrogen production using GdTe caused by charge transfer from Te to Gd. Production of highly pure and instantaneous hydrogen by GdTe could accelerate green and sustainable energy conversion technologies.

14.
Spectrochim Acta A Mol Biomol Spectrosc ; 283: 121721, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-35964352

RESUMO

This article reports the interaction of rifampicin, one of the important antituberculosis drugs, with Bovine Serum Albumin (BSA). Herein, we have monitored the fluorescence properties of tryptophan (Trp) residue in BSA to understand the interactions between protein and rifampicin. Fluorescence intensity of BSA was quenched tremendously upon interacting with the drug. Using steady state and time-resolved spectroscopic tools the static and dynamic nature of quenching have been characterised. Time correlated single photon counting technique confirmed that out of two lifetime components ∼6.2 ns and ∼2.8 ns of BSA, the rifampicin has affected only the shorter lifetime component a lot that was assigned to Trp-213 residue. Hence, it was thought that the drug must have been located near to the amino acid residue. Molecular docking studies have revealed the structural information of drug-protein complex which supported the above conjecture, confirming the nearest tryptophan as Trp-213 to the complexing rifampicin molecule.


Assuntos
Rifampina , Soroalbumina Bovina , Sítios de Ligação , Simulação de Acoplamento Molecular , Ligação Proteica , Soroalbumina Bovina/química , Espectrometria de Fluorescência , Termodinâmica , Triptofano/química
15.
Anticancer Agents Med Chem ; 22(3): 433-468, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33687887

RESUMO

BACKGROUND: The global alliance for genomics and healthcare facilities provides innovative solutions to expedite research and clinical practices for complex and incurable health conditions. Precision oncology is an emerging field explicitly tailored to facilitate cancer diagnosis, prevention, and treatment based on patients' genetic profiles. Advancements in "omics" techniques, next-generation sequencing, artificial intelligence, and clinical trial designs provide a platform for assessing the efficacy and safety of combination therapies and diagnostic procedures. METHODS: Data were collected from PubMed and Google Scholar using keywords "Precision medicine," "precision medicine and cancer," "anticancer agents in precision medicine," and reviewed comprehensively. RESULTS: Personalized therapeutics, including immunotherapy and cancer vaccines, serve as a groundbreaking solution for cancer treatment. Herein, we take a measurable view of precision therapies and novel diagnostic approaches targeting cancer treatment. The contemporary applications of precision medicine have also been described, along with various hurdles identified in the successful establishment of precision therapeutics. CONCLUSION: This review highlights the key breakthroughs related to immunotherapies, targeted anticancer agents, and target interventions related to cancer signaling mechanisms. The success story of this field in context to drug resistance, safety, patient survival, and improving quality of life is yet to be elucidated. We conclude that, in the near future, the field of individualized treatments may truly revolutionize the nature of cancer patient care.


Assuntos
Antineoplásicos/farmacologia , Vacinas Anticâncer/imunologia , Neoplasias/terapia , Medicina de Precisão , Antineoplásicos/química , Humanos , Imunoterapia , Neoplasias/imunologia , Transdução de Sinais/efeitos dos fármacos
16.
Int J Biol Macromol ; 218: 209-224, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35872310

RESUMO

Nanofibers are fibrous nanocarriers that can be synthesized from natural polymers, synthetic polymers, semiconducting materials, composite materials, and carbon-based materials. Recently, natural polysaccharides-based nanofibers are gaining attention in the field of pharmaceuticals and biomedical as these are biocompatible, biodegradable, non-toxic, and economic. Nanofibers can deliver a significant amount of drug to the targeted site and provide effective interaction of therapeutic agent at the site of action due to a larger surface area. Other important advantages of nanofibers are low density, high porosity, small pore size, high mechanical strength, and low cost. In this review, natural polysaccharides such as alginate, pullulan, hyaluronic acid, dextran, cellulose, chondroitin sulfate, chitosan, xanthan gum, and gellan gum are discussed for their characteristics, pharmaceutical utility, and biomedical applications. The authors have given particular emphasis to the several fabrication processes that utilize these polysaccharides to form nanofibers, and their recent updates in pharmaceutical applications such as drug delivery, tissue engineering, skin disorders, wound-healing dressings, cancer therapy, bioactive molecules delivery, anti-infectives, and solubility enhancement. Despite these many advantages, nanofibers have been explored less for their scale-up and applications in advanced therapeutic delivery.


Assuntos
Nanofibras , Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Polímeros , Engenharia Tecidual
17.
Environ Sci Pollut Res Int ; 29(41): 62111-62159, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34611806

RESUMO

The etiology of the majority of human cancers is associated with a myriad of environmental causes, including physical, chemical, and biological factors. DNA damage induced by such mutagens is the initial step in the process of carcinogenesis resulting in the accumulation of mutations. Mutational events are considered the major triggers for introducing genetic and epigenetic insults such as DNA crosslinks, single- and double-strand DNA breaks, formation of DNA adducts, mismatched bases, modification in histones, DNA methylation, and microRNA alterations. However, DNA repair mechanisms are devoted to protect the DNA to ensure genetic stability, any aberrations in these calibrated mechanisms provoke cancer occurrence. Comprehensive knowledge of the type of mutagens and carcinogens and the influence of these agents in DNA damage and cancer induction is crucial to develop rational anticancer strategies. This review delineated the molecular mechanism of DNA damage and the repair pathways to provide a deep understanding of the molecular basis of mutagenicity and carcinogenicity. A relationship between DNA adduct formation and cancer incidence has also been summarized. The mechanistic basis of inflammatory response and oxidative damage triggered by mutagens in tumorigenesis has also been highlighted. We elucidated the interesting interplay between DNA damage response and immune system mechanisms. We addressed the current understanding of DNA repair targeted therapies and DNA damaging chemotherapeutic agents for cancer treatment and discussed how antiviral agents, anti-inflammatory drugs, and immunotherapeutic agents combined with traditional approaches lay the foundations for future cancer therapies.


Assuntos
Mutagênicos , Neoplasias , Carcinógenos/metabolismo , Carcinógenos/toxicidade , DNA/metabolismo , Dano ao DNA , Reparo do DNA , Humanos , Mutagênicos/metabolismo , Mutagênicos/toxicidade , Neoplasias/epidemiologia
18.
J Family Med Prim Care ; 11(9): 5236-5240, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36505622

RESUMO

Background and Objectives: Pityriasis versicolor is a common fungal infection of the skin which leads to the formation of scaly and discoloured small lesions on skin. The main objective of this study is to describe clinical and mycological characteristics and the predisposing factors in patients with pityriasis versicolor. Material and Methods: In this prospective, observational, hospital-based cross-sectional study, patients of all ages with clinically suspected lesions of pityriasis versicolor were included. After detailed history and thorough clinical examination, skin scrapings were examined with 10% potassium hydroxide (KOH) under light microscope. The scrapings were also subjected to culture examination. Results: A total of 113 patients [78 (69.0%) male; 35 (31%) female] were included in the study. A total of 87 (76.9%) patients were from rural area. Outdoor occupation and positive family history of pityriasis versicolor was present in 65 (57.5%) and 38 (33.6%) patients, respectively. Recurrent episodes were reported by 66 (60%) patients. Excessive sweating and oily skin were seen in 36 (31.8%) and 24 (21.1%) patients, respectively. History of occlusive clothing was present in 22 (19.4%) patients. Chest, back, and shoulders were affected in 36 (31.8%), 22 (19.4%), and 08 (07.0%) patients, respectively. Hypopigmented lesions were seen in 97 (85.8%) patients. Patches and macules were observed in 60 (53.1%) and 53 (46.9%) patients, respectively. A total of 27 (23.8%) patients reported mild prutitus. A total of 79 (69.9%) patients were KOH positive and culture negative, whereas 26 (23.0%) patients were KOH as well as culture positive. Eight (7.0%) patients were both KOH and culture negative. Conclusion: Pytiriasis versicolor is more common in young adults and males with the most common presentation of hypopigmentation lesions. In our study population, presentation with large patches was more common than macular lesions. Pruritus was more in patients with large patches than those with macules.

19.
J Pharm Pharmacol ; 74(4): 461-484, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-34050648

RESUMO

OBJECTIVES: Oxidative stress is a major cellular burden that triggers reactive oxygen species (ROS) and antioxidants that modulate signalling mechanisms. Byproducts generated from this process govern the brain pathology and functions in various neurological diseases. As oxidative stress remains the key therapeutic target in neurological disease, it is necessary to explore the multiple routes that can significantly repair the damage caused due to ROS and consequently, neurodegenerative disorders (NDDs). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the critical player of oxidative stress that can also be used as a therapeutic target to combat NDDs. KEY FINDINGS: Several antioxidants signalling pathways are found to be associated with oxidative stress and show a protective effect against stressors by increasing the release of various cytoprotective enzymes and also exert anti-inflammatory response against this oxidative damage. These pathways along with antioxidants and reactive species can be the defined targets to eliminate or reduce the harmful effects of neurological diseases. SUMMARY: Herein, we discussed the underlying mechanism and crucial role of antioxidants in therapeutics together with natural compounds as a pharmacological tool to combat the cellular deformities cascades caused due to oxidative stress.


Assuntos
Antioxidantes , Doenças Neurodegenerativas , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , NADPH Oxidases/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
20.
J Ayurveda Integr Med ; 12(1): 119-125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33551337

RESUMO

BACKGROUND: Sports injuries are the second most common type of accident after domestic (3.7%) and occupational accidents (3.1%). There is an average annual estimate of 8.6 million sports and recreational related injury incidents with an age-adjusted rate of 34.1 per 1000 populations. Common sports injuries are musculoskeletal injuries i.e. Sprains, Strains, Joint injuries, soft tissue injury (STI). The sports injury in Ayurveda can be co-related within dissimilar facets of trauma related ailments. OBJECTIVE: To evaluate the efficacy of a protocol-based management of common sports injuries using an integrated approach. MATERIALS AND METHODS: Integration of Ayurveda and Physiotherapy procedures was done and phase wise treatment was framed. Total 30 patients of age between 10 and 60 years ful-filling the inclusion criteria were selected for the present study. The patients were treated with Phase wise protocol consisting of three phase's i.e. Inflammatory (1-5 days), Stabilization and recovery (6-10 days), Muscle strengthening (11-17 days). Assessments were done through various variables like pain, tenderness, swelling, local temperature, manual muscle testing (MMT) and range of motion (ROM) at different time points. STATISTICAL ANALYSIS: Wilcoxon matched pair test was used to assess within group results for subjective parameters and paired t-test (Dependent t-test) was used to assess for objective parameters. RESULT: The study showed that integrated treatment approach has given significant results in the parameters like pain, loss of function, tenderness, local temperature, MMT and ROM. CONCLUSION: Phase wise management through integrated protocol is effective in the management of common sports injuries.

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