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1.
Front Bioeng Biotechnol ; 10: 882100, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35662840

RESUMO

The understanding of the genesis of life-threatening cancer and its invasion calls for urgent development of novel technologies for real-time observations, early diagnosis, and treatment. Quantum dots (QDs) grabbed the spotlight in oncology owing to their excellent photostability, bright fluorescence, high biocompatibility, good electrical and chemical stability with minimum invasiveness. Recently, carbon QDs (CQDs) have become popular over toxic inorganic QDs in the area of bioimaging, biosensing, and drug delivery. Further, CQDs derived from natural sources like biomolecules and medicinal plants have drawn attention because of their one-pot, low-cost and ease of synthesis, along with remarkable tunable optical properties and biocompatibility. This review introduces the synthesis and properties of CQDs derived from natural sources, focusing on the applicability of CQD-based technologies as nano-theranostics for the diagnosis and treatment of cancer. Furthermore, the current issues and future directions for the transformation of CQDs-based nanotechnologies to clinical applications are highlighted.

3.
JAMA Netw Open ; 5(1): e2142210, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34994793

RESUMO

Importance: A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. Objective: To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. Design, Setting, and Participants: This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. Exposures: Vaccination with 0, 1, or 2 doses of BBV152. Main Outcomes and Measures: The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported. Results: Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. Conclusions and Relevance: These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.


Assuntos
COVID-19/epidemiologia , Pessoal de Saúde , Reinfecção , SARS-CoV-2 , Adulto , COVID-19/etiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Imunogenicidade da Vacina , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Centros de Atenção Terciária , Vacinas de Produtos Inativados/administração & dosagem , Vírion/imunologia , Adulto Jovem
4.
Am J Blood Res ; 11(5): 534-543, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824886

RESUMO

BACKGROUND: Mitochondrial bioenergetic alterations are commonly observed metabolic adaptation in malignancies including acute myeloid leukemia (AML). Mitochondrial DNA alterations are well known in pediatric AML with possible prognostic significance; however, mitochondrial complex activity and its impact on disease outcome have not been previously explored. The aim of this study was to evaluate the mitochondrial complex II and complex V activity and its prognostic significance in pediatric AML patients. METHODS: Consecutive 82 de novo pediatric (≤18 years) patients with AML were included in the study along with age and sex matched controls. Bone marrow mononuclear cells were isolated from baseline bone marrow samples from all patients and controls. DNA, RNA and proteins were extracted and relative expression of mitochondrial biogenesis genes TFAM, POLG, POLRMT were estimated along with mitochondrial DNA copy number. The mitochondrial complex II and V enzymes were immunocaptured and their activity was measured by substrate specific absorbance change by kinetic ELISA. The mitochondrial complex II and V activity was compared with controls and their association with clinico-pathological features and survival outcome were analysed. Complex activity was also correlated with relative expression of biogenesis genes. RESULTS: The activity of mitochondrial complex II and V were found to be significantly enhanced (P = 0.010 and P = 0.0013 respectively) in pediatric AML patients compared to controls. The activity of mitochondrial complex II and V showed significant positive correlation with relative gene expression of mitochondrial biogenesis genes TFAM (P = 0.001 and P = 0.016 respectively) and POLG (P = 0.005 and P = 0.006 respectively). Neither of the two complex activities showed any significant association with baseline disease demographics or any clinico-pathological feature. Furthermore, the complex II and V activity did not show any impact on event free survival (P = 0.25 and P = 0.24 respectively) and overall survival (P = 0.14 and P = 0.17 respectively) in our cohort. CONCLUSION: The activity of both mitochondrial complex II and V are significantly elevated in bone marrow mononuclear cells of children with AML compared to controls. The enhanced activity may be related to upregulation of mitochondrial biogenesis genes TFAM and POLG. The enhanced activity of either of the complexes did not impact disease biology or survival outcomes in pediatric AML.

5.
Appl Spectrosc ; 75(12): 1497-1509, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34346774

RESUMO

*These authors contributed equally to this work.The molecular-level insight of protein adsorption and its kinetics at interfaces is crucial because of its multifold role in diverse fundamental biological processes and applications. In the present study, the sum frequency generation (SFG) vibrational spectroscopy has been employed to demonstrate the adsorption process of bovine hemoglobin (BHb) protein molecules at the air-water interface at interfacial isoelectric point of the protein. It has been observed that surface coverage of BHb molecules significantly influences the arrangement of the protein molecules at the interface. The time-dependent SFG studies at two different frequencies in the fingerprint region elucidate the kinetics of protein denaturation process and its influence on the hydrogen-bonding network of interfacial water molecules at the air-water interface. The initial growth kinetics suggests the synchronized behavior of protein adsorption process with the structural changes in the interfacial water molecules. Interestingly, both the events carry similar characteristic time constants. However, the conformational changes in the protein structure due to the denaturation process stay for a long time, whereas the changes in water structure reconcile quickly. It is revealed that the protein denaturation process is followed by the advent of strongly hydrogen-bonded water molecules at the interface. In addition, we have also carried out the surface tension kinetics measurements to complement the findings of our SFG spectroscopic results.


Assuntos
Hemoglobinas , Água , Adsorção , Ligação de Hidrogênio , Análise Espectral
6.
Mitochondrion ; 58: 246-254, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33812061

RESUMO

Mitochondrial DNA (mtDNA) copy number alterations occur in acute myeloid leukemia (AML). We evaluated regulation and biological significance of mtDNA copy number in pediatric AML patients (n = 123) by qRT-PCR, and in-vitro studies. MtDNA copy number was significantly higher (p < 0.001) and an independent predictor of aggressive disease (p = 0.006), lower event free survival (p = 0.033), and overall survival (p = 0.007). Expression of TFAM, POLG, POLRMT, MYC and ND3 were significantly upregulated. In cell lines, PGC1A inhibition decreased mtDNA copy number while MYC inhibition had no effect. PGC1A may contribute to enhanced mtDNA copy number, which predicts disease aggressiveness and inferior survival outcome.


Assuntos
Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Leucemia Mieloide Aguda/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Criança , Humanos , Avaliação de Resultados em Cuidados de Saúde
7.
Mol Cell Biol ; 40(18)2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32661120

RESUMO

The DNA and protein complex known as chromatin is subject to posttranslational modifications (PTMs) that regulate cellular functions such that PTM dysregulation can lead to disease, including cancer. One critical PTM is acetylation/deacetylation, which is being investigated as a means to develop targeted cancer therapies. The histone acetyltransferase (HAT) family of proteins performs histone acetylation. In humans, MOF (hMOF), a member of the MYST family of HATs, acetylates histone H4 at lysine 16 (H4K16ac). MOF-mediated acetylation plays a critical role in the DNA damage response (DDR) and embryonic stem cell development. Functionally, MOF is found in two distinct complexes: NSL (nonspecific lethal) in humans and MSL (male-specific lethal) in flies. The NSL complex is also able to acetylate additional histone H4 sites. Dysregulation of MOF activity occurs in multiple cancers, including ovarian cancer, medulloblastoma, breast cancer, colorectal cancer, and lung cancer. Bioinformatics analysis of KAT8, the gene encoding hMOF, indicated that it is highly overexpressed in kidney tumors as part of a concerted gene coexpression program that can support high levels of chromosome segregation and cell proliferation. The linkage between MOF and tumor proliferation suggests that there are additional functions of MOF that remain to be discovered.


Assuntos
Dano ao DNA , Células-Tronco Embrionárias/citologia , Histona Acetiltransferases/metabolismo , Acetilação , Carcinogênese/metabolismo , Diferenciação Celular/fisiologia , Núcleo Celular/metabolismo , Proliferação de Células/fisiologia , Transformação Celular Neoplásica/metabolismo , Cromatina/metabolismo , Células-Tronco Embrionárias/metabolismo , Células-Tronco Embrionárias/fisiologia , Histonas/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/metabolismo , Processamento de Proteína Pós-Traducional
9.
Asian Pac J Cancer Prev ; 20(5): 1329-1337, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31127885

RESUMO

Esophageal cancer is the eighth most common occurring cancer type worldwide and 6th most common among the cancer related deaths of which the most common type is squamous cell carcinoma which comprise about 90% of esophageal cancer cases. The standard of care for esophageal cancer is neoadjuvant concurrent chemotherapy and radiation (NACRT) followed by surgery however the prognosis remains dismal with 5 year survival a meager 10-15%. The treatment modalities for esophageal cancer is associated with both long term and short term toxicities. Curcumin has been explored as a therapeutic modality as a chemo adjuvant in different cancers due to its low toxicity profile and potent anticancer effect however despite lot of promising preclinical data it has not progressed from bench side to bed side. The primary reason that has obstructed its application in clinic has been its low bioavailability which was seen in different clinical trials but there has been tremendous progress in developing formulations of curcumin which have significantly increased its bioavailability and are being tested in clinical trials. Esophageal cancer is associated with inflammation that's why curcumin being a natural antioxidant offer a potential avenue to reduce toxicity of current therapeutic modalities in a chemo adjuvant setting while simultaneously targeting different pro oncogenic pathways. The present review tries to cover in depth different aspects of curcumin application in treatment of esophageal cancer and progress of this potent anticancer agent in its treatment and prevention.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Curcumina/análogos & derivados , Curcumina/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Prognóstico
10.
RSC Adv ; 9(22): 12596-12605, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-35515878

RESUMO

Nanostructure morphology originating from the self-assembly of molecules has attracted substantial attention due to its role in toxic amyloid fibril formation and immense potential in the design and fabrication of novel biomaterials. This study presents the role of intermolecular electrostatic interaction on the self-assembly process of l-phenylalanine (L-Phe) amino acid. We have employed attenuated total reflection Fourier transform infrared spectroscopy to probe the existence of different ionization states of the amino acid in various pH aqueous solutions. The self-assembly process of L-Phe in the aqueous phase is explored by using circular dichroism absorption and nuclear magnetic resonance spectroscopic tools. The observed spectral features have shown the signature of higher order structures and possible perturbation in the π-π stacking aromatic interactions for the cationic and anionic states of the amino acid. Scanning electron microscopy is used to probe the self-assembled morphology of the L-Phe amino acid dried samples prepared from the same pH aqueous solutions. We find that for the case of zwitterionic states the self-assembly nanostructures are dominated by the presence of fibrillar morphology, however interestingly for cationic and anionic states the morphology is dominated by the presence of flakes. Our finding demonstrates the potential influence of intermolecular electrostatic interaction over the aromatic π-π stacking interaction in hindering the fibril formation.

11.
Indian Pediatr ; 55(6): 469-473, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29978812

RESUMO

OBJECTIVE: To analyze the cytogenetic abnormalities of a large cohort of consecutive pediatric Acute Myeloid Leukemia (AML) patients, treated on a uniform protocol. DESIGN: Review of case records. SETTING: Pediatric Cancer Center of tertiary care hospital between June 2003 and June 2016. PARTICIPANTS: 617 consecutive de novo pediatric AML patients were screened and 472 patients were found eligible. Eligibility criteria included non M3 patients, successful cytogenetic profile and availability of complete records. MAIN OUTCOME MEASURE: Cytogenetic profile. RESULTS: Gum-hypertropy, chloromas and rate of complete remission were significantly different between European Leukemia Network classification (ELN) cytogenetic risk groups (P<0.01). t (8;21) (141, 29.8%), loss of Y chromosome (61,12.9%) and trisomy 8 (39, 8.3%) were the most common abnormalities. Among the chromosomal gains, trisomy 8 and trisomy 21 (both P<0.01) were significantly different among the three ELN risk groups. Among the chromosome losses, monosomy 5, 7 (both P<0.01) and 9 (P=0.03), loss of X and loss of Y (both P<0.01) were statistically different amongst three cytogenetic risk groups. Event-free survival (P<0.01) and overall survival (P<0.01) were found to be significantly different among the three risk groups. CONCLUSIONS: The higher frequency of t (8; 21) and its association with chloroma in Indian pediatric patients is different from other studies around the world.


Assuntos
Aberrações Cromossômicas , Leucemia Mieloide Aguda/genética , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Prognóstico , Estudos Retrospectivos
12.
J Chem Phys ; 144(9): 094702, 2016 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-26957171

RESUMO

We have examined the geometric and electronic structures of iron phthalocyanine assemblies on a Cu(111) surface at different sub- to mono-layer coverages and the changes induced by thermal annealing at temperatures between 250 and 320 °C by scanning tunneling microscopy, x-ray photoelectron spectroscopy, and x-ray absorption spectroscopy. The symmetry breaking observed in scanning tunneling microscopy images is found to be coverage dependent and to persist upon annealing. Further, we find that annealing to temperatures between 300 and 320 °C leads to both desorption of iron phthalocyanine molecules from the surface and their agglomeration. We see clear evidence of temperature-induced homocoupling reactions of the iron phthalocyanine molecules following dehydrogenation of their isoindole rings, similar to what has been observed for related tetrapyrroles on transition metal surfaces. Finally, spectroscopy indicates a modified substrate-adsorbate interaction upon annealing with a shortened bond distance. This finding could potentially explain a changed reactivity of Cu-supported iron phthalocyanine in comparison to that of the pristine compound.

13.
J Colloid Interface Sci ; 461: 1-8, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26397901

RESUMO

One challenging task in building (bio)chemical sensors is the efficient and stable immobilization of receptor on a suitable transducer. Herein, we report a method for covalent immobilization of molecularly imprinted core-shell nanoparticles for construction of robust chemical sensors. The imprinted nanoparticles with a core-shell structure have selective molecular binding sites in the core and multiple amino groups in the shell. The model Au transducer surface is first functionalized with a self-assembled monolayer of 11-mercaptoundecanoic acid. The 11-mercaptoundecanoic acid is activated by treatment with carbodiimide/N-hydroxysuccinimide and then reacted with the core-shell nanoparticles to form amide bonds. We have characterized the process by studying the treated surfaces after each preparation step using atomic force microscopy, scanning electron microscopy, fluorescence microscopy, contact angle measurements and X-ray photoelectron spectroscopy. The microscopy results show the successful immobilization of the imprinted nanoparticles on the surface. The photoelectron spectroscopy results further confirm the success of each functionalization step. Further, the amino groups on the MIP surface were activated by electrostatically adsorbing negatively charged Au colloids. The functionalized surface was shown to be active for surface enhanced Raman scattering detection of propranolol. The particle immobilization and surface enhanced Raman scattering approach described here has a general applicability for constructing chemical sensors in different formats.


Assuntos
Carbodi-Imidas/química , Ouro/química , Impressão Molecular , Nanopartículas/química , Polímeros/química , Adsorção , Eletrodos , Tamanho da Partícula , Propriedades de Superfície
15.
J Colloid Interface Sci ; 445: 277-284, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25626133

RESUMO

Molecularly imprinted polymers (MIPs) can be used as antibody mimics to develop robust chemical sensors. One challenging problem in using MIPs for sensor development is the lack of reliable conjugation chemistry that allows MIPs to be fixed on transducer surface. In this work, we study the use of epoxy silane to immobilize MIP nanoparticles on model transducer surfaces without impairing the function of the immobilized nanoparticles. The MIP nanoparticles with a core-shell structure have selective molecular binding sites in the core and multiple amino groups in the shell. The model transducer surface is functionalized with a self-assembled monolayer of epoxy silane, which reacts with the core-shell MIP particles to enable straightforward immobilization. The whole process is characterized by studying the treated surfaces after each preparation step using atomic force microscopy, scanning electron microscopy, fluorescence microscopy, contact angle measurements and X-ray photoelectron spectroscopy. The microscopy results show that the MIP particles are immobilized uniformly on surface. The photoelectron spectroscopy results further confirm the action of each functionalization step. The molecular selectivity of the MIP-functionalized surface is verified by radioligand binding analysis. The particle immobilization approach described here has a general applicability for constructing selective chemical sensors in different formats.


Assuntos
Compostos de Epóxi/química , Impressão Molecular , Nanopartículas/química , Polímeros/química , Silanos/química , Nanopartículas/ultraestrutura , Espectroscopia Fotoeletrônica , Propranolol/química
16.
ACS Appl Mater Interfaces ; 6(8): 5971-6, 2014 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-24689785

RESUMO

In this work, a simple breath figure method was proposed to directly fabricate large-area and ordered honeycomb structures on commercial PMMA substrates or PS Petri dishes without the use of an external polymer solution. The obtained honeycomb structure is indeed part of the substrate, providing the honeycomb layer with enough mechanical stability. The breath figure method in this work for the synthesis of honeycomb structure is extremely simple with scale-up capability to large-area production, which offers new insights into surface engineering with great potential in commercial technologies. For example, using the honeycomb-patterned Petri dishes prepared via this method, cells can be easily separated into divided aggregation, which favors understanding of naturally occurring networks in higher organisms and cell-cell and cell-matrix interactions, and the therapeutic control of genetic circuits.


Assuntos
Técnicas de Cultura de Células/instrumentação , Polímeros/química , Linhagem Celular , Proliferação de Células , Humanos , Polímeros/síntese química , Propriedades de Superfície
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