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1.
Chemosphere ; 353: 141490, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417494

RESUMO

Fluoride ion (F-) is one of the major geogenic contaminants in water and soil. Excessive consumption of these geogenic contaminants poses serious health impacts on humans and plants. In this study, a novel carbonaceous material, nano-bonechar, was synthesized from cow bones and applied as a soil amendment at rates of 0, 0.5, 1, and 2% to remediate and revitalize naturally F--contaminated soil. The results revealed that the nano-bonechar significantly reduced the mobility and bioavailability of F- by 90% in the contaminated soil, and improved the soil quality by increasing the soil water holding capacity, soil organic matter, and the bioavailable contents of PO43-, Ca2+, and Na+. Subsequently, the pot experiment results showed a significant reduction in the uptake of F- by 93% in Zea mays plants. Moreover, the nano-bonechar application improved the plant's growth, as indicated by the higher fresh and dry weights, root and shoot lengths, and total content of PO43-, Ca2+, and K+ than those of un-amended soil. The F-immobilization in soil was mainly due to the presence of the hydroxyapatite [Ca10(PO4)6(OH)2] mineral in the nano-bonechar. Ion exchange between OH- (of nano-bonechar) and F- (of soil), and the formation of insoluble fluorite (CaF2) contributed to the attenuation of F- mobility in the soil. It is concluded that nano-bonechar, due to its size and enrichment in hydroxyapatite, could successfully be utilized for the rapid remediation and revitalization of F--contaminated agricultural soil.


Assuntos
Fluoretos , Poluentes do Solo , Humanos , Poluentes do Solo/análise , Solo , Água , Hidroxiapatitas
2.
Front Genet ; 12: 767298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35154242

RESUMO

Hematological malignancies (HM) are a group of neoplastic diseases that are usually heterogenous in nature due to the complex underlying genetic aberrations in which collaborating mutations enable cells to evade checkpoints that normally safeguard it against DNA damage and other disruptions of healthy cell growth. Research regarding chromosomal structural rearrangements and alterations, gene mutations, and functionality are currently being carried out to understand the genomics of these abnormalities. It is also becoming more evident that cross talk between the functional changes in transcription and proteins gives the characteristics of the disease although specific mutations may induce unique phenotypes. Functional genomics is vital in this aspect as it measures the complete genetic change in cancerous cells and seeks to integrate the dynamic changes in these networks to elucidate various cancer phenotypes. The advent of CRISPR technology has indeed provided a superfluity of benefits to mankind, as this versatile technology enables DNA editing in the genome. The CRISPR-Cas9 system is a precise genome editing tool, and it has revolutionized methodologies in the field of hematology. Currently, there are various CRISPR systems that are used to perform robust site-specific gene editing to study HM. Furthermore, experimental approaches that are based on CRISPR technology have created promising tools for developing effective hematological therapeutics. Therefore, this review will focus on diverse applications of CRISPR-based gene-editing tools in HM and its potential future trajectory. Collectively, this review will demonstrate the key roles of different CRISPR systems that are being used in HM, and the literature will be a representation of a critical step toward further understanding the biology of HM and the development of potential therapeutic approaches.

3.
J Ayub Med Coll Abbottabad ; 32(3): 356-358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32829551

RESUMO

BACKGROUND: Coronary angiography is the gold standard test for diagnosis coronary artery disease. It can be performed via various intra-arterial routes, i.e., femoral, radial, brachial, ulnar, or axillary arteries. Trans-Radial access for coronary angiography is a good approach with less major vascular complications, increased patient comfort and early mobilization and less hospital stay but is associated with radial artery spasm as the major complication affecting the success of the procedure. METHODS: This study was a descriptive cross-sectional study. It enrolled one hundred and thirty-six (136) consecutive patients who underwent the procedure of coronary angiography/PCI over a 6-month period. The study included both in and outpatients undergoing coronary angiography/PCI. Coronary angiography/Percutaneous coronary intervention was done via trans radial approach and the study participants were observed for development of radial artery spasm using clinical and angiographic parameters. Data was entered and analysed using SPSS-19. RESULTS: The frequency of radial artery spasm was 13.24% (n=18). Radial artery spasm was statistically significant in females (p<0.05), those who had severe pain during radial artery puncture (p<0.001) and those who had unsuccessful first attempt during radial artery puncture (p<0.001). No statistically significant association was found between radial artery spasm and other predictors such as age, hypertension and diabetes mellitus. CONCLUSIONS: Radial artery spasm is a common complication during trans radial approach for coronary angiography/percutaneous coronary intervention particularly in females, those who have unsuccessful first attempt and those who have severe pain during radial artery puncture.


Assuntos
Angiografia Coronária/efeitos adversos , Complicações Intraoperatórias , Intervenção Coronária Percutânea/efeitos adversos , Artéria Radial/fisiopatologia , Doenças Vasculares , Estudos Transversais , Feminino , Humanos , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Masculino , Espasmo , Doenças Vasculares/epidemiologia , Doenças Vasculares/etiologia
4.
Front Oncol ; 9: 1335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850220

RESUMO

Hepatitis B virus (HBV) is causally linked to hepatocellular injury and cell death, which are followed by hepatocellular carcinoma (HCC) after a long latent period. The HBV derived X protein (HBX) is the most potent carcinogenic factor for HCC, however, the molecular mechanism of HBX-induced transformation of hepatic cells in HCC is poorly understood. We have shown that nuclear receptor co-repressor (NCoR) is essential for the spatial repression of global transcription by the promyelocytic leukemia oncogenic domains (PODs), a frequent target of viral oncoproteins like HBX and that disintegration of PODs due to misfolded conformation dependent loss (MCDL) of NCoR is linked to promyelocytic and monocytic acute myeloid leukemia (AML). Given the key role of NCoR in cellular homeostasis across various tissue subtypes, we hypothesized that HBX-induced MCDL of NCoR might be linked to HCC through similar mechanism. Based on this hypothesis, the conformation of NCoR in HCC derived tumor cells and primary human tissue sections were analyzed and a selective MCDL of NCoR in HBX positive HCC cells was identified. HBX triggered the misfolding of NCoR through ubiquitination, followed by its degradation by autophagy, thus suggesting a cross talk between ubiquitin proteasome system (UPS) and autophagy lysosomal pathway (ALP) in MCDL of NCoR in HBX positive HCC cells. SiRNA-induced NCoR ablation selectively impaired the growth and survival of HBX positive HCC cells, suggesting a role of MCDL in the growth and survival of HBX positive HCC cells. These finding identify a possible crosstalk between UPS and ALP in the misfolding and loss of NCoR in HBX positive HCC cells and suggest a role of autophagic recycling of misfolded NCoR in the activation of oncogenic metabolic signaling in HCC. The misfolded NCoR reported in this study represents a novel conformation based molecular target which could be valuable in the design and development of tumor cell specific diagnostic and therapeutic approach for HBX positive HCC.

5.
J Ayub Med Coll Abbottabad ; 31(1): 36-38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30868780

RESUMO

BACKGROUND: Ischemic heart disease is responsible for approximately 1/3 of all global deaths, making it a leading cause of cardiovascular mortality. Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) which is an acute event in spectrum of coronary artery disease is a potentially lifethreatening emergency, makes up for the majority of admissions to a cardiac unit with one-year mortality rate of 23.5%. The objective of this study was to determine the association of degree of ST segment depression on hospital mortality in patients presenting with Non-ST segment elevation myocardial infarction (NSTEMI). METHODS: This descriptive case-series was carried out in the department of Cardiology, Punjab Institute of Cardiology Lahore. Using Non-probability purposive sampling technique, a total of 250 patients of age between 30-75 years of either gender, who reported during the study period, with NSTEMI were inducted in this study.. RESULTS: In our study, 33.2% (n=83) patients were between 30-50 years and 66.8% (n=167) patients were between 51-75 years of the age. Mean age was 54.64±9.69 years. 43.2% (n=108) patients were male and 56.8% (n=142) were females. Frequency of in-hospital mortality was 4.4% (n=11). Mortality increased with increasing degree of ST segment depression on admission Electrocardiogram (ECG).. CONCLUSIONS: In patients admitted with Non-ST segment elevation myocardial infarction (NSTEMI), degree of ST segment depression on admission ECG predicts In-Hospital mortality.


Assuntos
Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio sem Supradesnível do Segmento ST/fisiopatologia , Adulto , Idoso , Eletrocardiografia , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia
6.
Rev Environ Health ; 34(2): 141-152, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-30763030

RESUMO

In our environment, various naturally occurring radionuclides are present (both underground and overground) in several places, which results in lifelong human exposure. The radiation dose received by human beings from the radiation emitted by these naturally occurring radionuclides is approximately 87%. Exposure to radiation poses radiological health hazards. To assess the human health hazards from radiation, the concentration of these naturally occurring radionuclides are measured in soil (used for cultivation), building materials (soil, bricks, sand, marble, etc.), water and dietary items, worldwide. The available literature revealed that numerous studies related to the subject have been carried out in Pakistan. Most of these studies measured the radioactivity concentrations of primordial [uranium (238U), thorium (232Th), radium (226Ra) and potassium (40K)] and anthropogenic [cesium (137Cs)] radionuclide in soil samples (used for cultivation), fertilizers, building materials (i.e. bricks, rocks, sand, soil, marble, etc.), as well as water and dietary items, using a sodium iodide detector or high purity germanium. An effort was made in 2008 to compile these studies as a review article. However, since then, considerable studies have been undertaken and reported in the literature. Therefore, the main objective of the present article is to provide a countrywide baseline data on radionuclide levels, by overviewing and compiling the relevant studies carried out in Pakistan.


Assuntos
Monitoramento de Radiação , Radioisótopos/análise , Paquistão , Radioatividade
7.
J Ayub Med Coll Abbottabad ; 31(Suppl 1)(4): S674-S677, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31965774

RESUMO

BACKGROUND: Most of the admissions to the coronary care unit are patients who are having Non- ST-segment elevation acute coronary syndrome (NSTE-ACS). Inflammation has an important role in the pathogenesis of the acute coronary syndrome. Inflammatory marker such as Leukocyte counts & most importantly Neutrophils to Lymphocyte Ratio (NLR) has been found an important predictor of cardiovascular events. Few studies show the diagnostic role of Neutrophils to Lymphocyte ratio in the patient presenting with NSTE-ACS. The objective of this study was to determine the diagnostic role of Neutrophils to Lymphocytes ratio to predict the elevation of Troponin-I in patients presenting with suspected NSTE-acute coronary syndrome. METHODS: This was a Descriptive Case Series study, conducted in Cardiology department Ayub Teaching Hospital/Ayub Medical College Abbottabad, from 15th May 2017 to30th December 2018. A total of 203 patients with suspected NSTE-ACS were inducted in the study by non-probability, consecutive sampling. RESULTS: Results of this study shown a strong correlation between Neutrophils to Lymphocyte ratio (NLR) & rise in Troponin-I levels. Furthermore, results shown that at 4th quartile of Neutrophils to Lymphocyte ratio (NLR) there is high Specificity (97.8%) and very high positive predictive of value 96.7% for predicting the rise in Troponin-I levels. CONCLUSION: We concluded that there is a strong correlation between rising Neutrophils to Lymphocyte ratio (NLR) and cardiac Troponin-I elevation in patients presenting with suspected NSTE-acute coronary syndrome. Therefore, this parameter can be used to predict the rise in troponin level in patients presenting with suspected NSTE-ACS.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Contagem de Leucócitos/estatística & dados numéricos , Troponina I/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/fisiopatologia , Humanos , Linfócitos/citologia , Neutrófilos/citologia , Valor Preditivo dos Testes
8.
Microsc Res Tech ; 81(10): 1203-1207, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30365200

RESUMO

A major challenge when performing scanning electron microscopy and X-ray analysis on many ceramic materials is their electrical insulation properties, which leads to buildup of the surface charge and reduced contrast in the secondary electron image. A new procedure was established to quantitatively determine the neutral state values, E1 and E2 , of yttrium aluminum garnet (YAG) ceramics using the Duane-Hunt limit (EDHL ) of Bremsstrahlung, in order to eliminate this charge effect. Thirty-eight EDHL values were linearly fitted with the last portion of X-ray spectra acquired under the incident energy, E0 , from 0.35 to 5.0 kV. According to the distribution of EDHL , two piecewise linear fitting was first employed with a breakpoint of 1.0 kV. Consequently, two intersection points of 0.54 and 2.48 kV, which correspond to E1 and E2 for YAG ceramics, were directly determined using a theoretical curve (EDHL = E0 ). As a result, the high-resolution images of the YAG ceramic grain structure were successfully obtained using the calculated E1 and E2 values.

9.
Materials (Basel) ; 11(7)2018 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-30029462

RESUMO

Using first principle calculations, the effect of Ce with different doping concentrations in the network of Zirconium dioxide (ZrO2) is studied. The ZrO2 cell volume linearly increases with the increasing Ce doping concentration. The intrinsic band gap of ZrO2 of 5.70 eV reduces to 4.67 eV with the 2.08% Ce doping. In 4.16% cerium doped ZrO2, the valence band maximum and conduction band minimum come closer to each other, about 1.1 eV, compared to ZrO2. The maximum band gap reduction of ZrO2 is observed at 6.25% Ce doping concentration, having the value of 4.38 eV. No considerable shift in the band structure is found with further increase in the doping level. The photo-response of the ZrO2 is modulated with Ce insertion, and two distinct modifications are observed in the absorption coefficient: an imaginary part of the dielectric function and conductivity. A 2.08% Ce-doped ZrO2 modeled system reduces the intensities of peaks in the optical spectra while keeping the peaks of intrinsic ZrO2. However, the intrinsic peaks related to ZrO2 completely vanish in 4.16%, 6.25%, 8.33%, and 12.5% Ce doped ZrO2, and a new absorption hump is created.

10.
Artif Cells Nanomed Biotechnol ; 46(sup2): 1025-1034, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29873522

RESUMO

About one-third of the world population is prone to have infection with T. gondii, which can cause toxoplasmosis in the developing fetus and in people whose immune system is compromised through disease or chemotherapy. Surface antigen-1 (SAG1) is the candidate of vaccine against toxoplasmosis. Recent advances in biotechnology and nano-pharmaceuticals have made possible to formulate nanospheres of recombinant protein, which are suitable for sub-unit vaccine delivery. In current study, the local strain was obtained from cat feces as toxoplasma oocysts. Amplified 957 bp of SAG1 was cloned into pGEM-T and further sub-cloned into pET28-SAG1. BL21 bacteria were induced at different concentrations of isopropyl ß-d-1-thiogalactopyranoside for the expression of rSAG1 protein. An immunoblot was developed for the confirmation of recombinant protein expression at 35 kDa that was actually recognized by anti-HIS antibodies and sera were collected from infected mice. PLGA encapsulated nanospheres of recombinant SAG1 were characterized through scanning electron microscopy. Experimental mice were intraperitoneally immunized with rSAG1 protein and intra-nasally immunized with nanosphere. The immune response was evaluated by indirect ELISA. In results intra-nasally administered rSAG1 in nanospheres appeared to elicit elevated responses of specific IgA and IgG2a than in control. Nanospheres of rSAG1 are found to be a bio-compatible candidate for the development of vaccine against T. gondii.


Assuntos
Antígenos de Protozoários/química , Imunidade Humoral/imunologia , Imunização , Nanosferas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Proteínas de Protozoários/química , Células Th1/imunologia , Toxoplasma/imunologia , Administração Intranasal , Animais , Antígenos de Protozoários/administração & dosagem , Antígenos de Protozoários/imunologia , Portadores de Fármacos/química , Camundongos , Proteínas de Protozoários/administração & dosagem , Proteínas de Protozoários/imunologia
11.
Materials (Basel) ; 11(6)2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29874828

RESUMO

Due to the high formation energy of Indium interstitial defect in the TiO2 lattice, the most probable location for Indium dopant is substitutional sites. Replacing Ti by In atom in the anatase TiO2 shifted the absorption edge of TiO2 towards visible regime. Indium doping tuned the band structure of TiO2 via creating In 5p states. The In 5p states are successfully coupled with the O 2p states reducing the band gap. Increasing In doping level in TiO2 improved the visible light absorption. Compensating the charge imbalance by oxygen vacancy provided compensated Indium doped TiO2 model. The creation of oxygen vacancy widened the band gap, blue shifted the absorption edge of TiO2 and declined the UV light absorption. The 2.08% In in TiO2 is the optimal Indium doping concentration, providing suitable band structure for the photoelectrochemical applications and stable geometrical configuration among the simulated models. Our results provide a reasonable explanation for the improved photoactivity of Indium doped TiO2.

12.
Materials (Basel) ; 11(2)2018 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-29470393

RESUMO

The location and nature of the doped elements strongly affect the structural, electronic and optical properties of TiO2. To tailor the band structure and modify the photoelectrochemical properties of TiO2, a pair of dopants is selected. Fe and N atoms are inserted in the TiO2 network at substitutional and interstitial sites with different relative distances. The main objective behind the different locations and sites of the doped elements is to banish the isolated unoccupied states from the forbidden region that normally annihilates the photogenerated carriers. Fe at the Ti site and N at the O site doped in the TiO2 network separated at a distance of 7.805 Å provided a suitable configuration of dopant atoms in terms of geometry and band structure. Moreover, the optical properties showed a notable shift to the visible regime. Individual dopants either introduced isolated unoccupied states in the band gap or disturbed the fermi level and structural properties. Furthermore, the other co-doped configurations showed no remarkable band shift, as well as exhibiting a suitable band structure. Resultantly, comparing the band structure and optical properties, it is argued that Fe (at Ti) and N (at O) doped at a distance of 7.805 Å would strongly improve the photoelectrochemical properties of TiO2.

13.
J Ayub Med Coll Abbottabad ; 30(4): 585-588, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30632342

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide, and coronary artery disease (CAD) is the most prevalent manifestation associated with high mortality and morbidity. Older age is independent predictor of cardiovascular mortality and death. Elderly may experience high rates of complications following acute STEMI. Optimal reperfusion strategy in elderly following STEMI remains under debate due to their exclusion from trials evaluating various treatment modalities. Primary PCI has emerged as treatment of choice in patients presenting with acute STEMI in a certain window period. The rationale of this study is to help us determine the outcome of primary PCI in the local elderly population. METHODS: The study was designed as descriptive cross-sectional study and was carried out at AFIC, NIHD hospital Rawalpindi over a six months period. A total of 105 adults with STEMI were included in study. Data was analysed using SPSS-19.0. RESULTS: Total 105 patients were included in the study according to the inclusion criteria of the study. There were 102 (97.1%) patients who successfully achieved TIMI II flow post Primary PCI.. CONCLUSIONS: We concluded that outcome of primary PCI in local elderly population is favourable which leads to a consensus that primary PCI should be offered to every elderly patient presenting to tertiary care hospital with well-equipped Cath lab and experienced staff.


Assuntos
Circulação Coronária , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino
14.
Front Oncol ; 5: 210, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26500885

RESUMO

Nuclear receptor co-repressor (N-CoR) is the key component of generic co-repressor complex essential for the transcriptional control of genes involved in cellular hemostasis. We have recently reported that N-CoR actively represses Flt3, a key factor of hematopoietic stem cells (HSC) self-renewal and growth, and that de-repression of Flt3 by the misfolded N-CoR plays an important role in the pathogenesis of promyelocytic and monocytic acute myeloid leukemia (AML). The leukemic cells derived from the promyelocytic and monocytic AML are distinctly characterized by the ectopic reactivation of stem cell phenotypes in relatively committed myeloid compartment. However, the molecular mechanism underlying this phenomenon is not known. Here, we report that N-CoR function is essential for the commitment of primitive hematopoietic cells to the cells of myeloid lineage and that loss of N-CoR function due to misfolding is linked to the ectopic reactivation of generic stem cell phenotypes in promyelocytic and monocytic AML. Analysis of N-CoR and Flt3 transcripts in mouse hematopoietic cells revealed a positive correlation between N-CoR level and the commitment of myeloid cells and an inverse correlation between N-CoR and Flt3 levels in primitive as well as committed myeloid cells. Enforced N-CoR expression in mouse HSCs inhibited their growth and self-renewal potentials and promoted maturation toward cells of myeloid lineage, suggesting a role of N-CoR in the commitment of cells of myeloid lineage. In contrast to AML cells with natively folded N-CoR, primary and secondary promyelocytic and monocytic AML cells harboring the misfolded N-CoR were highly positive for Flt3 and myeloid antigen-based HSC marker CD34. Genetic and therapeutic restoration of N-CoR conformation significantly down-regulated the CD34 levels in monocytic AML cells, suggesting an important role of N-CoR in the suppression of CD34-based HSC phenotypes. These findings collectively suggest that N-CoR is crucial for the commitment of primitive hematopoietic cells to cells of myeloid lineage and that misfolded N-CoR may contribute to transformation of committed myeloid cells through the ectopic reactivation of Flt3/CD34-based stem cell phenotypes in promyelocytic and monocytic AML. Moreover, these findings provide novel mechanistic insights into the formation of leukemic stem cells in subsets of AML and identify the misfolded N-CoR as a subtype-specific biomarker of AML.

15.
J Med Chem ; 57(14): 5904-18, 2014 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-24960549

RESUMO

Curcumin is known to trigger ER-stress induced cell death of acute promyelocytic leukemic (APL) cells by intercepting the degradation of nuclear co-repressor (N-CoR) protein which has a key role in the pathogenesis of APL. Replacing the heptadienedione moiety of curcumin with a monocarbonyl cross-conjugated dienone embedded in a tetrahydrothiopyranone dioxide ring resulted in thiopyranone dioxides that were more resilient to hydrolysis and had greater growth inhibitory activities than curcumin on APL cells. Several members intercepted the degradation of misfolded N-CoR and triggered the signaling cascade in the unfolded protein response (UPR) which led to apoptotic cell death. Microarray analysis showed that genes involved in protein processing pathways that were germane to the activation of the UPR were preferentially up-regulated in treated APL cells, supporting the notion that the UPR was a consequential mechanistic pathway affected by thiopyranone dioxides. The Michael acceptor reactivity of the scaffold may have a role in exacerbating ER stress in APL cells.


Assuntos
Curcumina/análogos & derivados , Óxidos S-Cíclicos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Inibidores de Proteases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Óxidos S-Cíclicos/síntese química , Óxidos S-Cíclicos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Relação Estrutura-Atividade
16.
J Nanosci Nanotechnol ; 14(9): 6865-71, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25924342

RESUMO

In this paper, the effects of Mo doping on the geometrical, electronic, optical, and photocatalytic properties of TiO2 have been investigated theoretically and experimentally. The density functional theory based calculations show that Mo doping creates impurity states (Mo 4d) below the conduction band of TiO2 and the Fermi level is pinned inside the conduction band verifying n-type doping nature of the Mo in TiO2, which enhances its visible light absorption. Anatase TiO2 particles with Mo contents of 0.08, 0.1, 0.5, 1.0, 1.5 and, 2.0 at.% were synthesized by hydrothermal method without any post heat treatment for crystallization. Experiment results show that Mo ions have been successfully doped into the TiO2 lattice. The morphology of TiO2 particles is nearly spherical and the grain size is uniformly distributed as about 10 nm. Synthesized sample with 0.1 at.% Mo doping concentration shows the best visible light photocatalytic activity due to the reduced band gap and improved electron-hole pairs separation. However, the photocatalytic activity of the sample with 2.0 at.% Mo is relatively low although its visible light absorption is the best among the samples. The enhanced recombination of electron-hole pairs caused by the excessive Mo doping concentration may account for it.

17.
PLoS One ; 8(8): e70891, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23940660

RESUMO

The nuclear receptor co-repressor (N-CoR) is a key component of the generic co-repressor complex that plays an important role in the control of cellular growth and differentiation. As shown by us recently, the growth suppressive function of N-CoR largely relies on its capacity to repress Flt3, a key regulator of cellular gorwth during normal and malignant hematopoesis. We further demonstrated how de-repression of Flt3 due to the misfolded conformation dependent loss (MCDL) of N-CoR contributed to malignant growth in acute myeloid leukemia (AML). However, the molecular mechanism underlying the MCDL of N-CoR and its implication in AML pathogenesis is not fully understood. Here, we report that Akt-induced phosphorylation of N-CoR at the consensus Akt motif is crucial for its misfolding and subsequent loss in AML (AML-M5). N-CoR displayed significantly higher level of serine specific phosphorylation in almost all AML-M5 derived cells and was subjected to processing by AML-M5 specific aberrant protease activity. To identify the kinase linked to N-CoR phosphorylation, a library of activated kinases was screened with the extracts of AML cells; leading to the identification of Akt as the putative kinase linked to N-CoR phosphorylation. Consistent with this finding, a constitutively active Akt consistently phosphorylated N-CoR leading to its misfolding; while the therapeutic and genetic ablation of Akt largely abrogated the MCDL of N-CoR in AML-M5 cells. Site directed mutagenic analysis of N-CoR identified serine 1450 as the crucial residue whose phosphorylation by Akt was essential for the misfolding and loss of N-CoR protein. Moreover, Akt-induced phosphorylation of N-CoR contributed to the de-repression of Flt3, suggesting a cross talk between Akt signaling and N-CoR misfolding pathway in the pathogenesis of AML-M5. The N-CoR misfolding pathway could be the common downstream thread of pleiotropic Akt signaling activated by various oncogenic insults in some subtypes of leukemia and solid tumors.


Assuntos
Leucemia Monocítica Aguda/enzimologia , Correpressor 1 de Receptor Nuclear/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Substituição de Aminoácidos , Linhagem Celular Tumoral , Ativação Enzimática , Regulação Leucêmica da Expressão Gênica , Células HEK293 , Humanos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Correpressor 1 de Receptor Nuclear/genética , Fosforilação , Conformação Proteica , Dobramento de Proteína , Processamento de Proteína Pós-Traducional , Estabilidade Proteica , Proteólise , Serina/metabolismo
18.
J Phys Chem A ; 117(27): 5650-4, 2013 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-23773208

RESUMO

The first-principles study of Ni-doped InN has been carried out to explore the doping effect of various charge states of Ni on the structural, electronic, magnetic, and optical properties of InN using generalized gradient approximation. Structural properties like lattice parameters, aspect ratios, bond lengths, and formation energies of (In, Ni) N are used to determine the stability of each doped system. The formation energies of (In, Ni)N systems decrease with the increase in charge state of nickel, while the bond lengths show an opposite trend. The DOS diagram shows that the introduction of Ni-d states within the bang gap region reduces the band gap for Ni(1+)- and Ni(2+)-doped InN, while the isolated states are generated in the case of Ni(3+)- and Ni(4+)-doped systems. The Ni(1+)-, Ni(3+)-, and Ni(4+)-doped InN systems are ferromagnetic in nature, whereas the (In, Ni(2+))N depicts spin-glass-like behavior. The best possible magnetization is obtained for (In, Ni(4+))N with a total magnet moment of 2.42 µB per supercell. Because of the presence of nickel impurities, the optical properties of InN have been significantly improved. The pure and Ni(3+)- and Ni(4+)-doped InN systems show nearly the same values of absorption edges (∼0.56 eV), in contrast with the Ni(1+)- and Ni(2+)-doped systems, where these values are 0.37 and 0.51 eV, respectively. The shift in absorption edges of Ni(1+)- and Ni(2+)-doped InN to lower energies and increase in the intensity of absorption and broadening of absorption peaks can be attributed to the pronounced band-gap reduction for these systems. A negligible shift of absorption edges in the case of Ni(3+)- and Ni(4+)- doped InN is the characteristic of isolated charge states introduced around the Fermi level, which inhibit the band gap reduction, and hence the optical properties are not improved as expected. This study demonstrates an important fact that for best possible optical device applications Ni(1+)-doped InN system is excellent, while for better magnetic properties the (In, Ni(4+))N is more suitable.

19.
J Nanosci Nanotechnol ; 13(3): 1773-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23755589

RESUMO

Tin monoxide is a significant functional semiconductor material which employed to a wide area of applications especially optical and energy storage devices. Presently, template free hydrothermal technique has been employing to synthesize stannous oxide (SnO) clinopinacoid type controlled morphology using SnCl2 x 2H2O, NH3, and H2O as raw materials. The crystalline phase, morphology, particle size and component were characterized by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and field-emission scanning electron microscopy (FESEM). FESEM results exhibited the large scale homogeneous growth of clinopinacoid architecture with the obvious size of 5 - 7 micrometers. The XRD results showed that the average crystallite size of the tetragonal phase romarchite SnO was about 29 nm calculated from the FWHM of X-ray diffraction pattern. The dominant Raman active modes A(1g) = 205 cm(-1), B(1g) = 105-107 cm(-1) and about 6 cm(-1) redshift were observed by the Raman spectroscopy, which further confirmed the existence of the nano tetragonal phase SnO. The electrochemical performance of as-synthesized SnO clinopinacoid structure as the anode material for lithium ion batteries was investigated. It was observed that the first discharge capacity of the two samples could reach a very high value of 1502 mA h g(-1) and 1422 mA h g(-1) respectively. The effect of nitrogen concentration on morphology as well as cyclic performance of Li-Ion-batteries was also discussed.

20.
ChemMedChem ; 7(9): 1567-79, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22887959

RESUMO

Curcumin arrests the proliferation of acute promyelocytic leukemia (APL) cells by stabilizing the misfolded nuclear receptor co-repressor (N-CoR) protein, thereby sensitizing APL cells to apoptosis induced by the unfolded protein response. This phenomenon was attributed to inhibition of the proteasomal and protease-induced breakdown of misfolded N-CoR by curcumin. Curcumin is, however, a modest inhibitor and affected the viability of APL cells at micromolar concentrations. Modifying curcumin at its conjugated ß-diketone linker and terminal phenyl rings yielded potent congeners with sub-micromolar growth inhibitory activities which selectively kill APL cells over non-APL leukemic and nonmalignant cells. Analogues with pronounced APL-selective anti-proliferative activities, as observed in representative dibenzylidenecyclohexanones and dibenzylidenecyclopentanones, strongly promoted the accumulation of misfolded and nonfunctional N-CoR at significantly lower concentrations than their growth inhibitory IC(50) values. These compounds also inhibited the human 20S proteasome in an enzyme-based assay, thus providing convincing support for the prevailing hypothesis that impeding the degradation of N-CoR is a key mechanistic event contributing to APL cell death.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Proteínas Correpressoras/metabolismo , Curcumina/análogos & derivados , Curcumina/farmacologia , Leucemia Promielocítica Aguda/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proteínas Correpressoras/análise , Humanos , Leucemia Promielocítica Aguda/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Dobramento de Proteína/efeitos dos fármacos , Resposta a Proteínas não Dobradas/efeitos dos fármacos
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